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    62

    UNIT 1.6

    Technologies for Space

    Biology: New Horizons

    Presented by:

    Mr. John Hines

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    INTRODUCTION

    63

    UNIT 1.6

    Technologies for Space Biology: New HorizonsMr. John Hines

    Vocabulary:

    Biomimetics Biophotonics In situ Mesoscale Nanotechnology

    Outline:

    1. Technology Challenges of Biology in Space

    2. Scope of NASA Biological Sciences Research3. Introduction to NASA programs

    a. Astrobiology

    b. Fundamental Space Biology Programc. Biomolecular Systems Research Program

    4. Technology Drivers for Space Biology Research

    5. Advanced Technologies for Space Biotechnology

    6. Technology Application Examplesa. Automated Ion-Monitoring System for Cell-Culture Flight Experiments

    b. In situ Cell Flow Cytometer

    c. Maskless Array Synthesizer / Automated Gene Sequencer (In situGenomicsTechnologies)

    d. BioExplorer Program BioNanoSatellite

    e. In situ Gene Expression on Nanosatellites (ISGEN) Technology Accelerator

    Projectf. Remote Automated Yeast Gene Expression Analyzer using Gene-Promoterg. Pill-Shaped Biotelemetry Transmitters

    h. Sensors 2000 Flight Technology Demonstration

    i. Smart Healthcare Management Systems Physiological Monitoring ofAstronauts

    j. Stanford Cell-Based Biosensor System

    7. Reference Materials and Web Links

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    INTRODUCTION

    64

    Pump

    Reactor

    Motor

    Technology Challenges of Biology in Space

    As NASA defines and expands its goals and objectives for long duration exploration

    of space, interest in genetics, cell, and molecular biology have become key and critical

    topics. Increasingly, the capability to perform autonomous, in-situ acquisition,

    preparation and analysis of biological samples and specimens to determine thepresence and composition of biological components is required for both space biology

    and medical researchers. Technology developments and advances are needed to

    support applications across all of the relevant technology application areas, includingBioastronautics, Fundamental Biology, and Astrobiology.

    Biological and Biomolecular/Genomic research is enabling unprecedented insight intothe structure and function of cells, organisms, and sub-cellular components and

    elements, and a window into the inner workings and machinations of living things.

    Triggered by advances in microelectronics and related areas, we are now able tofabricate and construct devices and components such as sensors, actuators, machines,

    motors, valves, switches, pumps, and other items on the same scale as the biologicaltargets of interest, even in some cases on the order of tens of nanometers in size. This

    directly scaled relationship allows for new strategies and interactions between physicaldevices and living systems.

    These techniques and technologieshave permitted the emergence of a

    new class of instruments and devices,

    generally described as mesoscaletechnologies. Many devices,

    techniques and products are now

    available or emerging, which allowmeasurement, analysis andinterpretation of the biological composition at the

    molecular level, and which permit determination of

    DNA/RNA and other analytes of interest.

    Finally, advances in information systems and

    technologies, and bioinformatics, provide thecapability to understand, simulate, and interpret the large amounts of complex data being

    made available from these biological-physical hybrid systems. These synergistic

    relationships facilitate the development of revolutionary technologies in many areas, and

    bode well for the future of space biology research objectives.

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    INTRODUCTION

    65

    Scope of NASA Biological Sciences Research

    Human

    Operations

    Emphasis

    Biological

    Research

    Emphasis

    Astrobiology Emphasis

    Biochemistry,

    Fundamental and

    EvolutionaryBiology

    Fundamental Physics

    and Chemistry,

    Cosmology

    Geology, Planetary

    Ecosystems and

    Evolution

    Galactic

    Ecosystems

    Human Space

    Flight Tech. and

    Habitability

    Bio-Technology,

    Nanotechnology,Information Tech.

    Atomic,Molecular

    Physics

    and

    Biology

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    INTRODUCTION

    66

    Astrobiology

    Astrobiology is the study of life in the universe. It

    provides a biological perspective to many areas ofNASA research, linking such endeavors as the

    search for habitable planets, exploration missions toMars and Europa, efforts to understand the origin of

    life, and planning for the future of life beyond Earth.

    Interdisciplinary research is needed that combines

    molecular biology, ecology, planetary science,astronomy, information science, space exploration

    technologies, and related disciplines. The broad

    interdisciplinary character of astrobiology compelsus to strive for the most comprehensive and

    inclusive understanding of biological, planetary

    and cosmic phenomena.

    Astrobiology addresses three basic questions that have been asked in various ways for

    generations. How does life begin and develop?

    Does life exist elsewhere in the universe?

    What is the future of life on Earth and beyond?

