Biosensors Overview - Division on Earth and Life Studiesdels.nas.edu/resources/static-assets/bls/miscellaneous/CAS NAS... · Slide 3. Operated by Los Alamos National Security, LLC

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Biosensors OverviewPresented at the

TRENDS IN SCIENCE AND TECHNOLOGYRELEVANT TO THE BIOLOGICAL AND TOXIN WEAPONS CONVENTION

November 2, 2010

Gary Resnick, Ph.D.Director, Bioscience Division

Los Alamos National Laboratory

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Biosensors--

BWC Implications

Leveraging the Power of Evolution

• Biosensors have and will continue to accelerate our ability to characterize complex biological systems; enabling manipulation of those systems

• Development of a “handheld”

pathogen sensor has alluded developers, but will be revolutionary when it occurs

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Biosensor Defined

Biosensor--

an analytical device for the detection of analyte

that

combines a biological component with a physicochemical detector component, principal components:

• Sensitive biological element--

biological material (e.g., tissue,

microorganisms, organelles, cell receptors, enzymes, antibodies,

nucleic acids, etc), a biologically derived material or biomimic

• Transducer

or the detector element (works in a physicochemical

way; optical, piezoelectric, electrochemical, etc.) that transforms the signal resulting from the interaction of the analyte with the biological element into another signal

• Signal processors

that are primarily responsible for the display of

the results in a user-friendly way.

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Biosensor Approaches

“Software”

(Recognition) Approaches• Recognition binders• Signature design • Reporters (protein engineering)“Hardware”

(Transduction) Approaches• Electrochemical• Optical• PiezoelectricEnabling Infrastructure• Characterization of biological systems• Gene ontology• Quality control standards• Intellectual property managementMiniaturization of Chemical Instruments• Mass Spectrometry• Flow cytometry

• Highly specific signatures for any biological activity/function/state

• Binders on demand

• Inexpensive, facile, highly multiplexed, and field deployable biosensors

• Context for broad technology application

See review by Luong, H.T., et al. Biotechnonology Advances 26 (2008) 492-500

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Current Biosensor Applications & Development

• Research

• Medicine

• Food Safety

• Agriculture

• Environment

• Manufacturing

• SecurityDetection and forensics signature design

Multi-pathogen micro-array

Microbial community characterization

Soil microbes

Development of field-

deployable detectors

Detection ‘Dipstick’

from MESA Inc.

YSI Glucose Sensor Technology

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Drivers & Trends in Biosensor Development

• The Need--

The “Pull”– Societal challenges (e.g., food production, climate change,

public health, medicine, manufacturing, renewable energy)– Policy drivers (e.g., International Health Regulation)– Cost reduction (e.g., in-line process control, biomimetic

production systems)

• Technology Opportunity–

The “Push”– A convergence of diverse technological advances for

biosensor innovation and application– 21st

Century Biology driving need for high throughput/high content bioanalysis systems, rapid knowledge generation

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Biosensor Development and Applications Enabled by a Convergence of S&T Advances

• Bioengineering Technology– Highly specific/sensitive synthetic ligands– In situ reporters

• High Throughput/Content Bioanalytical Platforms

• Materials Science– Novel sensor platforms

• Information Science and Technology– Data/information management– Knowledge generation/application

• Communications• Geographic Information Systems

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21st

Century Biology

Accelerating Discovery & Reducing Cost

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DNA graphic credit: DOE:GTL

• High content/volume analyses

• Advanced information science & technology

• Comparative or horizontal & multi-scale versus vertical analyses

A Systems Biology approach enables an inter-disciplinary, comprehensive study of the complex interactions between components of a biological system and the emergent behavior that results. The approach employs:

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Biosensors for Pathogen Analysis

Signatures (Biomarkers)e.g. Epitopes, unique DNA/RNA,

SNPs (point mutations)

Assay Chemistrye.g. Ligand-based immunoassays,

taqman, pPCR, MOL-PCR, etc.

Instrumentatione.g. Plate reader, chip reader, gel

electrophoresis, RT-PCR machine, flow cytometer, etc.

Application SpecificationsApplication Specifications

Pathogen or Host

PropertiesBioassay Validated,

Deployed Solution

Testing and validation

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Screening assay parameters: application-dependent

NOTE: the values in the graph are for illustration purposes only. Higher values represent higher level of importance of the corresponding parameter.

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Biodefense, Biosurveillance, and Human Health assay requirements

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Tradeoffs are needed to achieve optimal solution

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Data Streams

dynamic

Applications

prediction

interpretive results

Information Management

Theory & Simulation

Inform data stream collection

Define data collection

Data stream Q&A and selection

• Ecosystem/Climat

e

• Population

• Host

• Cell/organ

• Molecular

• Atomistic

Tailored results

• Strategic Planning• Non-Proliferation• Risk assess/management• Operational Support• Unusual disease Dx• Vaccine Design• Therapeutic Design• Virulence Prediction• Bioforensics• Biodetection

Unusual disease analysis

Knowledge

Management

A Conceptual Vision for Integrated Biosurveillance

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Data Streams

dynamic

Applications

prediction

interpretive results

Information Management

Theory & Simulation

Inform data stream collection

Define data collection

Data stream Q&A and selection

Ecosystem/ClimatePopulation•Public health•Animal health•Syndromic dataHost•clinical tests•Animal models•Agriculture/wild life

Cell/organ•In-vitro modelsMolecular•proteomics•molecular structure•transcriptomics•metagenomics•genomics

Tailored results

• Strategic Planning• Non-Proliferation• Risk assess/management• Operational Support• Unusual disease Dx• Vaccine Design• Therapeutic Design• Virulence Prediction• Bioforensics• Biodetection

Unusual disease analysis

Knowledge

Management

A Conceptual Vision for Integrated BiosurveillanceBiosensor Enabled

Function Based Models (evolution) and Simulations:

• War planning• Hazard analysis• Biological: atomistic, molecular,

molecular machine, cellular, organismal, population (epi)

• Information visualization• Gene ontology• Disparate data fusion/analysis• Temporally/spatially referenced• Data management

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Biosensor Advances Will Continue to Impact Global Security and the BWC

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By Enabling Higher fidelity planning & prediction Increased food production Early disease detection Accelerated countermeasures

development Unusual disease outbreak resolution

Sustaining:• Health Security• Food & Water Security• Energy Security• Global Security