INNOVATIONS IN NANOTECHNOLOGY at the NSECs and NNIN

INNOVATIONS IN NANOTECHNOLOGY at the NSECs and NNIN 

Highlights of Achievements      

June 2011 

National Science Foundation Arlington, Virginia 

INNOVATIONS IN NANOTECHNOLOGY at the NSECs and NNIN 

 Highlights of Achievements 

June 2011

Prepared by

Courtland Lewis SciTech Communications LLC

Prepared for

National Science Foundation Arlington, Virginia

Award No. 0844639 (NSF/ENG)

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ACKNOWLEDGMENTS

This report was prepared by SciTech Communications LLC (STC) for Dr. Mihael Roco, Senior Advisor for Nanotechnology in the Directorate for Engineering of the National Science Foundation. Mr. David LaGesse carried out the majority of the research and writing as a subcontractor to STC. The report was prepared under an NSF subaward to the World Technology Evaluation Center (WTEC), Inc. The authors acknowledge the support and assistance of Dr. Roco as well as that of Dr. Robert D. Shelton and Mr. Geoffrey Holdridge, President and Vice President for Government Services, respectively, of WTEC.

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CONTENTS

List of Nanoscale Science and Engineering Centers (NSEC) .............................. 1 

List of National Nanotechnology Infrastructure Network (NNIN) Sites ........... 2 

OVERVIEW ............................................................................................................. 3 

BACKGROUND ...................................................................................................... 4 

INNOVATIONS AT THE NSECs .......................................................................... 7 Center for Nanotechnology in Society (CNS-ASU)—Arizona State University ....................... 9 

Center for Electron Transport in Molecular Nanostructures—Columbia University ............... 12 

Center for Nanoscale Systems (CNS)—Cornell University ..................................................... 15 

Center for the Environmental Implications of Nanotechnology (CEINT)—Duke University . 19 

Science of Nanoscale Systems and Their Device Applications—Harvard University ............ 22 

Center for High-Rate Nanomanufacturing (CHN)—Northeastern University ......................... 26 

Center for Integrated Nanopatterning and Detection Technologies (NU-NSEC)—Northwestern University ....................................................................................................... 31 

Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD)— Ohio State University ............................................................................................................ 35 

Center for Directed Assembly of Nanostructures (RNC)—Rensselaer Polytechnic Institute .. 39 

Center for Biological and Environmental Nanotechnology (CBEN)—Rice University .......... 43 

Center for Probing the Nanoscale (CPN)—Stanford University .............................................. 47 

Center of Integrated Nanomechanical Systems (COINS)— University of California at Berkeley ..................................................................................... 52 

Center for Scalable and Integrated Nanomanufacturing (SINAM)— University of California at Berkeley ..................................................................................... 56 

Center for Environmental Implications of Nanotechnology (UC CEIN)— University of California, Los Angeles .................................................................................. 60 

Center for Nanotechnology in Society (CNS-UCSB)— University of California, Santa Barbara ................................................................................ 65 

Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems (Nano-CEMMS)—University of Illinois at Urbana-Champaign ..................................................... 69 

Center for Hierarchical Manufacturing (CHM)—University of Massachusetts Amherst ........ 74 

The Nano/Bio Interface Center (NBIC)—University of Pennsylvania .................................... 78 

Center in Templated Synthesis and Assembly at the Nanoscale (UW NSEC)— University of Wisconsin-Madison ......................................................................................... 82 

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INNOVATIONS AT THE NINN .......................................................................... 87 

NNIN Research Highlights .................................................................................... 89 Health ........................................................................................................................................ 89 

Electronics ................................................................................................................................ 95 

Energy ....................................................................................................................................... 99 

Optics ...................................................................................................................................... 101 

Nano Tools .............................................................................................................................. 103 

Chemistry ................................................................................................................................ 106 

Example Startups Associated with NNIN Nodes .............................................. 108 Health ...................................................................................................................................... 108 

Electronics .............................................................................................................................. 110 

Energy ..................................................................................................................................... 111 

Optics ...................................................................................................................................... 113 

Nano Tools .............................................................................................................................. 115 

Sensors .................................................................................................................................... 116 

NNIN Outreach and Education .......................................................................... 118 

Profiles of the NNIN Nodes ................................................................................. 120

Closure…………………………………………………………………………. 125

LIST OF NANOSCALE SCIENCE AND ENGINEERING CENTERS (NSEC) Center for Nanotechnology in Society Arizona State University (cns.asu.edu) Center for Electron Transport in Molecular Nanostructures Columbia University (cise.columbia.edu/NSEC) Center for Nanoscale Systems Cornell University (cns.cornell.edu) Center for Environmental Implications of Nanotechnology Duke University (www.ceint.duke.edu) Science of Nanoscale Systems and their Device Applications Harvard University (nsec.harvard.edu) Center for High Rate Nanomanufacturing Northeastern University (northeastern.edu/chn) Center for Integrated Nanopatterning and Detection Technologies Northwestern University (nsec.northwestern.edu) Center for Affordable Nanoengineering of Polymeric Biomedical Devices Ohio State University (nsec.ohio-state.edu) Center for Directed Assembly of Nanostructures Rensselaer Polytechnic Institute (rpi.edu/dept/nsec) Center for Biological and Environmental Nanotechnology Rice University (cben.rice.edu) Center for Probing the Nanoscale Stanford University (stanford.edu/group/cpn) Center of Integrated Nanomechanical Systems University of California at Berkeley (mint.physics.berkeley.edu/coins) Center for Scalable and Integrated Nanomanufacturing University of California at Berkley (sinam.org) Center for Environmental Implications of Nanotechnology University of California at Los Angeles (cein.cnsi.ucla.edu) Center for Nanotechnology in Society University of California, Santa Barbara (cns.ucsb.edu) Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems University of Illinois at Urbana-Champaign (nano-cemms.illinois.edu) Center for Hierarchical Manufacturing University of Massachusetts Amherst (chm.pse.umass.edu) Nano/Bio Interface Center University of Pennsylvania (nanotech.upenn.edu) Center in Templated Synthesis and Assembly at the Nanoscale University of Wisconsin-Madison (nsec.wisc.edu)

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LIST OF NATIONAL NANOTECHNOLOGY INFRASTRUCTURE NETWORK (NNIN) SITES Nanofab Arizona State University (fulton.asu.edu/nanofab)

Cornell NanoScale Science & Technology Facility Cornell University (cnf.cornell.edu)

Nanotechnology Research Center Georgia Institute of Technology (nrc.gatech.edu)

Center for Nanoscale Systems Harvard University (cns.fas.harvard.edu)

Howard Nanoscale Science and Engineering Facility Howard University (msrce.howard.edu)

Penn State Nanofabrication Laboratory Pennsylvania State University (mri.psu.edu/facilities/NNIN)

Stanford Nanofabrication Facility Stanford University (snf.stanford.edu) Nanotech University of California at Santa Barbara (nanotech.ucsb.edu)

Colorado Nanofabrication Lab University of Colorado (cnl.colorado.edu)

Lurie Nanofabrication Facility University of Michigan (lnf.umich.edu) Nanofabrication Center University of Minnesota (nfc.umn.edu) Microelectronics Research Center University of Texas at Austin (mrc.utexas.edu) Center for NanoTechnology University of Washington (depts.washington.edu/ntuf) Nano Research Facility Washington University in St. Louis (nano.wustl.edu)

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OVERVIEW Nanotechnology is recognized as a revolutionary new field of science and technology, comparable to the introduction of electricity, biotechnology, and digital information. Research into nanotechnology is a broad-based, multidisciplinary field with discoveries that are leading to new products and applications projected to reach mass use by 2020, significantly changing and improving many aspects of human life.

Over the past decade, federal agencies in the United States have worked together under the National Nanotechnology Initiative (NNI) to coordinate funding for a wide array of research and development programs. The NNI aims to develop the field of nanoscale science and engineering for societal benefit.

The result has been soaring growth in nanotechnology discoveries, inventions, workers, research and development funding, and markets—all of which have seen yearly double-digit growth, usually at 25 percent or better. In the next decade, nanotechnology promises to transform fields that are crucial to human achievement and well-being, including health care, the environment, energy, and data processing. The worldwide market for products incorporating nanotechnology already reached about $254 billion in 2009, and is projected to reach $1 trillion by 2015 and $3 trillion by 2020 (see Nanotechnology Research Directions for Societal Needs in 2020, NSF/WTEC international study, 2010; available at www.wtec.org/nano2/).

Central to that progress are two major sources of nanotechnology research and development, both funded by the National Science Foundation: the Nanotechnology Science and Engineering Centers (NSECs) and the National Nanotechnology Infrastructure Network (NNIN). This report describes the landscape of NSECs and NNIN facilities and highlights many of the specific innovations they have achieved, including the most significant fundamental discoveries, powerful new applications of nanotechnology, and start-ups and other commercial ventures formed as a result of advances made at these centers and facilities. It also describes novel education and outreach efforts generated by the NSECs and NNIN. In other words, the report showcases how this NSF-funded work contributes to the nation’s vital “innovation ecosystem.”

The report, while extensive, captures but a subset of the programs' most notable innovations. It was compiled from information provided by the NSECs and the NNIN, principals of startup companies spun out of the centers, and from public reports and published databases. The emphasis is on discoveries that have done the most to advance nanotechnology research, and on technologies that are the most promising for commercial applications. Start-up companies generated out of the NSECs and/or that are supported by the NNIN are also an important form of technology transfer and a major route to successful commercialization of nanotechnology innovations. Where available, measures of a start-up's success are included, such as market data on sales or number of employees.

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BACKGROUND

Science and Engineering at the Nanoscale One nanometer is a magical point on the dimensional scale. Objects measured in nanometers are where human engineering and nature meet, the confluence of the smallest of human-made devices and the largest molecules of living systems.

A nanometer is one billionth of a meter. A sheet of paper is about 100,000 nanometers thick, a single gold atom is about one-third of a nanometer across. Advances in imaging technology, other instruments and experimentation have enabled scientists to see into the nanoscale, where they observe things never seen before—novel structures, phenomena, and processes.

Matter such as gases, liquids, and solids can exhibit unusual physical, chemical, and biological properties at the nanoscale. They differ in important ways not only from the properties of materials in more conventional sizes—what scientists call bulk materials—but also from single atoms or molecules. Some nanostructured materials are stronger or have different magnetic properties compared to other forms or sizes or the same material. Others are better at conducting heat or electricity. They may become more chemically reactive or reflect light better or change color as their size or structure is altered.

Nanoscience involves the research into and discovery of new principles and materials at the nanoscale. Nanoscience inherently bridges disciplinary boundaries, as the same principles and tools of nanotechnology apply to chemistry, biology, physics, and other fields. Scientists discover new phenomena, properties, and functions at the nanoscale; develop a library of components as building-blocks for potential future applications; and advance the tools used in characterizing, monitoring, and controlling matter at the nanoscale. They are also learning how to organize these new nanostructures into larger and more complex functional structures and devices.

Nanotechnology is the control and restructuring of matter at the nanoscale—that is, at the atomic and molecular levels in the size range of about 1 to 100 nanometers. The aim of nanotechnology is to create materials, devices, and systems with fundamentally new properties and functions by engineering their small structure. This is the ultimate frontier in changing the properties of materials in an affordable fashion, and it is the most efficient length scale for manufacturing and molecular medicine.

Nature exhibits a transition in behavior from single atoms or molecules to the collective behavior of atomic and molecular assemblies; nanotechnology exploits this natural threshold.

In capitalizing on the unusual properties of materials at the nanoscale, technology can profoundly affect how we live. Nanotechnology's discoveries will help determine how healthy we are, what we produce, how we interact and communicate with others, how we produce and use new forms of energy, and how we maintain our environment.

This is not a far-off revolution. In looking at two of the Earth's most pressing issues, clean energy and fresh water, applications of nanotechnology will make alternatives economically feasible in a matter of years. Nanotechnology should make solar energy financially viable around 2015 in the United States, and will provide breakthrough solutions for more than half of projects

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in energy conversion, energy storage, and carbon encapsulation. Nanotechnology will make the conversion of salt water (water desalinization) affordable around 2020 in some regions.

Already, hundreds of products sold to consumers and industry incorporate nanotechnology. Nanotechnology is expected to be in widespread use by 2020, with the potential to touch almost all industrial sectors and medical fields. Resulting benefits will include increased productivity, more sustainable development, and new jobs.

The National Nanotechnology Initiative 

A National and Global Priority In the United States, the financial investment in nanotechnology research and development has been considerable over the past decade. The U.S. government alone has spent more than $12 billion, placing it among the largest U.S. civilian technology investments since the Apollo Moon-landing program. And some 60 countries have adopted research programs, ranking nanotechnology among the largest and most competitive research fields globally.

This global endeavor was set in motion by a vision formulated in 1999 among key leaders in the field, whose work inspired the National Nanotechnology Initiative (NNI). It is the NNI that has guided the world-leading investment by U.S. federal agencies in nanotechnology.

Launched in 2001 with eight agencies, the NNI today consists of 25 federal agencies with a range of nanotechnology research and regulatory roles. Fifteen of the agencies have research and development budgets that relate to nanotechnology, with collective funding rising steadily over the past decade to about $2 billion a year. As an interagency effort, the NNI informs and influences the federal budget and planning processes through its member agencies and through the National Science and Technology Council.

By creating a powerhouse of discovery and innovation, the NNI has been the major driver for nanotechnology developments and applications in the United States and around the world.

NSF’s Role in Nanotechnology The National Science Foundation (NSF) created the first dedicated programs in nanotechnology in 1991, funded “Partnership in Nanotechnology” in 1997-1998, proposed the NNI in 1999, and is one of the leading federal agency sources for NNI funding. NSF has seen its yearly spending on nanotechnology steadily increase over the past decade to about $425 million. The NSF funds all areas of nanoscale science and engineering, from research into fundamental phenomena and processes and nanomaterials to nanomanufacturing, environmental and societal implications, and also supports investments in research facilities and instruments.

This report looks at the nanotechnology-related research and development contributions of two of the leading engines of NSF-funded research into nanotechnology: the Nanoscale Science and Engineering Centers (NSECs) and the National Nanotechnology Infrastructure Network (NNIN).

The NSF funds 19 NSECs, each based at a major research university in the United States, and each of which partners with other universities, industry, and other public and private organizations. The centers support education and fundamental research and encourage science and engineering cooperation in emerging areas of research at the nanoscale, including: biosystems; structures, novel phenomena, and quantum control; devices and system architecture;

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processes in the environment; multi-scale, multi-phenomena theory, modeling and simulation; manufacturing processes; and studies on the societal and educational implications of scientific and technological advances at the nanoscale.

The NSF also funds 14 user facilities that work cooperatively as a single network through the NNIN. The network's central mission is to provide hands-on nanotechnology science and engineering access for researchers from industry, government, and academia. The NNIN allows researchers to build and explore materials, structures, devices and systems using a combination of bottom-up and self-assembly techniques and top-down fabrication techniques. The network also has in place national and local efforts in support of education, public outreach, safety, and a mission to examine the societal and ethical implications of nanotechnology.

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INNOVATIONS AT THE NSECS The National Science Foundation initiated the Nanoscale Science & Engineering Center program in September 2001 to support fundamental research and to encourage scientists and engineers to work together on research and education in emerging nanoscience and technology.

The 19 centers, each based at a major research university in the United States, are at the forefront of nanotechnology—a revolution underway in science, engineering, and technology that is based on the ability to organize, characterize, and manipulate matter at the nanoscale. The centers are helping industry and academics to create and utilize functional materials, devices, and systems with novel properties and functions that are achieved through the control of matter, atom-by-atom, molecule by molecule, or at the macromolecular level.

Each of the 19 centers operates with a specific focus. Center researchers and managers have identified key nanotechnology research areas in advanced materials, biotechnology, electronics, healthcare, environmental improvement, energy conversion and storage, space exploration, transportation, and biosensors. They also have developed innovative outreach and education programs. All NSECs consider nanotechnology's implications for broader society, and some centers are devoted to studying those implications.

The NSEC program addresses opportunities too complex and multi-faceted for individuals or small groups of researchers. Centers bring together researchers with diverse expertise, often working at partner universities or other private- and public-sector organizations and from a broad spectrum of disciplines such as engineering, mathematics, computer science, the physical, biological, environmental, social and behavioral sciences, and the humanities. Research at the NSECs ranges from work focused on basic discoveries to technology innovation.

While this report concentrates on specific breakthroughs in center research and significant technological innovations, the overall academic contribution is impressive. An independent

NSF’s 19 Nanoscale Science & Engineering Centers

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evaluation in 2010 counted nearly 3,900 published research papers by 15 of the centers, with their work being cited by other academics in nearly 95,000 published research papers. Co-authorship of NSEC research extends the reach of the centers to nearly all 50 states.

Partnership with private industry is at the core of the NSEC network. Besides the spinoffs and startups cited here, the centers have industry members, advisory boards, and research collaborators. More than 420 private companies have worked with the centers, including nearly 150 whose scientists and engineers have co-authored papers with NSEC researchers, amounting to more than 10 percent of the papers published by the centers.

The current pace of revolutionary discoveries in nanoscale science and technology is expected to accelerate greatly over the next decade, with profound implications for existing technologies as well as the development of entirely new technologies. The NSECs will be central to these advancements.

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CENTER FOR NANOTECHNOLOGY IN SOCIETY (CNS-ASU)—ARIZONA STATE UNIVERSITY The Center for Nanotechnology in Society at Arizona State University is the largest center in the world for research, education, and outreach on the societal aspects of nanotechnology. The Center's goals are to research the societal implications of nanotechnology; to train a community of scholars with new insight into the societal dimensions of nanoscale science and engineering; to engage the public, policy makers, business leaders, and researchers in dialogues about the goals and implications of nanotechnology; and to partner with nanotech laboratories to introduce a greater capacity for social learning into the research-and-development process. By increasing awareness of its implications, CNS-ASU can help guide nanotechnology innovation toward more socially desirable outcomes and away from undesirable ones.

Research Highlights CNS-ASU pursues its goals through two cross-cutting research programs. One is grouped under the heading of real-time technology assessment (RTTA) and includes the analysis of nanotech research, surveying public opinion, encouraging public participation in decisions about nanotechnology, and evaluating the impact of CNS-ASU activities. Another group includes two research clusters, one investigating equity and responsibility and another studying "Nano and the City," which looks at urban design, materials, and the built environment.

The Center's work is increasingly shaped by its vision of anticipatory governance, a broad-based capacity extended throughout society that can act on a variety of inputs to manage emerging technology, while such management is still possible. CNS-ASU is pioneering anticipatory governance through engagement, anticipation, and integration activities with nanoscale scientists and engineers. While anticipatory governance is not yet widely or uniformly practiced, it has important potential as a creative instrument of innovation policy.

The Center’s core methods of real-time technology assessment and its vision of anticipatory governance have been recognized in important scholarly venues, including the field-defining Handbook of Science and Technology Studies, and in a series on innovation policy in Nature. A number of programs and scholars have begun to adopt the Center's concept of anticipatory governance and scrutinize it for their own purposes, from incorporation into the programmatic agenda of the public forms conducted by the Nano-scale Informal Science Education Network to sessions at the annual forums on science and technology policy held by the American Association for the Advancement of Science.

Product/Process Successes From passive to active nanostructures: A critical transition in nanotechnology’s development is the anticipated shift from passive to active nanostructures. Passive nanotechnology applications (such as nanocoatings, nanoparticles, and nanostructured materials) are already available. The second generation of nanostructures can actively evolve their properties, structure, and/or state during their operation—such as nanoelectro-mechanical systems, nanomachines,

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self-healing materials, and targeted drugs. This shift will likely increase nanotechnology’s impacts and require new approaches to assessing risks.

A CNS-ASU analysis of global nanotechnology publications, by a group of researchers led by Georgia Tech Prof. Philip Shapira, verified that the anticipated shift to active nanostructures is under way. The analysis showed that a sharp rise in publications focusing on active nanostructures began in 2006 and accelerated in 2007 and 2008.

Active nanostructures are likely to have a different and higher profile of impacts, including benefits as well as potential risks, compared to passive nanotechnology. The implications for society, health and safety, and the environment need to be addressed in other studies and in policy and governance processes.

The Center's analysis suggested that the following categories of active nanostructures are emerging in the research literature: remote-actuated nanostructures, such as light-actuated embedded sensors; environmentally responsive nanostructures, such as responsive drug delivery; miniaturized active nanostructures, such as synthetic molecular motors

and molecular machines; hybrid active nanostructures, or uncommon combinations of materials, such as silicon and organic materials; and transforming nanostructures, such as self-healing materials. (See Journal of Nanoparticle Research, January 2010)

Active nanostructures include synthetic molecular motors capable of self-propulsion.

Manipulating the brain: Enhancing cognitive functionality and other forms of manipulating the brain are arguably among the most morally significant emerging technologies that humans will face in the next quarter century. The human brain is intimately involved in the creation of thought, meaning, identity, and reasoning. The metaphorical and real transformation of the human brain into a biological machine capable of analysis, self-repair, and modification is likely to have enormous ramifications across human societies.

The End-to-End project, led by Prof. Clark Miller at Arizona State, is a real-time technology assessment of the application of nanotechnology to the human brain. It systematically assesses the convergence of nanotechnology with biotechnology, information technology, cognitive science, and neuroscience. At the same time that the assessments are done, they are fed back to the innovation process in order to shape new technology in ways that enhance societal outcomes.

End-to-End explores these themes of human identity, enhancement, and biology in a number of real-time technology assessment research projects. These RTTA projects include the characterization of nano-neuro research data, the characterization of public and scientist opinions and values, the construction of scenarios to encourage responsible debate about technological

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futures, and the implementation of nationwide citizen-deliberation panels on nano-neural research.

For example, the project has identified cochlear implants as the first widespread neural implant where nanotechnology may offer a range of potential applications to improve or enhance the devices. Studying the history of cochlear implant technologies offers numerous insights regarding the social meanings that neural implants can give rise to, such as debate over the "disabled" status of deaf culture, or the use of cochlear implants in children. This research will be represented in the multi-authored book, Nanotechnology, the Brain, and the Future, which will be published in 2011 as the third volume of the Yearbook of Nanotechnology in Society series.

Nanotech education gap: The gap in nanotechnology knowledge between the least-educated and the most-educated citizens widened over the five years through 2009, according to a CNS-ASU study of national survey data conducted by Prof. Elizabeth A. Corley of Arizona State and Prof. Dietram A. Scheufele of the University of Wisconsin-Madison.

Americans with at least a college degree have shown an increased understanding of the new technology since 2004. On the other hand, for those with education levels of less than a high school diploma, knowledge about nanotechnology declined significantly. These results raise concerns that the group most in need of knowledge and information—those with the lowest levels of formal education—are not being reached sufficiently by current outreach and education efforts.

Every day that researchers spend not addressing these emerging gaps will create a larger disconnect between scientifically literate audiences and the information-poor. There is an urgent need to find ways of communicating effectively with all groups in society.

Nanotechnology information is not reaching enough of those with the lowest levels of formal education.

Fortunately, the study also found that the Internet is one of the most effective methods for informing the less educated about nanotechnology. The number of days a week that respondents spent online was significantly related to nanotech-knowledge levels. In other words, the Internet may finally live up to its hype as a tool for creating a more informed citizenry by serving as a "leveler" of knowledge gaps about nanotech. The CNS-ASU study offers a clear mandate to researchers to explore the potential of nontraditional ways of connecting with lay audiences. (See The Scientist, January, 2010)

Education and Outreach Integrating social and natural sciences: Around the world, science policies are calling for “integration” to address broader societal dimensions of science research in ways that have the

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potential to influence both the process and the products of such research. Despite such calls, there is little understanding of either the capacity of laboratories to respond to them or the role that “socio-technical” collaborations may play in enhancing such responsiveness. .

Accordingly, the Socio-Technical Integration Research project investigates these questions by embedding social and human scientists in 20 labs across 10 nations on 3 continents. Social researchers learn the theory and observe the methods of their laboratory counterparts, but they also introduce a protocol that elucidates the social and ethical dimensions of the lab science itself in a real-time, hands-on collaborative manner.

The methods and inquiries of the social scientists become embedded in the laboratory during each engagement study. Integrative activities can trigger changes in laboratory practices, whether by expanding the values and questions researchers consider or by informing material practices themselves. For example, reflections on responsible innovation generated novel ideas for antenna structures and nanoparticle synthesis for researchers at Arizona State University's Center for Single Molecule Biophysics. Moreover, such inquiries often advance deliberation on public values.

Exploring the application of nanotech: InnovationSpace, at Arizona State, is a transdisciplinary education-and-research lab that teaches students how to develop products that create market value while serving real societal needs and minimizing impacts on the environment. CNS-ASU sponsors three teams to visualize how futuristic nanotechnology product scenes can translate into usable products. The teams include students from design, business, and engineering who must develop concept products that use nanotechnology.

Teams must critically examine how people's everyday lives could change because of nanotechnology. Each year presents a different theme for students to tackle, such as nanotech in the areas of human health and enhancement, or the promise of nanotech in solving energy problems. (See video of Everwell developed by InnovationSpace at http://vimeo.com/13842428)

CENTER FOR ELECTRON TRANSPORT IN MOLECULAR NANOSTRUCTURES—COLUMBIA UNIVERSITY The overarching goal of the Center for Electron Transport in Molecular Nanostructures, known as “the Nanocenter" and based at Columbia University, is to establish new paradigms for information processing using the characteristics of electron transport that are unique to nanoscale molecular structures. Recognizing that nanoscience and nanotechnology hold the key to the continuing evolution of information processing, the Center is responding to the finite limits of silicon-based technology to power faster and smarter devices.

Founded in 2001, the Columbia Nanocenter draws upon years of experience in chemical synthesis to design molecular structures with carefully crafted properties. This work has potential impact beyond electronics, including photonics, biology, neuroscience, and medicine.

Research Highlights The Nanocenter's program focuses on using single molecules as an attractive alternative to silicon circuitry for carrying out the logical operations of computing. The Center is generating

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fundamental knowledge regarding the transport of electrons in molecules and in molecular assemblies of nanometer dimension.

The Columbia Nanocenter has been instrumental in the development and characterization of graphene, a seemingly simple, one-atom-thick sheet of bonded carbon atoms. This transformative new material has the potential to combine the high performance of the best semiconductors with the novel functionality of the best nanostructures, thus promising revolutionary new applications. The Center studies the fundamental aspects of graphene growth and structure. Center researchers have carried out a number of basic studies of the novel electronic properties of graphene, and through their understanding of the mechanical properties of graphene sheets and membranes, have fabricated new electromechanical devices.

The Center has produced groundbreaking work on understanding how electrons move through single molecules. Its discovery of diamine-gold systems has allowed researchers for the first time to undertake systematic explorations of the influence of chemical structure on molecular conductance—or how electrons move through molecules. Center researchers' demonstration of direct measurement of conductance for a single molecule bonded across a nanometer-scale, carbon-nanotube junction has created a new platform for single-molecule conductance studies. These experiments are already demonstrating a rich variety of behavior and should become a primary tool for future explorations of molecular conductance. They also open new doors for sensitive single-molecule detection techniques, potentially useful for DNA sequencing and related technologies.

Center investigators also have made significant advances toward the characterization and understanding of isolated, single-walled carbon nanotubes (SWCNTs). These capabilities are allowing scientists to explore the electronic properties of carbon nanotubes and carbon nanotube devices that have been structurally identified. Center investigators have explored in detail the properties of electronic devices fabricated from carbon nanotubes of known structure. These fundamental measurements will open up new perspectives in our understanding of the electronic transport properties of carbon nanotubes and corresponding devices.

Electrons passing through this device, fabricated from a single sheet of graphene, generate reflected waves with characteristics similar to photons of light.

Product/Process Successes Simple electronic devices from graphene: A one-atom thick sheet of carbon atoms, graphene is already displaying in simple devices its potential to combine the high performance of the best semiconductors with the novel functionality of the best nanostructures. In theory, the electrons in graphene do not move like normal particles with mass but rather they behave much more like photons, mass-less particles of light. In short, the graphene crystal can conduct electricity faster than any other substance at room temperature. Specifically, electrons in graphene move more easily than in silicon, providing for display of quantum mechanical behavior even at room temperature.

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Center researchers led by Columbia Prof. Philip Kim have recently observed quantum interference phenomena in an electronic device fabricated from a single graphene sheet. The interference results from the reflection of electrons from two junctions that are created by applying electric fields to the graphene. These findings spur expectations that graphene-based devices will alter the decades-old paradigm of semiconductor technologies based on silicon, and promise revolutionary new applications capable of changing our world. (See Scientific American, April 2008 and Nature Physics 5, 222-226 (2009)

Measuring carbon nanotubes: Single-walled carbon nanotubes (SWCNTs) represent a very important new class of materials with tremendous potential for applications in electronics, materials, and medicine. But synthesis of these important compounds today produces a wide variety of different structures with varying properties. Thus it is critically important to identify individual tube structures and to simultaneously measure properties of specified structures.

Center scientists have developed a unique form of Rayleigh scattering spectroscopy which provides rapid spectral signatures for individual nanotubes. This discovery has dramatically influenced how the entire scientific community explores the fascinating phenomena associated with carbon nanotubes.

Combining electron diffraction with Rayleigh scattering spectroscopy, a team of research scientists at the Columbia Nanocenter and Brookhaven National Laboratories have for the first time simultaneously determined the physical structure and optical transition energies of individual single-walled carbon nanotubes. These data permit scientists to test directly a model for the behavior of the transition energies of nanotubes as a function of their precise atomic structure. They also have observed, for the first time, splitting of optical transitions in metallic SWCNTs.

The figure shows the observed Rayleigh scattering spectrum for one isolated nanotube as well as the diffraction pattern for the same tube, clearly identifying the structural parameters.

Toward single-molecule DNA sequencing: Via a group of researchers led by Columbia Prof. Colin Nuckolls, with additional collaboration with Prof. Stuart Lindsay at Arizona State, the Nanocenter has reported for the first time the use of single-walled carbon nanotubes as nanopores for analyzing molecular transport properties. Nanopores are orifices of molecular diameter that connect two fluid reservoirs. At this length scale, the passage of even a single molecule generates a detectable change in the flow of ionic current through the pore.

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In particular, the group has fabricated microfluidic devices in which one single-walled carbon nanotube spans a barrier between two fluid reservoirs, enabling direct electrical measurement of ion transport through the tube. Relative to carbon nanotube membranes, this arrangement makes it possible to detect signals from the translocation of a single molecule and to correlate transport with the properties of individual SWCNTs.

Carbon nanotubes simplify the construction of nanopores, permit new types of electrical measurements, and may open avenues for control of DNA translocation. Such devices may be

used as single-molecule Coulter counters and form the basis of new approaches to DNA sequencing.

Electron micrograph showing microfluidic chambers with interconnecting carbon nanotube and flow control electrode. Device is fabricated with a polymeric material.

Startups and Spin­offs Adesso Biosciences: Adesso Biosciences is a nanotechnology company with operations in the US and China. Currently, Adesso Biosciences is pursuing research and development of innovative nanofabrication technologies, as well as applications of nanotechnology in the molecular diagnostics field. Potential products include carbon nanotube-based sensors that might be used for single-molecule DNA characterization.

The company's products are based on several patent applications held by researchers at the Columbia Nanocenter, and one application held by the California Institute of Technology. The company has nine employees in 2011, according to Dun & Bradstreet.

Graphene Laboratories (graphenelab.com): The primary goal of Graphene Laboratories is to apply fundamental science and technology to bring functional graphene materials and devices to market. The company operates the Graphene Supermarket (graphene-supermarket.com), a leading supplier of nanocarbon and graphene products to customers around the globe.

The firm also offers analytical services, prototype development, and consulting—as well as access to the manufacturing capacities of a partner, CVD Equipment Corp. Dun & Bradstreet reports that Graphene Labs has five employees.

CENTER FOR NANOSCALE SYSTEMS (CNS)—CORNELL UNIVERSITY The Center for Nanoscale Systems seeks to better understand the electronic, optical, and magnetic properties of materials at the nanoscale, using that knowledge to develop devices and

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systems that will revolutionize information technology, including electronics, communications, information storage, and sensors. CNS investigators also develop new nanocharacterization tools and nanoprocessing techniques to support these information technology efforts and to generally advance nanotechnology and nanoscience research.

Research Highlights CNS investigators have made a number of fundamental advances that have promise for improving information processing. Conventional electronic components such as computer logic and memory chips essentially have a planar geometry, which means that information transport between components must take place over relatively large distances, resulting in sub-optimal performance. Industry has been trying to get around this problem for years by developing compact, three-dimensional silicon-based devices. Center researchers have taken a fundamental step toward improving this situation by developing the means to fabricate a simple microprocessor comprised of three stacked layers of silicon nanomaterials, marking the first reported implementation of a three-dimensional microprocessor.

Center research also is contributing to improved optical communications systems. Conventional systems rely on optical signal regeneration to restore data signals that are degraded as they travel long distances through optical fibers. This degradation can introduce errors in the data transmitted and reduce the rate at which data is transferred. But optical regeneration faces a number of limitations. CNS investigators have developed and demonstrated a new silicon-based chip that uses a nonoptical technique to improve signal transmission. In tests, the chip—which makes use of an electronic process known as four-wave mixing—significantly increases the quality of the signals and reduces the error rate. The devices are expected to be inexpensive to make and easy to integrate into various communications systems.

Product/Process Successes Enhancing memory: For some important memory applications, it is critical to switch the memory element as fast and with as little energy cost as possible. Toward this goal, CNS investigators have demonstrated a new way to switch the magnetic orientation of small magnets, an achievement that is spurring development at research facilities worldwide of a new form of magnetic memory. The idea is to eliminate the use of applied magnetic fields to control the magnets and manipulate them instead using torque generated from the intrinsic spin of electrons.