    Life is a central theme that unifies NASA's vision and mission. A golden age has begun for

    the life sciences, an age in which science and technology will benefit enormously from afundamental understanding of the full potential of living systems.

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    INTRODUCTION

    67

    Fundamental Space Biology Program

    Fundamental Space Biology is NASA's program for the study of fundamental biological

    processes through space flight and ground-based research. Bringing together state-of-the-art

    science and technology, the program seeks to answer the most basic questions regarding the

    evolution, development, and function of living systems.

    Yeast,Bacteria,

    CellsC. Elegans,

    Drosophila

    Arabidopsis

    Rodents,(Humans)

    Integrated Payloads

    (Multi-Specimen)

    Model

    Organism

    Emphasis

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    INTRODUCTION

    68

    Integrated Biology Research Program

    Technology Development Matrix

    Specimen/Sample

    ManagementExperiment

    Logistics

    Data Acquisition

    And MonitoringInformation

    Management

    Experiment

    Operations

    Technology Categories

    FBRP Program Elements

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    AArrttiiffiicciiaall IInntteelllliiggeennccee

    SSppeeccttrroossccooppy

    BBiioommiimmeettiiccss

    MMEEMMSS//MMOOEEMMSS//OOppttiiccss

    BBiiootteelleemmeettrryy

    SSaammpplleeFFiixxaattiioonnaanndd

    SSttoorraaggee

    Materials and

    Composites

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    BBiioollooggyy

    CCeellll

    BBiioollooggyy

    DDeevveellooppmmeennttaall

    BBiioollooggyy

    OOrrggaanniissmmaall&&

    CCoommppaarraattiivvee

    BBiioollooggyy

    GGrraavviittaattiioonnaall

    EEccoollooggyy

    BBiioosseennssoorrss

    BBiiooaannaallyyttiiccaall

    DDeevviicceess

    GGeennoommiiccss

    Naannootteecchhnnoollooggiieess

    Enabling

    Technologies

    IInnffoorrmmaattiioonn

    TTeecchhnnoollooggiieess

    MMiiccrroofflluuiiddiiccss

    MMoolleeccuullaarrSSttrruuccttuurreess

    aannddPPhhyyssiiccaall

    IInntteerraaccttiioonnss

    EEvvoolluuttiioonnaarryy

    BBiioollooggyy

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    INTRODUCTION

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    Biomolecular Systems Research Program

    The NASA Biomolecular Systems Research Program is an integrated

    research program focused on developing molecular level technologies to

    monitor cellular signals and processes with applications to crew health and

    safety, basic biology research, life detection, planetary protection, andnanotechnology.

    Biomolecular Signatureso Identification of signatures of life via thermodynamics and

    kinetics of metabolism

    o Detection of molecular level structures and anomalies

    o Detection of chemical disequilibria and microscale chemical analyses

    o Models for biological metabolism

    o Genomic and protein signatures indicative of disease

    Signal Amplificationo Single, specific molecular detection among high background noise

    o Sensitivity enhancerso Utilization of biological amplification or self-amplification of target

    molecules

    o Signal enhancement from targeted molecules

    Biomolecular Sensing and Manipulation

    o Biomolecular probes

    o Nanotube-based actuators and force sensors

    o Biologically-based and biomimetic sensors

    o Molecular engineered biosensors

    o Molecular manipulators

    o Single molecule sensing and recognition

    Biomolecular Imagingo New technologies for imaging protein expression in cells

    o Nanoscale imaging to resolve protein or DNA structure, correlate with

    function

    o Image cellular activities

    o Development and refinement of optical/electromagnetic techniques

    Biomolecular Informatics / Information Processingo Data: Pattern recognition, data mining, data fusion

    o Modeling: genomics, kinetics of biological processes and cellular function

    o Knowledge Discovery: real-time medical diagnostics and treatment

    Nanoscale Sensing

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    INTRODUCTION

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    Technology Drivers for Space Biology Research

    GROW - Autonomous, Multigenerational Habitatso In-flight systems and modules will permit growth and nurturing of cells,

    tissues, and higher organisms

    SENSE In Situ Biosensors and Sample Managemento Development of biosensors, DNA chips and automated sample management

    and handling systems will permit in-situ measurement and analysis of

    biological processes

    OBSERVE - Microscopy and Advanced Imaging Systemso Incorporation of new advances in optical, nano- and information technologies

    will allow in-situ imaging systems to visualize changes in cell

    shape and configuration

    ANALYZE - Information Systems and Technologies

    o Revolutionary developments in bioinformatics, modeling, simulation, and

    adaptive - autonomous bioanalytical systems will enable rapid conversion of

    raw data to information/knowledge FLY - Free Flyer BioNanosatellite Development

    o Development and flight demonstration of advanced in-situ biological

    technologies and platforms

    Critical Space

    Technology Drivers

    Reduce Crew Time Requirements Power

    Volume / Weight

    Accuracy / Stability

    Cost

    Operate in Remote Environments

    Operate In Microgravity

    Measurement Systems

    Design and Development Elements

    Sample Collection, Preparation,Handling, Reduction

    Parameter Sensing and Transduction

    Signal Pre-Conditioning

    Signal Processing

    Communications (all levels - interand intra)

