U.S. Department of Homeland Security

1. U.S. Department of Homeland Security Homeland Security Advanced Research Projects Agency Biological Countermeasures NDIA Homeland Security Symposium Dr Steven Buchsbaum Program Manager, HSARPA steven.buchsbaum@dhs.gov Dr Steven Buchsbaum, NDIA Homeland Security Symposium

2. Biological Countermeasures Thrust Areas • System Architecture Studies • End-to-End Studies Provide Quantitative Basis for Countermeasures Strategy • Define Future Directions and Requirements for Systems • Detection Systems • RA03-01, BAND & RABIS • Future Directions • Assays Development • BAA04-03, Bioinformatics and Assays Development Dr Steven Buchsbaum, NDIA Homeland Security Symposium

3. BW Architecture Studies • Architecture Study of Urban Outdoor Threat Scenarios • Exam both Reference Scenarios and Capabilities Based Threats • Preliminary Study of Indoor Threat Scenarios • Inclusive of Homeland Security Specific Challenges • Evaluate Threats to Food and Agriculture • Evaluate CBRN Threats to Water Dr Steven Buchsbaum, NDIA Homeland Security Symposium

4. Anthrax Attack BioSensors Bio-Aerosol Defense Architecture Study • Objective • Develop biosensing and medical response architecture for large scale bioaerosol attacks • Approach • Characterize performance of environmental sensing networks • Evaluate benefit of traditional and non-traditional medical surveillance options • Use epidemiological models to determine response requirements • Assess cost and benefit of different architecture options • Recommend near-, mid-, and far-term solutions National Pharmaceutical Stockpile Dr Steven Buchsbaum, NDIA Homeland Security Symposium

5. Bioagent Autonomous Networked Detectors(BAND) Upgrade and Expand BioWatch Reduce Costs While Expanding Coverage Support other Bioaerosol Surveillance Missions Enable “Detect to Treat” Response to Attacks Rapid Automated Biological Identification System (RABIS) Real-time Monitor for Buildings and Selected Outdoor Locations and Events Enable “Detect to Protect” Response to Attacks Detection Systems for Biological Countermeasures RA03-01 Dr Steven Buchsbaum, NDIA Homeland Security Symposium

6. Bioagent Autonomous Network Detector (BAND) Technical Topic Area 1 (TTA1) • Bioagent Autonomous Network Detector (BAND) • Detect-to-Treat Biological Surveillance Sensor System • Build on Current BioWatch Architecture • Current Biowatch System Exploits Distributed Collector Systems with Centralized Evaluation of Samples • Current Approach Limits Timeliness of Response • Current Approach Limits Spatial-Temporal Coverage Granularity • Current Approach Driven by Large Logistical and Labor Costs • BAND Will Permit Extending Breadth of Coverage in Threat Space and Increasing Spatial-Temporal Coverage • Must Significantly Reduce Total System Operating Costs • BW Architecture Studies Will Update Strategy and Requirements Dr Steven Buchsbaum, NDIA Homeland Security Symposium

7. BAND TTA-1 TTA-1 Goals – Performance Targets • Continuous, Fully Autonomous Operation with 3 Hour Sample Intervals and 1 Hour Latency (2920 Samples per Year) • Broad Agent Coverage > 20 Agents • Spore, Vegetative Cell, Toxin, DNA Virus, RNA Virus • High Sensitivity – Limit of Detection (LOD) of 100 Organisms • Assumes 3 Hour, 100 Liter/Minute, 90% Efficient Collection • Performers Free to Scale to Alternative Approaches • LOD of 10 nanograms for Toxins • Single Agent False Positive Rate of 10-7 with a goal of 10-8 Dr Steven Buchsbaum, NDIA Homeland Security Symposium