The CNS team developed a device that enables reliable magnetic reversal with current pulses as short as 0.1 billionth of a second, with an energy cost of only 0.1 trillionth of a Joule per reversal. It consists of three magnetic layers laid atop each other: a middle layer in which the magnetic field switches back and forth, sandwiched by two fixed layers on either side with magnetization oriented perpendicular to each other. One layer promotes very fast and energy-efficient magnetic reversals, while the other controls the final magnetic direction within the switchable layer. Based on current experiments, the CNS team believes that even shorter pulses and lower energies appear likely with improvements in materials and design.

Improving data transmission: Photonic systems offer the possibility of transmitting enormous amounts of data, but such systems cannot be fully utilized using standard electro-optical technologies that typically operate at limited bandwidths. To make use of larger bandwidths, devices will need “all-optical” processing based on nonlinear optical elements. Such devices

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might emerge from photonic integrated circuits, as evidenced by their recent application to various ultrahigh-bandwidth instruments.

At CNS, investigators have developed a “time-domain telescope,” constructed with nanofabricated silicon photonic chips, that allows for the temporal compression of optical waveforms. As a proof-of-principle demonstration, the team generated very high (270 gigabits/second) data rates by compressing lower-bandwidth replicas generated with an electro-optic modulator. In effect, the device allows for ultrahigh-speed direct modulation using relatively low-speed devices and represents a new class of high-data-rate sources and ultrafast waveform generators.

A simplified rendering of a time-domain telescope compressing data over two stages.

Nanotubes for solar energy: Cornell researchers have created a nanotube solar cell that could lead to much more efficient ways of converting light to electricity. The researchers fabricated, tested, and measured a simple solar cell formed from an individual carbon nanotube—a cylinder of carbon atoms one nanometer in diameter, about the same thickness as a strand of DNA.

Electrical current is produced in a photovoltaic cell when energy from a photon is transferred to an electron in the cell material. That excites the electron into the conduction band to leave behind a positively charged hole. Today's photovoltaics are based on materials that create just one pair per photon, which limits their efficiency.

A team at Cornell, led by Prof. Paul McEuen, found a way to boost the number of pairs by making photovoltaics from the carbon nanotubes. The nanotube, they discovered, made an excellent photovoltaic cell because it could utilize an electron’s excess energy to create more electrons and holes. This is unlike today's solar cells, in which extra energy is lost in the form of heat. This process, called impact ionization, could prove important for next-generation high-efficiency solar cells.

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Increasing information storage: Storage of information is ubiquitous in computing and communications. For example, computing employs a number of memory systems, including flash memories in thumb drives and digital cameras, magnetic media such as hard disks, and optical media including DVDs. Semiconductors, being electrical and reliable, are preferred in such applications where the cost is not prohibitive. With extremely small devices, however, issues arise from the reduced charge in tighter spaces and increased

disturbance from fluctuations and energetic disturbances.

In a carbon nanotube-based photodiode, electrons (blue) and holes (red) release their excess energy to efficiently create more electron-hole pairs when light shines on the device.

To overcome such limitations, CNS investigators have employed, for the first time anywhere, a correlated electron phase transition effect in a new memory that is integrated within a transistor. The memory system potentially can fit in extremely small dimensions (10 nanometers) and thus achieve high memory density. The use of a very dense single element in this memory, a characteristic it shares with flash memory, makes the structures potentially very inexpensive.

Education and Outreach CNS supports a strong program to attract, educate, and mentor a diverse population of students at the undergraduate and graduate level in nanoscale science and engineering, and to assist K-12 institutions in their science education programs.

As one key component in its educational outreach efforts, CNS has developed and disseminated a variety of hands-on laboratory kits and learning activities for high school classrooms. CNS graduate students, working with teachers, have created more than 50 sets of laboratory activities that collectively form a “lending library” that can supplement teacher resources. The free labs improve physics instruction and student interest in science through hands-on learning experiences while they also educate both students and teachers about physics, including nanoscale science and engineering. The CNS lending library has received an increasing number of requests for lab kits, with more than 30,000 students nationwide having used them.

Currently, CNS has scaled back the development of new lab kits to focus on new sources of funding to extend this highly successful program beyond the end of its grant period. CNS also is using commercialization to make the lab kits as widely available as possible. At least four of the labs have been developed into commercial kits that are available through West Hill Biological (www.westhillbio.com). Another popular lab—the Stunt Car Challenge, which teaches students about the physics of projectile motion—is available through Arbor Scientific (www.arborsci.com), a much larger distributor of science hardware.

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Startups and Spin­offs PicoLuz (picoluz.com): In June 2009, Alexander Gaeta, director of CNS, and Michal Lipson, a CNS investigator, formed PicoLuz to commercialize novel silicon nanophotonics technologies developed with CNS funding. Silicon photonics holds promise for a technological leap by seamlessly integrating photonic elements with electronics. The CNS technologies being explored include wavelength converters and instruments for performing “singleshot” measurements of optical waveforms at high resolutions. In particular, research in four-wave mixing (a type of modulation that occurs in optical systems) will help commercialize the silicon nanowaveguides technology. PicoLuz operates in partnership

with Thorlabs, a leading manufacturer of equipment for the photonics industry.

Arbor Scientific’s Stunt Car Challenge Lab science kit helps students investigate projectiles in an exciting fashion inspired by the movie “Speed.”

CENTER FOR THE ENVIRONMENTAL IMPLICATIONS OF NANOTECHNOLOGY (CEINT)—DUKE UNIVERSITY The Center for the Environmental Implications of NanoTechnology is exploring the relationship between a vast array of nanomaterials—natural, manufactured, and those produced incidentally by human activities—and their potential consequences for the natural environment and organisms. The Center was created in 2008 with funding from NSF and the U.S. Environmental Protection Agency, and performs fundamental research on the behavior of nano-scale materials in the laboratory and in complex ecosystems. Research includes all aspects of nanomaterial transport, fate, and exposure, as well as toxicity and ecosystem impacts, and development of tools for risk assessment.

Research Highlights The Center places particular emphasis on understanding factors that control environmental exposure to nanomaterials. Investigators seek to explain fundamental principles that determine nanoparticle surface chemistry, how the particles travel, and how they transform in the environment and in contact with organisms. Researchers connect the chemistry and size-effects of nanoparticles to how and why they aggregate and move in the environment. The Center is characterizing biological and chemical transformations of such materials as a basis for understanding their environmental persistence, transport, and bioavailability.

Center investigators also examine the impact of nanomaterials on complex systems of organisms and their environment, looking at ecological endpoints to understand how nanoparticles are absorbed, their developmental impacts, and their toxicity. Researchers, for example, at a scale never tried before are studying how a complex environmental matrix will change the properties

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of nanomaterials. In preliminary data, they are finding that results in conventional labs appear to be markedly different from those obtained in CEINT's “mesocosms,” a series of controlled ecosystems built outdoors where complex environments and variability appear to have a dampening effect on nanomaterials.

CEINT investigators also are constructing a comprehensive model of the potential environmental risks of nanomaterials, linking factors such as particle characterization, transport, and ecological effects into a probabilistic framework (Bayesian Network). They not only want to assess ecological risks, but also to highlight the uncertainty that currently surrounds many of them. The work includes significant progress by CEINT to estimate the global production of different nanoparticles, including titanium dioxide, silver nanoparticles, fullerenes, and carbon nanotubes.

Product/Process Successes Nanoparticles building up in the food chain: A study by CEINT investigators was the first to show that nanoparticles can build up in a land-based food chain. The concern is that so-called biomagnifications—concentrations growing up a food web—may lead to greater toxicity, much as was found with mercury and some pesticides.

Research led by Prof. Paul Bertsch at the University of Kentucky found that gold nanoparticles in the soil accumulate in tobacco plants. The particles concentrate further in certain insects that eat the tobacco plants, the tobacco hornworm. The finding has important implications for risks associated with nanotechnology, including the potential for human exposure.

The increasing use of nanoparticles in consumer and industrial products is leading to more of the particles finding their way into wastewater. Evidence suggests that several classes of nanomaterials may accumulate in sludge derived from wastewater treatment—sludge that farmers often use to fertilize land. Those applications could prove to be a major pathway for the introduction of manufactured nanomaterials to the environment. (See Environmental Science & Technology, 2011.)

Silver nanoparticles passed to offspring: Modern stores carry many products with added silver nanoparticles to kill bacteria, including antimicrobial socks, paints, and even computer keyboards. Why silver nanoparticles kill bacteria is unclear, but their increasing use raises concern that their release into the environment could pose a toxic risk.

Particles build up in tobacco hornworms that eat plants in which nanoparticles have accumulated.

CEINT investigators studied the physical and chemical behavior of three silver nanoparticles with different sizes and coatings, and how they inhibit the growth of a particular organism, a nematode called C. elegans. Using traditional and novel analytical methods, the team led by Dr. Joel Meyer of Duke observed significant aggregation of the silver nanoparticles, dissolution of silver outside the organism, and how the nematodes absorb silver.

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In one particularly significant finding, the investigators also found that silver nanoparticles were transferred to the worm's egg sacs—meaning that the silver was transferred across generations.

Although all the tested silver nanoparticles passed cell membranes in C. elegans, at least part of the toxicity observed was mediated by ionic silver, a form in which a silver atom is missing an electron. (See Aquatic Toxicology, Oct. 15, 2010)

Sunlight destabilizes silver particles: The unique advantages offered by nanomaterials in a wide range of applications, such as silver particles in antimicrobial textiles, can't be fully realized until concerns about environmental and health impacts are addressed. CEINT scientists are looking at the response of nanomaterials to the environmental conditions they will encounter in commercial applications. Many factors, including light, temperature, and salinity, are expected to affect the stability of the nanoparticle suspensions and their toxicity.

A team led by Dr. Jie Liu at Duke indeed found that sunlight destabilized silver nanoparticles and reduced their toxicity. The researchers looked at the effect of sunlight irradiation on silver nanoparticles of two sizes, 6nm and 25nm. The particles were coated with either gum arabic, a natural gum commonly used in numerous products including foods and paints, or polyvinylpyrrolidone (PVP), a polymer commonly used in pharmaceutical tablets.

Under sunlight irradiation, all of these nanoparticles irreversibly aggregated to different degrees depending on the surface coating. Aggregation, or clumping, of silver nanoparticles causes them to lose their nanoparticle properties. For example, exposure of the nanoparticles to a wetland plant called lolium multiflorum indicates that their toxicity is greatly reduced by sunlight irradiation.

Further research is examining other factors that might affect the aggregation of the nanoparticles, including salinity and light intensity.

Silver particles are taken up into the cells of a nematode (Fig. A), while exposure to the particles inhibits growth in the developing nematode (Fig. B).

Silver nanoparticles seen aggregating after sunlight irradiation

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Real-world testing: CEINT has built 30 tightly controlled and highly instrumented ecosystems, or "mesocosms," that are located in the Duke Forest, a campus research area. Each mesocosm is 3 ft. x 12 ft. and represents a wetland environment. Currently, researchers working on 26 different experiments have added nanoparticles and are studying the resulting interactions and effects on plants, fish, bacteria, and other elements within the contained systems.

 Education and Outreach High school curriculum: Nano2Earth was initially funded by the NSF and developed by Prof. Michael Hochella and colleagues at Virginia Tech University. Nano2Earth introduces nanotechnology through studies of groundwater and is targeted for use in high school biology, chemistry, and Earth science classes. CEINT supported refinement of the NSF-funded Nano2Earth curriculum so that it could be submitted to the National Science Teachers Association for review for publication.

The curriculum consists of a set of five nano-science lessons which can be taught as stand-alone lessons or as a whole curriculum. The materials span approximately three weeks of in-class instruction and activities. The curriculum booklet includes several introductory chapters that provide background on nanoscale science and technology. CEINT is seeking funding to create partnerships to hold teacher training workshops to optimize the use of Nano2Earth curriculum nationally and beyond.

The mesocosms serve as a unifying resource for experiments across all of CEINT's research.

SCIENCE OF NANOSCALE SYSTEMS AND THEIR DEVICE APPLICATIONS—HARVARD UNIVERSITY The goal of the Harvard NSEC is to better understand how nanomaterials interact with and control biological systems, using that knowledge to develop nanomaterials and engineered processes that can solve medical and environmental problems.

In studying nanobiology, the Center develops microfluidic tools based on technology from the physical sciences to investigate and understand biological systems on the nanoscale. The Center develops nanoelectronics and nanophotonics by building, imaging, and testing devices and systems comprised of nanocrystals, nanowires, and heterostructures grown through molecular beam epitaxy, a method for depositing single crystals. Finally, the Center works to understand the theories behind those devices and systems.

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Research Highlights The Center has developed powerful new tools to address the enormous range of engaging problems of biology and medicine found in functional biological systems. The work builds bridges between the physical sciences and biology in developing devices that can manipulate and test cells and tissues, using microfluidics and advanced technology. Notable achievements have ranged from handheld sensors that use nuclear magnetic resonance (NMR) to sophisticated tips for atomic force microscopes useful for targeting, manipulating, and extracting items of interest.

Another Center thrust is making new classes of nanostructures that exhibit size-dependent properties—the building-blocks of nano research and production. Researchers synthesize structures with unconventional shapes, as well as zero-, one- and two-dimensional nanostructures such as nanoparticles and nanowires. Nanowires, for example, made from polymers are a key feature in photodetectors developed at the Center that could answer crucial questions about collecting solar energy. Nanoscale building blocks are promising for nanoelectronics and photonics as well as for bio-sensors.

The Center also advances imaging at the nanoscale. Imaging is an essential tool for the development of new nanoelectronic and nanophotonic devices. Investigators explore new ways to image the quantum behavior of electrons and photons in nanostructures using custom-made scanning probe microscopes.

Product/Process Successes Handheld NMR: Protons, the nuclei of hydrogen atoms, act like tiny bar magnets due to their “spin," and can exchange energy with radio-frequency magnetic fields. This energy exchange, called nuclear magnetic resonance, has found a host of powerful applications in science and technology, such as biomolecular sensing, medical imaging, molecular analysis, and petroleum exploration. The benefits of magnetic resonance could be made broadly available if NMR instruments were small and inexpensive, but current NMR systems are large, heavy, and expensive. This has restricted the use of NMR to hospitals, central testing facilities, and laboratories.

Center doctoral student Nan Sun and his faculty advisor Donhee Ham have made a significant leap forward in NMR miniaturization. They built the world’s smallest NMR system, which weighs only 0.1 kg and can be held in the palm of the hand. This system is not only 1,200 times lighter than a commercial, state-of-the-art benchtop instrument that can weigh 250 pounds, but also is 150 times more sensitive.

In creating the “palm NMR” system, Sun and Ham rethought how NMR works. A magnet is essential to NMR. Because a larger magnet yields a stronger signal, most NMR machines use bulky magnets. Sun and Ham took a completely opposite approach, using a magnet only the size of a ping-pong ball and building a high-performing radio-frequency silicon chip that can retrieve the weaker signal generated by the small magnet. The result is the 0.1 kg handheld NMR system. In collaboration with Ralph Weissleder of Massachusetts General

Handheld NMR biosensor with all of the electronics on one chip

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Hospital, Sun and Ham demonstrated that the small NMR system can be used to spot proteins and cancer cells.

On the left is an image of a polymer/nanowire photodector, and on the right is the photosensitive region at the junction between the nanowire and the polymer.

The work’s intellectual span is across electrical engineering, physics, and biotechnology. Combining the physics of NMR with the radio-frequency silicon chip conventionally used for wireless communication, the small system opens the possibility for routine diagnostic tests in the doctor’s office or local pharmacy at an affordable cost. This can be especially valuable in emerging healthcare programs such as ubiquitous health monitoring and personalized medicine. In addition, the small size and low cost may also make the broad array of other NMR applications such as quantum computing, oil detection, and molecular analysis more practical and/or accessible.

Low-cost photovoltaics: Providing enough energy for an expanding world population is a serious problem that will only rise in importance. Solar cells can harvest the sun’s energy to provide energy locally for a wide range of applications. The elusive goal is to achieve low-cost and acceptable efficiency so that solar energy can compete with the burning of fossil fuels.

Polymers hold significant potential as low-cost, mechanically flexible, lightweight, and large-area photovoltaics. But their performance relies crucially on understanding and controlling their shape and structure at the nanometer scale. Researchers need to develop ways to separate positive and negative charges created by absorbed light—and it must be done over very short distances, before the charges recombine. This requires close spacing of the positive and negative contacts.

Prof. Hongkun Park has developed polymer/nanowire photodetectors aimed at understanding this problem. Nanowires have the small diameter and very high surface-to-volume ratio needed for this task.

Ultra-fast computer switching and its imaging: Evolutionary scaling in electronics is rapidly approaching physical limits. Disruptive approaches to information processing, storage, and architectures are needed to continue advances in computing science. The challenges are non-trivial: enhanced speeds at low power are needed that are not possible with conventional semiconductors.

Center investigators led by Prof. Shriram Ramanathan are exploring the room-temperature, electric triggering of an ultra-fast, metal-insulator transition, in which a material is switched from a conducting metal to a signal-suppressing insulator. Dr. Ramanathan's system is in vanadium

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oxide (VO2) thin films grown on semiconductor platforms. VO2 was known to undergo transitions driven by temperatures, but an electric-field driven transition is new. The approach could lead to ultra-fast circuits, low-power computing, and 3-D integration, in which highly integrated systems are formed by vertically stacking and connecting various materials and technologies.

Preliminary results suggest that devices using functional oxides could lead to novel, high-performance logic and memory devices. They could also lead to neuromorphic circuits, in which electronics mimics the architectures of nervous systems, and to electronics that are rapidly and easily reconfigured.

Understanding how this works is difficult, because the VO thin films are polycrystalline and their lengths are very small. Using her expertise in scanning probe microscopy, Prof. Jenny Hoffman provided insight by imaging the electric-field driven metal-insulator transition.

Hoffman is expert at designing and constructing custom scanning tunneling and scanning probe microscopes (SPM) and using them to understand how electrons move inside new materials. Her work shows the important role that SPM imaging can have in the development of new materials and devices.

Education and Outreach The Center promotes education in nanoscale science and engineering and develops human resources at the pre-college, undergraduate, graduate, and postdoctoral levels through a range of activities. The Center has developed a particularly strong partnership with the Museum of Science, Boston to inform the public about advances in nanoscience and technology in an entertaining and informative way through presentations, forums, displays, and student internships. The NSEC has supported Carol Lynn Alpert at the museum as a part of its effort to bring ideas from nanoscience to the public in an engaging and enjoyable way. The museum also is part of the Nanoscale Informal Science Education (NISE) network. The NISE network provides a nationwide partnership to foster public awareness, engagement, and understanding of nanoscale science, engineering, and technology. Center faculty are members of the NISE Net Scientific Advisory Board.

A topological image on the upper left panel shows the polycrystalline grain structure of the film. The next images show the local conductance as the electric field is turned on. The individual grains switch at once, while the metal insulator transition spreads across the device.

Startups and Spin­offs Arsenal Medical (arsenalmedical.com): A 2005 startup co-founded by Center investigator George Whitesides is developing devices with bioactive composites, which are combinations of materials that elicit targeted therapeutic effects. Its biomaterials-based systems provide targeted local and systemic therapies to treat chronic diseases and conditions. They offer precise, tailored dosing of drugs, mechanical and biochemical compatibility with tissues, and complete bioabsorption.

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Arsenal Medical has raised more than $30 million in debt and equity financing.

Vista Therapeutics (vistatherapeutics.org): Based in Santa Fe, New Mexico, Vista is a start-up company founded by Dr. Spencer Farr, who helped start several other companies, and Prof. Charles Lieber of Harvard, who also founded Nanosys Inc., a pioneer company in nanotechnology.

Vista has broad, world-wide exclusive rights from Nanosys, Inc. and Harvard University for use of nanowires and nanostructures in biomedicine and drug discovery. The company is developing a nanotechnology-based device to continuously monitor body fluids in trauma patients. Vista’s nanowire technology provides label-free, continuous and simultaneous measurement of biomolecules in urine, serum, tissues, and tissue culture. Vista has also obtained world-wide exclusive rights for core patents to detect and treat wet and dry forms of age-related macular degeneration.

Vista has raised nearly $2 million in venture capital.

QD Vision (qdvision.com): A nanomaterials company, QD Vision has developed a proprietary, scalable printing technique for manufacturing displays based on quantum dots, semiconducting materials that display colors that differ with their dimensions at the nanoscale. The technology is delivering a new generation of display and lighting solutions that provide unmatched color, power efficiency, and cost savings. Currently the only quantum dot company solely focused on displays and lighting, QD Vision's advanced materials and components are found in a broad range of applications, including flat-panel displays, solid-state lighting systems, and defense and security projects.

The company's technology is based on work by MIT professors Vladimir Bulovic and Moungi Bawendi, a Center investigator and considered the father of quantum-dot technology. QD Vision has raised more than $33 million in financing from top-tier venture funds including North Bridge Venture Partners, Highland Capital Partners, DTE Energy Ventures, and In-Q-Tel.

Nano Terra (nanoterra.com): Formed in 2005, NanoTerra uses soft lithography—or techniques that rely on printing and molding to make microstructures and nanostructures—as well as nanofabrication and surface science to enhance existing or create entirely new products. The company's technology is largely based on the research of Prof. Whitesides and has licenses on more than 50 patents from Harvard. Nano Terra has raised more than $20 million in capital, including a round of more than $17 million in late 2010 and $2 million in early 2011.

In early 2011, Nano Terra bought Surface Logix, which uses microfluidic technology in drug development and also was founded by Prof. Whitesides. Surface Logix, whose 1999 founding predated the Center but whose technology was partly developed by Center-supported research, itself had raised more than $80 million in capital.

CENTER FOR HIGH-RATE NANOMANUFACTURING (CHN)—NORTHEASTERN UNIVERSITY The Center for High-rate Nanomanufacturing is focused on developing tools and processes that enable bottom-up, precise, parallel, high-rate and high-volume assembly of nanoelements and

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polymer nanostructures. The Center's nanotemplates are used to conduct fast, massive, directed assembly of nanoscale elements by controlling the forces required to assemble, detach, and transfer nanoelements at high rates and over large areas. The developed nanotemplates and tools will accelerate the introduction of commercial products and enable a new generation of applications.

Research Highlights CHN designs and builds nanotemplates that are capable of directing the self-assembly of nanoelements and then transferring those patterned assemblies of nanoelements onto receiving substrates. A key component of this strategy is the design and construction of nanoelements with appropriate physical and chemical characteristics such that they can be assembled and transferred efficiently. CHN is developing a range of nanotemplates with structures down to a few nanometers based on conventional and unconventional nanolithographies, and self-assembly of functionalized fullerenes and acenes.

Center researchers work to construct self-assembling, nano-building blocks over large areas in high-rate, scalable, commercially viable processes such as injection molding and extrusion. They are working on the synthesis of carbon nanocups and nanorings with the desired size, functionality, and solubility for high-rate manufacturing. Chemical guides are being developed for self-alignment and registration. Also, to mitigate the defects that may occur during fabrication, CHN is addressing three related functions: preventing failure, removing defects, and developing fault tolerance and self-repair. Among the challenges the Center faces are selectively removing impurities and being able to clean nanostructures without destroying them.

To demonstrate the commercial application and utility of the nanotemplates, as well as the wide range of possible products in biomedical, energy, electronics, and structured materials sectors, CHN has developed a number of practical devices. They include more than a dozen sensors with potential applications in industry, medicine, and elsewhere. In all cases, the Center is working closely with partner companies, a step CHN considers vital to manufacturing success and product realization.

Product/Process Successes A nonacene that hangs around: A team of CHN chemists has synthesized the first-ever stable derivative of nonacene, an organic semiconductor that holds significant promise in the manufacture of flexible organic electronics such as large displays, solar cells, and radio frequency identification tags.

Nonacene, a compound with nine rings of benzene fused in a linear fashion, belongs to a class of organic semiconductors called acenes, widely recognized to be among the very best in terms of electronic performance. Yet they are highly unstable—they oxidize rapidly. The team, led by Center investigator Glen Miller of the University of New Hampshire, overcame the fleeting nature of acenes by building the large nonacene derivative from smaller pieces, the way one might build a Lego structure—while also adding arylthio functional groups, stable collections of atoms that contain sulfur.

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Nonacenes hold promise for further development of flexible organic electronic devices: computer displays so thin they could be rolled up or even worn. The researchers note that the military is interested in the technology that would allow for chameleon-like camouflage clothing that could change with the environment. Organic solar cells are another potential application of nonacenes; such cells could cut the cost of solar power by making use of inexpensive organic molecules rather than the expensive crystalline silicon

that is used in most solar cells. (See Journal of the American Chemical Society, 2010, 132 (4), pp 1261–1263)

Nonacene derivative

High-speed and flexible assembly of nanoelements: CHN has developed a suite of templates and assembly processes for directing the assembly of a variety of nanoelements. These assembly processes utilize both electric fields and/or chemical functionalization.

Carbon nanotubes, for example, are promising candidates for use as components in nanoscale electronics and electromechanical devices due to their superior mechanical properties, high electron mobility, large current capability, and unique one-dimensional nanostructure. In order to implement these applications, it is essential to develop a simple and reliable manufacturing process that controllably assembles CNTs in desired locations with controlled orientations and nanoscale dimensions.

CHN researchers found that chemical and physical enhancements, such as using compounds that attract or repel water as water-friendly hydroxides do, can manipulate a nanotube solution. That allows them to effectively build highly organized and very large scale nanotube-network architectures in various dimensions and geometries. These results will enable scientists to fabricate large-scale and highly organized nanotube networks that can be used in various applications such as nanotube interconnects, transistors, sensors, and flexible electronics.

Center investigators have also used chemically functionalized templates to direct the assembly of polymer blends into uniform and nonuniform patterns. The selective assembly process is also quick, finishing in 30 seconds from a solution of the two polymers. Using a short solvent annealing step allows the assembly of multiple length scales on a single template.

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A CHN team led by Joey Mead and Carol Barry, both of the University of Massachusetts Lowell, used different types of electric fields, for example, in assembly processes that pattern conducting polymers. At CHN, researchers have also successfully transferred nonoelements, such as conducting polymers and carbon nanotubes, to secondary substrates. The entire process of patterning and transfer takes less than five minutes, which is commercially relevant and can be used for real-time processing. (See Small Vol. 5, Issue 24, pages 2788–2791, Dec. 18, 2009)

Nanosensors with real-world applications: The Center has developed a number of sensors, including a biosensor that can detect as many as four different biomarkers such as cancer or other types of diseases, with a detection limit that is about two orders of magnitude smaller than current technology. Where current technology can detect 3,000 picograms per milliliter, the CHN sensor has a detection limit of 15 pg/ml. The sensor, developed by a team led by CHN Director Ahmed Busnaina, features a nanochip smaller than a grain of sand (100 microns or less) that would use nanoparticles to recognize those extremely low levels of disease markers. The sensor would benefit patients through early detection.

The Center has also developed a sensor, based on functionalized carbon nanotubes and for detecting very low traces of hydrogen sulfide, a carcinogen, in harsh environments such as very high temperatures and pressures. The sensors are extremely small (can’t be seen by the naked eye), are specific to the targeted gas, and hence are very accurate. These sensors would find applications in oil fields to map out the composition and nature of the oil well for enhanced oil and natural

Chemically functionalized templates assemble polymer blends into non-uniform geometries.

Image of an in-vivo biosensor (0.1 mm x 0.1 mm) after animal testing

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gas recovery and production. In addition, these sensors can also be modified to identify harmful chemicals, thereby minimizing the exposure of first responders during catastrophic accidents.

CHN researchers also have developed a sensor from nanotubes, which already have a high capacity to absorb gas, that uses single-strand DNA to enhance its sensitivity to certain chemicals. Nanotubes were assembled onto CMOS circuitry via a low-voltage process, and after adding the DNA, were found to have three times the sensitivity to methanol vapor and two-and-a-half times the sensitivity to isopropanol alcohol vapor. The simple and versatile methodology used by the researchers is a key step toward the realization of high-sensitivity and low-power nanotube-based biological and chemical sensors. (See Nanotechnology Vol. 21 (2010), No. 9, 095504)

Education and Outreach Geckoman! Center faculty created a nanotechnology video game based on learning about nanoscale forces. The premise of Geckoman is that, through an explosion of an incredible shrinking machine, budding scientist Harold is shrunk to the nanoscale. His lab partner, Nikki, helps him navigate three “worlds,” beginning at the nanoscale and growing slightly larger until returning to normal size.

Before exiting each level in all three “worlds,” Harold must also pick up one of Nikki’s notebook pages, which were scattered in the explosion. To help Harold return to normal scale and avoid enemy attack, the notebook pages provide short tips and lessons that are aligned with national and Massachusetts state K-12 science and engineering standards. A movie trailer describes the game’s premise at the game's start.

For a more structured educational use of the game, four lesson plans were developed by school teachers and are available at the Geckoman web site, along with additional information to introduce scientific content about nanotechnology that can be used for classroom, home, or afterschool instruction.

Nikki and Harold, transformed into Geckoman, fight the evil Nanoids.

A pre-release discussion of Geckoman identified two critical problems: Did the player really need to learn about nanoscale forces in order to win the game? And would the targeted audience of middle school students identify with Harold and Nancy?

As a result, the game was revised to transform Harold from “nerd boy” into “wild guy.” Nancy became Nikki, got an extreme make over, and received equal billing in the game. Revision of this game involved collaboration among CHN faculty, game designers at Metaversal Studios, and informal science educators at the Museum of Science in Boston.

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Startups and Spin­offs Innovacene (innovacene.com): Founded in 2010, Innovacene manufactures organic semiconductors for thin-film electronic applications including organic photovoltaic cells and organic light-emitting diodes. The company, for example, has created an extremely thin, organic, ultra-lightweight surface-emitting semiconductor coating for use in organic light-emitting diodes. OLEDs are currently used in light-emitting screens for devices such as mobile phones and computers.

Innovacene’s technology would allow manufactures to apply the coating to large surfaces, such as wallpapers and ceiling tiles, to create a more natural style of lighting. Its products can result in higher performing, lower cost, longer lasting, environmentally friendly alternatives to conventional electricity and lighting technologies. Among other start-up funding, Innovacene attracted a $100,000 grant from the New Hampshire Innovation Research Center to help commercialize its semiconductor technology.

CENTER FOR INTEGRATED NANOPATTERNING AND DETECTION TECHNOLOGIES (NU-NSEC)—NORTHWESTERN UNIVERSITY The overarching research goal of the Center for Integrated Nanopatterning and Detection Technologies is to develop new and powerful biological and chemical detection systems, based on nano-engineered materials, that have the potential to revolutionize many diverse fields—particularly medical diagnostics.

Research Highlights  Substantial progress has been made toward realizing the Center's goal. The Center has targeted two systems that already are leading to practical research and commercial applications. One is an automated, massively-parallel system for printing nanopatterns that is capable of routinely generating soft-matter features, each less than 100 nanometers in size, over large areas.

A second system is an integrated, ultrasensitive biodetection system capable of identifying protein and nucleic acid disease markers with complex samples at the point-of-care.

Progress has been achieved at the Center through three research thrusts that work independently and together. The respective groups focus on nanopatterning, signal transduction and receptor design, and integrated biodetection chips.

Product/Process Successes 

Low-cost, high resolution lithography: NU‐NSEC researchers invented a low‐cost, high‐throughput lithography technique that merges the feature size control of dip‐pen nanolithography with the large‐area capability of contact printing. Polymer pen lithography uses arrays of pyramid‐shaped polymer pens whose tips are dipped in solutions of chemicals that can feature almost any molecule, including proteins and acids. The pens are then traced over a surface by a mechanical arm to create millions of structures in parallel. The width of the lines

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drawn by each pen can be carefully controlled by varying the force exerted on the flexible pen tips.

Because ink delivery is time and force dependent, features on the nanometer, micrometer, and macroscopic length scales can be formed with the same tip array. Arrays with as many as 11 million pyramid‐shaped pens can be brought into contact with substrates and readily leveled optically to ensure uniform pattern development. (See Science 2008, 321, 1658‐1660)

Researchers led by Chad Mirkin, NU-NSEC's director, recently found a way to combine the low cost and easy implementation of polymer pen lithography with the high resolution of scanning-probe lithography. The resulting hard-tip, soft-spring lithography offers a new technique for rapidly prototyping nanoscale devices and structures that is so inexpensive the “print head” can be thrown away when done.

Hard-tip, soft-spring lithography uses a soft polymer backing that supports sharp silicon tips as its print head. The spring polymer backing allows all of the tips to come in contact with the surface in a uniform manner and eliminates the need to use cantilevers. Essentially, hard tips are floating on soft polymeric springs, allowing either materials or energy to be delivered to a surface.

The technology could be used for printing electronic circuits, for medical diagnostics including gene chips and arrays of biomolecules, and for producing arrays for screening drug candidates.

(See Nature 469, 516–520, Jan. 27, 2011)

Ultrasensitive detection with gold nanoparticles: Treating an illness is often a race against time, and early diagnosis can be the equivalent of a head start. Diagnosing disease requires the ability to detect small molecular targets associated with disorders. The use of gold signal enhancement could be valuable as an experimental tool, as it could enable medical researchers to measure lower concentrations of many disease markers, potentially leading to earlier disease detection.

Researchers duplicated a bitmap representation of the pyramid on the U.S. one-dollar bill and the surrounding words approximately 19,000 times at 855 million dots per square inch.

Recently, a new method of metal deposition was used to increase the sensitivity of detection in “scanometric” assays (in this case, a procedure measuring the activity of markers associated with cancer) based upon gold nanoparticle probes. When compared to the previous chemistry, which deposited silver metal, the sensitivity of an assay for protein cancer markers was increased 10,000-fold.

These researchers compared the sensitivity of the scanometric assay as a function of different metal deposition conditions, in the context of a protein cancer marker assay. The assay starts by capturing the cancer marker on a piece of glass. Next, the gold nanoparticle probe finds and binds to the cancer marker. The probe is then used as a catalyst to deposit either silver or gold.