    Data Acquisition, Monitoring,Control, Display

    Power Conditioning andManagement

    Data Reduction, Analysis,Distribution, Archiving

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    INTRODUCTION

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    Advanced Technologies for Space Biotechnology

    Tools of the Trade (In Situ)

    Sample Management and Handlingo Microfluidics

    o Mesoscale Systems Nanotechnologies

    Biosensors

    Tissue-Based Biosensors

    DNA Technologieso Isolation

    o DNA Detection

    o Purification

    o Amplification

    o Decision making

    o Analysis

    Gene Chips and Arrays

    cDNA Libraries

    Bioinformatics / Biocomputation

    Bioimaging / Biophotonics

    Biomaterials

    Micromachining

    Biomimetics

    Optics and Optical processing

    Microscopy (some examples)o Confocal

    o

    Atomic Forceo Scanning Tunnel

    o Fluorescence

    o Multi-Photon

    o Hyperspectral

    Cell Culture Systems

    Molecular Components and Function Blocks

    Biotelemery and Wireless, Modular Instrumentation Architectures

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    INTRODUCTION

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    TECHNOLOGY APPLICATION EXAMPLES

    BIONA-C

    Automated Ion-Monitoring System for Cell-Culture Flight Experiments

    STS-93

    July 23-27, 1999

    Sensor array onpre-amplifier PCB(Sensor Card)

    Foursensor cards oncontroller CB

    Sensors andcontroller onCCM rail withpumps, valves

    SensorArray

    Indicator electrodeReference electrode

    Thermistor

    Reference Indicator

    Electrolyte

    Ag/AgClWire

    Epoxyplug

    p-HEMAplug

    PVCbody

    Ion-SelectiveMembrane

    Ag wire

    Sensor Electrodes

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    INTRODUCTION

    73

    TECHNOLOGY APPLICATION EXAMPLES (continued)

    In SituCell Flow Cytometer Flow Cell

    InjectorTip

    Sheath

    fluid

    FFlluuoorreesscceennccee

    SSiiggnnaallss

    FFooccuusseedd

    LLaasseerrBBeeaamm

    Purdue University

    Cytometry Laboratories

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    INTRODUCTION

    74

    TECHNOLOGY APPLICATION EXAMPLES (continued)

    Maskless Array Synthesizer / Automated Gene Sequencer

    (In SituGenomics Technologies)

    Objective

    To develop the capability to:

    Produce DNA array chips (MMaasskklleessssAArrrraayy

    SSyynntthheessiizzeerr). The MAS can print DNA microarrays on

    any simple UV transparent surface glass or plastic

    substrate, which could be produced on a spacecraft.The MAS could also be integrated into multipurpose

    platforms or a fully automatic system

    Expand MAS capabilities and develop an AAuuttoommaatteeddGGeenneeSSeeqquueenncceerr((AAGGSS)) to provide the capability to

    manufacture in-situ biological countermeasures, andother biological/genetic products.

    These systems are intended to allow state of the artgenomic analysis and intervention in space on any

    biological sample: human, animal, bacterial or

    unknown with a minimum of operator input, and with

    remote operator capabilities.

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    INTRODUCTION

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    TECHNOLOGY APPLICATION EXAMPLES (continued)

    BioExplorer Program

    The intent of this new program is to develop, demonstrate and utilize small free-flying

    orbital spacecraft, BioExplorers, to support Principal Investigator-led sciencemissions that have been selected through peer review.

    BioNano SatelliteSatellite with Cage Assembly and Biology Module Exploded

    Experiment Systemo Cage Assembly

    o Biology Module

    Satellite Buso Structure

    o Control and Data Handling

    o External Camera System

    o Power System

    o Communication System

    o Stabilization Systemo Data logger System

    o Software

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    INTRODUCTION

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    TECHNOLOGY APPLICATION EXAMPLES (continued)

    In SituSpace Gene Expression on Nanosatellites (ISGEN) Technology

    Accelerator Project

    1. Single protein: fluorescent/ luminescent assay in

    multiwell plate

    a. Multiple proteins: different target in each

    well (12 - 48)

    b. Multiple proteins: multiple color (2 - 4)indicators per well

    2. Tissue-type-specific proteins: 5 - 10 m lateral

    resolution imaging fluorescence/luminescence

    a. Multiplex: multiple wells, colors; multiple

    constructs by tissue type

    3. Multiplexed proteins: Liquid arrays requiring

    minimal sample prep from Luminex, Qdot,Nanoplex, ACLARA (3 - 50 targets per assay)