8. BAND TTA-1 TTA-1 Goals – Cost & System Requirements Cost of Ownership • BAND Unit Acquisition Cost of $25K per Unit or Less • Assume Quantities of 1,000s • BAND Operating Costs per Unit of $10K per Year or Less • Inclusive of all Costs: Consumables, Maintenance, Spare Parts, etc. System Requirements • Preserve Samples for 5 Days • Confirmation and Forensics • Robust Wireless, Autonomous Remote Operation • Maintenance Interval Exceeding 1 Month • Operation in Full Range of Outdoor Environments • Modest Packaging and Logistical Requirements • (Ex: 2 cubic feet Volume) Dr Steven Buchsbaum, NDIA Homeland Security Symposium

9. BAND TTA-1 Key Technical Challenges • Very High Sensitivity in Cluttered Background • 100 Organisms in a Backgound of > 18,000 liters of air • Extending Breadth of Threat Coverage (>20) • Either Multiplexed Testing or Large Number of Tests • Alternative Approach – Universal Analysis • Achieving Very Low False Alarm Rate • Single BAND System Pfain the Range of 1 per 10 to 100 Years • Proliferation of BAND Systems Requires Low Single System Pfa • Achieving Low Cost of Ownership • Single Sample Cost Goal of ~ $3.50 per Test (Multiplexed) • Single Sample, Single Agent Cost Goal of ~ $0.17 per Test(Non-Multiplexed) Dr Steven Buchsbaum, NDIA Homeland Security Symposium

10. BAND TTA-1 Requirements – Additional Thoughts • Sensitivity of 100 Organisms in 18,000 liters of air • Drives Technology • Limited Exploration of Full Range of Alternative CONOPS • Same Sensitivity Required of Viruses • Individual Viral Threat Particles too Small • Multiple Organisms per ACPLA • Order 10^5 in DoD Speak • Toxin Detection • Drives Complexity and Cost • Possibly Detectable from Residual DNA • Cost Targets Extremely Aggressive at this Performance Dr Steven Buchsbaum, NDIA Homeland Security Symposium

11. BAND TTA-1 Key Decision Points Notional Program Schedule FY04 FY05 FY06 FY07 FY08 TTA-1 Phase I Phase II Phase III PDR Lab Prototype EvaluationField Prototype CDR • Proposal includes: • Preliminary Conceptual Design • Preliminary Estimates of Performance Relative to Goals • Key Issues for Phase I Execution • Test & Validation plan • Requested GFE • Phase I Completion: • Detailed PDR for both Lab & Field Prototype • Validated Performance Predictions for Lab and Field Prototype • Work Plan for Phase II • Phase II Completion: • CDR for Field Protoype • Work Plan for Phase III • Detailed Cost Estimates for Manufacture • Plan for Commercialization Scientific Development – PDR Risk Reduction Performers are encouraged to accelerated schedules if possible! Engineering for CDR Field Prototype Production & Testing Dr Steven Buchsbaum, NDIA Homeland Security Symposium

12. BAND TTA-1 Programmatic Strategy • IQuum • New tape encapsulated PCR • New assay concepts (padlock probes for high multiplexing) Diversify Engineering Challenge • Autonomous Multiplexed Micro-fluidic PCR • Nanolytics • Miniaturized assay volume by evaporative concentration • Nanofluidics via electrowetting microactuation Diversify Risk in Two Dimensions • MFSI • Next generation reusable microfluidic platform • Modular components - decreased size, increased longevity, increased functionality • Northrop Grumman • Baseline automated PCR / Immunoassay • Spiral development of advanced isothermal assays • USG • Genomic BarCodes, Fast, No amplification • Single reagent set for all pathogens Diversify Scientific Challenge • Broadband Approaches for Sequence Diversity • SAIC • Highly multiplexed amplification • CGE & microarray readout Dr Steven Buchsbaum, NDIA Homeland Security Symposium

13. BAND TTA-1 USGenomics Broadband Approach for Detection Dr Steven Buchsbaum, NDIA Homeland Security Symposium

14. BAND TTA-1 MFSI Technical Approach • Flow-through process • archiving, sample preparation and detection • Dried-down reagents and stable wet chemistries • Two-mode wireless connectivity • Sonication lysis and pillar chip nucleic acid purification • Flow-through PCR and immunoassay detectors • Embedded pumps and valves Dr Steven Buchsbaum, NDIA Homeland Security Symposium

15. BAND TTA-1 Northrop GrummanBroadband Approaches for Detection • Common integrated weatherproof chassis containing: • Sample aerosol collection on a dry surface • Dry surface serves as sample archive • Common HVAC, communications and control systems • Initial deployment of mature automated identifiers • PCR • Immunoassay • Future insertion of advanced identifiers • Fast isothermal reactions • Microfluidics to reduce consumable costs • MEMs based transduction • Advanced amplification and orthogonal approaches reduce FAR Dr Steven Buchsbaum, NDIA Homeland Security Symposium

16. BAND TTA-1 A • SAIC/GHC/Ibis BAND System Exploits Many Genome Identification Sites with Two Different Technologies D C 1 2 3 4 5 6 • • De-multiplex by sequence, using DNA microarray Amplify many sites in the genome in one reaction 1 4 3 2 2 1 2 3 1 2 6 3 4 2 6 3 2 6 4 1 6 6 6 4 3 4 1 1 6 4 3 5 1 3 4 5 6 B 2 3 2 2 Each genome yields a unique pattern Label them with fluorescent dye 6 1 2 4 3 4 6 1 6 2 4 6 3 1 2 4 De-multiplex by length, using electrophoresis Broadband Approach for Detection Dr Steven Buchsbaum, NDIA Homeland Security Symposium

17. RABIS TTA-2 Rapid Automated Biological Identification System (RABIS) TTA-2 • Rapid Automated Biological Identification System (RABIS) • Detect-to-Protect Biological Surveillance Sensor System • Enable New Paradigms in Biodefense • Building Protection Architecture • Selected Outdoor Event Coverage • Detect-to-Protect Requires • Very Fast Response Time (< 2 Minutes) • Very Low False Alarm Rates • Broad and Sensitive Threat Coverage • TTA-2 Will Require Significant Innovation • Extraordinarily Challenging Technical Goals Dr Steven Buchsbaum, NDIA Homeland Security Symposium

18. RABIS TTA-2 TTA-2 Goals – Performance & Cost Targets • Continuous, Fully Autonomous Operation with 2 Minute or Shorter Sample Intervals Including Latency • ~250K Samples per Year • Broad Agent Coverage > 20 Agents • Spore, Vegetative Cell, Toxin, DNA Virus, RNA Virus • Limit of Detection (LOD) of 100 Organisms per Liter of Air • LOD of 0.05 nanograms per Liter of Air for Toxins • System False Alarm Rate of No More than Once per Month • Goal to Reduce System False Alarm Rate < 1 Year • RABIS Unit Acquisition Cost of $50K per Unit or Less • Assume Quantities of 100s • RABIS Operating Costs per Unit of $20K per Year or Less • Inclusive of all Costs: Consumables, Maintenance, Spare Parts, etc. Dr Steven Buchsbaum, NDIA Homeland Security Symposium

19. RABIS TTA-2 Key Technical Challenges • Combined Goals of Short Response Time with High Selectivity • Likely to Require Significant Innovation • Short Sample Interval Exacerbates Technical Challenges to Achieve Low System False Alarm Rates • Approximately 250K Threat-Multiplexed Tests per Year • Short Sample Interval Exacerbates Technical Challenges to Achieve Low Cost of Ownership • Multiplexed (or Broadband) Single Interval Test Cost of ~ $0.08 Dr Steven Buchsbaum, NDIA Homeland Security Symposium

20. RABIS TTA-2 Lab Prototype EvaluationField Prototype CDR Feasibility Decision PDR Feasibility Analysis Scientific Development – PDR Risk Reduction Engineering for CDR Key Decision Points Field Prototype Production & Testing Notional Program Schedule Bidders are encouraged to provide accelerated schedule if possible FY04 FY05 FY06 FY07 FY08 TTA-2 Phase III I-A Phase I-B Phase II • Proposal includes: • Preliminary Conceptual Design • Preliminary Estimates of Performance Relative to Goals • Work Plan for Both Phase I-A & Phase I-B • Feasability Decision Criteria for Continuation from Phase I-A to Phase I-B • Phase I-B as Executable Option • Key Issues for Phase I Execution • Test & Validation plan • Requested GFE • Phase I Completion: • Detailed PDR for both Lab & Field Prototype • Validated Performance Predictions for Lab and Field Prototype • Work Plan for Phase II • Phase II Completion: • CDR for Field Protoype • Work Plan for Phase III • Detailed Cost Estimates for Manufacture • Plan for Commercialization • Phase I-A Completion: • Detailed evaluation of RABIS feasability • Updated Phase I-B work plan Dr Steven Buchsbaum, NDIA Homeland Security Symposium

21. Key Characteristics Nearly instantaneous detection Extremely low acquisition costs Extremely low operation costs Design Trade Characteristics LOD as a function of FAR Key Characteristics Nearly instantaneous trigger detection Moderately low acquisition costs Extremely low operation costs Moderately fast confirmation step Extremely low false alarm rate for confirmation step Design Trade Characteristics LOD as a function of trigger FAR and number of confirmation tests (cost of operation). Possible Future HSARPA Directions Development of Family of Detection Technologies to Enable Detect-to-Protect Trigger for Rapid Automated Detection Trigger and Confirmation Detection System Dr Steven Buchsbaum, NDIA Homeland Security Symposium

22. BIAD BAA04-03 BIAD Program Technical Topic Areas • TTA-1 Extension of Baseline Protein and Nucleic Acid Assays • TTA-2 Assays for New, Emerging, or Engineered Threats • TTA-3 Bioinformatics Tools • TTA-4 Assays and Tools for Forensic Analysis • TTA-5 Methods to Characterize Extraction and Preparation Methods Dr Steven Buchsbaum, NDIA Homeland Security Symposium

23. BIAD BAA04-03 BAA04-03 BIAD Program Goals • Enabling future enhancements to existing detection systems • Enabling new types of detection systems • Supplementing our current family of confirmatory assays • Supplementing our current family of forensic assays • Creating next generation assays which are robust against novel and engineered threats • Creating new bioinformatics tools to enhance assay development • Characterizing and increasing sample extraction efficiencies Dr Steven Buchsbaum, NDIA Homeland Security Symposium

24. BIAD BAA04-03 Legend Phase I Phase II Phase III Schedule for BAA04-03 Bidders are encouraged to provide accelerated schedule if possible FY04 FY05 FY06 FY07 FY08 TTA-1 Assay formulation Assay Optimization Test & Eval. of Assays Transition to Baseline TTA-2 Concept & Strategy Development Assay Formulation Test & Eval. of Assays Demonstration Part I TTA-3 Evaluate Bioinformatics Tools New Tools Advocacy & Development Implement Tools Final Report TTA-4 Concept Development Test & Eval. of Assays Transition to Customer TTA-5 Method & Concept Development Method Test & Optimization Performance Analysis Final Report Re-open BAA TTA 1 - 5 Part II Dr Steven Buchsbaum, NDIA Homeland Security Symposium

25. For HSARPA R&D funding opportunities, please monitor: www.dhs.gov, www.hsarpasbir.com, www.hsarpabaa.com, and www.fedbizopps.gov Dr Steven Buchsbaum, NDIA Homeland Security Symposium

26. Dr Steven Buchsbaum, NDIA Homeland Security Symposium