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The cancer marker assay was more sensitive by four orders of magnitude with gold than with silver. Gold-deposition chemistry should dramatically increase the sensitivity of any scanometric assay, including those for nucleic acids, proteins, virons, and toxic metals, which could ultimately lead to increased reliability and speed of diagnosis. (See Analytical Chemistry, 2009, 81, 9183)

Nanoflares light up molecules in live cells: By combining a gold nanoparticle with a unique family of nucleic acids, NU-NSEC researchers have created a new type of intracellular reporting system that uses a flash of light to reveal the presence and quantity of biologically important molecules. These so-called nanoflares could provide cancer biologists with a highly sensitive method of tracking complex biochemical processes in real time without interfering with those processes.

These non-toxic nanoparticle-based gene probes are designed to enter living cells and are equipped with fluorescent molecules termed "flares" to provide a robust and discernible signal when they encounter specific molecular targets—such as messenger RNA, which is essentially a blueprint for protein production. Nanoflares provide exceptional benefits and opportunities for studying and detecting disease in living systems, including being stable inside cells, and emitting a bright signal only when they encounter their gene target. They also remain stable for long periods of time and have a low background or false-positive signal.

New techniques for using gold metal deposition increased the sensitivity of nanoparticle-based assays by four orders of magnitude.

In one demonstration, researchers led by Dr. Chad Mirkin developed a real-time assay for intracellular adenosine triphosphate (ATP), one of the key energy sources of cellular metabolism. Current methods for ATP analysis require that a cell be destroyed and provide only an average measurement of ATP levels from a large number of cells, rather than time- and cell-specific measurements.

At the center of the nanoflare is a gold nanoparticle coated with a dense layer of nucleic acid “aptamers.” Aptamers, which are synthesized in the lab, are molecules designed to mimic antibodies in that they bind tightly to a specific chosen molecule. These aptamers are also equipped with a reporter molecule that is capable of producing a bright fluorescent signal.

The key to the nanoflare's unique signaling ability is that gold nanoparticles will quench, or prevent, the reporter molecule from emitting its light signal when the attached aptamer is stuck to the nanoparticle. However, when ATP is present, it causes the aptamer to change shape, releasing it from the nanoparticle and allowing the reporter molecule to fluoresce. The amount of aptamer released from the nanoparticle, and hence the intensity of the fluorescent signal, is directly proportional to the amount of ATP present in a cell.

Nanoflares also enter cells easily and without toxicity. In addition, they have the potential to enter cells and turn on and off the genetic switches that regulate what the cell can produce. That offers the potential to correct problems associated with disease in the emerging field of gene therapy. (See Nano Letters,2009, 9 (9), pp 3258–3261)

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Education and Outreach Undergraduate nanotechnology journal: The Center has provided unique interdisciplinary, hands‐on research opportunities in nanoscience and nanotechnology each summer since 2002. During the nine‐week summer program, participants work full‐time on individual research projects under the guidance of a graduate student or postdoctoral associate mentor and a faculty advisor. The program is enhanced with professional development training including: public speaking and technical writing, seminars by well‐known scientists and engineers, workshops on getting into graduate school and the graduate school experience, and a field trip to Argonne National Laboratory’s Advanced Photon Source.

The program culminates with a closing symposium where all participants present their research to faculty, mentors, and cohorts. Participants also submit their final papers for potential publication in peer‐reviewed journals including Nanoscape: The Journal of Undergraduate Research in Nanotechnology, which is published each year by the NU‐NSEC.

Startups and Spin­offs Nanosphere (nanosphere.us): A nanotechnology-based healthcare company, Nanosphere offers breakthrough technologies that provide a unique and powerful solution to greatly simplify diagnostic testing. The company's technology enables the consistent manufacturing and functionalization of gold nanoparticles with oligonucleotides (DNA or RNA), or antibodies that can be used in diagnostic applications to detect nucleic acid or protein targets, respectively.

Since its founding in 2000, Nanosphere has made continuous enhancements to the original technology with advances, many developed at NU-NSEC. They include coupling the gold nanoparticle chemistry and capabilities with multiplex array analysis and microfluidics in a diagnostics workstation called the Verigene System. The system will greatly simplify molecular diagnostic testing, making it accessible to virtually any clinical laboratory, allowing for localized molecular diagnostic testing and decision-making at more than 4,000 hospital-based laboratories in the United States, as well as around the world.

Nanosphere is a public company, having raised nearly $100 million in a 2007 initial public offering.

NanoInk (nanoink.net): NanoInk, Inc. is an emerging growth technology company specializing in nanometer-scale manufacturing and applications development for the life sciences, engineering, pharmaceutical, and education industries. Using Dip Pen Nanolithography (DPN), a patented and proprietary nanofabrication technology, scientists are able to rapidly and easily create micro-and nanoscale structures from a variety of materials on a range of substrates. This low-cost, easy-to-use and scalable technique brings sophisticated nanofabrication to the laboratory desktop.

A direct write, tip-based lithography technique, DPN operates under ambient conditions, allowing it to successfully deposit a wide range of organic, inorganic, and biological molecules. DPN platforms are capable of generating features as large as 10 µm and as small as 50 nm. NanoInk’s proprietary software suite and microfabricated DPN tools simplify the process of simultaneously depositing multiple materials, enabling researchers to rapidly pattern arbitrary micro- and nano-scale features.

Nanoink is a private company with about 100 employees.

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Aurasense (auresense.com): AuraSense's engineered nanoparticles offer a high degree of biocompatibility and versatility as therapeutics and as novel assays within live cells. Based on research at NU-NSEC, they hold great promise for combating the most threatening diseases, including heart disease, cancer, and bacterial infection.

These nanoparticles include constructs that overcome one of the most difficult obstacles to gene regulation: safe and effective delivery into cells. AuraSense particles exhibit high stability, high binding specificity, and excellent transfection efficiency into numerous cell and tissue types. Needing no carriers or transfection agents, they provoke minimal immune response and have no known toxicity. AuraSense has also developed nanoparticles that mimic the natural function of HDL ("good" cholesterol). These structures bind cholesterol tightly and have demonstrated activity and minimal toxicity in animal models.

A private company, Aurasense has about 10 employees.

CENTER FOR AFFORDABLE NANOENGINEERING OF POLYMERIC BIOMEDICAL DEVICES (CANPBD)—OHIO STATE UNIVERSITY The primary goal of the Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD) is to revolutionize medical diagnosis and treatment by establishing affordable, environmentally and biologically benign nanoengineering techniques that can be used outside the laboratory. Such techniques use biocompatible polymers, biomolecules, and nanoparticles as building blocks in a mechanism to design, synthesize, and fabricate the next generation of diagnostic and therapeutic devices for personalized nanomedicine.

Research Highlights CANPBD researchers have pursued the fundamental research needed to design and fabricate polymer-based, 3D nanofluidic circuits for manipulating the shape, orientation, and transport behavior of individual biomolecules. Such novel circuits offer a controlled, yet dynamic environment for biomedical diagnostics and molecular transport of drugs and gene therapies.

The Center's work has led to a number of advanced devices. Testbed examples include a simple, magnetic cell separation and diagnostic device; a nanochannel electroporation device that can deliver genes and medicines into cell walls; and immune-targeted nanoparticles that act as synthetic versions of the viruses that play a crucial role in the transport of DNA/RNA to cells in vivo.

The Center's current research includes two highly integrated nanofactory assembly (or disassembly) systems that target automated cell-to-biomolecule analysis (ACBA), which disassembles cells into their components for analysis. ACBA seeks to transform diverse, living cell populations into groups of cell sub-types, showing profiles of components such as DNA and RNA for a given cell type, and to detect critical responses to controlled doses of chemo- and gene-therapy.

Significant progress has been made on the two core platforms in support of the proposed ACBA Nanofactory System. One platform uses "optical tweezers" and another uses "magnetic tweezers." The ultimate aim is to design and test an automated, low-cost system that can separate

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circulating tumor cells from blood samples and analyze their biomolecules to better understand cancer cells and their response to therapy—i.e., a “liquid biopsy.” The Center wants to commercialize its biomedical devices through affordable manufacturing methods and novel design, and eventually to extend their application beyond medicine to water treatment, homeland security, environmental protection, and food industry safety.

Product/Process Successes Electrosprayed nanoparticles: For more than 30 years, researchers have worked to alleviate disease by delivering genes to cells, allowing them to produce their own therapeutic proteins. Gene therapy has typically transferred genes in viruses that would infect cells and deposit DNA that takes over the cells’ functions to produce the desirable proteins.

Bundling genes into nanoparticles made of lipids or polymers is a means to improve the delivery of these materials to targeted cells in the body in a way that does not involve viruses. Common techniques for making nanoparticles include bulk mixing and solvent depletion. Limitations associated with these techniques include poor control over the particle size and/or the length of time required to remove the solvent.

Researchers led by Yun Wu at Ohio State have shown that a coaxial electrospray device can rapidly produce structured nanoparticles for gene delivery. In this device, a solution that contains DNA or other nucleic acids flows through the center needle, and a solution such as a lipid mixture flows through the outer needle. An aerosol is produced by applying a positive high voltage. For lipid-based systems, the large surface area of the aerosol ensures rapid removal of the solvent.

The structure and efficiency of nanoparticles produced by coaxial electrospray differ from those produced by bulk mixing. For example, some nucleic acids produced by the electrospray have a one-layer structure rather than the multi-layer structure produced by bulk mixing. Furthermore, DNA nanoparticles produced by the coaxial electrospray are more efficient at delivering genes than those produced by bulk mixing. Finally, because the particles are produced as an aerosol, this technique may prove useful in pulmonary gene or drug delivery. (See Molecular Pharmaceutics, June 5, 2009)

A coaxial electrospray device Optical tweezers: Also called "optical trapping," focused laser beams manipulate micrometer-size particles. Optical trapping is particularly useful as a nondestructive, noninvasive method of manipulating cells.

A research group led by Prof. L. James Lee has used optical trapping to examine the properties of bulk electroporation. Electroporation is a commonly used method of delivering drugs and genes to cells in a laboratory setting by creating small pores in the cell membrane through the use of electric fields. The optical tweezers made it possible to easily observe single-cell

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electroporation of a cell in suspension. Similar previous experiments had focused on cells attached to a surface—a situation which is not the case in conventional bulk electroporation.

Additional experiments utilized optical trapping to manipulate multiple objects to examine cell shielding effects. By manipulating two cells, the effects of orienting the cells close to each other and far from each other, as well as parallel and perpendicular to the electric field, were examined. It was found that electroporation occurred at lower values when the cells were positioned perpendicular to the field, and at higher values when they were positioned parallel to the field.

Dr. Lee's group has also developed technology to produce arrays of nanochannels for delivering genes or drugs to large numbers of cells by electroporation. Optical-trapping techniques facilitate easy probing of the properties of this nanochannel electroporation by allowing cells to be placed directly up against the nanochannels. Current experiments are focused on determining the effects of the field on the delivered “dosage.”

Magnetic tweezers: Directed and controllable manipulation of fluid-borne cells is gaining importance in a wide range of applications, including cellular diagnostics, stem cell sorting, gene and molecular delivery, and single cell-based assays. Direct manipulation also offers much more precise selection, and thus better understanding of cell properties, than data-averaging over a large group of cells. While single-molecule force approaches—such as those based on atomic force microscopy, optical- and magnetic-tweezers—can trap and move individual microscopic objects with remarkable accuracy, there is a need for technologies capable of simultaneously manipulating large numbers of individual cells with directed forces.

By using thin magnetic wires laid in a zigzag pattern together with five tiny electromagnets, a team of CANPBD researchers led by Prof. R.

Sooryakumar of Ohio State is now able move individual cells. The team's approach is based on magnetic microstructures—both continuous and digitized elements—imprinted on a surface that extract and apply forces to individual, fluid-borne biological entities such as human T-cells, the white blood cells that destroy infected cells in the body. In addition to applications related to biology, other functions could emerge from the ability to translate, rotate, and “hop” magnetic particles across surfaces with high precision.

A mouse embryonic stem cell held against a nano-channel in an optical trap

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In fact, biomedical research could one day look a lot like playing video games. A new device using the magnetic tweezers allows users to manipulate cells with the swerve of a joystick. Scientists can program a computer to move the cells in a specific pattern, or move them using a standard video game controller. The weak magnetic fields that move the cells are gentle and do not damage the specimens. In addition, the whole setup could cost less than $200.

Education and Outreach Teachers’ workshop: As part of the Center's outreach efforts to introduce nanotechnology into high school classrooms, CANPBD conducts a one-day workshop for area high school science teachers each year. As many as 40 teachers from high schools in and around central Ohio participate in the daylong events, where they learn about nanotechnology, observe and perform experiments, and receive kits that contain materials for hands-on classroom activities.

An Ohio State undergraduate uses a video game controller to manipulate biological cells.

Experiments range in complexity from measuring a nanometer to modeling tissue engineering using nanotechnology. The teachers also tour the nearby Nanoscale Science and Engineering Center cleanroom facility, where they observe researchers at work on cutting-edge projects. Afternoon activities include a fun and hugely popular cryogenics and phase-change demonstration involving the preparation of liquid-nitrogen ice cream.

Startups and Spin­offs Nanofiber Solutions (nanofibersolutions.com): This 2009 startup has a unique approach that can provide high-throughput solutions to help biomedical researchers and cell biologists study cells and model cancer more effectively, faster, and more cheaply than other options currently on the market. The company sells a variety of cell-culture products, including 24- and 96-well plates along with larger dishes that each contains nanofiber. The company was founded by Dr. John Lannutti and Dr. Jed Johnson as an extension of Dr. Johnson's doctoral research at Ohio State.

PreCelleon (precelleon.com): Founded in 2008, Precelleon uses magnetic-cell separation to inexpensively separate molecules at the submicron scale. The PreCelleon CellGenus separator has been designed to separate a prepared sample of blood into constituent parts. This is done by introducing prepared samples of blood that flow through a special separation tube which has been routed through a powerful magnet. The tool, based partly on research by Ohio State Prof. Jeffrey Chalmers, will allow researchers to collect more cancerous cells and also might gauge the severity of cancer in a body. The company received $1.4 million in funding through a grant from the Ohio Department of Development.

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CENTER FOR DIRECTED ASSEMBLY OF NANOSTRUCTURES (RNC)—RENSSELAER POLYTECHNIC INSTITUTE The directed assembly of nanostructures is the fundamental gateway for the eventual success of nanotechnology, leading the Center for Directed Assembly of Nanostructures at Rensselaer Polytechnic Institute to focus on discovering and developing the means to organize nanoscale building blocks into functional structures under well-controlled, intentionally directed conditions.

Research Highlights Center researchers are now able to create a wide range of inorganic, organic, and hybrid nanoscale building blocks, and their ability to assemble complex hierarchical structures is significantly improving. The Center's integrated research program combines computational design with experimentation to focus on the discovery of novel pathways to assemble functional, multiscale nanostructures with junctions and interfaces between structurally, dimensionally, and compositionally different building blocks.

One research thrust focuses on nanoparticle gels and polymer nanocomposites. The work includes the synthesis, phase behavior, structure, and assembly of organic and inorganic nanoparticles with homogeneous or heterogeneous surfaces under chemical and/or physical control. Researchers have generated an understanding of the structure, assembly, and elasticity of nanoparticle-polymer systems, spanning from nanoparticle gels to polymer nanocomposites. In doing so, they have conceptually bridged the fields of colloid science and polymer science.

A second research thrust looks at nanostructured, biomolecule composite architectures. That includes the incorporation of biological macromolecules into composite materials to enable specific applications. These materials include tailored assembly based on different capabilities, such as biorecognition and biocatalysis, tissue engineering and biosensing, self-cleaning and self-repair, as well as novel lamellar structures, which are alternating layers of different materials.

Understanding the interactions among diverse nanoscale constituents is enabling researchers to design directed nanoscale assemblies with specific properties and to specify the process and parameters required for each unique assembly. This systematic integration of computational models and design principles forms the basis for the emerging practice of nanoengineering and its application to the development of new materials, structures, and devices to benefit society.

Product/Process Successes Paper batteries: Center researchers have developed composite materials that exhibit enhanced compatibility with living tissues while still retaining important properties associated with nanomaterials. They prepared nanoporous, cellulose-heparin composites that could serve as blood-compatible membranes for kidney dialysis and as electrospun fibers that could be woven as vascular grafts.

RNC researchers generated particular interest in ultra-thin, lightweight paper batteries developed by combining biological cellulose with aligned carbon nanotubes. The composite contains ionic liquids that act as batteries and supercapacitors, leading to flexible, scalable energy storage

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sheets. The technology will make energy storage ubiquitous by integrating it into existing structures.

More than 90 percent of the device is cellulose infused with aligned carbon nanotubes acting as electrodes and enabling electrical conduction. The battery can be rolled, twisted, folded, or cut into any shape with no loss of mechanical integrity or electrical efficiency, and it can even be printed like paper. Battery sheets can be stacked to boost total energy and the devices can function either as high-energy batteries or high-power supercapacitors. (See Biomacromolecules, 2006, 7 (2), pp 415–418)

Eradicating resistant bacteria: Infection with pathogens that resist antibiotics is one of the primary causes of hospitalizations and deaths. RNC researchers have responded with a promising coating that kills the pathogens using carbon nanotubes and natural enzymes.

Researchers led by Rensselaer Prof. Jonathan S. Dordick developed the coating, which kills bacterial cells through the action of an otherwise safe enzyme already found in nature. The material may prove useful as a coating to resist and destroy pathogens that come in contact with a surface coated with the bionanocomposite, which could include clothing, surgical equipment, and hospital walls. The treatment safely eradicates methicillin-resistant Staphylococcus aureus (MRSA), the bacteria responsible for antibiotic resistant infections.

The enzyme is safe to handle, does not appear to lead to resistance, does not leach into the environment, and does not clog up with cell debris. In tests, 100 percent of MRSA in solution were killed within 20 minutes of contact with a surface painted with latex paint laced with the coating. It can be washed repeatedly without losing effectiveness and has a dry storage shelf life of up to 6 months.

Paper batteries can be rolled, twisted, folded, or cut.

Enzymes attached to nanotubes endow a coating with biocatalytic activities.

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Specifically, researchers incorporated conjugates of carbon nanotubes with lysostaphin, a cell-wall degrading enzyme. The work is part of the Center's effort to enable the efficient and selective interaction of biomolecules with synthetic nanoscale building blocks to generate functional assemblies. The resulting functional hybrid materials, which integrate biotic and abiotic components, can be used to generate “smart materials” that can sense, assemble, clean, and heal. (See ACS Nano, 2010, 4 (7), pp 3993–4000)

Self-repairing electronics: In nature, damage to an organism elicits a healing response. RNC researchers are applying the same concept to synthetic materials and are designing self-healing polymers and other materials that could also enable electronic components that fix their own defects. Structural polymers in particular are susceptible to damage in the form of microcracks, which often develop deep within a material, where detection is difficult and repair is nearly impossible. Self-healing polymers and perhaps even wires would greatly extend the lifetime of such materials.

RNC researchers, led by University of Illinois Prof. Jeffrey Moore, have synthesized microcapsules that contain single-wall carbon nanotubes suspended in organic solvents. When ruptured, these microcapsules release their liquid cores laden with the nanotubes.

Earlier research had shown that carbon nanotubes migrated when an external electrical field was applied. In the case of the ruptured microcapsules, and when a voltage was applied, the nanotubes migrated to form a conductive pathway across the probe tips. Enough nanotubes released from the microcapsules migrated so that it was possible to measure the resulting current.

This research could contribute to the ultimate development of strategies for the automatic self-repair of defects that can occur in electronic components and assemblies as a result of a variety of factors. Developing capsules that release their

contents under various conditions could extend the self-healing capability to a number of applications, including safer and longer-lifetime batteries or nanowire self-assembly.

Carbon nanotubes suspended in microcapsules

Education and Outreach Stealth education: A growing challenge in the 21st century is to educate and excite the general public about our scientific world, and help create a more science-literate society. Center investigators have increasingly embraced the challenge with significant programs designed to raise public awareness of science, and to enhance the responsible and efficient transfer of nanotechnology developments to industry.

In one significant example, RNC researchers created the Molecularium, a project to develop movies that are shown in digital dome theaters. But instead of taking audiences on a ride into the stars that is typical of planetariums, the 23-minute animated Molecularium movies take audiences on a ride into the world of atoms and molecules. The first Molecularium show, Riding Snow Flakes, premiered in 2005 and is now being distributed worldwide with translations into several foreign languages, including Arabic, Korean, and Spanish.

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In 2009, supplemented with private funding of $3.6 million, the project released its second animated feature, the 42-minute Molecules to the MAX! The movie is designed for large-format (e.g., IMAX) and high-definition video screens to further advance public science literacy worldwide. This new movie was released for worldwide distribution in March 2009 in a 2D version, and in September 2009 in a 3D version. The film has already been translated into Japanese and Mandarin, with a Spanish version coming soon.

The Molecularium shows are accompanied by both classroom preparation materials for teachers and hands-on activities for the students. The Center is actively assessing the learning of both school groups and the general public as they participate in the Molecularium® program. Preliminary assessments show significant learning benefits.

Startups and Spin­offs ANDalyze (andalyze.com): ANDalyze produces instruments capable of high-resolution chemical sensing using functional DNA molecules. One of the most important discoveries in the last decade is that DNA and RNA are not only materials for genetic information storage and transfer, but also catalysts for a variety of biological reactions, and thus can be called catalytic DNA—or DNAzymes. Because metal ions play essential roles in the structure and function of DNAzymes, the study and application of these new metalloenzymes has become a new frontier in bioinorganic chemistry, which studies the role of metals in biology.

Founded in 2005, the company is based on research by RNC investigator Yi Lu, of the University of Illinois at Urbana-Champaign (UIUC) and an RNC investigator, who has also received funding from another NSEC, the Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems based at UIUC. ANDalyze has raised $1 million in capital and has about 10 employees.

Solidus Biosciences (solidusbiosciences.com): Solidus aims to improve the process for developing new drugs. It is providing new, decision-enabling technology to enhance the productivity of pharmaceutical industry drug research and development. The same decision-enabling technology will enable the cosmetics and related industries to develop safe and effective ingredients for their spectrum of products.

The company's MetaChip and DataChip are designed to mimic how a human body would react to a new drug. The company currently provides the analysis, and plans to soon sell the screening assays to customers. The company has six employees, according to Dun & Bradstreet.

Paper Battery Company (paperbatteryco.com): Started in 2008, the company has developed its PowerWrapper product based on the Center's research into ultra-thin, lightweight batteries that combine cellulose with carbon nanotubes. This multi-functional material reduces system weight and distributes part of the energy storage into structures as a power plane. The first-generation sheet incorporates supercapacitor technology in a massively parallel array of cells for long cycle life. Packing efficiencies give twice the energy capacity of existing rigid devices at high voltages. Roll-to-roll printing processes generate high-volume, low-cost production.

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The company plans to produce and sell flexible power storage devices directly to manufacturers of medical devices and portable electronics. Second-generation devices will incorporate hybrid chemical storage and will be sold as integrated structural body panels for air or ground transport vehicles and for local regenerative power reuse. Paper Battery has four employees and has attracted more than $1 million in early venture financing.

CENTER FOR BIOLOGICAL AND ENVIRONMENTAL NANOTECHNOLOGY (CBEN)—RICE UNIVERSITY The Center for Biological and Environmental Nanotechnology seeks to better understand how nanomaterials interact with and control biological systems, using that knowledge to develop nanomaterials and engineered processes that can solve medical and environmental problems. The same size as many biological molecules that play important roles across a range of natural systems, nanomaterials possess chemical, magnetic, and optical properties that can interact with biological systems in unique ways. CBEN investigators capitalize on these traits in designing nanomaterials and engineered processes tailored to perform specific functions in biological and environmental systems. They focus on two potential applications in particular: detecting and treating disease, and treating water to remove hazardous pollutants.

CBEN investigators also are addressing broad issues that could impede the commercialization of nanotechnology. One roadblock looms in the lack of inexpensive, environmentally clean methods for producing large quantities of nanomaterials. Another is public concern about potential adverse effects of engineered nanomaterials on human health and the environment.

Research Highlights CBEN investigators have made significant advances in investigating and developing nanoscience at the “wet/dry” interface. As the Earth’s most abundant solvent, water is of unique importance as the medium of life. Center researchers explore how nanomaterials interact with aqueous systems at various scales, including biomolecules and cells, entire organisms, and the environment. Such knowledge forms the basis for designing biomolecular/nanomaterial interactions, solving bioengineering problems with nanoscale materials, and constructing nanoscale materials useful in solving environmental engineering problems.

Among recent research advances, CBEN investigators have developed new families of nanoparticles with optical and magnetic properties that may prove valuable in disease detection. They also have developed carbon nanotubes outfitted with molecular antioxidants that can seek out and remove dangerous substances called free radicals from human cells. The nanotubes ultimately may help to improve the outcomes of radiation therapies for cancer by protecting patients receiving treatment. In addition, investigators have tested new methods for using namomaterials to remove viruses from drinking water. Viruses often evade conventional disinfection techniques and their presence in drinking water leads to significant suffering and loss of life for people worldwide.

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Product/Process Successes Improving manufacturing: For nanomaterials to work in the human body or in water purification, they must be dispersible in water. The making of some promising materials—iron oxide and cadmium selenide nanoparticles—involves oily solvents, but this approach limits the particles’ application in water‐based systems. CBEN investigators led by Center Director Vicki Colvin have developed a technique that allows nanoparticles to be transferred from oily solvents, where they are synthesized, into water-based solutions while retaining their attractive properties. (See CBEN website)

Using a trick borrowed from the way that laundry detergents surround oil and dirt on clothes and wash them away, the investigators add a small amount of a fatty acid, called oleic acid, to the starting solution. Oleic molecules, which have an oil-compatible end and a water‐compatible end, bind to the nanoparticles in a way that enhances their transfer into water. Using this technique, the investigators can transfer 70 percent of the nanoparticles in the oily solvent into water. Follow‐up experiments showed that the nanoparticles retained their unique optical and magnetic properties in their new watery environment.

Fighting diseases: In patients undergoing breast cancer surgery, surgeons want to remove all cancer cells to reduce the risk or recurrence of the disease, while leaving surrounding healthy tissues unharmed. This requires surgeons to determine the edges of the tumor precisely. Current techniques rely on the surgeon’s assessment during the surgery, followed by postoperative examination of the tissue samples. Some larger hospitals have specialized facilities for examining the cells under a microscope while the patient is still on the operating table, but this is a lengthy procedure.

Targeted gold nanoshells create a red hue in tumor tissue that can be visualized macroscopically (top image) as well as microscopically (bottom image).

CBEN investigators, including Profs. Rebekah Drezek and Jennifer West, have developed ways to make gold “nanoshells” that can act as beacons for detecting and imaging breast cancer cells during surgery. The nanoshells, which are particles of silica with a gold coating, were invented by Rice University Prof. Naomi Halas. For this application, the nanoshells are tagged with a marker that can identify and link to breast cancer cells that carry specific proteins called human epidermal growth factor receptors on their surfaces, a characteristic of particularly aggressive types of breast cancers. (See International Journal of Nanomedicine, Aug 9, 2010, page 445.)

Surgeons inject the nanoshells during surgery and they circulate throughout the patient’s body. The patient then is exposed to a beam of near-infrared light that can spot any nanoshells at the tumor site—making them light up—and indicate the presence of cancer cells. Using the technique, surgeons can get an answer in the operating room within five minutes. The CBEN team, together with researchers at Rice University and the University of Texas’ MD Anderson Cancer Center, has launched a pilot study of the technique in a small number of women, and plans have been approved to expand the patient test population.

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Cleaning water: In many locations worldwide, arsenic contamination of drinking water supplies presents a significant health risk. Long-term exposure to arsenic causes cancers of the skin, lungs, urinary bladder, and kidneys, as well as several skin diseases. In the United States, the Environmental Protection Agency limits the presence of arsenic in drinking water to 10 micrograms per liter. Large-scale water treatment plants now have technology in place that can economically remove arsenic. But the technology is not easily scaled down to sizes that would be economical for use in smaller communities or other small-scale applications.

CBEN investigators, including Prof. Mason Tomson, are overcoming this limitation by using a type of iron-oxide sorbent called nanomagnetite that can magnetically remove arsenic from water. The ability of nanomagnetite to bind to arsenic is well known, but until recently there had been little effort beyond small “batch” studies to design processes large enough for field applications. The CBEN team developed a system that uses columns packed with nanomagnetite and sand to filter arsenic and other heavy metals from water.

After conducting extensive laboratory evaluations, in December 2009 the team field tested the system at a water treatment plant in the city of Guanajuato, Mexico, where arsenic has contaminated groundwater supplies. The team believes this is the first test of nanoparticles for water treatment in a municipal water treatment plant. The pilot study provided baseline data on the system’s ability to remove arsenic and pointed to additional process modifications aimed at boosting arsenic removal efficiency. The team returned to Guanajuato in March 2010 to further study the system’s performance, and the investigators believe the results demonstrate the process’ considerable potential for commercialization. (See CBEN website. Also, the team chronicled its experiences at a team blog, and a video of the field test is available at YouTube).

Enhancing safety: Although nanomaterials hold promise for making important contributions to the nation’s economy and society, some of the novel particles pose potential hazards. Current government guidance suggests caution when handling them in the laboratory or factory. CBEN is addressing this issue with a new online resource that can provide researchers and workers with the information they need to handle nanomaterials safely.

In June 2009, the International Council on Nanotechnology, which CBEN organized in 2004, launched the GoodNanoGuide (http://goodnanoguide.org). Created in a wiki format, the site allows registered users to create and edit content with the latest information from around

the world. Features include an occupational health and safety manual, a detailed listing of safe practices for specific tasks, and a forum where people can post and discuss items of interest to the nanoscience community. Preliminary support for developing the GoodNanoGuide came from several Canadian organizations. The U.S. National Institute for Occupational Safety and Health has provided $50,000 for further implementation of the project. The council is seeking sustaining funds from a variety of sources and aims to make the GoodNanoGuide fully self‐supporting in the near future.

Test strips illustrate the ability of nanomagnetite to remove arsenic from polluted water.

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GoodNanoGuide homepage (http://goodnanoguide.org)

Startups and Spin­offs Nanospectra Biosciences (nanospectra.com): CBEN investigators Profs. Jennifer West and Naomi Halas founded this privately held company to commercialize therapies that use nanoparticles and near-infrared light to thermally destroy solid tumors while minimizing damage to adjacent tissue. In one approach, which the company has named AuroLase Therapy, the investigators use gold nanoshells (silica coated with a thin layer of gold) that are 1/20th the size of red blood cells and “tuned” to respond to near-infrared light. Injected into the patient’s blood stream, the nanoshells enter the tumor through leaky blood vessels that are characteristic of rapid tumor growth. The area is then illuminated with a laser that emits near-infrared light, a wavelength that passes easily and harmlessly through soft tissue. The nanoshells convert the light into heat that destroys the tumor cells. The heating is very localized and does not affect healthy tissue adjacent to the tumor.

A phase I clinical trial of this “particle-based ablation therapy” targets head and neck cancers that are recurring or have not responded to conventional therapies. This is the first test in humans, and the trial is being conducted under an Investigational Device Exemption approved by the U.S. Food and Drug Administration. About 20,000 Americans each year are diagnosed with a cancer originating in the brain, and an additional 200,000 people develop brain tumors that have metastasized from tumors in other parts of the body. These tumors are difficult to treat, resulting

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in high mortality rates, and current therapies can have substantial side effects. In the trial, which involves 15 patients and is scheduled to conclude in 2011, company investigators are working with researchers at the Baylor College of Medicine, the University of Texas Health Science Center at San Antonio, and University of Texas Southwestern Medical Center, Dallas. In August 2010, the company received a three-year, $1.3 million grant from the National Cancer Institute to support continued development and clinical trials of the new therapy. The University of Texas MD Anderson Cancer Center is a research partner in the latest award.

Applied Nanofluorescence (appliednanofluorescence.com): CBEN investigator Prof. R. Bruce Weisman founded this company to commercialize the Center’s research findings in nanotube spectroscopy. Prof. Weisman serves as the company’s president, and CBEN investigator Prof. Sergei M. Bachilo is chief scientific officer. Both are leaders in the discovery and interpretation of fluorescence spectra from an important class of nanomaterials called single-walled carbon nanotubes. The company’s first product, the NS1 NanoSpectralyzer, combines a specialized optical system with sophisticated software to rapidly give detailed analyses of bulk samples of carbon nanotubes. The instrument won a Nano 50 Award as one of the best nanotechnology products of 2006. A later product, the NS2 NanoSpectralyzer, expands on the first version’s capabilities. The company currently has distributors in Europe, India, Japan, Korea, China, Taiwan, and New Zealand.

Oxane Materials (oxanematerials.com): This company is commercializing nanoceramics developed by CBEN investigators, including Prof. Andrew Barron, that may increase the production of oil and natural gas. The company’s first product is a nanoceramic called OxFrac that can serve as an enhancer, or proppant, for boosting oil and gas recovery, particularly from unconventional sources such as shale, coal beds that contain methane, and deposits where the oil or gas is held tightly within the surrounding rock.

To improve production at a well, companies often force proppant-bearing liquids into underground rock formations to create fractures. As their name suggests, proppants “prop” open the tiny fractures so that oil or gas can flow more easily. The oil industry currently uses several types of proppants. Oxane Materials says OxFrac is stronger and more economical than conventional proppants. The company has estimated that the product could increase a well’s initial production by 50 percent.

In 2008, Norway-based Energy Ventures invested an undisclosed amount to help Oxane commercialize OxFrac. In late 2009, Oxane announced plans to invest $15 million to build a manufacturing plant in Van Buren, Arkansas, to produce the proppant. The company said the plant would hire up to 50 workers initially, and with planned expansions over several years could employ 300 workers.