    4. Multiplexed genes: amplification plus fluorescent

    tagging

    a. Cepheid system adapting PCR to zero

    gravity (2 - 5 targets per optical unit)

    b. Multiplexed genes (5 - 30 targets):

    ACLARA eTag system or Luminex beads

    incorporating amplification step5. Gene microarray: fully automated sample prep,

    hybridization, readout (100s - 1000s of targets)

    T

    0

    2 yr

    4 yr

    ISGEN Stages

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    INTRODUCTION

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    TECHNOLOGY APPLICATION EXAMPLES (continued)

    Remote Automated Yeast Gene Expression Analyzer using Gene-Promoter

    / Luciferase-Reporter Constructs

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    INTRODUCTION

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    TECHNOLOGY APPLICATION EXAMPLES (continued)

    Pill-Shaped Biotelemetry Transmitters

    ASIC

    Ion-selective Micro-Electrode

    ..

    Drug Reservoir

    Biosensor Drug Release Holes

    Pressure/Temperature Pill

    pH/Temperature Pill

    pH/Temperature/Pressure Pill

    Heart rate/Temperature Pill

    pH/Pressure/Temperature/Heart Rate Pill

    ECG/Temperature Pill

    Responsive Drug Delivery Pill

    35 mm (1.38)

    Printed Circuit Boards with

    SMT components and bare diesSilver-Oxide

    Batteries

    Shell coated with silicone Pressure Sensor

    Pressure/Temperature Pill-Transmitter

    9 mm(0.35)

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    INTRODUCTION

    79

    TECHNOLOGY APPLICATION EXAMPLES (continued)

    Sensors 2000 Flight Technology Demonstration

    WASP

    Cell-Culture Modu le Rail

    pH-Tx Ca2+-Tx K

    +-Tx pH-Tx Wearable

    Computer

    Displayand

    AnalysisDevicesReal-Time

    Data-Baseand Data

    Server

    WASP

    AEM

    AEM

    WASP

    WASP

    AEM

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    INTRODUCTION

    80

    TECHNOLOGY APPLICATION EXAMPLES (continued)

    Smart Healthcare Management Systems: Developing systems to monitor thehealth and performance of NASA personnel and the functional status of the

    systems that support them.

    Physiological Monitoring of Astronauts

    Biotelemeter implanted in animals,or ingested by/attached toastronauts senses BodyTemperature, Blood Pressure,Blood pH, and Heart Rate.

    TriSponderquickly displaysHealth Status.

    Physiological Signal

    Conditioner (PSC)acquiresECG, EEG, EMG, and EOG(and other bio-parameters ofinterest).

    Transponderrelaysbiotelemeter signalto other monitoring

    devices.

    Laptop monitorsand analyzesPhysiologicalParameters.

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    INTRODUCTION

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    TECHNOLOGY APPLICATION EXAMPLES (continued)

    Stanford Cell-based Biosensor System

    Cardiac cells growing on a sensor chip

    Portable, hand-held cell sensor system

    with microenvironment chip.

    50 m

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    INTRODUCTION

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    Reference Materials and Web Links

    Astrobiologyhttp://www.nai.arc.nasa.gov/

    http://astrobiology.arc.nasa.gov/http://astrobiology.arc.nasa.gov/roadmap/index.html

    Fundamental Space Biology and Ames

    http://fundamentalbiology.arc.nasa.gov/

    Biomolecular Systems Research Program

    http://nasa-nci.arc.nasa.gov/

    Liquid Array examples:QuantumDot Qbead system

    http://www.qdots.com/new/technology/beadtech.html

    ACLARA eTag system

    http://www.aclara.com/etag_reporters.asp

    Luminex LabMap systemhttp://www.luminexcorp.com/

    GeneXpert Products

    http://www.cepheid.com/

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    INTRODUCTION

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    Notes:

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    UNI T ONE: INTRODUCTION

    Evaluation

    Please complete the following evaluation questions for this unit and return this form to thecourse coordinator at the beginning of the next day. All responses are anonymous and willbe kept confidential. We appreciate your taking the time to help us improve futureeducational programs.

    Please complete the following statements using the provided scale:Excel-

    lentVeryGood Fair Poor

    1) The unit as a whole was: ! ! ! !

    2) Overall, the knowledge I gained in this unit was: ! ! ! !

    3) The overall pace of this unit was: ! ! ! !

    4) The opportunity to ask questions during this unit was: ! ! ! !

    5) The presentation materials for this unit were: ! ! ! !

    Additional Comments: