UNIT 1.

Technologies for Space Biology: New Horizons

Presented by: Mr. John Hines

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INTRODUCTION

UNIT 1.6
Technologies for Space Biology: New Horizons
Mr. John Hines

Vocabulary:

Biomimetics Biophotonics In situ Mesoscale Nanotechnology

Outline:
1. Technology Challenges of Biology in Space 2. Scope of NASA Biological Sciences Research 3. Introduction to NASA programs a. Astrobiology b. Fundamental Space Biology Program c. Biomolecular Systems Research Program 4. Technology Drivers for Space Biology Research 5. Advanced Technologies for Space Biotechnology 6. Technology Application Examples a. Automated Ion-Monitoring System for Cell-Culture Flight Experiments b. In situ Cell Flow Cytometer c. Maskless Array Synthesizer / Automated Gene Sequencer (In situ Genomics Technologies) d. BioExplorer Program BioNanoSatellite e. In situ Gene Expression on Nanosatellites (ISGEN) Technology Accelerator Project f. Remote Automated Yeast Gene Expression Analyzer using Gene-Promoter g. Pill-Shaped Biotelemetry Transmitters h. Sensors 2000 Flight Technology Demonstration i. Smart Healthcare Management Systems Physiological Monitoring of Astronauts j. Stanford Cell-Based Biosensor System 7. Reference Materials and Web Links

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INTRODUCTION 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 the presence 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, including Bioastronautics, Fundamental Biology, and Astrobiology. Biological and Biomolecular/Genomic research is enabling unprecedented insight into the 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 to fabricate and construct devices and components such as sensors, actuators, machines, motors, valves, switches, pumps, and other items on the same scale as the biological targets 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 physical devices and living systems.

These techniques and technologies have permitted the emergence of a new class of instruments and devices, generally described as mesoscale technologies. Many devices, techniques and products are now available or emerging, which allow measurement, analysis and interpretation of the biological composition at the molecular level, and which permit determination of DNA/RNA and other analytes of interest.

Pump

Reactor

Motor

Finally, advances in information systems and technologies, and bioinformatics, provide the capability 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 Scope of NASA Biological Sciences Research

Astrobiology Emphasis

Galactic Ecosystems

Human Operations Emphasis

Geology, Planetary Ecosystems and Evolution

Biological Research Emphasis

Human Space Flight Tech. and Habitability

Bio-Technology, Nanotechnology, Information Tech.

Atomic, Molecular Physics and Biology Fundamental Physics and Chemistry, Cosmology

Biochemistry, Fundamental and Evolutionary Biology

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INTRODUCTION Astrobiology
Astrobiology is the study of life in the universe. It provides a biological perspective to many areas of NASA research, linking such endeavors as the search for habitable planets, exploration missions to Mars 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 compels us 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 a fundamental understanding of the full potential of living systems.

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INTRODUCTION 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, Cells

C. Elegans, Drosophila

Model Organism Emphasis

Integrated Payloads (Multi-Specimen)

Arabidopsis

Rodents, (Humans)

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INTRODUCTION Integrated Biology Research Program Technology Development Matrix FBRP Program Elements

Molecular Structures and Physical Interactions

Molecular Biology

Cell Biology

Organismal & Developmental Gravitational Evolutionary Comparative Biology Ecology Biology Biology

Specimen/Sample Management

Experiment Logistics

Data Acquisition And Monitoring

Information Management

Experiment Operations

Technology Categories

Biomimetics Sample Fixation and Storage Microfluidics

Enabling Technologies

Biotelemetry

Biosensors

Genomics

Bioanalytical Devices Robotics

Nanotechnologies Spectroscopy

Materials and Composites MEMS/MOEMS/Optics Information Technologies Imaging, Optics, Biophotonics

Artificial Intelligence

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INTRODUCTION 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, and nanotechnology. Biomolecular Signatures o 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 Amplification o Single, specific molecular detection among high background noise o Sensitivity enhancers o 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 Nanoscale Sensing o Single molecule sensing and recognition Biomolecular Imaging o 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 Processing o 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

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INTRODUCTION Technology Drivers for Space Biology Research

GROW - Autonomous, Multigenerational Habitats o In-flight systems and modules will permit growth and nurturing of cells, tissues, and higher organisms SENSE In Situ Biosensors and Sample Management o 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 Systems o 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

Measurement Systems Design and Development Elements

Sample Collection, Preparation, Handling, Reduction Parameter Sensing and Transduction Signal Pre-Conditioning Signal Processing Communications (all levels - inter and intra) Data Acquisition, Monitoring, Control, Display Power Conditioning and Management Data Reduction, Analysis, Distribution, Archiving

Critical Space Technology Drivers

Reduce Crew Time Requirements Power Volume / Weight Accuracy / Stability Cost Operate in Remote Environments Operate In Microgravity

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INTRODUCTION Advanced Technologies for Space Biotechnology Tools of the Trade (In Situ)
Sample Management and Handling o Microfluidics o Mesoscale Systems Nanotechnologies Biosensors Tissue-Based Biosensors DNA Technologies o 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 Force o 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 TECHNOLOGY APPLICATION EXAMPLES BIONA-C Automated Ion-Monitoring System for Cell-Culture Flight Experiments

Sensor Electrodes
Reference
p-HEMA plug PVC body Electrolyte Reference electrode Ag/AgCl Wire Epoxy plug Ag wire

Indicator
Ion-Selective Membrane Thermistor

Sensor Array

Indicator electrode

Sensor array on pre-amplifier PCB (Sensor Card)

STS-93 July 23-27, 1999

Four sensor cards on controller CB Sensors and controller on CCM rail with pumps, valves

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) In Situ Cell Flow Cytometer

Flow Cell
Injector Tip Sheath fluid

Fluorescence Signals

Focused Laser Beam

Purdue University Cytometry Laboratories

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) Maskless Array Synthesizer / Automated Gene Sequencer (In Situ Genomics Technologies)
Objective To develop the capability to:

Produce DNA array chips (M Maskless Array Synthesizer). 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 Automated Gene Sequencer (AGS) to provide the capability to manufacture in-situ biological countermeasures, and other biological/genetic products. These systems are intended to allow state of the art genomic 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 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 science missions that have been selected through peer review.

BioNano Satellite
Satellite with Cage Assembly and Biology Module Exploded Experiment System o Cage Assembly o Biology Module Satellite Bus o Structure o Control and Data Handling o External Camera System o Power System o Communication System o Stabilization System o Data logger System o Software

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) In Situ Space Gene Expression on Nanosatellites (ISGEN) Technology Accelerator Project

T
0

ISGEN Stages
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 step 5. Gene microarray: fully automated sample prep, hybridization, readout (100s - 1000s of targets)

2 yr

4 yr

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) Remote Automated Yeast Gene Expression Analyzer using Gene-Promoter / Luciferase-Reporter Constructs

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) Pill-Shaped Biotelemetry Transmitters

Silver-Oxide Batteries Printed Circuit Boards with SMT components and bare dies

9 mm (0.35)

35 mm (1.38) Shell coated with silicone Pressure Sensor

Pressure/Temperature Pill-Transmitter

Pressure/Temperature Pill
Ion-selective Micro-Electrode

pH/Temperature Pill pH/Temperature/Pressure Pill

Heart rate/Temperature Pill

ECG/Temperature Pill
ASIC

pH/Pressure/Temperature/ Heart Rate Pill

Biosensor Drug Release Holes

..
Drug Reservoir

Responsive Drug Delivery Pill

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) Sensors 2000 Flight Technology Demonstration

WASP

Cell-Culture Module Rail pH-Tx Ca2+-Tx K+-Tx pH-Tx

Wearable Computer

WA

AEM

AEM

AEM WASP

WASP

WASP

Real-Time Data-Base and Data Server

Display and Analysis Devices

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) Smart Healthcare Management Systems: Developing systems to monitor the health 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 to astronauts senses Body Temperature, Blood Pressure, Blood pH, and Heart Rate.

TriSponder quickly displays Health Status.

Transponder relays biotelemeter signal to other monitoring devices.

Physiological Signal Conditioner (PSC) acquires ECG, EEG, EMG, and EOG (and other bio-parameters of interest).

Laptop monitors and analyzes Physiological Parameters.

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INTRODUCTION TECHNOLOGY APPLICATION EXAMPLES (continued) Stanford Cell-based Biosensor System

Cardiac cells growing on a sensor chip

50 m
Portable, hand-held cell sensor system with microenvironment chip.

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INTRODUCTION

Reference Materials and Web Links

Astrobiology http://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 system http://www.luminexcorp.com/ GeneXpert Products http://www.cepheid.com/

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INTRODUCTION

Notes:

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UNIT ONE: INTRODUCTION

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