CENTER FOR PROBING THE NANOSCALE (CPN)—STANFORD UNIVERSITY The Center for Probing the Nanoscale seeks to develop novel probes for measuring, imaging, and controlling objects and phenomena at the nanoscale. Using this toolbox of nanoprobes, scientists and engineers within CPN and elsewhere can better answer fundamental questions and advance technological innovation across a range of areas. Stanford and IBM have distinguished histories

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and programs in nanoprobe research, including working together on the atomic force microscope that was invented at Stanford, and together they formed the Center to propagate this legacy into the next generation.

Research Highlights CPN’s work in nanoscale electrical imaging is yielding new types of microscopy that are helping researchers better understand the behavior of devices and materials important in the electronics industry. CPN is developing Scanning Gate Microscopy and Scanning Microwave Microscopy in order to measure electrical properties at the nanoscale. Both advances are enabled by center-developed design and production of specialized scanning probe cantilevers. The capability to measure the local variations in modern electronic devices has important implications for the behavior of materials or structures and ultimately determines the properties and performance of advanced devices.

The properties of magnetic nanoparticles are inherently sensitive to small variations in volume, shape, and structure, and therefore it is vital to characterize them individually. CPN researchers are developing a variety of nanoprobes, such as Magnetic Force Microscopy, Scanning Sagnac Microscopy, and microscopy that uses superconducting quantum interference devices (SQUID), which employs ultra-sensitive magnetometers to measure extremely weak magnetic fields. The new probes have the spatial resolution and magnetic sensitivity to detect and characterize individual nanomagnets for potential applications, such as magnetic nanoparticles serving as contrast agents for magnetic resonance imaging or for the treatment and removal of cancer cells.

Understanding the principles and processes that govern the functions of cell membranes will help scientists to tailor drugs to effectively penetrate the membrane for efficient treatment. The Center is developing novel bioprobes that will directly study the membrane and measure the forces, mechanical stiffness, electrostatics, and sequence of biological processes to replace and complement more traditional remote-sensing techniques. These metrologies will unlock the real-time mechanical and electronic processes at and within biological membranes that are currently inaccessible by any other technique.

Extending the sensitivity of magnetic resonance imaging to the level of individual nuclear spins would enable the development of a “molecular structure microscope” capable of imaging the atomic structure of molecules in three dimensions. Such a capability would have revolutionary impact on structural molecular biology, since it would allow atomic structures to be obtained for proteins that cannot be crystallized for x-ray diffraction analysis.

Recent work sponsored by CPN has proven that magnetic resonance force microscopy (MRFM) can achieve three-dimensional imaging with spatial resolution of about 4 nm. Center investigators are currently focusing on extending MRFM resolution to below 1 nm—or roughly an order of magnitude improvement over today’s capability. If sub-nanometer can be achieved, then MRFM’s true 3D imaging capability, lack of radiation damage, and elementally specific contrast would make it a powerful tool for structural biologists.

Product/Process Successes Viewing a virus: Researchers from CPN and IBM have improved the sensitivity of magnetic resonance imaging (MRI) by 100 million times using a new technique for measuring tiny

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magnetic forces. The sensitivity improvement allowed a dramatic improvement of resolving power, achieving a resolution down to 4 nanometers.

Frequently employed by doctors to look below the surface of the skin, traditional MRI takes advantage of the magnetic signals generated by spinning protons within the nuclei of hydrogen atoms contained in water and organic materials inside the body. The directions of the spins of the protons are aligned using a powerful magnetic field. Then, radiofrequency fields are applied to alter this alignment. A detector measures the resulting changes in the overall magnetic field. A computer transforms this information into a three-dimensional map of hydrogen density that distinguishes different types of tissue. This technology can reveal a tumor among healthy tissue, for example.

But it is difficult to adapt conventional MRI to small scales. The new technology, called magnetic resonance force microscopy (MRFM), relies on manipulating hydrogen nuclei just like traditional MRI. However, Daniel Rugar and his team of Stanford and IBM researchers devised a much more sensitive technology that detects if two magnets repel or attract each other. To measure such minute forces, Rugar and his team invented a setup in which samples sit on an extremely flexible microscopic cantilever, which researchers described as being similar to a tiny diving board. Then, using an oscillating magnetic field, researchers essentially flip the direction of the nuclear spin. Bringing another tiny magnet close to the spinning particles will produce either an attractive or repulsive force that is measured by vibrations in the cantilever.

By measuring forces generated as the tiny magnet is positioned at 8,000 different points around the sample, scientists can generate a three-dimensional map of hydrogen density, thereby creating a three-dimensional image.

The researchers hope to improve the technique to determine the atomic structures of proteins, giving biologists unprecedented insight into how and why proteins perform their biological function and broadening the potential for targeted drug design. (See New York Times, Jan. 12, 2009 and Proceedings of the National Academy of Sciences 2009 USA 106, 1313-1317)

Probing cellular communication: A nanometer-scale probe designed to slip into a cell wall and fuse with it could offer researchers a portal for extended eavesdropping on the inner electrical activity of individual cells. Everything from signals generated as cells communicate with each other to "digestive rumblings" as cells react to medication could be monitored for up to a week.

An image obtained with the new MRI technology of tobacco virus particles that span only 18 nm.

Current methods of probing a cell are so destructive they usually only allow a few hours of observation before the cell dies. The researchers, led by Center investigator Nick Melosh of Stanford, are the first to implant an inorganic device into a cell wall without damaging it.

The key design feature of the probe is that it mimics natural gateways in the cell membrane. With modification, the

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probe might serve as a conduit for inserting medication into a cell's heavily defended interior. It might also provide an improved method of attaching neural prosthetics, such as artificial arms that are controlled by pectoral muscles, or deep brain implants used for treating depression.

The 600-nanometer-long, metal-coated silicon probe has been integrated so smoothly into membranes in the laboratory that researchers christened it the "stealth" probe. Up to now, poking a hole in a cell membrane has largely relied on brute force. The key to the probe's easy insertion is that the CPN team based its design on a type of protein naturally found in cell walls that acts as a gatekeeper, controlling which molecules are allowed in or out. The scientists essentially made an inorganic version of one of those membrane proteins, which sits in the membrane without disrupting it.

To build their probe, Melosh and Benjamin Almquist, a Stanford graduate student, appropriated nanofabrication methods from the semiconductor industry to make tiny silicon posts, the tips of which they coated with three thin layers of metal—a layer of gold between two of chromium—to match the sandwich structure of the membrane.

The next step is to demonstrate the functionality of the probe in living cells. Almquist and Melosh are now working with human red blood cells and cervical cancer cells, as well as ovary cells from a species of hamster. (See Proceedings of the National Academy of Sciences, March 30, 2010)

World's smallest letters: CPN researchers claimed bragging rights for creating the world's smallest writing with letters in the words assembled from subatomic sized bits as small as 0.3 nanometers.

A team led by Hari Manoharan of Stanford encoded the letters "S" and "U" (as in Stanford University) within the interference patterns formed by quantum electron waves on the surface of a sliver of copper. The wave patterns even project a tiny hologram of the data, which can be viewed with a powerful microscope.

The quest for small writing has played a role in the development of nanotechnology for 50 years, beginning decades before "nano" became a household word. Stanford researchers held an early record, set in 1985, for tiny print that held until until 1990, when researchers at a certain computer company famously spelled out the letters IBM by arranging 35 individual xenon atoms.

The CPN-backed team of Stanford researchers made their letters four times smaller than the IBM initials. They began their writing project with a scanning tunneling microscope, a device that not only sees objects at a very small scale but also can be used to move individual atoms around. The CPN team used it to drag single carbon monoxide molecules into a desired pattern on a copper chip the size of a fingernail.

By altering the arrangement of the molecules the researchers can create different waveforms, effectively encoding information for later retrieval. To encode and read out the data at unprecedented density, the scientists devised a new technology, Electronic Quantum Holography. The new technology upends previous assumptions that the ultimate limit to storing data is that one atom would represent one bit. In their experiment, the CPN team stored some 35 bits per electron to encode each letter, and wrote them so small that the bits that comprise them are subatomic in size. (See Nature Nanotechnology 4, 167 – 172; 2009)

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Education and outreach Reaching younger students: Beyond its research, CPN also helps educate the next generation of scientists and engineers and helps create a scientifically literate society. The center, for example, conducts each year a Summer Institute for Middle School Teachers. While many other outreach activities focus on the high school years, the institute tries to build students’ interest in science before they might fall out of the education pipeline. Many of the teachers who participate come from middle schools attended by children from minority populations and other groups underrepresented in the sciences.

CPN also produces a variety of prepackaged hands-on activities and supporting materials for teachers to use in their classrooms. In addition, the center provides a series of short educational videos, called CPN Close-Up on Science, that explain science topics in easy-to-understand language. They often feature video footage and interviews with center researchers working in their laboratories. The videos are posted on YouTube.

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Stanford University's initials were written in electron waves on a piece of copper and projected into a tiny hologram.

Researchers explain their research in videos of 3 minutes or less posted on YouTube.

Startups and Spin­offs Alion (alion.co): Originally called SunPrint, Alion was co-founded by former CPN research associate Mark Topinka. The company has developed acoustic printing processes that use intense sound beams to eject tiny droplets from liquid surfaces for high-resolution output. Alion has refined the process for printing thin-film photovoltaic (PV) cells, for which conventional printing processes are not suitable. Alion's acoustic printheads are designed to print photovoltaic material for solar cells in single scans in only one direction of the substrate at a cost significantly less than conventional PV manufacturing methods. The process can make it more affordable to develop large, utility-scale arrays of photovoltaic cells.

The company, which Dun & Bradstreet reports has 25 employees, has attracted venture capital from Sequoia Capital and Global Cleantech Capital.

Solum (solumtech.com): Former CPN student Nick Koshnick co-founded Solum in 2009 to give farmers immediate answers regarding the nutrients needed in their fields. Solum makes a measurement tool that can be taken to the field for immediate soil analysis. The tool allows more efficient applications of fertilizer, at the right place and the right time. Fertilizer is a major cost for commodity crops, accounting for as much as half the operating expense of raising corn, for example. Solum's analysis also makes farming more sustainable by reducing nitrogen runoff (which causes "dead zones" in areas such as the Gulf of Mexico) and combating the dominant source of nitrous oxide—the third most important greenhouse gas.

Solum grew from Koshnick's work within CPN on SQUID sensors, leading him to become an expert on sensing technology. Dun & Bradstreet reports that Solum has five employees.

PrimeNano: CPN investigator Mike Kelly co-founded PrimeNano to develop a production version of a Microwave Impedance Microscope system that can be used on existing Atomic Force Microscopes. The company holds two exclusive licenses from Stanford. According to Dun & Bradstreet, the company has two employees.

CENTER OF INTEGRATED NANOMECHANICAL SYSTEMS (COINS)—UNIVERSITY OF CALIFORNIA AT BERKELEY The Center of Integrated Nanomechanical Systems seeks to improve environmental sensing technologies across a range of applications, such as monitoring air quality and detecting explosives and hazardous materials. Specifically, the technical focus of COINS is to develop the means for realizing its three major environmental monitoring applications—personal monitoring, community monitoring, and mobile monitoring.

Research Highlights As a key to its efforts, COINS researchers are developing a Platform for Advanced Nanomechanical Detection Applications (PANDA) that incorporates advances in nanoscale sensing, energy harvesting and conversion, electronic signal processing and wireless communication, and mobility. Using PANDA as a cornerstone, researchers have focused on

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applications in two areas: personal and community-based environmental monitoring, and tagging, tracking, and locating materials that could threaten human health and well-being.

COINS investigators are making major improvements in environmental monitoring technology that promises better resolution over space and time. Current air quality monitoring, for example, typically involves measurements taken over broad areas, from regions to neighborhoods, using the ambient data as an imperfect proxy for human exposure. Center researchers are developing portable, low-cost nanomonitors for more targeted use where people live and work. Providing real-time measurements that closely reflect human exposures can enable communities, companies, or other organizations to have more accurate pollution alerts and on-going exposure data.

Center investigators also are investigating and developing technologies that could fundamentally change the way the nation responds to natural catastrophic events or major security threats. As part of its security measures, for example, the United States needs effective methods for detecting chemical and biological weapons. A number of industries also need to detect hazardous materials. But most detection devices have limited sensitivity, specificity, speed, power consumption, cost, and size. COINS researchers are developing miniature mobile sensors that could detect the “scent” of biological weapons or other chemicals of environmental concern. The sensors will be inexpensive, easily deployable, able to run for months or years at a time, and will communicate wirelessly. The researchers expect the sensors to fundamentally improve the way authorities can respond to weapons threats, provide countermeasures, and enhance public safety.

Product/Process Successes Nanotube radio: Over the past century, radio has shrunk dramatically from the wooden-case "cathedral" style radios of the 1930s to the pocket-sized transistor radios of the 1950s and more recently to the single-chip radios found in cell phones and wireless sensors. Continuing this trend, COINS researchers further miniaturized the radio by cleverly implementing multiple radio functions with a single component, a carbon nanotube.

A COINS team led by Center Director Alex Zettl developed and demonstrated in 2007 a carbon-nanotube radio that is one ten-thousandth the diameter of a human hair. The device is a fully functional, fully integrated radio receiver with an antenna, tuner, amplifier, and demodulator for both AM and FM. It requires only a battery and earphones to operate. Researchers used the radio to receive and play music from FM radio transmissions, enjoying music such as "Layla" by Derek and the Dominos and, appropriately, "Good Vibrations" from the Beach Boys.

Moreover, the antenna and tuner are implemented in a radically different manner than traditional radios, receiving signals via high frequency, mechanical vibrations of the nanotube rather than through traditional electrical means. First configured as a receiver, it also can be built as a transmitter.

The nanotube radio's extremely small size could enable radical new applications such as radio-controlled devices small enough to exist in the human bloodstream, or simply smaller, cheaper, and more efficient wireless devices such as cellular phones. (See COINS website and Zettl Research Group)

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Enhanced mobility: It sometimes can be dangerous for humans to conduct search and detection operations. Examples include locating survivors in earthquake-damaged buildings, pinpointing natural gas leaks or explosives in buildings, and tracking the paths of toxic plumes. Authorities need mobile robot platforms that can explore and place sensors in these dangerous environments; but current robotic technology is too large, too slow, and too clumsy to maneuver in rubble.

COINS researchers, led by Prof. Ronald Fearing, have developed a robot platform tailored to such missions. The Dynamic Autonomous Sprawled Hexapod (DASH) has six legs, is slightly larger than a deck of cards, and has a flat back that can accommodate relatively large payloads of sensing

equipment. DASH can travel across flat surfaces fairly rapidly (roughly 5 feet per second), make nimble turns, and survive falls from 100-foot heights. In the future it will also climb vertical surfaces and climb over fairly tall obstacles, thanks to adhesive nanofibrillar materials in its feet. Patterned after the natural materials that give geckos “sticky” feet, the nanoadhesives are adapted from the research of other COINS investigators, including Prof. Roya Maboudian. (See COINS website and Science Daily)

DASH’s body is made of rigid cardboard beams and flexible polymer hinges; it carries miniature onboard control and communication electronics and a tiny DC motor. The research team can make them for less than $1 each, which suggests they can be mass-produced at very low cost. Thousands of robots could be deployed after an earthquake, for example, to speed the locating of buried victims.

Measuring the mass of a single gold atom: Nanoscale mechanical resonators are exquisite sensors for a variety of quantities such as force, position, and mass. Using a carbon nanotube-based nano-mechanical resonator, researchers in the COINS program led by Professor Zettl have constructed an atomic-resolution mass sensor.

As atoms or molecules land on the resonator, they induce a shift in its mechanical resonance frequency, from which it is possible to infer the mass of the adsorbed particle. Using this technique, researchers were able to measure the mass of a single gold atom.

While several nano-electromechanical systems (NEMS) that function as mass sensors have been developed, most of these previous devices were fashioned from silicon, and none could measure the mass of a single atom at room temperature. This sensitivity is due to the very small size of the spectrometer—it is a thousand times smaller

Built initially as a receiver, the nanotube radio can also work as a transmitter.

DASH robot platform

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by volume than typical NEMS resonators, measuring only about a billionth of a meter, or one nanometer, in diameter and 200 billionths of a meter in length. (See Nature Nanotechnology 3, 533–537, July 2008)

Looking past CMOS: Power consumption has emerged as a major challenge for continued scaling of CMOS technology—the key to computing growth. In particular, static power is an issue because current leakage, when a transistor is in the off state, increases exponentially as the transistor size decreases.

In contrast, nano-electromechanical (NEM) relays offer ideal switching behavior over a wide range of

operating temperatures: zero off-state leakage, abrupt switching, and high on-state conductance. NEM relays can be co-fabricated with CMOS circuitry on the same substrate for managing CMOS static power consumption, and for ultra-low-power, embedded static memory (SRAM).

Furthermore, logic operations can also be performed only with NEM relays in a very innovative, CMOS-less technology with zero standby power. Due to their high tolerance to radiation and heat, NEM relays can provide for robust electronic systems. As the dimensions of a relay are scaled down, its switching speed increases. The feasibility of high-speed relays with about one nanosecond switching time is now being explored by COINS researchers led by Prof. Tsu-Jae King Liu.

A single vibrating carbon nanotube has been used to measure a single gold atom.

Electrostatic force actuates cantilever beam, and resistive contact is made in the on state.

Startups and Spin­offs Alphabet Energy (alphabetenergy.com): Cofounded by Prof. Peidong Yang, Alphabet Energy focuses on technologies that could break through the cost barrier that prevents utilities from capturing the energy lost as heat at power plants. Prof. Yang and COINS colleagues developed and demonstrated a low-cost method for synthesizing and processing “rough” nanowires made of silicon that can efficiently convert heat into electric current. A cheap raw material, silicon is not ordinarily good at thermal conversion, but the rough silicon nanowires are 100 times more efficient. (See Berkeley Lab website)

Alphabet is funded by leading investors in the field of cleantech, including Claremont Creek Ventures, the CalCEF Clean Energy Angel Fund, and individuals from the renewable energy project finance industry. The company also has received grants from the U.S. Department of Energy, the Army, and the Air Force to support its efforts, and has five employees.

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Shrink Nanotechnologies (shrinknano.com): Formed originally as Shrink Technologies in 2008, the company's products are based on a summer undergrad research project at COINS of Michelle Khine, now at the University of California, Irvine. While working on her COINS project, she developed a plastic substrate material in an effort to fabricate tiny features onto plastic chips, discovered by using material from one of her favorite childhood toys, Shrinky Dinks. In her research, she was able to create a fully customized and functional microfluidic device that was made without the need for a clean room and millions of dollars in sensitive and expensive equipment.

The work led to the company’s unique NanoShrink material. Because of the unique characteristic of NanoShrink to uniformly compress during heating, complex structures can be designed at the macro-scale level that, upon heating, retain the design at the micro or nano-scale. The company has developed numerous applications in the solar energy, human and animal diagnostics, and biotechnology research and development tools industries. Dun & Bradstreet reports that the company has 18 employees.

Silicon Clocks (siliconclocks.com): Silicon Clocks, founded in 2006, pioneered the development of a micro-electromechanical systems (MEMS) technology that allows for the fabrication of MEMS resonators and other sensor structures directly on top of standard CMOS wafers. This approach will eliminate the need for boutique semiconductor processing and enables new levels of performance, integration, and size by eliminating the electrical parasitics and packaging issues associated with traditional solutions that co-package a standalone MEMS device and an integrated circuit.

Silicon Clocks drew venture funding from leading investors including Tallwood Venture Capital, Charles River Ventures, Formative Ventures, Lux Capital, and Silicon Labs. Silicon Labs acquired the company in 2010.

Kalinex (kalinex.com): Kalinex’s unique patented technology and products are based on 10 years of research and development conducted at the University of California, Berkeley and the Lawrence Berkeley National Laboratory. This technology allows for DNA and RNA sequence detection that is rapid, inexpensive, and simple to perform in order to move detection beyond a laboratory setting to solve problems in “point of” applications such as: point of sale, point of production, and point of treatment.

An early stage startup company founded by UC Berkeley professors and based in the San Francisco Bay Area, Kalinex is pushing the frontiers at the intersection of bio-nano information technology.

CENTER FOR SCALABLE AND INTEGRATED NANOMANUFACTURING (SINAM)—UNIVERSITY OF CALIFORNIA, BERKELEY With the vision of a new nanotechnology manufacturing paradigm combining fundamental scientific research with industrial outlook, the Center for Scalable and Integrated Nanomanufacturing is striving to overcome the major challenges that face the nanotechnology

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revolution: manufacturing nanodevices smaller than 20 nanometers in size, fabricating 3D complex nanostructures, and integrating multiple and diverse functionalities at the nano scale.

Research Highlights Center researchers are exploring high-speed plasmonic nanolithography and integrating it with the Multi-scale Alignment and Positioning Systems (MAPS) testbed. Plasmonic nanolithography takes advantage of surface plasmon waves on metals, which fulfill a mantra of “optical frequencies, but with X-ray wavelengths.” Amazingly, surface plasmons at visible frequencies can have wavelengths approaching 1 nanometer, allowing vast improvements in the resolution of lithography-based manufacturing tools toward the critical 1-to-50 nm range. SINAM researchers have developed new technological platforms for the manipulation and construction of high-dimensional nanostructures. Now investigators are utilizing these technologies to build a plasmonic-based healthcare platform. The platform consists of a versatile and flexible delivery system that is capable of providing a wide range of stimuli dynamically to cells under investigation. The flexibility of the delivery system allows for many different combinations of molecules to be tested simultaneously. In addition, the responses from the stimulated cells are monitored by an integrated nanoscale plasmonic sensing array.

A third thrust of Center research is reducing the barrier of solar energy utilization both by lowering the manufacturing cost and increasing the efficiency of solar energy conversion into electricity, and by developing revolutionary solar energy storage routes. Solar energy is widely recognized as a strong candidate to provide much of humanity’s future energy needs. The keys to accelerating the deployment of solar energy are the cost and conversion efficiency from solar energy into electricity and the storage of this energy. The Center is developing second- and third-generation solar cells that include solid-state, thin-film solar cells and electrochemical solar cells.

Product/Process Successes Invisibility cloak: Never mind Harry Potter—researchers at Berkeley have made an invisibility cloak of their own. A team led by Xiang Zhang, SINAM director, has created a “carpet cloak” from nanostructured silicon that conceals the presence of objects placed under it from optical detection. Shining a beam of light on the bulge shows a reflection identical to that of a beam reflected from a flat surface, meaning both the object itself and the carpet have essentially been rendered invisible.

While metallic metamaterials have been successfully used to achieve invisibility by cloaking at microwave frequencies, until now cloaking at optical frequencies—a key step towards achieving actual invisibility—has not been successful because the metal elements absorb too much light.

Right now the cloak operates for light between 1,400 and 1,800 nanometers in wavelength, which is the near-infrared portion of the electromagnetic spectrum, just slightly longer than light that can be seen with the human eye. However, because of its all dielectric composition and design, researchers say the cloak is relatively easy to fabricate and should be upwardly scalable. They are also optimistic that, with more-precise fabrication, this all-dielectric approach to cloaking should yield a material that operates for visible light—in other words, true invisibility to the naked eye. (See Nature Materials 8, 568–571, 2009)

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The research is based on 3D materials developed earlier by SINAM scientists that can reverse the natural direction of visible and near-infrared light. Besides the science-fiction-like concept of cloaking devices, the development could help form the basis for higher-resolution optical imaging and nanocircuits for high-powered computers.

SINAM researchers overcame challenges in manufacturing negative-index metamaterials (NIMs) that had stymied their use in experimentation. NIMs have been the subject of intense interest for several years due their exotic optical properties, such as negative refraction. In contrast, all materials found in nature have a positive refractive index, a measure of how much electromagnetic waves are bent when moving from one medium to another—such as a pole inserted into water. If water exhibited negative refraction, the submerged portion of the pole would appear to jut out from the water's surface. (See Nature 455, 376-379, 2008)

Nanodiamonds for delivering drugs: A SINAM research team has developed a promising nanomaterial-based biomedical device that could deliver chemotherapy drugs to sites where cancerous tumors have been surgically removed. The flexible microfilm device, which

resembles a piece of plastic wrap and can be customized easily into different shapes, has the potential to transform conventional treatment strategies and reduce patients' unnecessary exposure to toxic drugs.

SINAM researchers stacked alternating layers of silver and non-conducting magnesium fluoride, and cut nanoscale-sized fishnet patterns into the layers to create a bulk optical metamaterial.

The device takes advantage of nanodiamonds, an emergent technology, for sustained drug release. Nanodiamonds are 2 nanometers in diameter in single-particle form, and can be manipulated to form clusters with diameters in the 50-100nm range. This makes them ideal for drug delivery by shielding and slow releasing drugs trapped within the cluster of diamond aggregates.

The researchers demonstrated that the device releases a chemotherapy agent in a sustained and consistent manner—a requirement for any implanted device used for localized chemotherapy. If a surgical oncologist, for example, were removing a tumor from the breast or brain, the device could be implanted in the affected area as part of the same surgery. This approach, which confines drug release to a specific location, could mitigate side effects and complications from other chemotherapy treatments.

In their study, led by Prof. Dean Ho of Northwestern University, the scientists embedded millions of tiny drug-carrying nanodiamonds in an FDA-approved polymer. Currently used as a coating for implants, the biostable polymer is a flexible and versatile material. A substantial amount of drug can be loaded onto clusters of nanodiamonds, which have a high surface area. The nanodiamonds then are put between extremely thin films of parylene, resulting in a device that is minimally invasive.

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To test the device's drug release performance, the researchers used Doxorubicin, a chemotherapeutic used to treat many types of cancer. They found the drug was slowly and consistently released from the embedded nanodiamond clusters for one month, with more Doxorubicin in reserve, indicating that a more prolonged release (several months and longer) was possible. The device also avoided the "burst," or massive initial release of the drug, a common disadvantage with conventional therapy.

The device could house other treatments, such as those based on RNA or DNA. This gives the technology the potential to impact a range of treatment strategies where implanted, long-term drug release is needed. (See ACS Nano, 2008, 2 (10), pp 2095–2102)

Flying plasmonic lens: To leverage the dramatic advancements in nanoscale science and engineering, there is an urgent need for high-throughput, nano-fabrication technologies that are versatile enough to enable frequent design changes. Commonly used direct-writing nano-lithography methods—such as electron-beam, focused ion-beam, and scanning-probe lithography—can provide the desired flexibility without using expensive and time-consuming photo-masks. But they are limited by low throughput, mainly due to their slow scanning capabilities.

Researchers from SINAM have proposed and developed a novel, high-throughput, direct-writing nano-lithography method utilizing plasmonic lenses. The metal lenses focus light through the excitation of electrons flying at a speed of greater than 20 mph to generate nano-scale structures. An advanced air-bearing technology, also used in hard drives, was employed to ensure precise control of the flying height at 20 nanometers, plus-or-minus 2 nanometers, which is equivalent to flying a Boeing 747 at 2 millimeter height.

Such a low cost, high-throughput nano-fabrication method promises a new route towards the next-generation nanomanufacturing of electronic materials. In addition, the technique is highly adaptable to optical and magnetic storage technologies. (See Nature Nanotechnology 3, 733–737, 2008)

The nanodiamond clusters trap the Doxorubicin drug and slow its release.

Plasmonic lens array

Startups and Spin­offs Ardica Technologies (ardica.com): Founded in 2004, Ardica Technologies is a San Francisco-based company dedicated to creating better personal power solutions for consumers through innovation, integration, and development of fuel cell technologies. Ardica’s approach to the challenge and opportunity of micro fuel cells has been to develop scalable, platform fuel cell

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technologies, such as compact on-demand hydrogen generators, planar fuel cells, and fuel cell system design and integration, which enable a whole new class of innovative products.

Ardica, cofounded by SINAM researcher Fritz Prinz of Stanford University, is focused on applying its unique technology to a host of innovative, high-visibility products that capitalize on fuel cells’ inherent benefits while partnering with industry-leading companies to help launch these products. Dun & Bradstreet reports that the company has 12 employees.

Fluid Medical (fluidmedical.com): Fluid Medical, started in 2004, developed micro-size electromechanical devices capable of complex motion in interventional devices. Near-term products include the smallest available intravascular ultrasound device. The company's technology has additional applications in interventional cardiology, neurology, and other fields.

Fluid Medical was acquired in 2010 by Volcano Corp., a leading developer and manufacturer of precision intravascular therapy guidance tools designed to enhance the diagnosis and treatment of coronary and peripheral vascular disease. The purchase price was $2.4 million.

CENTER FOR ENVIRONMENTAL IMPLICATIONS OF NANOTECHNOLOGY (UC CEIN)—UNIVERSITY OF CALIFORNIA, LOS ANGELES The University of California Center for Environmental Implications of Nanotechnology was established in September 2008 to help ensure that nanotechnology is introduced in a responsible and environmentally compatible manner. Doing so is essential for developing a sustainable technology in this vital emerging field and can help domestic and international communities to leverage the benefits of nanotechnology from an economic, societal, and environmental perspective.

Research Highlights The Center is developing a series of broad-based scientific models to predict how engineered nanomaterials (ENMs) might impact a variety of biological life forms in different environmental settings. By developing decision-making tools, UC CEIN researchers are able to rank hazards and predict some of the risks associated with ENM impact on the environment. This work is helping researchers, industry, and policy makers understand how nanomaterials spread to and interact with biological life forms in the environment, the ultimate fate of ENM in the environment, and how these materials could catalyze environmentally hazardous outcomes. The Center is studying these issues at the level of cells, tissues, organisms, populations, and ecosystems in fresh water, sea water, and terrestrial environments. To accomplish this, UC CEIN has established a multidisciplinary team comprised of chemists, nanomaterial scientists, mathematicians, biologists, ecologists, toxicologists, computer scientists, and sociologists.

In order to develop integrated scientific models with sufficient predictive power to understand the larger picture, the Center has established a well-characterized set of nanomaterial libraries that is premised on those types of ENMs that are being produced in the largest volumes and are most likely to come in contact with the environment. By studying the characteristics of these materials, the Center can determine which nanomaterial properties are key to the spreading of

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ENM to the environment; are responsible for biological uptake and interaction with cells, tissues, organisms, and populations; and have the potential to generate biological hazard and risk. In order to facilitate knowledge generation at the rapid rate at which nanomaterial technology is growing, UC CEIN researchers have also implemented high-content and high-throughput toxicological screening methods that can be used to rapidly screen a wide range of nanomaterials and to identify the series of properties that can contribute to hazards and adverse impacts. Moreover, the high-content knowledge generation is also being used to make predictions about the interplay of nanomaterials with more complex environmental life forms and ecosystems.

The societal and outreach activities of the UC CEIN are informing science experts, regulatory agencies, and the public about nanotechnology environmental health and safety (nano-EHS) issues as well as how to implement risk-reduction strategies. This includes knowledge sharing that can be used for decision-making about hazard and risk, risk-reduction strategies, and safe-by-design production approaches. An important task of the UC CEIN is to train a new generation of scientists in NanoSafety as well as how to participate in making nanotechnology a sustainable enterprise.

Center Product/Process Successes High-throughput screening methods that accelerate knowledge generation about ENM hazards: Traditional toxicology testing relies on time-consuming and expensive whole-animal testing that often is carried out one material or toxicant at a time. Such an approach will not handle the rapid pace at which nanotechnology is introducing new materials. To prevent a backlog between the fast-growing list of nanomaterials and their safety profiling, the UC CEIN has developed a series of high-throughput screening (HTS) methods for testing the potential threat of the most widely used materials in cells, bacteria, and fish embryos. One major platform that has emerged is an HTS screen for multiple toxicological responses at the cellular level that allows comparison of large batches of nanoparticles.

Researchers in UC CEIN have implemented the use of automated, robotic techniques for microscope image-processing of cells that are stained with a cocktail of fluorescent dyes that detect a range of cellular injuries in response to potentially harmful ENMs. The percentage of cells that are damaged or killed are scored by computer-assisted image analysis, resulting in a hazard diagram in which the yellow and red colors show particles with higher toxic potential. In the example shown for metal nanoparticles, zinc oxide as a representative high-volume nanomaterial in the

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Zinc oxide nanoparticles (upper left) were made less toxic by adding iron (upper right).

marketplace posed the most hazard to the culture cells used in the screen. Moreover, the screen demonstrated that this toxicity is due to the dissolution of the zinc oxide nanoparticles, leading to shedding of toxic zinc ions. Armed with this knowledge, nanochemists in the UC CEIN were able to redesign the zinc oxide nanoparticle to be less soluble by adding iron to the particle matrix. Not only was the iron-supplemented zinc oxide shown to be safer in the cellular screening assay, but it also reduced the hazardousness of this material in experiments using fish embryos or rodent exposures. This is a strong example of the implementation of a safe-by-design approach to make ENMs less dangerous.

This work demonstrates the utility of a high-throughput screening approach for hazard ranking of a set of nanoparticles that are representative of high-volume ENMs being produced and used by industry. The work also shows how the HTS tool can be used to improve nanosafety by decreasing zinc oxide dissolution through iron supplementation. (See ACS Nano, 2010, 4 (1), pp. 15–29)

Computerized modeling of high-throughput data: Computers that can efficiently evaluate the mass of data generated by high-throughput screening are crucial for transforming the data into a decision-making tool. Utilizing computer-assisted statistical and data analysis tools allows a clear and unambiguous approach to hazard ranking of large batches of nanomaterials. One approach employed by the Center’s researchers is to rank and classify nanoparticles according to their physical and chemical properties. Moreover, computer analysis permits data modeling that can be used to provide simulation of the hazard and risk as a prelude to developing a sustainable ENM technology. Because computer technology allows the implementation of intelligent decision-making tools for nano-EHS, the UC CEIN efforts have made a national-scale impact on nano-informatics development in the US, including providing approaches for high-volume data collection, processing, and utility for predictive modeling of nano-EHS issues.

The research is currently being performed using diverse data-collection methods, data transformation and feature-selection approaches, and hazard software that is being used to analyze the high-throughput data collection as well as the information about nanomaterial properties, fate and transport, and eco-toxicological outcomes to speed up our predictive decision-making tools. An example of how these computer-assisted decision tools have proven useful is the ability they provided to predict toxicological responses in zebrafish and oyster

embryos as well as phytoplankton based on the toxicological screening in tissue-culture cells. Moreover, the researchers have gathered ideas about potentially hazardous nanomaterial properties that can lead to toxicological responses and were able to redesign zinc oxide nanoparticles, as discussed above. A later phase of this work will allow the Center to perform multimedia modeling to predict in larger-scale systems (e.g., ecosystems) how nanotechnology might impact the environment.

Machine learning, a branch of artificial intelligence, will help capitalize on UC CEIN data.

Toxicity assessments in freshwater, seawater, and terrestrial environments: Discharge of engineered nanomaterials into the environment is expected to increase with growing use of the particles in manufacturing. UC CEIN researchers have successfully carried out research on

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the impact of nanoparticles in seawater, fresh water, and terrestrial environments. UC CEIN research has identified these areas as environments that host biological life forms that could be impacted by nanotechnology. They are therefore fruitful environments for translating the work being done on nanomaterial properties, high-throughput screening, and how that could lead to adverse impacts on organisms, populations, and ecosystems. To explore how nanomaterials are transformed under these environmental conditions, a major study looked at the spreading and sedimentation behavior of metal-oxide nanomaterials in seawater, freshwater, and groundwater conditions. As one example, UC CEIN researchers have analyzed the physical and chemical parameters that influence the clumping/sedimentation or coating/spread of metal-oxide nanoparticles in eight representative sea, lagoon, river, and groundwater media. Based on these characterizations, it was possible to formulate predictions about whether organisms might be exposed when they crawl around in sediments or swim around in the aqueous layer when the nanoparticles are suspended.

An important finding was that the electrophoretic mobility of the particles—i.e., how particles move when an electric field is applied—in a given environmental medium is statistically related to the ionic strength of the particular medium as well as to the concentration of natural organic materials that may be present in that medium. Because the electrophoretic mobility reflects whether a nanoparticle might sediment or spread in a particular medium, these results are of critical importance in predicting where nanomaterials might end up in the environment or how protective measures can be used to prevent the spread of ENMs to the environment. These measures could help in designing wastewater systems.

In order to model the environmental fate and transport of nanomaterials on a smaller scale, ecologists in the Center are utilizing a series of experimental microcosms that are designed to mimic what might happen to selected organisms in a freshwater, seawater, or terrestrial environment. These microcosms are designed to include and combine characteristic sentinel species in each microcosm, including selections of the simplest life forms (e.g., bacteria) to more complicated organisms that feed on the primary producers and that may bioaccumulate ENMs as we move up the food chain. These experimental environments designed to mimic real-life conditions are being used to determine whether the Center's high-throughput screening is predictive of outcomes in more complex environments. One series of microcosm experiments found strong evidence that in aquatic systems, zinc oxide is significantly toxic to primary producers, but titanium oxide is not. Zinc oxide nanoparticles are toxic to marine phytoplanktons because they dissolve and release zinc into seawater. Titanium dioxide particles, by contrast, do not dissolve and had no effect on plankton growth, unless the microcosm is subjected to ultraviolet light—in which case the titanium dioxide could utilize its quantum mechanical properties to generate a toxic reaction.

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Decreased survival rates in marine amphipods due to exposure to zinc oxide nanoparticles

Bottom-dwelling marine amphipods, which live in soft sediments and can trap and accumulate nanoparticles, died when exposed to low doses of zinc oxide particles dissolved in seawater. However, when exposed to the zinc oxide in sediments, amphipods tolerated very high concentrations of nanoparticles. This work suggests that the toxicity of metal oxide nanoparticles in marine environments could be alleviated when they end up in bottom sediments. However, this research has not as yet taken into consideration that chronic accumulation of nanoparticles in sediments might create problems due to complex changes in sediments over time. (See Environmental Science & Technology, 2010, 44 (6), pp 1962–1967)

Education and Outreach An important UC CEIN goal is to use the knowledge generated through research and surveys to inform the public, academia, industry, and government agencies how nanotechnology can be safely implemented in society and the marketplace. By reducing uncertainty about nanomaterial safety issues, the Center's goal is to promote widespread acceptance of nanotechnology in society. UC CEIN researchers are actively engaged in assessing public and special-interest views of the risks in nanotechnology. For instance, a survey of nano industries found that while 87% of companies report having generic environmental, health, and safety (EHS) programs, only 45% of companies have a nano-specific EHS program. A majority of participants cited a lack of information about the impact of nanotechnology on the environment as impeding the implementation of nano-EHS programs, which was particularly true for companies that employed more than 20 workers. Through interactions with industry, UC CEIN is assisting in the diffusion of knowledge about the impacts of nanotechnology on the environment. Center investigators have also surveyed experts outside science and engineering to assess views of nanomaterial risks and regulations. The results provide a vital comparative framework for UC CEIN studies of public and industry risk perception.

In education, UC CEIN has developed a broad network of internet teaching activities that were made available to participants nationally and internationally, including a Nanotoxicology Capstone Course as well as a graduate-level short course on an integrative model (Dynamic Energy Budget Theory) that can be used to study nanomaterial impacts across different environmental populations. These lectures have been archived and made available to the public through iTunes U. Additionally, work is underway to translate the Center's Nanotoxicology Capstone course into an online version that will be made available to research and education partners and will be taught to partner institutions in collaboration with other agencies. Other Center-wide seminars are webcast, including a day-long workshop on the environmental health and safety of engineered nanomaterials that drew 200 participants across the Web as well as the 100 who attended in person.

The UC CEIN leadership has played an active role both nationally and internationally in helping to integrate nano-EHS efforts in the US as well as internationally by fostering collaboration with Europe, Russia, China, Singapore, and Japan. This includes providing testimony to the President's Council of Advisors on Science and Technology and helping to shape the 2010 NNI Nano EHS report. The center director also served on the Bilateral Presidential Commission promoting US/Russia collaboration in the field of nanotechnology and nano-EHS. Members of the UC CEIN also made contributions in five of the major forms that were discussed in the comprehensive NNI/NSF International Study that was published by Springer under the title,

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“Nanotechnology Research Directions for Societal Needs in 2020” (Roco M., C. Mirkin, and M. Hersam, (eds.), Springer 2011, Boston and Berlin).

CENTER FOR NANOTECHNOLOGY IN SOCIETY (CNS-UCSB)—UNIVERSITY OF CALIFORNIA, SANTA BARBARA The Center for Nanotechnology in Society at UCSB provides a clear and comprehensive approach to understanding the challenges to the successful development of nanotechnology in the US, Europe, Asia and other regions by addressing nanotechnology origins, innovations, and perceptions in a global society.

The Center seeks to further the global vision of nanotechnology maturing into a transformative technology by understanding the array of interconnected and complex factors within a rapidly changing international economic, political, and cultural environment. These include the resolution of scientific and technological questions; the safe creation, development, and commercialization of nano-products; and the acceptance of nanotechnology by diverse publics.

Research Highlights Through a mixed and complementary portfolio of interdisciplinary research, education, and engagement activities, the CNS-UCSB produces basic knowledge about a linked set of social and environmental issues at a time of sustained technological innovation. This is achieved through close examination of the development, commercialization, production, consumption, and control of nanoscale technologies.

The Center also addresses education for a new generation of social science and nanoscience professionals as it fosters research on the origins of the nanotechnology enterprise, the innovation systems for nanotechnology, as well as globalization, cooperation, and competition in the development of nanotechnology. The Center also looks at the social response, media framing, and emerging risk perceptions of nanotechnology.

With an outlook that is global in scope, detailed in its focus, and rigorous in its methodologies, the CNS-UCSB uses its evolving international research infrastructure to create a genuine learning community of diverse participants who can pool their knowledge for the simultaneous benefit of society and technology.

Product/Process Successes Nanotechnology’s roots in biotechnology and semiconductors: Understanding nanotech’s societal implications requires a clear and comprehensive understanding of its historical context. This requires examining nanotech’s history at multiple levels of analysis—scientists’ careers, research communities, instrumentation, national and state policies, and the role of public imagination and interest in “visionary engineering ideas.” The Center's goal is to produce and integrate a diverse range of historical sources and research tools in order to understand specific facets of the nano-enterprise’s history.

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For example, CNS-UCSB researchers Cyrus C.M. Mody of Rice University and Hyungsub Choi of the Chemical Heritage Foundation have shown how it was the emergence of biotechnology in the 1970s that also gave rise to a key innovation in industry: small, high-tech firms that sprang from the research of prominent academic scientists. In particular, the patenting of recombinant-DNA research by Herbert Boyer of the University of California, San Francisco, and Stanley Cohen of Stanford University in 1980 marked a new, self-conscious era of professorial start-ups.

With Boyer and Cohen’s patent, the venture-capital industry expanded out of its most successful niche—funding spin-off firms from established semiconductor companies—and into financing professorial start-ups. The CNS-UCSB researchers link those innovations to the success of one nanotech star scientist, Rick Smalley, and the commercialization of his work through a start-up company, Carbon Nanotechnologies, Inc., or CNI (now part of Unidym). (See Studies in Materials Innovation 2010, Chemical Heritage Foundation)

CNS-UCSB researchers have also demonstrated the salience of earlier nanoelectronics research and nanofabrication techniques from the 1970s and 1980s in laying the foundation for the main research thrusts of the National Nanotechnology Initiative. For example, the Center's work noted the relevance of early “proto-nano” work—such as research on molecular electronics and the discovery of giant magnetoresistance in 1988, as well as its subsequent commercialization, for later nanotechnology initiatives in the US and abroad.

Researchers have also noted that, while the semiconductor industry was miniaturizing microelectronic components long before nanotechnology, it failed to develop an alternative to silicon despite its interest in molecular electronics. Only at the turn of the century, with new nanotechnology institutions and new models of industry-university collaboration, has some form of molecular electronics neared acceptance by the semiconductor industry. (See Social Studies of Science 39 (1): 11-50)

Nanotech in China: Center researchers led by Richard Appelbaum of UCSB have examined the globalization of nanotechnology, focusing initially on China, then expanding to a comparative analysis that includes the United States and Japan. The primary focus has been to better understand the interplay of national and transnational forces in shaping the development of nanotechnology. At the national level, science and technology policy has been a driver of nanotechnology, with many countries (including China) modeling their approach on the U.S. National Nanotechnology Initiative. China, however, has pushed governmental support further towards the commercial end of the innovation/commercialization continuum, in an effort to become globally competitive. The Center's research has sought to better understand this tension between national and transnational forces.

China, along with some forty other countries, is investing in nanotechnology as a major key to its future global economic competitiveness. Reviewing efforts by the Chinese government to become a world leader in nanotechnology, from fundamental research to the incubation of commercial products, CNS-UCSB researchers concluded that while China has made strides on such indicators as scientific publications and in some commercial sectors, the long-term returns from this effort remain uncertain. While the combination of international collaboration and increased public investment in nanotechnology holds promise for advancing nanoscience in China, most commercial returns still appear to be a long way off.

Specifically, the researchers found that there was a significant increase in Chinese nanotech patents in the six years following 2000, with domestic applications increasingly surpassing

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foreign applications since that time. Most domestic applications, however, were from Chinese institutions of learning, while most foreign patents were from companies. This suggests that while China is becoming globally important in nanotechnology-related research, its commercial potential has yet to be realized. (See Nanotechnology Law & Business Review (6) 524-539, Winter 2009)

Context matters in public response to nanotechnology: While "size matters" is a ubiquitous theme in nanotechnology research, Center researchers found that the context of the research—both national/cultural and, more importantly, type of application—matters a great deal in determining public response to specific nanotechnology applications.

Public surveys had already found that people in the United States and Europe currently view the benefits of nanotechnology applications as outweighing their risks—although, overall, knowledge about nanotechnology remains very low. However, surveys cannot easily uncover the ways that people will interpret and understand the complexities of nanotechnology (or any other topic about which they know very little) when asked to deliberate about it in more depth, so new approaches to engaging the public are needed.

A group led by Barbara Herr Harthorn of UCSB, also the Center's director, conducted the comparative public-engagement experiment that looked at the United States and the United Kingdom. Based upon four concurrent half-day workshops—two in the United States and two in the United Kingdom—that debated energy and health nanotechnology applications, the researchers found commonalities that were unexpected given the different risk regulatory histories in the two countries. Participants focused on benefits rather than risks and, in general, had a high regard for science and technology.

As for differences, application context was much more salient than geography, with energy applications viewed in a substantially more positive light than applications in health and human enhancement in both countries. More subtle differences were present in views about the equitable distribution of benefits, corporate and governmental trustworthiness, the risks to realizing benefits, and in consumerist attitudes. Overall, societal implications trumped concerns about technological implications for risk. (See Nature Nanotechnology 4, 95 – 98, 2009)

Education and Outreach Nanotechnology for equitable development: Emerging technologies hold the promise of solving some of the world’s most critical problems. Nanotechnology, along with information technology, biotechnology, and other new technologies, has great potential for addressing such challenges as energy, environmental degradation, providing clean water, increasing the availability of sustainable food resources, and combating pandemic diseases. Moreover, increased international collaboration on technological innovation will both help to advance our understanding in these areas and lessen inequalities between the global North and South.

CNS-UCSB convened 85 participants from the United States, Europe, Japan, three of the largest emerging economies (China, India, and Brazil), and other emerging economies for a conference on "Emerging Technologies/Emerging Economies: (Nano)technology for Equitable Development." The Center worked with the Woodrow Wilson International Center for Scholars, which hosted the conference in Washington, D.C. Conference participants included leaders from non-governmental organizations, government, the private sector, science and technology, and

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academia, who discussed new pathways for technology-based solutions to problems in four inter-related areas: energy/environment, water, food security, and health.

The goal of the conference was to aid in the exchange of ideas and experiences between the development stakeholders mentioned above. The Center sought to initiate a dialogue between the research community and on-the-ground actors working to find solutions to the world’s most pressing challenges. The long-term goal is to bridge the gap between the developed and developing worlds, by promoting a two-way exchange of ideas about the ways in which innovation in emerging technologies might better contribute to equitable development outcomes in the four conference areas.

Besides an edited volume scheduled for publication in 2011, as well as a series of policy statements aimed at government officials in participating countries, the conference also afforded an opportunity for networking among the diverse groups of participants, including a limited number of graduate students, whose participation provided them with an opportunity to interact with the leaders in their fields.

Spreading social science education: A unique and truly interdisciplinary program at CNS-UCSB trains science and engineering graduate fellows in social science research, and gives social science and humanities students access to the expertise and knowledge of their science and engineering education peers. For example, CNS-UCSB in 2008/09 funded nine graduate fellows to work in interdisciplinary research groups mentored by a Center faculty researcher. Fellows gain an appreciation of how different fields approach problems, learn to communicate across disciplines and points of view, and take a broader perspective back to their own research and their departments.

They also get published: Since 2006, eight fellows have co-authored peer-reviewed publications with Center researchers.

Events included an address at the National Press Club, group discussions, and a lunch with Capitol Hill policymakers.

Graduate research fellows from UCSB's chemistry and geography departments explain their nano risk-perception research during a poster session.

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CENTER FOR NANOSCALE CHEMICAL-ELECTRICAL-MECHANICAL MANUFACTURING SYSTEMS (NANO-CEMMS)—UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN The Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems, based at the University of Illinois at Urbana-Champaign (UIUC), is developing reliable, robust, and cost-effective techniques for fabricating structures with micron-and nano-scale dimensions, with a focus on fluidic-based approaches. The Center's overarching objective is to make manufacturing at the nanoscale a routine operation.

Research Highlights Center researchers are developing a variety of new scalable process technologies, each with unique capabilities that can be employed with Center-developed manufacturing platforms to produce large arrays of nanoscale lines, dots, patterns, and structures using a wide variety of materials.

To employ those technologies, Nano-CEMMS researchers are developing technologies for monitoring and controlling processing at the micron and nano scales. These include microfluidic networks with embedded micro/nano-scale pumps, valves, and sensing elements as well as advanced positioning stages and control schemes.

The Center is also developing the sensing technologies needed for nano-precision positioning and control of a manufacturing platform, as well as electronic and optical sensing elements for controlling and monitoring nano/pico-liter fluid flows in microfluidic networks. Also, new optical and electronic sensing technologies are arising from the nanoscale structures and patterns made possible with the Center process technologies.

Using Center-developed transfer-printing technology, the patterns and structures produced through the process technologies can be combined with other micro/nano elements, components, and devices to make new integrated electronics, optoelectronics, and microfluidic products.

Product/Process Successes E-jet printing at high resolutions: The versatility of inkjet printers has enabled them to dominate many fields, including graphics and the growing industry of printed electronics. The ability to print circuits onto boards—so-called direct-write technology—also holds great promise for the electronics industry because inks are deposited only where needed, different functional inks are readily printed on a single substrate, and because inkjets can print on large substrates, are relatively low cost, and their software can alter patterns on the fly.

For commercial applications in graphics and electronics, inkjets have largely depended on piezo and thermal technologies, the first using sound and the latter heat to push fluids from the printheads. Researchers led by Nano-CEMMS Director John Rogers of the UIUC have developed electrohydrodynamic, or E-jet, printers that use electrical fields to pull a fluid through a printhead and that can produce images far beyond the resolutions of other inkjet technologies. Whereas piezo and thermal inkjets can produce resolutions of 1 to 2 microns, the new E-jet printers are approaching resolutions of 25 nanometers. In former incarnations, E-jet printing was limited to dot diameters of about 15 microns.

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These E-jets use fluid that has some electrically charged particles, or ions. Capillary forces pull the fluid to form a semispherical droplet that hangs from the tip, much like a drop of water on a faucet. Electrodes that generate an electric field between the nozzle tip and the substrate extend the droplet to a conical shape where ions accumulate at the apex. That causes only the tip of the cone to break away, forming a droplet a fraction of the size of the originating nozzle tip.

The E-jet system could rapidly synthesize complex nanoscale structures out of various materials. Already, the Nano-CEMMS group has successfully printed various inks that included fragile biomaterials such as DNA, as well as suspensions of single-walled carbon nanotubes and solutions of conducting or insulating polymers. The system has also produced simple devices, including flexible transistors that use aligned arrays of nanotubes and biochips that use spotted arrays of DNA probes. (See Nature Materials 6, (2007) 782–789)

Surprising response of polymers to nanoimprinting: The single greatest cost associated with chip fabrication is the optical lithography tool used to print the circuit patterns. To achieve nanometer-scale resolution on chips also requires high-powered lasers and large stacks of precision-ground lenses. Consequently, researchers have taken great interest in an alternative technology for nano-scale devices, nanoimprint lithography, which requires no complex optics or lasers. Costs are greatly reduced by the simplicity of nanoimprint lithography, in which a mechanical deformation is pressed into a substrate, typically a polymer.

Polymers are ubiquitous in the microelectronics industry and are used as sensing materials, lithography tools,

replication molds, microfluidics, nanofluidics, and biomedical devices. The many applications will require a range of materials with different properties to reduce production costs, shrink device scales, and generate engineered devices with new functional properties. Nanoscale control of polymer deformation at a massive scale would enable breakthroughs in a wide range of applications, but is beyond the current capabilities of large-scale manufacturing.

An E-jet's nanoscale nozzle (top), and printed pattern with dot diameters of 500 nm

Nano-CEMMS scientists led by William King of UIUC have developed fundamental insight into how polymers behave under different loads and environments at the nanoscale. They showed, for example, that when in a glassy state, polymers were less elastic and less yielding at the nanometer scale than in the bulk, but these properties were not a function of molecular weight. When heated into the viscous state, films of high molecular weight were softer than films of lower molecular weight. Both of these results ran counter to conventional wisdom in polymer physics developed over the last 50 years and have profound consequences for nanometer-scale manufacturing. (See Science 31 October 2008: Vol. 322 no. 5902 pp. 720-724)

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3D printers, which assemble an object through a layer-by-layer application of materials, have emerged as a tool for creating unique products ranging from children's toys to models of sophisticated structures. They have also developed as a nanomanufacturing tool for patterning materials in three dimensions at the nanoscale, including composites, microfluidics, photonics, and tissue engineering. Direct-write assembly allows scientists to design and rapidly fabricate materials in complex 3D shapes without the need for expensive tooling, dies, or lithographic masks.

Data on imprinted polymers overturned five decades of conventional wisdom.

Often called "direct-ink writing," this printing process is particularly useful because it can pattern soft materials at the microscale. That is critical for several emerging technologies, including the fabrication of crystals that affect the motion of photos, sensors, self-healing materials, and scaffolds used to grow tissues. The scaffolds are often made of a material called hydrogel, which can be fabricated through several processes. But most cannot produce hydrogels with varied spacing, much less with the widely varied patterns that are valuable for certain nano-scale applications. Direct-write assembly, by contrast, enables a wide array of materials to be patterned in nearly arbitrary shapes and dimensions.

Center researchers led by Jennifer Lewis of UIUC successfully used 3D printers to direct-write and assemble 1D and 3D hydrogel scaffolds from a specially formulated ink containing acrylamide, a chemical compound that is a crystalline solid. The process includea ultraviolet light that causes the ink to transform, or cure, into the hydrogel as it is released through a micronozzle, allowing the scientists to assemble scaffolds with micrometer-sized features.

This novel ink design can be readily extended to other chemistries, including those more suitable for tissue-engineering scaffolds. The ability to create hydrogel scaffolds with microscale features

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in both planar and 3D forms opens a new avenue for tailoring scaffolds for a broad array of applications, including tissue engineering, tunable optical sensors, and stimuli-responsive soft materials.

Education and Outreach Educational modules: The Center has created an extensive array of programs to educate a diverse group of university and K-12 students and their teachers in nanomanufacturing while also advancing the public’s knowledge of nanoscience and technology. For example, the Center has developed educational kits called Exploring Nano Products, based on the Center’s research, for loan to educators through a web-based facility. The modules contain materials needed for 30 students—including guides, presentations, handouts, assessment, and evaluations. They have reached audiences that include urban and rural students, young children and college students, homeschooled families, and large-scale outreach programs at museum and campus events.

Illustration of direct-writing a hydrogel-based ink, left, and optical image of a scaffold

An essential factor in Nano-CEMMS’ education programs is the dedication of all Center participants—including faculty, graduate students, undergraduate students, and post-doctoral and research fellows—of at least 15% of their total committed time to the education activities of the Center. Each participant contributes to the Center's education programs by transferring knowledge through writing papers, giving seminars, supplying content for education programs, presenting educational modules in teacher institutes, or participating in summer camp sessions. Many faculty members work directly with teachers and high school students on various research projects. Some also have hosted students for lab visits.

Startups and Spin­offs Semprius (semprius.com): Semprius has licensed the micro-transfer printing technology developed in the Center by Nano-CEMMS Director Rogers and is developing low-cost, high-performance concentrator photovoltaics. This technology, based on a pick-and-place type of process, provides an economical method of transferring printing and dispersing devices manufactured on single crystalline silicon wafers to other substrates such as glass, polymers, and elastomers. Semprius is also sublicensing this micro-transfer printing technology for non-solar applications to enable a wide variety of new products requiring large-area, thin, lightweight form factors, unprecedented performance, high reliability, and low cost. Potential applications include

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flat-panel displays, flexible electronics, large areas sensors, RF devices, and other applications requiring heterogeneous integration of high-performance semiconductors.

Started in 2005, Semprius has raised $13.5 million in capital and has about 30 employees.

ANDalyze (andalyze.com): ANDalyze produces instruments capable of high-resolution chemical sensing using functional DNA molecules. One of the most important discoveries in the last decade is that DNA and RNA are not only materials for genetic information storage and transfer, but also catalysts for a variety of biological reactions, and thus can be called catalytic DNA—or “DNAzymes.” Because metal ions play essential roles in the structure and function of DNAzymes, the study and application of these new enzymes has become a new frontier in bioinorganic chemistry, which studies the role of metals in biology.

Founded in 2005, the company is based on the research of Yi Lu of UIUC, who has also received funding from another NSEC, the Center for Directed Assembly of Nanostructures, at Rensselaer Polytechnic Institute. ANDalyze has raised $1 million in capital and has about 10 employees.

mc10 (mc10.com): Founded in 2008, mc10 is a company developing the next generation of electronic systems through its Conformal Electronics Platform. mc10's platform enhances and enables new applications by allowing high performance electronics to occupy spaces and geometries not possible in their traditional, rigid form. Backed by an extensive patent portfolio secured both through in-licensing and continued developments at mc10, the company is targeting applications in consumer electronics, medical devices, industrial products, and defense systems.

mc10 was formed based on research by founders Prof. John Rogers of UIUC and Prof. George Whitesides of Harvard University. mc10 is backed by North Bridge Venture Partners and Osage University Partners with $6.5 million in capital, and has about 10 employees.

Hoowaki (hoowaki.com): Hoowaki develops microtechnology for use by manufacturers, including parts, products, or processes. Hoowaki technology improves energy efficiency through friction and lubrication control, increase in heat transfer coefficients, and reduction of fluid drag. Using a low-cost, proprietary route, the company sells tooling to create micron-size features on the surfaces of metals, ceramics, and polymers. Hoowaki serves customers in a wide range of industries, including medical, transportation, HVAC, and materials companies.

Started in 2008, Hoowaki's unique manufacturing technology grew from groundbreaking work of Prof. King of the Nano-CEMMS. The company has about eight employees.

Microlution (microlution-inc.com): Microlution is a machine tool manufacturer specializing in building high performance machine tools that have been optimized to fabricate small, high-precision parts. Microlution's "micro" machine tools are based on the concept that small, high-precision parts should be machined on small, high-performance machine tools. The company’s high performance micro-machining centers have been used to fabricate small, high-precision parts from a wide range of materials ranging from plastics to metals, glass, and ceramics and have proven to be a cost-effective solution for both prototyping and high-volume applications.

Started in 2005, Microlution has raised more than $2 million in capital and has about nine employees.

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CENTER FOR HIERARCHICAL MANUFACTURING (CHM)—UNIVERSITY OF MASSACHUSETTS AMHERST The Center for Hierarchical Manufacturing, based at the University of Massachusetts Amherst, strives for the cost-effective manufacturing of devices that employ nanotechnology for enhancements in computing, energy conversion, and human health. The Center's research focuses on the two- and three-dimensional integration of components and systems across multiple length scales. The approach integrates nanofabrication processes based on directed self-assembly, nanoimprint lithography, conformal deposition, and template replication using high-fidelity 3-D polymers. Together with silicon wafer technologies and roll-to-roll production tools, the processes yield materials and devices with unprecedented performance.

Research Highlights Center researchers are developing the tools and building blocks needed for cost-effective manufacturing of nanotechnology devices. Essential elements include the massively parallel generation of nanostructures, their functionalization to achieve desired physical or chemical properties, and the development of models and simulations to understand and, ultimately, predict the assembly process, system dynamics, transport, and materials properties of nanostructures.

A second thrust of CHM research is centered on system design and the metrology that is crucial to manufacturing. The work includes studies in magnetics, photonics, and device design to generate proof-of-concept prototypes that can be assembled using advances from the Center's process platforms. It provides theoretical and experimental components to guide a system-level, design-for-manufacturing approach and the development of metrology methods for property characterization and nanomanufacturing control.

Another thrust reflects the recognition that engineered nanomaterials provide both opportunities and challenges in environmental and health sciences. It develops new sensors for monitoring the dissemination of nanoparticles that incorporate unique, on-chip separations and diagnostics. Center investigators then employ new strategies for tracking nanomaterials in the environment and assessing their toxicity and biodistribution in plant and animal species.

Product/Process Successes Combining bottom-up assembly with roll-to-roll processing: Nearly two centuries of mill history in Massachusetts are taking a new and promising turn with advances at the CHM, which is now pursuing precise and cost-effective nanomanufacturing through the convergence of polymer self-assembly and roll-to-roll process technology. The advances are so promising that the focus of the CHM system-level testbeds has shifted from processes for silicon wafer platforms to a roll-to-roll processing platform that would enable the low-cost, large-area fabrication of nanomaterials and devices.

The Center's plans for developing the roll-to-roll platform are framed by the challenge of fabricating nanostructured thin films on a high-speed, high-reliability platform. Likewise, the manufacturing must be accomplished with relatively low complexity using inexpensive materials that will enable low-cost, high-volume commercial applications—applications that could include water purification and filtration, batteries, and thin-film, organic-based photovoltaics.

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CHM researchers led by James Watkins, of UMass Amherst and the Center's director, have demonstrated that highly-ordered periodic templates could be obtained from blends of commercially available commodity materials. Further, specifically functionalized metal and semiconductor nanoparticles can be used to drive strong order, enabling high loadings in hybrid materials.

The CHM recently created an industry advisory board comprised of 14 companies to enhance the development of the manufacturing platform. New roll-to-roll process tools have been developed in collaboration with a private company, Carpe Diem Technologies, to enable scale-up and demonstration projects. Once validated in the Center's testbed, these tools will be made available commercially through Carpe Diem. (See Journal of the American Chemical Society, Web publication: April 11, 2011 and Advanced Materials Vol. 20, Issue 9, pages 1603–1608, May 5, 2008)

Dense data storage using block copolymers: An innovative and easily implemented technique in which nanoscale elements assemble themselves over large surfaces could soon foster dramatic improvements in electronic data storage, such as hard drives.

Drawing of roll-to-roll nanoimprint lithography tool for CHM testbed

The electronics industry faces limits in conventional manufacturing of ever-denser semiconductors in its nanolithography that uses ever-shorter wavelengths of light at greater cost. As an alternative, researchers have tried to capitalize on the promise of self-assembling polymers. Self-assembly is highly parallel, quite versatile, and easy to implement—and results in a "bottom-up" approach to semiconductor manufacturing as opposed to the "top-down" process now used to produce smaller features.

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Especially promising are the novel compounds known as block copolymers—two or more chemically dissimilar polymer chains linked together—that will self-assemble into an extremely precise, equidistant pattern when spread out on a surface, much like a regiment of disciplined soldiers lining up in formation. For more than a decade, researchers have tried to exploit this characteristic for use in semiconductor manufacturing, but the order starts to break down as the size of the area increases. Once the formation breaks down, it is rendered useless as a form of data storage.

To overcome this problem, a CHM team lead by Prof. Thomas Russell of UMass Amherst heated sapphire crystals to create a specific pattern of ridges on the surface. This ridging serves as a guide for the semiconductor film. Dr. Russell conceived of this new approach with co-lead investigator Ting Xu of the University of California, Berkeley.

With this technique, the researchers were able to achieve defect-free arrays of nanoscopic elements with feature sizes as small as 3 nanometers, translating into densities of 10 terabits per square inch. One terabit is equal to 1 trillion bits, or 125 gigabytes. The advance would, for example, allow manufacturers to stuff the data stored today on 250 DVDs into a single disk no larger than a quarter. (See Science 20 February 2009: Vol. 323 no. 5917 pp. 1030-1033)

Chemical nose sensors for rapid cancer diagnosis: Rapid and effective differentiation between normal and cancer cells is an important challenge for the diagnosis and treatment of tumors. Building off fundamental studies on the interactions of nanoparticles with proteins and cells, CHM researchers have developed unique “chemical nose” sensors for cells and serum. Pilot studies have indicated the utility of these sensors in the rapid and efficient identification of healthy, cancerous, and metastatic cells for cancer diagnosis. Similar approaches are now being explored to modify this approach for enzyme-nanoparticle sensors for bacterial contamination that can be implemented in a mass-producible and cost-effective test strip format

Sawtooth ridges on a sapphire crystal, top, guide the self-assembly of nanoscale elements.

Center researchers led by Vincent Rotello and Joseph Jerry of UMass Amherst developed an array-based system for identifying normal and cancer cells based on a “chemical nose/tongue” approach that exploits subtle changes in the physicochemical nature of different cell surfaces. The sensor array contains conjugates of gold nanoparticles and fluorescent polymers that are capable of detecting, identifying, and quantifying protein targets. CHM researchers also developed unique “chemical nose” sensors for cells and serum. These sensors target the rapid and efficient identification of healthy, cancerous, and metastatic cells for cancer diagnosis.

In the case of cancers, the distinctions between normal vs. tumor and benign vs. metastatic cells are often subtle. The identification of cellular signatures for early cancer cell detection is a major hurdle for cancer therapy; the earlier these signatures can be established, the more effectively the

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disease can be treated. Cancerous cells are differentiated from noncancerous ones on the basis of intracellular or cell-surface biomarkers.

Pilot studies have indicated that these sensors can rapidly and efficiently identify healthy, cancerous, and metastatic cells for cancer diagnosis. Similar approaches are now being explored to modify this approach for nanoparticle sensors for bacterial contamination that can be mass produced in a cost-effective strip format. (See Proceedings of the National Academy of Sciences 2009, 106, (27) 10912-10916)

Surface properties determine environmental distribution: Very little is currently understood about how surface properties help govern the accumulation of nanomaterials in organisms. CHM scientists developed a new technique based on laser desorption/ionization mass spectrometry to track the distribution and fate of nanoparticles in the environment.

The sensor identifies cancerous cells within minutes based on differences in cell surfaces..

In studies using Medaka fish, Center researchers found that nanoparticles with positively charged surfaces were 3 to 10 times more likely to accumulate in fish than negative or neutral particles. These results may inform the development of more environmentally sustainable nanomaterials for inclusion into commercial products, a result that is important to the CHM and to the broader nanomanufacturing community. (See Small Volume 6, Issue 20, pages 2261–2265, October 18, 2010)

Education and Outreach National Nanomanufacturing Network (NNN): The CHM is the administrative hub of the National Nanomanufacturing Network, a catalyst for U.S. nanomanufacturing-based economic development and research collaboration. The network links manufacturing facilities and expertise, provides a dynamic web-based information resource, and is a pathway for university-industry-government partnerships.

The NNN functions as an electronic resource, community of practice, and network of experts working on the development of nanomanufacturing. The network has launched InterNano, a

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freely accessible digital library and information resource on nanomanufacturing where the network archives information on processes and tools, standards, reports, events, and environmental health and safety databases. The network also facilitates and organizes workshops and events with topical focus on critical and emerging nanomanufacturing issues, and contributes to critical areas of informatics, standards, education, and workforce training.

The goal of the NNN is to build a network of experts and organizations that expedite the transition of nanotechnologies from core research and breakthroughs in the laboratory to production manufacturing.

Startups and Spin­offs Alenas Imaging (alenasimaging.com): Alenas Imaging was co-founded by CHM researcher Janice Hudgings of Mount Holyoke College to commercialize the applications of stochastic resonance-enhanced thermoreflectance (SRETR). Thermoreflectance relies on the slight change in the brightness of optical reflection caused by changes in a material's temperature. Stochastic resonance takes advantage of the power of sound to enhance measurements; that is, if many measurements are averaged, a vibrating ruler can measure more precisely than a fixed ruler.

This inspection method offers high spatial resolution and low cost for a wide range of nanomanufacturing applications. Alenas Imaging has won several grants for its work, including $150,000 from the U.S. Department of Energy to test if its technology can detect microcracks in solar cells.

THE NANO/BIO INTERFACE CENTER (NBIC)—UNIVERSITY OF PENNSYLVANIA The mission of the Nano/Bio Interface Center at the University of Pennsylvania is to understand molecular interactions at the interface of biological systems and physical systems, specifically the interactions of designed proteins with non-biological systems. The work is indispensable to broad efforts underway to use biomolecules to mimic or enhance the functionality of non-biological devices.

Research Highlights The Center has developed next-generation probes of nanoscale phenomena that enable fundamental science studying the molecular interactions of physical-bio interfaces. NBIC’s success in developing new probes of molecular and nanostructural behavior cuts across all aspects of the Center's work, as these advances in physical measurement are prerequisite not only to advancing new frontiers in science but for reliable manufacturing at the nanoscale. The NBIC has established a unique facility that makes the new inventions in local probes available to the community at large. It contains 10 instrumentation platforms and serves over 100 academic and industry researchers. The facility will move into a new Penn nanotechnology center planned for occupancy in 2013.

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Center scientists also pursue two multidisciplinary thrusts: understanding of optoelectronic function in natural and bio-inspired hybrid systems (biomolecular optoelectronics), and mechanical motions in biomolecular systems and devices.

In biomolecular optoelectronics, NBIC researchers unite novel approaches in the design of molecular structure to create and control electro- and electro-optic functionality in synthetic biomolecules, specifically de novo-designed proteins that bind nonbiological chromophores synthesized within the team. To explore the effect of physical interfaces on the behavior of these molecular nanostructures, scientists have developed methods for fabricating nanoscale electrical contacts and for coupling protein-based assemblies to active surfaces, including carbon nanotubes and graphene. Studies of model systems that address fundamental issues at this interface are enabled by new approaches to manipulation and control of multi-component nanostructures.

In the second thrust, focusing on molecular motions, researchers develop novel techniques to manipulate and characterize the motion of motor proteins, DNA, and protein folding; study the mechanical and electrical properties of single molecules and the interface between the molecule, the solvent and nearby surfaces; exploit microfluidics and surface engineering to control local environments; and design, construct, and test a unique molecular motor-driven device that demonstrates separation, concentration, purification, and detection of proteins or nucleic acids

In addition, an overarching activity concerns the ethical implications of nanotechnology specific to these research themes and to the broader society.

Product/Process Successes Sunlight into power: Recent advancements made by NBIC researchers have given a new twist to turning sunlight into electrical power. Their research has uncovered a way to turn optical radiation into electrical current that could lead to self-powering molecular circuits and efficient data storage.

Led by NBIC Director Dawn Bonnell, the team of scientists placed light-sensitive gold nanoparticles on a glass substrate, minimizing the distance between the nanoparticles. The team then stimulated conductive electrons with optical radiation to ride the surface of the gold nanoparticles, creating so-called "surface plasmons" that induce electrical current across molecules.

Under these conditions, surface plasmons were found to increase the efficiency of current production by a factor of 4-to-20. The size, shape, and separation of the array of gold nanoparticles can be customized independently of the optical characteristics of the molecule. Optimization of these parameters could, the researchers say, produce enhancement factors of thousands, and the resulting electrical current could be easily transported to the outside world.

The results may provide a technological approach for higher-efficiency energy harvesting with a nano-sized circuit that can power itself, potentially through sunlight. Recently, surface plasmons have been engineered into a variety of light-activated devices such as biosensors.

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The system also could be used for computer data storage. While the traditional computer processor represents data in binary form, either on or off, a computer that used such photovoltaic circuits could store data corresponding to wavelengths of light.

Because molecular compounds exhibit a wide range of optical and electrical properties, the strategies for fabrication, testing, and analysis elucidated in this study can form the basis of a new set of devices in which plasmon-controlled

electrical properties of single molecules could be designed with wide implications for plasmonic circuits and optoelectronic and energy-harvesting devices. (See ACS Nano, 2010, 4 (2), pp 1019–1025)

A schematic of the plasmon-mediated molecular device

Friction at the nanoscale: A team of NBIC researchers has used friction-force microscopy to determine the nanoscale frictional characteristics of four atomically-thin materials, discovering a universal characteristic of these very different materials—namely, friction across these thin sheets increases as the number of atomic layers decreases, all the way down to one layer of atoms. This friction increase was surprising; there previously was no theory to predict this behavior.

The finding reveals a significant principle for these materials, which are widely used as solid-lubricant films in critical engineering applications and are leading contenders for future nanoscale electronics.

Researchers led by Prof. Robert Carpick of Penn and Prof. James Hone of Columbia University found that friction progressively increased as the number of layers is reduced on all four materials, regardless of how different the materials may behave chemically, electronically, or in bulk quantities. These measurements, supported by computer modeling, suggest that the trend arises from the fact that the thinner a material, the more flexible it is, just as a single sheet of paper is much easier to bend than a thick piece of cardboard.

The team tested the nanoscale frictional properties of graphene and three other substances down to single-atomic sheets. Each material exhibited the same basic frictional behavior despite having electronic properties that vary from metallic to semiconducting to insulating.

Because the sheet is so thin—in some samples only an atom thick—it deflects toward the tip, making a puckered shape and increasing the area of interaction between the tip and the sheet, which increases friction. When the tip starts to slide, the sheet deforms further as the deformed area is partially pulled along with the tip, rippling the front edge of the contact area. Thicker sheets cannot deflect as easily because they are much stiffer, so the increase in friction is less pronounced.

The researchers found that the increase in friction could be prevented if the atomic sheets were strongly bound to the substrate. If the materials were deposited onto the flat, high-energy surface of mica, a naturally occurring mineral, the effect goes away. It is another example of a property

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that changes as a material gets smaller, a hallmark of nanotechnology. (See Science, April 2, 2010.)

De novo proteins: Combining proteins with functional non-biological cofactors, which are molecules that help with the protein's biological activity, holds great potential for the development of new materials and nanostructures. The protein may serve as a scaffold to modulate the local cofactor environment and control solubility and processing. This effort is inspired in part by natural systems for light harvesting and electron transfer, such as the proteins involved in plant photosynthesis. But de novo, or newly designed, proteins can be tailored to accommodate a wide range of non-biological cofactors, and with functionalities not known in nature.

A major goal of the Center is the creation of proteins that contain non-biological cofactors that can be used to assemble, position, and control large molecules that are sensitive to light. Such molecules have potential applications in optical and molecular electronic devices. In each case, the protein’s structure and sequence are designed de novo to accommodate a given cofactor.

NBIC researchers developed, for example, the first computationally designed de novo protein that binds selectively with an emissive, non-biological chromophore. In designed protein complexes containing non-biological cofactors, electron and energy transfer reactions can be activated with light, and novel properties can be controlled including nonlinear optical and photophysical properties.

Although scientists have previously designed de novo proteins capable of binding non-biological cofactors, such systems have typically mimicked the structures, functions, and spectral features of naturally occurring proteins. (See Journal of the American Chemical Society; March 24, 2010; 132(11): 3997–4005)

Single-molecule probes: The ability, or inability, to probe behavior at the nanometer and molecular scale limits almost every endeavor involving nanotechnology. Enabling new scientific discovery, gearing up for manufacturing, determining environmental impact, and evaluating toxicity all rely on manipulating and characterizing structure beyond our current capability. Recent advances have opened pathways to a new generation of local probes of molecular function that combine optical, electrical, and magnetic signals with the ability to access dynamic phenomena.

NBIC scientists, for example, have been using tips with nanocrystalline diamond surfaces in atomic-force

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Model of a de novo protein with four non-biological cofactors

Image showing diffraction pattern confirming nanocrystalline diamond structure

microscopy. The diamonds have been getting the attention of many material chemists due to their stability and robustness. Compared to the common materials used in atomic-force microscopes, such as gold, crystalline diamonds can provide a much more stable element. Center scientists have developed and confirmed the functionalization of a nanocrystalline diamond tip for atomic-force microscopy.

Startups and Spin­offs Anima Cell Metrology (animapsl.com): Anima has developed a method for testing the activity of proteins in real time. That's a vast improvement over current methods, in which proteins are first destroyed and then analyzed to analyze their activity in retrospect. The company's main target market is research laboratories. A company cofounder is Prof. Yale Goldman of Penn, whose work is supported by NBIC.

Anima has raised private funding alongside a $2 million grant from the prestigious NIST Advanced Technology Program.

CENTER IN TEMPLATED SYNTHESIS AND ASSEMBLY AT THE NANOSCALE (UW NSEC)—UNIVERSITY OF WISCONSIN–MADISON The University of Wisconsin-Madison Center in Templated Synthesis and Assembly at the Nanoscale addresses grand challenges associated with directed assembly of nanoscale materials into functional systems and architectures through the use of self-assembly, chemical patterning, and external fields.

Research Highlights Center researchers are developing new materials and processes for advanced lithography in which self-assembling block copolymers advance the performance of nanomanufacturing processes. In the particular case of block copolymer materials, the thermodynamic forces that drive self-assembly are small, and low-energy defects can easily get trapped. The Center's work is responsible for conceiving and implementing the leading approach for the integration of copolymer directed self-assembly into the lithographic process that is used by the semiconductor industry.

In a second research thrust, the UW NSEC is exploring directed assembly through the synthesis of folded amino acids that provide a general and facile approach to the synthesis of organic nanostructures with well-defined shapes and precisely controlled patterns of surface chemistry. The thrust seeks to understand the functional properties of these nanostructures, including biological activities, as well as to understand how the nanoscopic chemical patterning of these organic structures can be exploited to direct their assembly into organized materials.

A third research group aims to harness non-equilibrium processes, such as the use of flow and electric fields, for controlled assembly and manipulation of nanoscale objects, including particles and macromolecules. Strategies to date for nanoscale assembly have largely revolved around searches for thermodynamic equilibrium to attain desirable end states. Supplementing traditional assembly techniques with the rational use of internal and external fields, and removing the

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constraints imposed by equilibrium conditions, offers substantial opportunities to expand the options available for directed assembly.

UW NSEC scientists also seek to identify the properties of nanomaterials that adversely affect embryonic development in organisms. Because the weathering of nanomaterials has the potential to alter their biological effects, the Center is focusing in particular on the environmental transformations of engineered nanomaterials and how that changes their interaction with organisms.

Product/Process Successes Integrating block copolymers with lithography: Electronic devices such as computer chips and data-storage drives that are the heart of products from laptops to cell phones are manufactured using photolithography. But limitations in the lithographic process may stall future progress, and thus the production of new generations of high-performance products.

A team of UW NSEC researchers, led by Center Director Paul Nealey and working with Hitachi Global Storage Technologies, has recently developed the technology to dramatically improve the quality and decrease the cost of patterning at nanoscopic scales. The method builds on existing approaches by combining the lithography techniques traditionally used to pattern microelectronics with novel self-assembling materials called block copolymers. When added to a lithographically patterned surface, the copolymers' long molecular chains spontaneously assemble into the designated arrangements. This innovation markedly improves both the density (by as much as a factor of four) and the quality of the process.

These results have profound implications for the many essential modern devices that rely on this nanomanufacturing process. The technology is particularly well-suited for designing hard drives and other data-storage devices. They need uniformly patterned templates, which are exactly the types of arrangements that block copolymers form most readily. Already, similar approaches based on the Center's innovations are being developed by data-storage manufacturers including Hitachi and Seagate.

With additional advances, the approach may also be useful for designing more complex patterns such as microchips. Researchers in Nealey's group, for example, have also shown that the capabilities of block copolymer lithography can include non-regular patterns of perfect and registered sharp bends. The ability to pattern these types of non-regular, device-oriented structures strongly suggests that the insertion of self-assembling materials into existing nanomanufacturing processes—including those used to fabricate microchips—may be possible in the near term.

Comparison of the quality and resolution of patterns created with current materials and processes (c, d) versus patterns created with self-assembling block copolymer materials (g, h).

The potential for commercialization of the Center-supported approach is high. Leading semiconductor manufacturing, equipment, and materials companies—including IBM, Applied Materials, and AZ Chemicals—have adopted the UW NSEC strategy and established internal

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programs. (See Science 15 August 2008: Vol. 321 no. 5891 pp. 936-939 and Science 3 June 2005: Vol. 308 no. 5727 pp. 1442-1446)

Potential nanorod lifesavers: UW NSEC researchers have designed and characterized a series of β-peptide nanorods with potent, specific activity against a human pathogen that kills thousands of immune-compromised persons each year. These nanorods bind and kill the fungus Candida albicans in multiple forms—including yeast and filamentous, in suspension and in biofilms—with minimal effects on human cells.

The initial generation of antifungal nanorods was inspired by peptides synthesized by human skin, and other animal tissues, that fight microbial infections. The β-peptide nanorods exhibit superior stability and activity as compared to analogs, and therefore represent a promising class of compounds to prevent and treat candidiasis, a disease that lacks effective pharmaceutical remedies.

Researchers led by Professors Samuel Gellman and Sean Palecek of UW identified several key features of the β-peptide nanorods that confer activity and selectivity. The nanorods must have localized positively-charged and water-resistant regions to interact with each other and with cell membranes. Also, the nanorods must be of a length on the order of the thickness of a cell membrane. Finally, the specific chemical groups attached to the nanorods regulate the ability to recognize fungal cells but not human cells. (See Journal of the American Chemical Society, 2006, 128 (39), pp 12630–12631)

Reading DNA barcodes: Nanotechnology is offering new ways to rapidly extract genetic information from very, very long DNA molecules. Within human chromosomes, these molecules can be 5 inches in length; an entire genome within each human cell comprises more than 6 feet of DNA. The challenge is how to reliably unravel such long molecules so that genetic information encoded within the DNA sequence can be read. A good analogy is to think of very long DNA molecules as a sprung mass of VCR tape released from a cassette.

UW NSEC scientists have developed a new system for both reeling long DNA molecules into very small cassettes, consisting of cheaply manufactured nanochannels, and reading “barcodes” that have been placed on these molecules, thereby revealing sequence information.

C. albicans yeast cells treated with β-peptide nanorods (left) and C. albicans filaments treated with β-peptide nanorods (blue)

The new system exploits a well-known attribute of highly charged polymer molecules, in that they become thicker and stiffen when salt is removed from solution. Remarkably, when salt-deprived DNA molecules are squeezed into tiny nanoscale slits, they greatly elongate, effectively displaying their barcoded information in images obtained by fluorescence light microscopy.

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Gaining physical insights into how nanochannel dimensions affect the elongation of DNA molecules played a key role in the development of this new system. And, because high-throughput systems have been developed by these scientists to quickly read single molecule barcodes, the resulting single-molecule displays will be efficiently folded into a new platform for genome analysis, thereby enabling the genetic analysis of individuals within clinical settings. Other applications promise new ways for patterning very long molecules, offering unprecedented opportunities for self-assembly and precise localization of nanoscale objects. (See PNAS February 20, 2007, vol. 104 no. 8, 2673-2678.)

Environmental conditions increase nanoparticle toxicity: Environmental conditions have the potential to alter nanoparticles in a variety of ways, such as dissolving or aggregating. The changes make it unlikely that organisms will be exposed to nanoparticles only in their original form. However, few toxicity studies have focused on environmentally altered nanoparticles. Center scientists examined the oxidative stability of quantum dots—a type of semiconductor—with cadmium selenide cores and zinc sulfide shells under environmental conditions that might be typical for lignolytic fungi. Scientists anticipate that industry will produce substantial volumes of the quantum dots, with accompanying environmental releases.

UW NSEC researchers used embryonic zebrafish as a model to investigate changes in toxicity between as-synthesized and weathered quantum dots. Following five days of exposure, weathered dots were more potent in causing mortality than as-synthesized dots. Interestingly, both as-synthesized and weathered quantum dots were more potent in causing early-life-stage toxicity than equivalent concentrations of dissolved cadmium. Although morphological endpoints of toxicity were the same for as-synthesized and weathered quantum dots,

weathered dots had higher potency.

DNA molecules revealed by a bright fluorescent dye are trapped in narrow nanochannels.

Additionally, the severity of some morphological endpoints increased following exposure to weathered quantum dots. Zebrafish embryos/larvae exposed to the nanoparticles alone showed minimal mortality and no morphological endpoints of toxicity. However, embryos co-exposed to selenide nanoparticles and dissolved cadmium recapitulated the profile of toxicity endpoints observed following exposures to weathered

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Toxicity observed in zebrafish embryos include pericardial edema (pe), ocular edema (oe), yolk sac malformations (ysm), tail malformations (tm), and craniofacial malformations.

quantum dots. The selinide-containing aggregates produced following assay exposure likely modulate the toxicity of the weathered quantum dots. Thus, environmental weathering is capable of increasing the potency of quantum dot toxicity to an aquatic vertebrate.

Education and Outreach Tactile nanoscale models: The UW NSEC has developed a method to convert scanning electron microscope images of nanoscale materials into 3D tactile models for the blind and visually impaired. A short software script converts 2D microscope images into 3D data which are printed using rapid prototyping technology. The 3D models can be printed nearly 12,000 times larger than the original nanoscale surface.

The tactile models, built directly from data collected at the nanoscale, allow one to feel the surface of nanoscale materials for the first time. The first tactile model of “Nanobucky” allows users to feel the individual nanofibers that comprise the original. The models are being used to teach blind and visually impaired students at the Indiana School for the Blind about nanoscale science and engineering.

Tactile Nanobucky (left), 20 cm wide is based on the original image (right), 15 nm wide.

Startups and Spin­offs Silatronix (silatronix.com): Founded in 2007, Silatronix is an early-stage start-up company co-founded by Robert Hamers, a UW NSEC researcher at UW-Madison. The company's technology combines the expertise of Dr. Hamers in nanostructured electrodes and electronic properties of materials with that of Robert West, also of UW-Madison, in organosilicon, organic compounds containing carbon silicon bonds.

The company's goal is expand the use of organosilicon compounds as safe, environmentally friendly electrolytes for use in energy storage devices such as ultracapacitors (electrochemical double-layer capacitors), lithium-ion batteries, and other electrochemical energy storage devices. The compounds could, for example, make big batteries used for backup power systems last longer and keep them stable in desert heat.

The company has attracted $1 million invested from the Wisconsin Alumni Research Foundation and Venture Investors, an investment fund, as well as $1.75 million in federal Small Business Innovation Research grants.

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INNOVATIONS AT THE NINN The National Nanotechnology Infrastructure Network (NNIN) is a collective of 14 university-based facilities across the United States that provide open and efficient access to nanoscale fabrication. The network enables researchers to reduce ideas to practice across disciplines, facilitating rapid advancements in nanoscale science, technology, and engineering. The NNIN facilities are open to the nation’s students, academic scientists, small and large companies, and national and state laboratories, among other users.

The network also supports research and engineering with computational resources primarily designed for modeling and simulation, using open and tested software and hardware. The NNIN leverages its resources and its geographic and institutional diversity to have a broad impact in other areas, including education, enhancing diversity in technical disciplines, studying societal and ethical implications of nanotechnology, and protecting human health and the environment. All NNIN sites provide a broad array of technology resources, and each has leadership responsibilities in areas reflected in its instruments and staff.

The NNIN serves the world’s largest community of experimental graduate students, engineers, and scientists under one umbrella. In 2010 alone, NNIN resources were tapped by more than 5,900 unique users. Of these, more than 4,800 were graduate students, about 900 were industrial users, and the rest were from federal, state, and foreign laboratories. This user community in turn

The National Nanotechnology Infrastructure Network  

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is also a laboratory for understanding and building societal and ethical consciousness in the community and a resource for science and engineering outreach.

More than 300 small companies use NNIN facilities each year. Many thousands of publications, including several significant scientific and engineering research highlights each year, typically result from the work of the user community. During NNIN’s history, nearly 50 companies have been founded based on technology developed in NNIN facilities; more than 100 small companies currently employ NNIN for their primary research and development, and more than 30 companies employ the network for building prototypes as small-scale manufacturing.

More than 1,200 PhD awards rely on NNIN resources each year, amounting to about a quarter of the PhDs awarded nationwide in nano-related disciplines. Among small companies, meanwhile, NNIN resources are used by more than 10% of professionals supported through federal small-business grants. A large percentage of nano-related small business grants and venture capital seeded companies employ NNIN resources because of the large knowledge and experience base and cost effectiveness it provides in pursuit of commercialization opportunities.

In short, the NNIN is a major force in developing the human and industrial resources needed for the nation's nano research, and in turning that research into viable products. This report looks at highlights of the ground-breaking research enabled and encouraged by the NNIN, the products and companies that benefit and that are produced through work carried out at NNIN facilities, and its educational offerings; and provides a brief profile of the institutions and resources available through the network.

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NNIN Research Highlights 

Health Gold “nanocages” for smart drug delivery: The search for a way to release medications only at the site of a tumor or infection has presented great challenges in disease treatment. Scientists have tried to solve the problem with photosensitive caged compounds, but activating these treatments often requires ultraviolet light—a method harmful to living tissue and, therefore, suitable only for in vitro applications.

A group led by Washington University researcher Younan Xia, using NNIN resources at the campus' Nano Research Facility, has developed a potentially effective drug delivery system triggered by near-infrared light, which can penetrate deep into soft tissues without harming living cells. In their demonstration, gold nanocages are covered with a smart polymer that seals the chemicals loaded into hollow nanoparticles up to a critical temperature of 39⁰ C. When triggered by infrared light, the polymer-coated gold nanocages absorb the light, heating the polymer above the critical temperature so that it contracts, exposes the nanocages’ tiny holes, and releases a drug.

The work was published in Nature Materials (2009, 12, 935-939) and highlighted in the New York Times.

Rapid DNA sequencing: Scientists have invested enormous effort in understanding and decoding the DNA molecule, the blueprint of life. But reading three billion nucleotide components to unveil a person's full genome is an expensive and complex process.

A group led by Stuart Lindsay, an Arizona State University (ASU) biophysicist, has demonstrated a technology that should lead to rapid, inexpensive decoding of entire genomes. Dr. Lindsay's technique relies on electron tunneling, an exotic property of matter that operates at

the subatomic scale. Electron tunneling involves passing DNA between two electrodes that can detect the chemical makeup of each individual base.

Processing steps used to integrate the carbon nanotube with the microfluidic delivery system.

Another important element of the new technology is the nanopore, which directs the DNA between the electrodes. Nanopores were once made through processes that were difficult to complete, and there was a problem of reliably printing electrode pairs very close to DNA.

Lindsay's team showed that a single carbon nanotube can grow easily on a silicon wafer using conventional methods. The DNA will then slip through the inside of the carbon nanotube in a way that was highly unexpected. As the DNA passes through the nanotube, changes in electrical current can be measured to identify the chemical bases. (See Science, Jan. 2010)

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With part of the work accomplished at the ASU NanoFab, the long-term goal is to take DNA sequencing from something that requires tens of thousands of dollars and several months to a

process done in hours for a few dollars.

In 2010, Dr. Lindsay joined a number of scientists and U.S. Vice President Joe Biden at a Washington, DC, gathering to highlight fields of investigation such as this one that are likely to spur growth in biomedical research and development.

Contacts that communicate: Conventional contact lenses are polymers formed in specific shapes to correct faulty vision. To turn such lenses into a functional communications system, scientist Babak Parviz worked at the University of Washington Center for NanoTechnology to

integrate control and communication circuits and miniature antennas into the lens, using custom-built optoelectronics components. These components will eventually include hundreds of LEDs which will form images in front of the eye such as words, charts, and photographs, while remaining semi-transparent so that wearers can navigate their surroundings.

Besides their potential to unlock a whole new world of visual information through internet connectivity, such lenses could be used to monitor biomarkers and health indicators such as blood glucose without needles or lab chemistry. The crucial data could be instantly relayed to the wearer

or to medical practitioners.

Implantable eye-pressure sensor: Fluid pressure inside the eye is a significant key in detecting and treating glaucoma, the second-leading cause of blindness affecting 65 million people worldwide. Working at the University of Michigan’s Lurie Nanofabrication Facility, a team of researchers from the university has developed a tiny pressure sensor that can be implanted in

Huge ion-current spikes signal the translocation of DNA.

Time Magazine named Parviz's contacts one of the 50 top inventions of 2008

Small eye-pressure sensors on the back of a U.S. penny

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the eye and can automatically take pressure readings every 15 minutes.

The sensor stores the data and transmits it on-demand, perhaps once a day, to an external probe over an ultra-wideband radio link. A plastic-coated glass package holds the pressure sensor, rechargeable microbattery, wireless link, and embedded processor. The device is optically triggered and scavenges energy from external light using a solar cell working in tandem with its microbattery.

The solar-powered eye pressure sensor utilizes a record-low-power microprocessor and could be inserted and removed with no sutures. A working prototype was introduced in early 2011, with commercial versions expected in a few years. The device would make it easier for glaucoma patients to measure eye pressure, which must be closely regulated to avoid vision loss. Today, patients must travel to a doctor's office for readings.

Hearing implants: Cochlear implants work by bypassing damaged hair cells in the ear to directly stimulate the auditory nerve electronically. Traditionally, they're built with bundles of wire electrodes. It is hard to get these wires properly positioned; and there’s room for no more than 20 or so. Researchers led by Prof. Kensall Wise of the University of Michigan, working at the campus' Lurie Nanofabrication Facility (LNF), are using photolithographic techniques borrowed from integrated circuit manufacturing to fashion a thin-film array of as many as 100 electrodes to improve perceived pitch and frequency range. Some of these devices are now being

tested.

The arrays would replace the traditional wire bundles now used in cochlear implants, offering many times more stimulating sites. Molded backing structures are being developed with Cochlear Corp. and monolithic parylene-ring backing structures are being prototyped at the LNF.

The entire sensor is only 2mm long, 1mm wide, and 0.5mm thick.

Molded backing of a cochlear implant array.

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The sensor works with a hermetically packaged microcontroller and a bidirectional wireless interface over an eight-lead polymeric cable. The array contains nine polysilicon strain gauges to detect array position and tip contact. (See Microelectromechanical Systems, Oct. 2008)

Artificial retinas for the blind: Blindness is one of the most devastating consequences of ocular disease. A team of Stanford University researchers has developed an electronic retinal prosthesis for restoring sight to patients suffering from degenerative retinal diseases such as Retinitis Pigmentosa and Age-Related Macular Degeneration.

In these conditions the photoreceptor cells slowly degenerate, leading to blindness. However, many of the inner retinal neurons that transmit signals from the photoreceptors to the brain are preserved to a large extent for a prolonged period of time. Electrical stimulation of these remaining retinal neurons can allow the perception of light.

The first retinal implants involving a small number of electrodes (16 to 60) yielded encouraging results in patients with retinal degeneration. However, the functional restoration of sight, including reading and recognizing faces, might require thousands of electrodes.

The latest generation of retinal implant from the Stanford group has approximately 1000 electrodes. Also, as each photovoltaic pixel operates independently, segments of the array may be separately placed into the subretinal space, greatly simplifying surgery.

Researchers led by Stanford's Peter Peumans, assistant professor of electrical engineering, used the Stanford Nanofabrication Facility to build a silicon implant with tiny bridges that allow it to fold over the shape of the eye. That makes the implant the first to be flexible. (See IEEE Spectrum, December 2009)

Vastly more sensitive MRI: Scientists from Stanford University and IBM Corporation have improved the sensitivity of magnetic resonance imaging (MRI) by 100 million times using unique cantilevered arms in a new technique for measuring tiny magnetic forces. The sensitivity improvement allowed a dramatic improvement in resolving power, achieving a resolution down to 4 nanometers.

Frequently employed by doctors to look below the surface of the skin, traditional MRI takes advantage of the magnetic signals generated by spinning protons within the nuclei of hydrogen atoms

Data stream from a video camera is processed by a pocket PC, and the resulting images are displayed on a liquid crystal microdisplay similar to video goggles.

Specimens on the cantilever arm are moved in and out of proximity to a tiny magnet.

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contained in water and organic materials inside the body. But traditional MRI is quite insensitive.

The barrier to increased sensitivity lies in the way the machine detects magnetic signals. An MRI machine detects the signals with a looped coil placed near the person's body. This new technology, called magnetic resonance force microscopy (MRFM), relies on manipulating hydrogen nuclei just like traditional MRI does, but it uses a novel type of detector.

The theory behind MRFM relies on the forces between two magnets that either attract or repel. To measure the minute forces involved at the atomic level, the team invented a setup where virus samples sit on an extremely flexible microscopic cantilever. The cantilever devices were fabricated at the Stanford Nanofabrication Facility.

Using an oscillating magnetic field, researchers flip the direction of the nuclear spin. Bringing another tiny magnet close to the spinning particles will produce either an attractive or repulsive force that is measured by vibrations in the cantilever. Using these measurements, the researchers can generate a three-dimensional map of hydrogen density, from which a three-dimensional image can be derived. (See PNAS Jan. 12, 2009)

Animal-on-a-chip: Researchers led by Prof. Michael Schuler of Cornell University have used Cornell’s NanoScale Science and Technology Facility to fabricate microfluidic devices, or devices that manipulate fluids at tiny scales, to mimic the response of humans or animals to drugs and toxins. Each device contains an array of “pseudo tissues” that are connected to each other by microfluidic channels. A fluid (a blood surrogate) circulates through the microchannels to enable the study of tissue-to-tissue interactions, such as the breakdown of a parent compound in the liver and how it is subsequently transported and reacted to in the lung.

One experimental model designed to study drugs to fight cancers is composed of four or more chambers microfabricated on a silicon substrate, with a network of microchannels allowing a liquid to flow between the

chambers. Each chamber is designed, both in size and in how rapidly fluids can penetrate, to replicate the behavior of a specific tissue in the body. One device, for example, contains tissue mimics for the liver, bone marrow, and tumors, as well as other tissues.

By measuring forces generated as a tiny magnet is positioned at 8,000 different points around the sample, scientists can generate a three-dimensional map of hydrogen density, thereby creating a three-dimensional image.

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Researchers combine the results with computer modeling to predict toxin and drug dynamics in humans. The long-term goal is to develop alternatives to animal testing with devices that are not only more humane but that also provide faster, less expensive, and more quantitative results. (See the Cornell website)

Quorum sensing in bacteria: Bacterial gene expression, in which DNA is transcribed into RNA and then into protein, is frequently regulated by small molecules secreted into the surrounding medium. These autoinducers build up until a critical population density or “quorum” is achieved, at which point the cells produce a response such as virulence or biofilm formation that requires the coordinated activity of large numbers of individuals.

This accumulation should depend on the geometry of their surroundings, which are the physical boundary conditions for a confined system. Such environments can be fabricated in bio-compatible materials and observed. A team led by Robert Austin of Princeton, using the Cornell Nanoscale Facility to fabricate structures, showed that self-attraction could readily produce local cell densities that exceed the threshold necessary for quorum-dependent processes.

Since this is an engineered system, the researchers could also observe bioluminescence confirming that associations that involve chemotaxis (the ability of cells to direct their movements according to certain chemicals in their environment) and are facilitated by closed geometries can lead to activation of quorum sensing-dependent genes and their associated behaviors. (See Science 11 July 2003: 188)

The fastest global events in RNA folding: RNA molecules fold into specific, intricate structures to carry out numerous biological functions. A deep understanding of RNA folding is thus a prerequisite for explaining the workings of RNA in current biology and throughout evolution, especially given RNA’s

likely role as the dominant biomolecule in the early stages of life. From a physical point of view, an outstanding challenge remains in characterizing the fundamental forces that guide RNAs along their folding pathways to their native structures.

"Body analog" for evaluating the efficacy of drugs on colon cancer

Demonstration of quorum sensing in confined geometries observed through bioluminescence.

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Large RNAs can collapse into compact conformations well before the stable formation of the tertiary contacts that define their final folds. In a multi-institution collaboration that involved researchers from Chicago, Cornell, Stanford, and Yale universities as well as Argonne National Lab, a study identified the likely physical mechanisms driving these early compaction events in RNA folding. The work combined fabrication with in-situ, time-resolved small-angle X-ray scattering.

The experiments identified electrostatic screening and tertiary collapse as the likely physical mechanisms involved in the earliest global folding events of the Tetrahymena ribozyme. The generic nature of these mechanisms suggests that the results may be relevant to the early folding pathways and collapsed intermediates of other large, structured RNAs.

The group studied Tetrahymena ribozyme under different ionic conditions and with RNA mutations that remove long-range tertiary contacts. A partial collapse in each of the folding time-courses occurs within tens of milliseconds with either monovalent or divalent cations; that is, when the ribozyme is missing one or two electrons. Combined with comparison to predictions from structural models, this observation suggests a relaxation of the RNA to a more compact but denatured conformational ensemble in response to enhanced electrostatic screening at higher ionic concentrations. Further, the results provide evidence against counterion-correlation-mediated attraction between RNA double helices. (See Journal of Molecular Biology., V332, P. 211, 2003)

Real-time DNA sequencing: Using the Cornell NanoScale Science and Technology Facility, industrial researchers have developed a new method for real-time sequencing of single DNA molecules. The technology enables researchers to sequence DNA molecules at speeds 1000 times faster and with much less expense than previous methods.

Investigators tether DNA molecules within large arrays of nanoscale apertures. Using the cell’s natural biological machinery to copy the DNA, researchers can rapidly read out the molecular code by observing individual chemical units as they assemble one by one. The method can complete in minutes sequencing jobs that previously took days. (See Science, Vol. 323, page 133)

Electronics Electron spin for computer processing: Spintronics is a potential replacement for the CMOS technology used in constructing integrated circuits. A group led by Prof. Paul Crowell of the University of Minnesota is studying the interface between magnetism and semiconductors, which now rely on electric charges to process information. But computer memory relies on magnetic materials, which serve as the basis for the media used in disk drives.

The basic feature of magnetic materials that makes them magnetic is the spin of the electron. In a crude sense, one can think of electrons as miniature bar magnets. Generally speaking, a sector in a hard drive consists of an ensemble of these miniature magnets. In principle, manipulating an electron's spin for information processing would result in transistors that would be faster and more powerful than today's technology.

Using facilities at the university’s Nanofabrication Center, Dr. Crowell's group is developing a simple method to generate and detect spin currents within standard semiconductors. A critical step in implementing such a technology is transferring magnetic information from a conventional

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ferromagnet, such as iron, into a semiconductor. Dr. Crowell's group is investigating spin transport across the ferromagnet-semiconductor interface and how spins introduced into a semiconductor can be manipulated and detected. (See Science, Sept. 30, 2005)

Large-area graphene production: The creation of large-area graphene using copper may enable the manufacture of new graphene-based devices that meet the scaling requirements of the semiconductor industry, leading to faster computers and electronics. Graphene has distinctive band structure and physical properties but is limited to small sizes because it is produced mostly by exfoliating graphite. Working at the Microelectronics Research Center, the NNIN node at the University at Austin, UT professor Rod Ruoff and his coworkers grew graphene on copper foils whose area is limited only by the furnace used.

They demonstrated for the first time that centimeter-square areas could be covered almost entirely with a mono-layer of graphene, with a small percentage (less than five percent) of the area being bi-layer or tri-layer flakes. The team then created dual-gated field effect transistors, with the top gate electrically isolated from the graphene by a very thin layer of alumina, to determine its ability to carry electrons. The devices showed that the electron mobility in the graphene is significantly higher than that of silicon and comparable to that of natural graphite. (See Science, June 5, 2009: “Large-Area Synthesis of High-Quality and Uniform Graphene Films on Copper Foils”)

Single-electron transistors: Instead of controlling the flow of several electrons through a gate as in conventional transistors, a novel design uses electromagnetic forces to control the path of single electrons. The Ballistic Deflector Transistor essentially

manipulates the ballistic trajectory of a single electron to register a "one" or a "zero" depending on the path in which it is deflected, much like registering in which pocket a ball lands in a game of billiards.

Spin-polarized electrons (black circles) tunnel across a gap, recombining with holes (white circles). This produces polarized light whose properties can carry information.

Graphene film transferred onto a silica substrate

The layout of the novel transistor can be described as a highway intersection, with the triangle shaped deflector sitting in the middle. An electron approaching from one direction passes through an electric field that causes its trajectory to shift. The electron can be made, depending on the field's polarity, to move in one of two directions that would be registered as either a "0" or a "1." This binary numeral system of 1s and 0s is the digital language of modern computers.

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The advantage is an immense gain in speed, with chips operating at terahertz speed compared to the gigahertz that is common today. The deflector transistors would also operate at lower power than today's transistors because they would bounce electrons into a trajectory using their inertia instead of forcing electrons onto and off of capacitors. Conventional transistors also generate immense heat when emptying the energy from capacitors.

Work on the Ballistic Deflector Transistor was conducted at Harvard's Center for Nanoscale Systems by Vikas Kaushal, Ignacio Iniguez-de-la-Torre, and Martin Margala of the University of Massachusetts–Lowell.

Three-dimensional integration and adaptation in electronics: One way that electronics are achieving higher performance is by integrating larger number of devices—digital and analog together—using multiple planes, and by making the structures adaptive. That is, they change themselves to respond to constraints such power or the required function. New silicon-based technologies are necessary for such approaches to succeed.

A group of researchers working at the Cornell Nanoscale Facility have been instrumental in the development of techniques for three-dimensional fabrication as well as for building device structures with underlying gates that help transistors to adapt. The group has demonstrated it can integrate as many as four layers of device layers. They’ve also demonstrated transistors whose threshold voltages can be varied by as much as a volt or can function as transistors as well as memories. (See IEEE Electron Device Letters, 705, 2007; IEEE Electron Device Letters, 606, 2007; and MRS Bulletin 845, 2004)

An artist's conception of the deflector transistor, left, and an image of a microscopic prototype

Source DrainSi Channel

GateSiO2 SiO2

Back Gate

SiO2

Source DrainSi Channel

GateSiO2 SiO2

Back GateSource DrainSi Channel

GateSiO2 SiO2

Back Gate

SiO2

An adaptive transistor that can change characteristics at speeds similar to those of transistor switching.

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Quantum cryptography: The splendor of diamonds arises from their brilliant appearance, sometimes blended with subtle impurities that give some diamonds an unusual and attractive color. Researchers think they can manipulate a diamond's imperfections to turn them into antenna-like devices that emit robust light, one photon at a time.

Researchers had known they could exploit a particular kind of defect, a "nitrogen-vacancy center" in which a nitrogen atom sits astride a spot where an atom is missing from what otherwise would be a perfect lattice in the diamond crystal's structure. The nitrogen-vacancy exhibits photoluminescence, and researchers can manipulate its resonance with electric or magnetic fields. The result is the promise of quantum computing, where manipulations of photons—the basic units of light—can represent data and perform operations on data. Quantum computing would lead to super-powerful computers that could generate, for example, uncrackable cryptographic communications.

What was missing was a link between the nano-world of a diamond's luminescent center and the outside “macro” world of computer networks—i.e., optical fibers cables and lenses. A research team led by Marko Loncar at Harvard crafted a nanowire from a diamond crystal that emits a stream of single photons, providing the link that could help make quantum computing possible. Until now, researchers had not engineered such a diamond yielding a complete device that can be integrated into existing technologies.

The current product is an array with thousands of diamond nanowires—each only a few millionths of a meter tall and 200 billionths of a meter in diameter—sitting atop the macroscopic diamond crystal from which they came. The diamond

nanowire antenna was fabricated using a combination of electron beam lithography and reactive ion etching at Harvard's Center for Nanoscale Systems.

The successful fabrication of diamond nanowires, left, was featured in the Feb. 14, 2010 issue of "Nature Nanotechnology."

High-speed, low-cost computer memory: Several academic research groups and companies have used the Cornell Nanoscale Science and Technology Facility to generate an important breakthrough in the field of magnetic devices and data storage. They have demonstrated an entirely new mechanism to manipulate the magnetic orientation in small devices—using the intrinsic spin of electrons to directly apply a “spin torque” to a magnet—thereby replacing the use of applied magnetic fields. A spin-polarized current can, for example, switch the orientation of a thin nanomagnet, promising data storage at the nanoscale.

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Schematic of spin-torque memory circuit, and a cross section of an individual 40 nm-wide memory element (images courtesy of Daniel Worledge, IBM)

The technology results in data storage that is fast, dense and non-volatile—and that doesn't wear out. Several companies are focusing on using the technology for magnetic random access memories, or RAM, and have achieved multi-megabit demonstration circuits. The first large-scale commercial products are expected within 2-3 years. (See Science, Vol. 307, page 228)

Another important recent invention for achieving such memories is the use of phase-transition phenomena, which occur when a matter moves from one state to another, arising in complex oxides that have correleated-electron or spontaneous-polarization effects. In a collaboration of researchers from Cornell and Harvard universities, vanadium dioxide has recently been shown to allow low-power memories that operate at a few volts and that are simple, three-terminal elements. The work was conducted at the Cornell Nanoscale Facility. (See Tech. Dig. IEEE Nano, p. 439, 2010)

Energy Chips that convert heat to electricity: Conceived nearly 50 years ago, thermophotovoltaic devices capture heat that is radiated across a gap onto a photovoltaic device, which in turn converts the radiant power into electricity. To work, the devices have generally required very high temperatures and didn't generate enough power to be economically viable.

But a breakthrough by MIT researchers led by Bob DiMatteo transfers more power between the emitter and receiver by dramatically reducing the size of the gap between them. By employing a gap of about a few hundred nanometers, the power density for a thermophotovoltaic device can be increased by an order of magnitude. The MIT discovery led to solid-state semiconductor chips that convert heat directly to electricity, and work on the chips has continued at Harvard's Center for Nanoscale Systems.

Initially, the chips could prove most profitable for companies with factories that employ extremely hot machinery, such as glass furnaces, refineries that burn off excess gas, or power plants. The technology one day could be found inside personal electronics, extending the life of batteries by capturing heat generated by power sources or hot microprocessors.

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Less expensive efficiency in solar cells: Georgia Tech researchers have helped develop high-efficiency silicon solar cells using low-cost techniques. Led by Prof. Afeet Rohatgi of Georgia Tech, researchers developed cells made from polysilicon through a screen-printing process that uses a fraction of the polysilicon that other silicon cells do. Reducing polysilicon can dramatically cut the cost of solar cells, as it is one of the more expensive elements used in their production.

The trick is maintaining power-generation efficiency. Cells based on the Georgia Tech research can achieve efficiencies of more than 18 percent in commercially produced panels, and researchers can achieve 20 percent in the lab. Thin-film solar makers that cut out the polysilicon often realize efficiencies closer to 10-12 percent. In this research, Dr. Rohatgi frequently uses the facilities of the campus NNIN node, Georgia Tech’s Nanotechnology Research Center (NRC).

Another team, led by Prof. Phillip Bonhomme of the University of Louisiana, has used NRC facilities to study the use of three-dimensional carbon nanotubes in the production of silicon-based photovoltaic collectors. 3-D solar cells have the potential to increase the overall efficiency of collecting sunlight by providing a scaffolding that increases the amount of light incident on the photovoltaic material. Researchers used 3-D nanotubes to build this scaffolding for 3-D photovoltaic cells.

Efficient LED lamps: Solid-state white lighting is poised to displace both incandescent and fluorescent lamp technology in the coming years. Years of research—partially conducted at Nanotech, the NNIN node at the University of California, Santa Barbara—helped develop the next generation in efficient LED lighting using surface emitter chips. Continuous improvements over years of research and development have resulted in white LED efficiency of greater than 200 lumens per watt in the lab, with the goal of reaching 1,000 lumens per watt. Commercial components with efficacies up to 140 lumens per watt are now in volume production.

Cost-efficient, solid-state thermophotovoltaic chips are the culmination of 15 years of research.

3-D photovoltaic cells promise more efficient gathering of the sun's energy.

This surface emitter chip technology serves as the “filament” for high performance solid state lighting systems. The platform features a proprietary optical design that delivers an optimal radiation pattern, reducing emission losses and significantly increasing efficiency. This increase

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in efficiency scales well with the size of the chip, which is a significant achievement for the industry.

Optics More powerful telescopes: Researchers led by Prof. Jian Ge at the University of Florida are developing high-resolution spectrometers that will enable the search for habitable Earth-like planets. Spectroscopy, in which researchers identify substances through the radiation they emit, is a major tool for astronomical observation. It is the method used to determine masses, ages, evolutionary histories, chemical composition, quasars, and other phenomena. Infrared spectroscopy, especially moderate to high resolution spectroscopy, plays a particularly central role in astronomical studies with both ground-based and space-based telescopes.

The Ge group is working with infrared spectrometers that use immersion gratings, in which the radiation strikes grooves fabricated in silicon substrates. The gratings are immersed in a medium, offering significant infrared resolving power in a compact device. The silicon immersion gratings promise a major advance in infrared spectroscopy, including a convenient and inexpensive way to implement intermediate and high spectral resolution in any existing infrared camera.

Graph showing the progress in both LED efficiency and production over the years of development

Custom silicon immersion grating with gold coating

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Working at the Penn State Nanofabrication Laboratory, Dr. Ge's group has developed etching processes that have been used to develop new generations of silicon immersion gratings. Such high-resolution spectroscopy can detect emission lines caused by the residual gas from young planets. The high-resolution spectroscopy allows us to study the location, total mass of the planets, and the density and temperature of the residual gas associated with the planet formation.

More sensitive infrared imaging: Researchers are using the Cornell Nanoscale Science and Technology Facility to develop an infrared imaging detector based on an advanced microcantilever design. The design uses a combination of metallic and dielectric materials, which can distort electric charges, to create a structure that bends in response to infrared light. The motion can be detected electrically, enabling infrared detection with an order-of-magnitude improvement over existing industry standards for imaging. All of the microcantilever materials are compatible with standard processing for foundries that produce silicon-based integrated circuits.

Manipulating light waves at sub-nano lengths: Plasmonics is a technology that squeezes light, after it hits the surface of a metal under precise circumstances, into a dense carrier of data. The resulting plasmons can in theory encode much data and yield a new generation of superfast computer chips and ultrasensitive molecular detectors.

Plasmonic structures at the core of the nanoscale light manipulation and light concentration technology have generated considerable interest with the development of nano-fabrication and characterization techniques. Working at the University of Michigan's Lurie Nanofabrication

Facility, a group led by L. Jay Guo, associate professor at the university, has exploited a number of applications in recent years in the area of photonics and energy conversion devices. For example, his group has applied nanoimprint techniques to fabricate metallic nanoparticle arrays that can be controlled in size and shape over large areas.

The group also exploited the plasmons generated by arrays for sensors that use biological or chemical receptors to detect molecules in a sample. In addition, their work with nanostructures has yielded high-efficiency and high-resolution color filtering and spectral imaging elements. The spectrum filtering, using plasmonic nanoresonators, could simplify the design and fabrication of LCD displays. (See Nature

Schematic of a microcantilever

Continuous roll-to-roll nanoimprinting.

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Communications, Aug. 24, 2010)

Wideband infrared detection: Objects generally emit infrared radiation across a spectrum of wavelengths, but sensors usually collect radiation only within a specific bandwidth. When talking of sensors, scientists usually divide the infrared band into smaller sections, including three atmospheric windows commonly called short-wave, mid-wave, and long-wave infrared. Each can only be detected by a different type of detector.

Scientists led by Clayton Bates of Howard University have been investigating the feasibility of simultaneous detecting IR radiation at the three atmospheric windows. The group is working with nanocomposite films of silver and silicon, which are the first metal-semiconductor composite system to demonstrate a response to radiation across the three atmospheric IR windows.

Nanostructures can provide color filtering and spectral imaging for extremely compact devices.

The Bates group has developed a formula for the room-temperature quantum efficiency of metal-semiconductor composite systems that would be easy to integrate into existing systems and compatible with current processing technology. (See Thin Solid Films, Vol. 517, Issue 19, 3 Aug. 2009, Pages 5783-5785 and Journal of Applied Physics, Oct 2008, Vol. 104)

Nano Tools Single nuclear-spin detection: Detecting the spin of an individual electron was one of the major accomplishments in condensed matter sciences in 2004. This became possible because magnetic resonance force microscopy could detect a spatial resolution of 25 nm and attonewton force sensitivity (the force from a single spin) by the use of a custom-fabricated silicon cantilever with an attached magnetic tip. The necessary mix of materials and the nanoscale processing capability are not possible in advanced industrial laboratories. The NNIN made the breakthrough possible through its large set of instrumentation that allow such mixing to take place, advanced instruments for nanoscale, and for new processes to be developed specific to the individual research goals.

Since this early demonstration, further progress has allowed measurement of dielectric fluctuations via probing of electric field gradient fluctuations. The innovation also has demonstrated it can detect a single phonon, a challenging goal for the scientific community. (See Nature V430, 329 (2004) and Nano Letters, 2009, 9 (6), pp 2273–2279)

Measuring persistent currents in normal metals: Quantum mechanics predicts that the equilibrium state of a resistive metal ring will contain a current that does not dissipate. This persistent current has been the focus of considerable theoretical and experimental work, but its basic properties remain a topic of controversy. The main experimental challenges in studying

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persistent currents have been the small signals they produce and their exceptional sensitivity to their environment.

This persistent current is quantum in nature and is similar to the net orbital angular momentum of the electrons orbiting some atoms. The persistent current in a normal metal ring can only be observed when the ring is closed, meaning that a direct current measurement is not possible. A Yale group, using the Cornell Nanoscale Facility, fabricated micromechanical cantilevers with metal rings integrated near the cantilever tips which act as sensitive torque magnetometers. The

measured persistent current, over a wide range of parameters, showed good agreement with single particle diffusive theory. The technique also allows the measurement of persistent current in metal rings over a wide range of temperatures, ring sizes, and magnetic fields. (See Science 326.5950; Oct 9, 2009; p. 272)

Using sound to manipulate particles: Researchers using the Penn State NanoFab and led by the university's Prof. Tony Jun Huang invented “acoustic tweezers” that use sound waves to manipulate particles into desired patterns on a microchip. The technology answers a critical need for nonoscale biological studies and applications such as tissue engineering, regenerative medicine, and microarrays.

Researchers have developed numerous other methods for patterning control, including microcontact printing, as well as optical and

magnetic tweezers. But limitations to existing techniques leave researchers looking for cell-patterning technology with the right balance of miniaturization, versatility, speed, and power consumption.

Sound “tweezers” arrange nanoparticles on a microchip.

Measured persistent current with magnetic field for an array of 990 rings.

The Penn State researchers used surface acoustic waves (SAW), which are sound waves that propagate along the surface of an elastic material. Most of the wave’s energy is confined within one to two wavelengths. This characteristic makes SAW an energy-efficient tool for manipulating particles and biomaterials.

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The sound-wave tweezers work on virtually all kinds of cells and other biomaterials, regardless of size, shape, or charge/optical properties. They also require power intensity that is 500,000 times less than optical tweezers, an existing patterning method. This makes them cheaper and safer, ready to be used in many applications such as tissue engineering, cell studies, and drug screening and discovery. (See Lab on a Chip, Oct. 21, 2009)

Testing nanomaterials: Nanowires and nanotubes are among the one-dimensional nanomaterials that are the foundation for nanoscience and nanotechnology. They have emerged as key components in a number of advanced and miniaturized electronic, optical, thermal, and electromechanical systems that are important to advances in biomedicine, electronics, sensors, alternative energy and defense, among other applications.

Scanning electron microscope image of the microdevice and its components.

Research conducted at the University of Minnesota Nanofabrication Center contributed to the development and fabrication of a silicon microdevice for testing the tensile strength of 1-D nanomaterials within a scanning electron microscope. The micro-electromechanical system features a design that makes it possible to convert a compressive force applied to a shuttle into tension applied to a specimen attached to a sample stage. Analysis and experimental calibration enabled the researchers to calculate the stress on the specimen.

The device relies on a simple “push–pull” mechanism, as opposed to most of the existing techniques that involve electro- or thermo-mechanical coupling. Its simple design helps minimize errors and overcomes key challenges associated with other methods of studying nanostructures. (See Journal of Microelectromechanical Systems, June 2010)

Safer synthesis of semiconductor materials: Researchers led by Prof. Jason S. Matthews of Howard University have focused on the synthesis of new precursors for the growth of

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semiconductor materials, including gallium nitride and other components of light-emitting diodes. Researchers hope these new precursors will allow single-source platforms for the deposition process for semiconductor materials.

Such precursors will allow deposition at lower temperatures and in principle be safer than some currently used materials, especially ammonia. In a series of recent experiments, different alkyl silyl amines were synthesized and characterized and exposed to gallium and indium to enable the desired metal complex. The compounds will be evaluated for their ability to deposit the metal nitride via the deposition process. The Howard Nanoscale and Science and Engineering Facility has provided characterization support for the research.

Chemistry Exploiting palladium as a nanocatalyst: Palladium has an extraordinary ability to absorb hydrogen. Small palladium particles also can serve as a catalyst for hydrogenation and dehydrogenation reactions as well as cracking, where complex organic molecules are broken into simpler molecules. Palladium is also commonly used in catalytic converters.

Designing nanoscale catalysts with high activity and selectivity is currently an industry focus in pharmaceutics and petroleum production. The Washington University Nano Research Facility (NRF) synthesizes palladium nanocrystals with well-controlled shapes or facets and can manipulate their activity and selectivity in catalytic reactions by tailoring the ratio of facets. Currently, the facility is providing palladium nanoparticles to two external user groups.

Designing nanoscale catalysts with high activity and selectivity is currently an industry focus in pharmaceutics and petroleum production. The NRF synthesizes palladium nanocrystals with well-controlled shapes or facets and can manipulate their activity and selectivity in catalytic reactions by tailoring the ratio of facets. Currently, the facility is providing palladium nanoparticles to two external user groups.

Covidien/Mallinckrodt, a leading pharmaceutical company, aims to employ shape-controlled palladium nanocrystals as catalysts and to improve catalytic activity in the synthesis of active pharmaceutical ingredients, which are active chemicals used in the manufacturing of drugs. These chemicals in turn can reduce the impurity level in drugs. The company is also collaborating with the NRF to monitor the concentration of catalysts in pharmaceutical ingredients and to optimize synthetic processes in manufacturing, using mass spectrometry.

Transmitting electron microscope image of palladium nanocubes

Charles Werth’s group at the University of Illinois at Urbana-Champaign is investigating the selectivity of palladium nanocrystals with different facets in the catalytic reduction of nitrate to dinitrogen in water treatment, which eliminates the side reaction of nitrate to ammonia.

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Fast detectors for biotoxins: Researchers from the Centers for Disease Control (CDC) in Atlanta are designing and making microfluidic assemblies to capture protein toxins. The goal is to develop detectors that speed the identification of protein toxins like Botulinum neurotoxin and anthrax, agents that are likely candidates for use in bioterrorism.

The team, including Susan Kuklenyik and John Barr from the CDC, used the Georgia Tech Nanotechnology Research Center to develop a coupled microfluidic enzyme reactor mass spectrometry platform for the detection of protein toxins such as anthrax.

The assembly captures protein toxins using antibodies cross-linked to magnetic beads. These products were then analyzed by mass spectrometer coupled to the microfluidic reactor.

Protein toxins like Botulinum neurotoxin and anthrax are likely agents for bioterrorism. A major drawback of current detection methods is a lack of sensitivity and speed. In case of a national emergency, it is critical to be able to use rapid screening assays. Dr.’s Kuklenyik and Barr are designing and making microfluidic assemblies that perform the analysis in less than 15 minutes, much faster than current technology. (See Proceedings of the EMBC, 2009)

A schematic of a microfluidic assembly for detecting bioterrorism toxins

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Example Startups Associated with NNIN Nodes 

Health Semprus Biosciences (semprusbio.com): Founded in 2006, Semprus BioSciences’ mission is to establish a new standard of care by significantly reducing serious health complications associated with medical devices. The company, founded out of MIT and using the facilities of Harvard University’s Center for Nanoscale Systems, has a multi-faceted approach to surface modifications that amounts to a breakthrough in medical device technology that far exceeds the medical benefits of current offerings containing silver, heparin, and antibiotic coatings.

Through a chemical bonding that is covalent (i.e., shares pairs of electrons between atoms), the Semprus Surfaces product is a permanent, non-leaching biomaterial modification to the device surface. The technology is expected to prevent serious medical complications, such as infection, blood clots, improper healing, and cell overgrowth. The company's current focus is to enable the first permanently dual-functional (anti-colonization and anti-thrombogenic) vascular access catheter with a single surface modification.

Semprus has about 20 employees and has raised more than $28 million in equity capital.

CardioMEMS Inc. (cardiomems.com): The EndoSure Wireless Pressure Measurement System is composed of two components: a miniaturized, wireless implantable sensor the size of a paperclip and an external electronics module. The external electronics module wirelessly communicates with our sensors to deliver vital patient data. The wireless sensors are powered by radio frequency energy delivered by an external module and transmit data without batteries.

CardioMems began fabricating their EndoSure prototypes in Georgia Tech’s Nanotechnology Research Center. The EndoSure system has been cleared by the FDA for the measuring of intrasac pressure during endovascular abdominal aortic aneurysm repair and during endovascular thoracic aortic aneurysm repair.

In May 2010, CardioMems raised $37.9 million in financing for a clinical trial, which showed a 30% reduction in heart failure. In September 2010, the company received an equity investment of $60 million, with the investors fund having the option to buy the remaining stock for $375M.

Complete Genomics (completegenomics.com): A life sciences company founded in 2006, Complete Genomics has developed and commercialized an innovative DNA sequencing platform for complete human genome sequencing and analysis. A regular user of the Stanford Nanofabrication Facility, the company offers DNA sequencing as a service and predicts that it can complete a sequencing for about $5,000, compared to the $1 million it cost in 2007.

Complete Genomics raised several rounds of venture funding and sold $54 million in stock to public investors in the fall of 2010.

NABsys (nabsys.com): NABsys aims to make whole-genome DNA sequencing fast, inexpensive, and accurate enough to be used in clinical care. Founded in 2004, the company is using solid-state technologies to create a whole-genome sequencing technology that employs electronic detection, does not depend on enzymes call polymerases, and directly obtains DNA sequence information over hundreds of thousands of bases. Much of the development of the NABsys detector device was done at the Cornell NanoScale Science & Technology Facility.

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Advion Biosystems (advion.com): A leading analytical laboratory for the pharmaceutical industry, Advion was founded in 1993 in Ithaca. To enhance its analytical throughput, in the late 1990s it embarked on the development of a microfluidics input system. This technology was developed at the Cornell NanoScale Science & Technology Facility and was successfully turned into a product line. Advion Biosystems sells microfluidic injector systems worldwide to enhance leading gas chromatography-mass spectrometry systems, with all development work done at the Cornell NNIN facility. Advion has recently entered a joint marketing agreement with Agilent for this technology. Advion has 180 employees.

Pacific Biosciences (pacificbiosciences.com): Started in 2004, Pacific Bioscience is developing a revolutionary gene sequencing capability based on real-time DNA sequencing technology developed at Cornell. The critical part of these devices is fabricated at the Cornell NanoScale Science & Technology Facility using ebeam lithography. The technology tethers DNA molecules within large arrays of nanoscale apertures and uses the cell’s natural biological machinery to copy the DNA. Researchers can rapidly read out the molecular code by observing individual chemical units as they assemble one-by-one. Pacific Biosciences was featured in Discover, the New York Times, and other leading publications and has attracted $375 million in capital to commercialize its technology. The company, with about 100 employees, went public in 2010 by selling $200 million in stock.

Eksigent Technologies (eksigent.com): A 2000 startup, Eksigent designs, develops, manufactures, and sells instruments and medical devices. Its products include fluid delivery, liquid chromatography, microfluidic flow control technology, capillary, reaction monitoring, and nanoflow metering systems, as well as infusion devices for drug discovery and development applications.

Eksigent's use of the Stanford Nanofabrication Facility included fabricating three prototypes of miniaturized, high-performance liquid chromatography (HPLC) systems on chips. HPLC is the most widely used purification and quality-control method in the pharmaceutical industry. The miniaturized HPLC systems sought to eliminate analysis bottlenecks hindering the pharmaceutical industry.

In spring 2010, Eksigent sold its portfolio of HPLC technologies to AB Sciex, a global leader in life science analytical technologies. Around 50 employees in Eksigent’s research and development, manufacturing, and sales teams will continue to operate at the company's Dublin, Calif., headquarters.

Healionics Corp. (healionics.com): A research team led by Dr. Buddy Ratner and Dr. Andrew Marshall of the University of Washington worked at its Center for NanoTechnology in developing the precise pore size and geometry that allows a biomaterial to promote the acceptance of biomedical devices within the body. Their startup, Healionics, partners with medical device manufacturers to enhance biocompatibility and performance of current and next generation devices using their STAR (Sphere Templated Angiogenic Regeneration) biomaterial.

STAR materials are 3-dimensional scaffold structures taking advantage of the body’s natural healing mechanisms to create an integrated interface between implanted devices and the surrounding tissue. Precisely sized pores match the biomaterial closely to natural tissue structures. This encourages rapid tissue growth, stimulates the formation of new blood vessels, and reduces fibrous scar tissue.

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The STAR technology was commercialized in a device used to treat glaucoma in dogs in 2009, and the material is under consideration for a broad range of medical applications ranging from advanced wound care to regenerative medicine and cardiac tissue repair.

Electronics Nantero Inc. (nantero.com): A nanotechnology company using carbon nanotubes for the development of next-generation semiconductor devices, Nantero was founded in 2001. Its potential products include memory, logic, and other semiconductor products. In the field of memory, Nantero is developing NRAM, a high-density Nonvolatile Random Access Memory. The company's objective is to deliver a product that will replace all existing forms of memory, such as DRAM, SRAM, and flash memory. NRAM would be a universal memory product.

The potential applications are extensive and include the ability to enable instant-on computers. The chips, developed through work carried out at Harvard’s Center for Nanoscale Systems, could be found in a wide variety of devices such as cell phones, MP3 players, digital cameras, and PDAs, as well as in PCs and networking.

Nantero has about 60 employees and has raised more than $30 million in venture capital.

Grandis (grandis.com): Grandis, a Stanford Nanofabrication Facility member and regular user, was founded in 2002 to develop non-volatile memories derived from spintronics, the application of the electron’s spin to store, manipulate, and transmit information. Grandis projects that its spin transfer torque random access memory (STT-RAM) can replace today's computer memories, including DRAM and NAND (flash) memory.

Several companies, including Renesas Technology and Hynix Semiconductor, have licensed Grandis’ technology and have begun developing STT-RAM for standalone applications. In 2008, Grandis was awarded $6 million by the Defense Advanced Research Projects Agency (DARPA) to develop its memory technology. The defense contract could reach $14.7 million over four years.

Grandis also has received private funding of $15 million from investors that include Applied Ventures, Sevin Rosen Funds, Matrix Partners, Incubic, and Concept Ventures.

NVE Corp. (nve.com): The initials stand for Nonvolatile Electronics, the name of the company when founded in 1989 in Edina, Minn., a suburb of Minneapolis. NVE was a pioneer in developing spintronics, a nanotechnology that uses electron spin rather than electron charge to aquire, store, and transmit information.

The company manufactures high-performance spintronic products including sensors and couplers that are used to acquire and transmit data. It has also licensed its spintronic magnetoresistive random access memory technology, commonly known as MRAM.

NVE's designs use one of two types of patented spintronic nano-scale structures: spin-dependent tunnel junctions and giant magnetoresistors. Both structures produce a large change in electrical resistance depending on the predominant spin of electrons in a thin metal layer. In this way electron spin can be converted to an electrical signal compatible with conventional electronics.

Tools at the Nanofabrication Center at the University of Minnesota were essential for early research and development of NVE's products. The company continues to be a frequent user of the NNIN facilities for work such as E-beam lithography.

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NVE has annual sales of about $23 million and about 50 employees.

Veratag (veratag.com): Veratag is commercializing a new type of security technology that is simple, cost effective and highly secure for use in radio-frequency identification, locks, and other applications for identification, authentication, and anti-counterfeiting. The product offering is based on a MEMS-based chip that possesses a unique, unclonable “voiceprint” or spectral signature that can be incorporated into all manner of electronic devices, as well as RFID-like tags that can be applied to goods that are vulnerable to counterfeiting. Veratag is a privately funded company formed to commercialize work done at the Cornell Nanoscale Science and Technology Facility to develop micro-electromechanical resonators that produce unique analog signals.

Energy MTPV, LLC. (mtpv.com): This 2005 startup is offering its first products based on novel semiconductor chips that transform heat into electricity. The technology from which the company derives its name (micron-gap thermo-photovoltaics) was conceived at MIT and developed over 10 years at the Charles Stark Draper Laboratory. The technology, with further work at Harvard's Center for Nanoscale Systems, takes advantage of new efficiencies made possible by dramatically reducing the gap between a device that emits heat and a receiver that converts it into electricity.

MTPV's initial line of solar panels can be used in industrial environments for converting waste heat to electricity. In addition to creating electricity for either sale or use, this process can also become a source for reducing the amount and temperature of vented waste heat and emissions from the industrial plant process. MTPV says its prototypes have shown that heat can be converted into electricity with an increase of 5 to 10 times the electricity available in a given area as compared to conventional thermophotovoltaic devices. The company has about 15 employees.

AstroWatt (astrowatt.com): AstroWatt was formed in the summer of 2008 to meet the growing global demand for renewable energy. It is a venture-backed company developing a proprietary solar cell technology. Working at the NNIN node at the University of Texas at Austin—the Microelectronics Research Center—AstroWatt has developed a proprietary semiconductor-on-metal technology for creating thin silicon wafers that can be processed using today’s photovoltaic manufacturing tools. The approach allows companies to reuse the expensive silicon substrate, leading to a 75% reduction in substrate costs and a 50% cut in the per-kilowatt cost of solar cells. Its investors include Austin Ventures and NEA. AstroWatt has seven employees.

Suniva (suniva.com): Founded in 2007, Suniva manufactures and markets high-efficiency silicon solar cells using low-cost techniques and offers high-power solar modules containing Suniva's core cell technology. Suniva uses its proprietary approach to optimize cell processing based upon keen modeling insights, intimate materials knowledge, and deep process know-how. The company refers to its approach as "integrated cell design and development."

Suniva evolved from the work of Dr. Rohatgi of Georgia Tech, much of it conducted at Georgia Tech’s Nanotechnology Research Center (NRC). The company has outgrown the NRC and has established a 70,000 sq. ft. manufacturing facility in Norcross, Ga., with 150 employees. The Wall Street Journal in March 2010 ranked Suniva second on its list of “Top 10 Venture-Backed, Clean Technology Companies.” The company has raised more than $130 million in venture capital.

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Solarity: This company is focused on novel solar cell technologies originating from organic and inorganic precursors and was formed by Dr. Stephen Fonash at Penn State. All of the device development originated and continues at the Penn State Nanofab. Solarity, founded in 2006, has three employees with estimated annual revenue of $300,000.

Bandgap Engineering, Inc. (bandgap.com): Bandgap has pioneered the development of highly tunable and inexpensive methods for nano-structuring silicon. The company calls it nano-silicon and is applying these technologies to high-efficiency photovoltaic systems and high-capacity Li-ion batteries. Nano-silicon has several advantages over its conventional, “bulk” cousin and over other methods for micro- or nano-structuring. Relative to bulk silicon, nano-silicon's optical properties can be tuned to dramatically reduce reflection and increase absorption—critical parameters for a high efficiency solar cell. It can also enable silicon to realize its potential as a material for high-capacity lithium ion batteries, as it can expand and contract during cycling without degrading. Relative to other methods for achieving nano-structured silicon, Bandgap's nano-silicon processes are inexpensive, fast, and controllable. Founded in 2007, Bandgap has used the Cornell Nanoscale Science and Technology Facility and has raised $6 million in financing.

MicroGen Systems (microgensystems.com): Microgen develops MEMS-based energy-harvesting devices for long-term, low-power applications like embedded sensors. The intent is to extend the lifetime of rechargeable batteries or eliminate them altogether using ambient vibration as the energy source and storing power on an ultra-capacitor or rechargeable battery. The system would provide power for more than 20 years. Long-term sensors embedded in highways and bridges could harvest energy from structural vibrations. Development activities are carried out at the Cornell Nanofabrication Facility. MicroGen has six employees and is funded in part by the New York State Energy Research and Development Authority.

Lightwave Power, Inc. (lightwavepower.com): Founded in 2008, Lightwave is developing novel solar energy products based on nanoarrays and 2-dimensional plasmonic and photonic crystal arrays, based on work at Harvard's Center for Nanoscale Systems. The company's technology roadmap includes the development of large-area thin sheets of repeating nano- and micro-sized structures that can be designed to absorb, convert, re-emit, and guide light. These structures are thin, are generally fashioned out of common metals and dielectrics, and are manufactured on flexible substrates using a roll-to-roll process, leading to low manufacturing cost projections. The company has four employees.

ChemUrja Technologies Inc.: Co-founded by former Arizona State University (ASU) student Pankaj Sinha in 2007 to develop and supply fuel cell stacks to provide affordable portable electric power for all geographies. The fuel cells would be small enough to fit in ultraportable devices like smart phones, while costing less than a penny an hour to run. The silicon-based alkaline fuel cells include high-aspect and double-side etching of silicon conducted at ASU’s NanoFab, helping to yield catalytic pillar electrodes with ultra-high surface areas.

Widetronix (widetronix.com): Founded in 2007, Widetronix designs and builds low-power, long-life batteries for microelectronics. With grant funding from the United States Navy, Widetronix has created semiconductor materials for betavoltaic batteries. These self-charging batteries provide lifetime charges of greater than 25 years, enabling solutions for medical implants, security, and logistics. Based in Ithaca, New York, Widetronix started in Cornell

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University's Wide Bandgap Laboratory and recently received seed funding from several venture funds. Development activities are taking place at the Cornell Nanofabrication Facility.

Amprius (amprius.com): Amprius is a leading battery and materials developer focused on silicon-enabled lithium ion batteries. The silicon nanowire anode technology was initially developed by Prof. Yi Cui of Stanford. Working at times at the Stanford Nanofabrication Facility, Prof. Cui has demonstrated that the unique, defect-free, one-dimensional nature of nanowires allows silicon nanowires to survive the rigors of repeated cycling in a lithium ion battery, with dramatic improvements in energy density.

The market for batteries is currently about $6 billion and growing rapidly. The market for lithium ion batteries alone is forecast to grow by a factor of 100 over the next 10 years. In March 2009, Amprius secured funding from leading cleantech investors including Vantage Point Venture Partners, Trident Capital, Google Inc. CEO Eric Schmidt, and Stanford University. The company has 11 employees.

Optics Microvision, Inc. (microvision.com): Develops platform technologies for the next generation of display and imaging products. The trademarked PicoP display engine enables an ultra-miniature video projector that produces large, color-rich, high-resolution images, while remaining small and low-power enough to be embedded into mobile devices, such as smart phones and media players. At the heart of the display engine is a high-performance, microelectromechanical (MEMS) scanning mirror fabricated using bulk silicon etch techniques. In a long-term collaboration with the University of Washington’s Center for Nanotechnology, Microvision has developed this robust, reliable, high angle, and high frequency MEMS device which has been successfully transferred to an external volume manufacturing partner.

In April 2010, Microvision received an $8.5M order for its new ultra-miniature laser projector from a consumer electronics manufacturer that plans to embed the engine within a high-end mobile media player.

NanoLambda (nanolamda.net): NanoLambda is developing the Spectrum Sensor—ultra-compact, low-cost spectrometers on a chip. Each pixel of the sensor detects a predefined wavelength of light from an input source, yielding a spectral fingerprint for each material being imaged. Unlike expensive and bulky conventional solutions, the high-resolution spectrometer-on-a-chip enables non-invasive and multi-target monitoring capability at an ultra-compact size. Its sensing capability enables mobile or wearable health monitors such as a “truly non-intrusive glucose monitor” and high-standard RGB color sensors that can be used in LED displays.

The device was originally developed at the University of Pittsburg, the company started in 2005, and the original prototypes and the current manufacturing process developed at the Penn State Nanofabrication Laboratory. The company has five employees.

Mesmeriz: This Ithaca-based startup manufactures pico-projector modules that can be embedded within mobile devices. These tiny modules consist of two microscopic mirrors that scan red, green, and blue laser light to project vivid, always-in-focus video images onto any surface. Mezmeriz’s unique carbon-fiber, MEMS micro-mirror platform results in high-resolution images that are 10-to-15 inches wide and are projected from less than 6 feet away. The technology extends a mobile phone display to provide a laptop-like experience. Development activities are

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conducted at the Cornell Nanoscale Science and Technology Facility based on technology developed at Cornell. Mesmeriz has five employees and estimated current annual sales of $320,000.

BinOptics Corp. (binoptics.com): Founded in 2000, BinOptics manufactures monolithically integrated optoelectronic components based on indium phosphide and other semiconductor materials. BinOptics’ current products include a variety of edge-emitting and surface-emitting lasers, including some with integrated monitoring photodiodes that provide transceiver and transponder manufacturers with price-to-performance advantages. The technology behind the Bioptics etched-facet, folded lasers was developed in the Cornell Nanoscale Science and Technology Facility, which has supported the company's research and development since its founding. Ithaca-based BinOptics has about 40 employees.

Multispectral Imaging (agiltron.com): This 2003 startup designs, develops, manufactures, and supplies infrared imaging detectors and arrays. The company provides technologies for night vision and thermal-imaging products. Its solutions include infrared imaging detector modules that use microelectromechanical sensor and other technologies, including microcantilevers. Multispectral Imaging was bought in 2008 by Agiltron, Inc., a leading developer and manufacturer of optical components and systems, where it operates as a subsidiary. All development activities for the Multispectral Imaging cantilever-based IR imager were carried out at the Cornell Nanoscale Science and Technology Facility.

Discera Inc. (discera.com): Discera is a timing and clock oscillator company utilizing a proprietary MEMS resonator enabling lower cost, enhanced ruggedness, smaller size and wider temperature range than conventional quartz-based solutions offer. Using its proprietary ultra-miniature PureSilicon resonator technology, Discera has developed a wide range of oscillator solutions that address the performance, size, power, and cost requirements for the consumer, enterprise, industrial, and communication markets.

Established in 2001, Discera was formed to commercialize research originally performed at the University of Michigan, including at the Lurie Nanofabrication Facility, and the University of California at Berkeley. ReferenceUSA reports that the company has nearly 20 employees and more than $5 million in annual sales.

SiTime Corp. (sitime.com): Although stand-alone MEMS devices are now commonplace, environmental requirements for operation and processing constraints of MEMS devices have traditionally prevented full integration with advanced electronics. SiTime develops and markets chips incorporating MEMS-based reference timing devices within standard silicon chips, which eliminate the need for quartz microcrystals. The result is the world’s smallest fully integrated, fully packaged resonators and oscillators, which can be used in hand-helds, wireless, and other miniaturized communication devices.

The technology that made SiTime possible arose out of academic research collaboration between the Bosch Corp. and Prof. Thomas Kenny of the Stanford University Department of Mechanical Engineering, which was funded through DARPA and largely carried out at the Stanford Nanofabrication Facility (SNF). As the technology became more developed, wafers were shuttled between Bosch and SNF at appropriate process points. Later, the process was transferred to a foundry so that SiTime is now a fabless company.

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SiTime was founded in 2004 and received three rounds of funding totaling about $43.5M from NEA, Greylock, CampVentures, and Bosch. With 85% market share and more than 30 million devices shipped, SiTime is driving the $5 billion timing market's transition to one based entirely on silicon.

Nano Tools Lurie Midwest Micro Devices (midwestmicrodevices.com): The company serves the MEMS market as a contract manufacturer, or foundry, of customer-specific MEMS devices, a business model readily embraced in other electronics markets such as semiconductors and electronic systems. Founded in 2005, Midwest Micro offers no branded products of its own in order to focus entirely on the manufacturing needs of its MEMS customers.

A heavy user of the University of Michigan’s Lurie Nanofabrication Facility, Midwest Micro offers a wide range of device foundry services to this fast-growing MEMS market. The company's key initial service offerings include manufacturing for moderate to high volume MEMS customers (a few thousand to a few million units per year) and process/product development for new customer applications. The company has 10 employees and annual sales of more than $10 million, according to ReferenceUSA.

Applied Nanostructures (appnano.com): This Silicon Valley company was started in 2004 to develop, manufacture, and supply atomic force microscopy and scanning probe microscopy devices for all applications. The company, a Stanford Nanofabrication Facility member, has eight employees and annual revenue of more than $1 million.

Ultool (ultool.com): Ultool is a 2009 startup specializing in applications at extreme environments—deep vacuum and high pressure. Ultool’s core businesses are vacuum deposition processes and hardware that cover an array of critical applications, such as electrolytic hard chrome replacement coatings, tribological coatings, magnetron sputtering sources, and ion sources. Ultool has been working with the Penn State Nanofabrication Laboratory on the development of wear-resistant coatings for defense applications.

Carbon Nanoprobes (cnprobes.com): Carbon Nanoprobes was founded in 2003 around the commercialization of nano-powered solutions in the field of molecular imaging. Their probe product creates the sharpest possible imaging tip by attaching single-walled carbon nanotubes to the end of an Atomic Force Microscope probe. Their mass-produced tiny needles make possible direct tracings of nano-sized structures, like proteins. This allows the analysis of soft structures, a boon to pharmaceutical and biotech companies. Carbon Nanoprobes used the Penn State and University of Washington NNIN sites to develop scalable processes for producing its probes. The company has six employees.

Orthogonal: Based in Ithaca, New York, Orthogonal develops and markets a new class of photosensitive materials for nanofabrication. Conventional photoresists are not useful for patterning organic semiconductors, a class of materials with significant potential for fabrication of low-cost electronics for energy and flexible display applications. Orthogonal’s materials are based on unique chemistry that is compatible with organic semiconductors, making photolithography on organic materials possible. These products are based on technology developed at Cornell University, and technology demonstrations and characterizations are conducted at the Cornell Nanoscale Science and Technology Facility. Orthogonal has five employees.

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Sensors Aerospace Missions Corporation (aerospacemissions.com): A Texas company started in 2004, Aerospace Missions is pursuing development at the Stanford Nanofabrication Facility to build prototypes of several nanosensors as part of the company's work on aerospace technologies.

Nanoselect (nanoselect-sensors.com): Carbon nanotubes possess remarkable electrical, chemical, and structural properties that can revolutionize sensors and their applications. When nanotubes are incorporated into sensor design, their unique properties offer outstanding performance by reducing size and cost and improving selectivity and durability.

NanoSelect is centered on its unique nanotube structures, developed partly at the University of Michigan’s Lurie Nanofabrication Facility, and on its ability to manipulate these structures in novel ways. Using proprietary technologies, it is developing a series of carbon nanotube-based sensors that are durable, inexpensive to produce, and can be integrated into a network to provide real-time monitoring of municipal water supply systems.

NanoSelect plans to introduce a sensor module the size of a postage stamp equipped with nano-scale sensors and communication electronics to provide real-time, contiguous monitoring of the quality and safety of water distribution systems. The company employs 10 people.

Evigia Systems (evigia.com): Evigia Systems is working to make commercial and government supply chains safer and more efficient by developing RFID tags and sensors that are smaller, cheaper, and have multiple functionalities. Among other projects, Evigia researchers use the University of Michigan’s Lurie Nanofabrication Facility for developing prototype accelerometers and sensors for temperature and humidity measurement.

PicoCal (picocal.com): A 2004 startup, PicoCal is a technology-based venture whose objective is to provide novel measurement solutions to its customers. The company's first product, developed with work at the University of Michigan’s Lurie Nanofabrication Facility, is a MEMS scanning thermal probe that enables users to quickly and clearly view and measure thermal properties at the nanoscale.

PicoCal's products are designed to help researchers and manufacturers view critical characteristics that were not detected earlier. PicoCal's team has more than 14 years of technical experience in scanning thermal microscopy and more than 20 years of microfabrication expertise. The fields that gain from PicoCal's technology include semiconductors, nanotechnology, biomedicine, and advanced materials. The company has three employees.

Evigia Systems (evigia.com): Evigia Systems is working to make commercial and government supply chains safer and more efficient by developing RFID tags and sensors that are smaller, cheaper, and have multiple functionalities. Among other projects, Evigia researchers use the University of Michigan’s Lurie Nanofabrication Facility for developing prototype accelerometers and sensors for temperature and humidity measurement.

Kionix (kionix.com): A leading manufacturer of accelerometers for the consumer market, Kionix is a global leader in the design and fabrication of high-performance, silicon-micromachined inertial sensors for micro-electromechanical systems. Kionix was founded in 1993 upon single-crystal MEMS technology developed at the Cornell Nanofabrication Facility (CNF). Early stages of the company depended on access to the facility, and CNF continues to

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support Kionix. In 2001, a portion of the company dealing with MEMS optical actuators was sold to Calient for more than $100 million. The company was immediately refounded as Kionix (II) and refocused on the MEMS accelerometer market. Kionix currently employs 150 people in its facility in Ithaca, N.Y. In 2009, Kionix was sold to Rohm, a leading Japanese integrated electronics company, for $233 million. It now operates as a wholly owned subsidiary of Rohm but remains in Ithaca.

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NNIN Outreach and Education The NNIN has a broad portfolio of education and outreach efforts that draw on its strengths in nanotechnology research and fabrication, geographic and intellectual diversity, and national reach. Its national scope allows both broad and selective outreach, with objectives that can include rigorous technical experience, enhancing knowledge, increasing diversity, and exposing youth and the population at large to a stimulating educational experience.

Undergraduate research: The national programs include NSF’s Research Experiences for Undergraduates (REU), which gives about 80 students a thorough exposure to graduate-level research. The 10-week summer program assigns each student to a substantive project at an NNIN facility that often results in publishable research. The successful program has proven popular, with only about 1-in-7 applicants being selected. Participants are highly valued by industry, graduate schools, and other internship programs.

Enhancing diversity: NNIN-sponsored education programs include Laboratory Experience for Faculty (LEF), which brings opportunities for cutting-edge research experience to faculty from under-represented communities or institutions devoted to under-represented communities. The Showcase for Students is a day-long showcase of nanotechnology at major conferences devoted to underrepresented science and engineering students, including those participating in the National Society of Black Engineers and the Society of Women Engineers, among others. The showcase features hands-on, table-top laboratory demonstrations with accompanying short lectures.

International experience: The NNIN has developed its own follow-on to the REU program, the International Research Experience for Undergraduates (iREU), in which about 10 REU graduates get a second year of experience at a major international or U.S. national laboratory. The NNIN’s International Winter School for Graduate Students (iWSG) combines a high-level, focused nanotechnology course with field experience. The technical course is held in conjunction with a leading academic institution in a developing country, such as India. From 10 to 12 highly selected U.S. graduate students join students at a foreign university for the experience.

Broad outreach: Four times a year, the NNIN brings together leaders in nanotechnology for symposia on major technical themes. Participants discuss the challenges of critical issues in nanotechnology and how the NNIN can contribute. The network also has developed Open Textbook, a web-based senior/graduate-level text that grows and changes with learning in the field, and conducts topical and hands-on workshops connected to research. Nearly 20,000 people have participated in these events during the year, including nearly a thousand in the technically rigorous workshops and symposia.

Each NNIN nodes also conducts local activities that include day-long and longer camps for middle and high school students, as well as workshops for teachers, schools, and communities.

Social and ethical issues: NNIN seeks the integration and development of a social and ethical consciousness of issues that arise in the network's nanotech activities. The NNIN has organized its efforts to take advantage of the network’s unique strengths as a national resource with broad geographic diversity, technical breadth, and strong community interests. Within its user community, network leaders provide training and educational opportunities through modules focused on social and ethical issues, along with supporting teaching materials.

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Children's science magazine: Nanooze is a print and web-based kids’ science magazine that is supported by the Cornell Nanoscale Science and Technology Facility (CNF) as part of the NNIN. The mission of Nanooze (nanooze.org) is to stimulate, excite, educate, and challenge kids ages 6-to-10 years old and their teachers. The goal is to get them engaged in science and engineering through fun, informative, and science-based learning activities.

Nanooze is primarily the work of Prof. Carl Batt and his students, with support from the CNF. Nanooze has been available in English, Spanish, and Portuguese. Circulation has grown to over 50,000 copies per issue as requests from classroom teachers continue to grow.

In 2010, Prof. Batt and his team worked with Walt Disney World in Florida to open a long-term exhibition designed to bring visitors face-to-face with the nanoworld. Housed in the Innoventions pavilion at Epcot Center, the exhibition "Take a Nanooze Break" features a series of interactive, continually updated displays that allow visitors to manipulate models of molecules, study everyday items at the nanoscale, and interact with scientists and engineers who conduct the latest nano research.

NanoExpress: A mobile-science theme park that exhibits some of the latest science and technology at the nano dimension in a variety of disciplines, The NanoExpress is part of a major campaign designed to provide information on the current state of research and development in nanotechnology. It also aims to promote dialogue between the world of science and the general public. The NanoExpress is a mobile van with more than 200 sq. ft. of lab space designed to facilitate hands-on experiments; but it is also capable of doing nanotechnology research.

Introduced in the summer of 2006, the NanoExpress was launched through the Howard University Nanoscale Science and Engineering Facility (HNF). The NanoExpress presents the complex, fascinating world of nanotechnology to the general public from K-to-Grey. The campaign was designed to provide information and training on the current state of research and development potential in nanotechnology.

Undergraduate and graduate lab assistants help supervise experiments on the NanoExpress.

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Profiles of the NNIN Nodes Cornell Nanoscale Science and Technology Facility (CNF)—Cornell University: Founded in 1977, the Cornell Nanoscale Science and Technology Facility is a national NNIN user facility that serves as an open resource for a broad range of nanotechnology areas. The facility holds particular leadership in electronics, optics, micro-electro-mechanical systems and in education efforts. The center also offers particular emphasis on complex integration of various nanotech capabilities. Cornell also serves as one of four NNIN nodes supporting an effort to build a national computing network for nanotechnology, and provides key support for the study of nanotech's social and ethical issues.

In addition to its management and administrative staff, CNF has a technical staff of 20 who maintain the equipment and baseline processes and assist all users. The center serves an unusually large external user community that is often as populous as researchers from Cornell itself. The facility maintains a full spectrum of processing and characterization equipment, with emphasis on electron beam lithography at the smallest dimensions, and a wide array of deposition and etching resources. In total, the center offers more than 90 major processing tools. CNF also has nanoscale computation facilities (hardware, software, and support) that specialize in assisting users in interfacing with the various computation programs.

The Center operates in a suite of labs in Duffield Hall, a state-of-the-art research building built in 2004 in Cornell’s Engineering College. CNF user facilities include a 16,000 sq. ft. clean room, as well as wet and dry labs for additional chemistry and biology research. There is also a characterization lab, a computer-aided design room, and an ion implantation laboratory.

Stanford Nanofabrication Facility (SNF)—Stanford University: Descended from an integrated circuit laboratory established at Stanford University in the 1960s, the Stanford Nanofabrication Facility opened its doors in 1994 to non-Stanford researchers as a founding member of the NNIN. The SNF offers expertise and equipment in a broad range of micro- and nano-fabrication techniques. Research is particularly focused on optics, micro-electromechanical systems, biology, and chemistry, as well as process characterization and fabrication of more traditional electronics devices. The facility remains especially committed to supporting use of micro- and nano-fabrication technologies in non-traditional research applications.

The SNF is housed in the Paul G. Allen building. Originally constructed in 1985 with generous funding from twenty founding industrial members of the earlier Center for Integrated Systems, the facility added 52,000 square feet in a dramatic 1996 expansion funded by the foundation of Microsoft co-founder Paul G. Allen.

The facility extends over three floors. The class-100 cleanroom is 10,500 square feet in area and is vibration-isolated from the rest of the building. Support facilities, such as the stockroom, semi-clean labs and maintenance work areas, and staff offices, are located near the cleanroom. More than 30 full- and part-time technical and research staff support more than 600 registered lab members at the SNF. Stanford also provides access to the Stanford Nanocharacterization Laboratory.

Nanotechnology Research Center (NRC)—Georgia Institute of Technology: The NRC emphasizes the application of nanofabrication to bioengineering, biomedicine, life sciences, integrated systems and electronics. The NRC has historically supported research on a wide

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variety of materials, structures, and processes, much of which is nonstandard. The NRC has also taken a leadership role in education and outreach efforts for the entire NNIN.

The NRC consists of the Pettit Microelectronics Building and the newly completed Marcus Nanotechnology Building. The Pettit building includes a cleanroom of 8,500 sq. ft., while the Marcus building features an inorganic cleanroom of 10,000 sq. ft. and an organic cleanroom of 5,000 sq. ft. The Marcus cleanrooms allow for an innovative combination of traditional inorganic cleanroom space adjacent to one designed for research at the interface between life sciences and nanotechnology. This connectivity will foster novel designs and applications through interdisciplinary research collaboration

Other NNIN resources include the GIT Electron Microscopy Center and the Laser Dynamics Lab. These facilities are open to a NNIN user community from a wide range of disciplines including electrical, computer, mechanical, chemical, materials, and biomedical engineering as well as physics, chemistry, and biology.

Lurie Nanofabrication Facility (LNF)—University of Michigan: The LNF operates as part of the university's Solid-State Electronics Laboratory in its Electrical Engineering and Computer Science department. The LNF is one of the leading centers worldwide on micro-electromechanical systems (MEMS) and microsystems. It specializes in the integration of silicon integrated circuits and MEMS with nanotechnology, leading to applications in biology, medical systems, chemistry, and environmental monitoring.

The LNF builds on its experience in integration of silicon-based electronics with MEMS and micropackaging to push these interfaces into the realm of nanotechnology. The emphasis is on the fabrication, packaging, and testing of integrated devices for chemical and biological sensing, electrical stimulation of biological systems, and integrated fluidic systems. Other capabilities are available for research on high-speed micro-, nano-, and opto-electronics, including microwave/millimeter wave devices and circuits, and integrated optical devices.

The facility is run by a manager and staff of twenty engineers and technicians. The LNF consists of a class-1000 cleanroom with about 12,500 sq. ft. of work area. The LNF offers a complete laboratory for the fabrication of solid-state MEMS—including bulk, surface, polymer/plastic, and molded electroplated micromachining—and equipment for developing and fabricating silicon circuits. The facility also encourages researchers from non-traditional disciplines to make use of its processes.

Center for NanoTechnology (CNT)—University of Washington: The University of Washington NNIN node was originally established in 1998 as the NanoTech User Facility at the Center for Nanotechnology. It was designed to provide the Pacific Northwest nanotechnology community with access to advanced characterization and nanofabrication tools. In 2004, facility expanded its role when it joined the NNIN.

The center offers emerging nanoscale tools with an emphasis on their use in biology and life sciences. In addition, CNT coordinates other NNIN nodes working with the NSF Ocean Observatories Initiative and is in charge of promoting research in underwater sensing made possible by recent advances in nano- and micro-technology.

CNT employs a technical staff of 8 and consists of the Nanotech User Facility and the Washington Technology Center Microfabrication Laboratory. The User Facility occupies more than 3,000-square-feet of newly renovated laboratory space equipped with tools and facilities

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targeted at the investigative needs of nanotech users. The adjacent Microfabrication Laboratory occupies 15,000-square-feet of space and provides access to added tools.

Penn State Nanofabrication Laboratory (NanoFab)—Pennsylvania State University: The primary focus of the NanoFab is to provide specialized instruments and technical support in the areas of chemical and molecular-scale nanotechnology and for the fabrication of complex nanoscale devices using the ferroelectric oxide that is critical to computing power.

The NanoFab has adopted nanomaterials assembly techniques from the nearby Penn State Materials Research Science and Engineering Center (MRSEC), as well as chemical-patterning methods that use self-assembled monolayers. The strong coupling of traditional top-down nanofabrication and bottom-up molecular self assembly offers a unique capability within the NNIN. The NNIN staff also works with the Penn State faculty at the Keck Smart Materials Integration Laboratory to develop and document robust baseline processes for fabricating complex oxide microelectromechanical systems (MEMS).

The Nanofab facilities consist of approximately 6,000 sq. ft. of cleanroom space and over 3,000 sq. ft. of supporting non-clean lab space that is located at the materials research institute and research lab, and at Penn State’s Electrical Engineering West Building. As part of a construction project that began in 2008 and is scheduled for completion in 2011, the Penn State NNIN site will be relocated into a 10,000 sq. ft., class 100/1000 clean room with an additional 6,500 sq. ft. of non-clean support space beneath the cleanroom.

The Nanofab is part of the Penn State Materials Research Institute’s shared user facilities, which also includes the Materials Characterization Lab (MCL). The MCL is a fully staffed analytical laboratory that offers researchers convenient and affordable access to a wide range of state-of-the-art analytical instrumentation that complements the Nanofab tool sets. They include a second Keck Smart Materials Laboratory cleanroom in the MCL with several instruments specialized for complex ferroelectric oxide materials processing.

Nanotech—University of California, Santa Barbara: Nanotech brings particular expertise in compound semiconductors, photonics, quantum structures, and non-standard materials and fabrication processes. The facility is located in UCSB’s new Engineering Sciences building, a three-story structure of 52,000 sq. ft., where Nanotech occupies 12,700 sq. ft. of class-100 and -10,000 clean space.

The nanofabrication facility has comprehensive and advanced semiconductor and thin film processing equipment and provides access and professional consultation to industrial and internal and external academic users. A wide range of materials including silicon, compound semiconductors, and novel and unusual materials including polymers and ceramics are processed in the facility. Professional staff consists of six engineers supporting facilities and three Ph.D.-degreed engineers supporting process.

UCSB has extensive facilities and research for nanotechnology, as well as a wide range of well-funded centers of excellence in areas of electronics, optoelectronics, energy efficiency, materials, biology, and physics. These centers are funded by a wide variety of government agencies and industrial partners. Researchers from these centers use the nanofabrication facility and provide resources and knowledge that benefit the entire user community. The UCSB research centers have also funded equipment purchases for the facility, benefiting the entire research community.

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Nanofabrication Center (NFC)—University of Minnesota: The Nanofabrication Center is an interdisciplinary facility that focuses on a number of areas including microelectromechanical systems, remote processing, characterization and, most recently, alternative energy.

The NFC runs a class-10 clean room with 14 permanent staff members. The node is currently planning for a major expansion as part of the planned Experimental Physics and Nanotechnology Building on the university campus. Expected to open in 2012, the new facility will triple the existing clean room space. The Center operates within the University of Minnesota's Institute of Technology, with particular success in developing a large set of external users.

NFC hosts a full suite of processing tools for building micro and nano devices. The Minnesota node brings specialized equipment and expertise to two areas of technical excellence. In energy, the Minnesota NNIN has developed a system for layer-by-layer deposition of specialized chemical compounds used to research new types of photovoltaic materials. The research promises less-expensive alternatives to current, thin-film solar cell technology. In remote access, the Minnesota node can perform sophisticated fabrication and/or characterization sequences under the direction of a remote user.

Microelectronics Research Center (MRC)—University of Texas at Austin: Established in 1983, the MRC is a key element in a partnership for advancing microelectronics between the university and the state of Texas. The NNIN node provides opportunities to perform research on novel materials of interest to the integrated-circuit industry, as well as in optoelectronics and nanophotonics, novel electronic devices and nano-structures, and interconnects and packaging.

The MRC is located on the Pickle Research Campus in the Microelectronics and Engineering Research Building, which was completed in 1993. To date, more than $50 million has been committed to build and equip this facility for both silicon-related and compound-semiconductor research. The facilities at the MRC include 12,000 sq. ft. of class-100 and class-1000 cleanroom space for crystal-growth and device processing. In addition to state-of-the-art cleanroom facilities, MRC has 15,000 sq. ft. of characterization laboratories and office space for 15 faculty, support staff, and 120 graduate students.

The Center's location within the electronics community of Austin, Texas, provides MRC with distinct advantages. For example, its solid-state electronics faculty has close ties with the Microelectronics and Computer Technology Corporation, SEMATECH, and IC2; all are located in Austin, Texas. Support from these consortia, as well as from many industry and government laboratories, contributes to the MRC’s versatility.

Center for Nanoscale Systems (CNS)—Harvard University: CNS was originally started at Harvard in 1999 as the Center for Imaging and Mesoscale Structures. The Center became part of the NNIN in 2004. CNS emphasizes soft lithography and the assembly of nanoparticle and molecular electronics, theoretical simulations of electron states and transport in nanoscale systems, and the establishment of core computational resources used in understanding and visualizing new device structures.

The Center's nanofabrication facility provides a wide range of resources and a staff of more than 20 technicians. The facility currently operates a 10,000 sq. ft. cleanroom with leading-edge equipment. The Center is also incorporating a new, class-10,000 soft-materials fabrication facility that is in the final stage of commissioning and will complement the existing,

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conventional cleanroom facility. The new facility will include dedicated workspace for soft materials projects including microfluidics and soft-lithographic reproduction.

The computation project of the National Nanotechnology Infrastructure Network, NNIN/C, is also centered at Harvard University. The computation project recently upgraded and expanded its computation services when its computational infrastructure was transferred within Harvard, allowing NNIN/C users access to a Harvard computing cluster of 8000 nodes. The project's main workhorse, a 224-node cluster, was physically moved and embedded in the Harvard cluster.

Howard Nanoscale Science and Engineering Facility (HNF)—Howard University: HNF researchers routinely engage in research and development in diverse areas, with the Center offering particular expertise in general microfabrication, electronics and materials, characterization science, and nanofiltration.

The Center occupies a specially renovated wing on the first floor of the Engineering Building at Howard. The five large laboratories cover about 6,000 sq. ft. of space, with about 2,000 sq. ft. of contiguous office space. The HNF is an established, centralized user facility containing micro- and nano-fabrication and characterization equipment, and is accessible by external and internal academic, government, and industrial users.

The Colorado Nanofabrication Laboratory (CNL)—University of Colorado at Boulder: CNL research covers a broad range of nanoscale science, with special expertise in general microfabrication, electronics, optoelectronics, and micro-mechanical systems. The Colorado Lab is one of three recently added NNIN sites and has undergone a rapid transition from a single faculty-owned facility to a campus-wide open user facility.

The facility is run by a staff of three professionals and covers 5,500 sq. ft. including a 1,000 sq. ft. class-100 cleanroom. The facility offers a broad range of processing and characterization tools. The same building also houses the Nano Characterization Facility, which provides access to a field-emission scanning-electron microscope and a focused ion-beam system.

ASU NanoFab—Arizona State University: The NanoFab is operated by the Center for Solid State Electronics Research (CSSER) within the Ira A. Fulton School of Engineering at ASU. CSSER was established in 1981 and historically has supported research on a wide variety of materials, structures, and processes.

The NNIN node's core strengths are in nanofabrication, CMOS processing, molecular and bio-electronics, microelectromechanical systems (MEMS), nano-fluidics, benign semiconductor processing, optoelectronics, and device characterization. The ASU facility offers a wide variety of state-of-the-art device processing and characterization tools to individuals, companies, and government labs that need occasional or recurring access.

The core cleanroom is a 4,000 sq.ft. class-100 facility. The cleanroom fabrication facility is supported by an additional 5,000 sq.ft of multi-user laboratory space. A full-time technical staff of eight coordinates the day-to-day activities, and includes research scientists as well as equipment and process engineers.

Nano Research Facility (NRF)—Washington University: The NRF, launched in 2009, is building a niche at the intersection of nanotechnology and important needs in public health and the environment. The effort includes a focus on nanostructured materials, the bottom-up approach to nanofabrication; nanotoxicology, which puts nanotechnology in the context of public

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health and environment; and photoacoustic microscopy, the use of nanotechnology as an enabler for early cancer detection.

The Facility opened in 2009 with support from Washington University, which constructed a new building with space of 8,000 sq. ft. The NRF established operation in class-100/1000/10,000 clean rooms, a particle technology lab for nanomaterials synthesis, and a surface characterization lab for morphology and composition analysis.

The Center has acquired a dynamic light-scattering system and inductively-coupled, plasma-mass spectrometer system. When integrated with electron microscopes, these tools can precisely define nanomaterial parameters such as particle size, shape, surface area, morphology, composition, and surface functionality. The NRF aims to build a toxicity core on the university's medical campus that can perform in-vitro and in-vivo characterizations.

Closure The NSECs and NNIN are two examples of long-term investments in nanoscale science and engineering at NSF that together represent less than ten percent of its FY 2011 budget for nanotechnology. Other research and education programs in nanotechnology can be found at www.nsf.gov/nano (for NSF alone) and www.nano.gov (for all NNI).