Dr Steven Buchsbaum, NDIA Homeland Security Symposium
27 May 2004
U.S. Department of Homeland Security
Homeland Security Advanced Research Projects Agency
Biological Countermeasures NDIA Homeland Security Symposium
Dr Steven BuchsbaumProgram Manager, [email protected]
27 May 2004Dr 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
27 May 2004Dr 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
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 4
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
AnthraxAttack
NationalPharmaceutical
Stockpile
BioSensors
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 5
Detection Systems for Biological Countermeasures RA03-01
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
27 May 2004Dr 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
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 7
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
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 8
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)
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 9
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 Pfa in 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)
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 10
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
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 11
Notional Program Schedule
Phase ITTA-1TTA-1 Phase IIPDR
Phase IIILab Prototype EvaluationField Prototype CDR
FY06FY05FY04 FY08FY07
Scientific Development – PDR Risk Reduction
Engineering for CDR
Field Prototype Production & Testing
Key Decision Points
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
Performers are encouraged to accelerated schedules if possible!
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 12
Programmatic Strategy
Northrop Grumman • Baseline automated PCR / Immunoassay• Spiral development of advanced isothermal assays
MFSI• Next generation reusable microfluidic platform• Modular components - decreased size, increased
longevity, increased functionality
Nanolytics• Miniaturized assay volume by evaporative
concentration• Nanofluidics via electrowetting microactuation
IQuum• New tape encapsulated PCR• New assay concepts (padlock
probes for high multiplexing)
SAIC• Highly multiplexed
amplification• CGE & microarray
readout
USG• Genomic BarCodes, Fast, No
amplification• Single reagent set for all pathogens
Diversify Risk in Two
Dimensions
Diversify Risk in Two
Dimensions
Diversify Engineering Challenge Autonomous Multiplexed Micro-
fluidic PCR
Diversify Engineering Challenge Autonomous Multiplexed Micro-
fluidic PCR
Diversify Scientific Challenge Broadband Approaches for
Sequence Diversity
Diversify Scientific Challenge Broadband Approaches for
Sequence Diversity
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 13
© 2004 U.S. Genomics, Inc.
BAND Using Genomic Barcoding
Environmental Sample Taken
DNA Prepared & Tagged
Barcode Generated
Barcode Compared Against dBase
-5 0123456789 HPVC 18
HPVC 11
-4 -2 0 2 4012345
E. coli
B. anthracis strainX
B. anthracis strainY
S. aureusSample barcode
USGenomics Broadband Approach for Detection
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 14
MFSI Technical Approach
Air Collector
EluteNucleic Acids
Sonicate
PCR
Agitate
Add/mix 3 ml6 M GuSCN
Pillarchip
Prepare 10-ulaliquots
SampleAerosol
Archive 1 ml
EtOH
Air
Tris-Buffer
Waste
Add/mix
Collector
Sample Processing
NA Analysis
5 ml
4 ml
10-100 ul
Pillar chip with antibodies
Toxin Analysis 3 ml
1 ml
Reconstituted reagents
Add/mix
Command and control
(after 3 hours of collection)
• 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
Protective case that maintainsconstant internal temperature.
Aerosol collector inlet
Hardware and bulk reagents
Reusable Cartridge
Peristalticpumps
Archivedsamples
Sets ofantibodychips
PCRreactors
Dried-downreagents
Hydrated reagentsholding chambers
NA chipsSonicationchambers
Dockingstation forcartridge
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 15
Northrop GrummanBroadband Approaches for DetectionCommon 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
BAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 16
2
2
22
22
11 1
13
3 33
34
4
4
55
666
6
1 2 3 4 5 6 • •
Amplify many sites in the genome in
one reaction
De-multiplex by length, using electrophoresis
De-multiplex by sequence, using DNA microarray
Each genome yields a unique pattern
22
2
3
336
6
66 1
1
1 44
44
6 6633 4
4441
1 1
22 2
Label them with fluorescent dye
• SAIC/GHC/Ibis BAND System Exploits Many Genome Identification Sites with Two Different Technologies
A
B
6
C D
GCGC
Broadband Approach for DetectionBAND TTA-1
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 17
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
RABIS TTA-2
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 18
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.
RABIS TTA-2
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 19
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
RABIS TTA-2
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 20
Notional Program Schedule
FY06FY05FY04 FY08FY07
Feasibility Analysis
Scientific Development – PDR Risk Reduction
Engineering for CDR
Field Prototype Production & Testing
Key Decision Points
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
Bidders are encouraged to provide accelerated schedule if possible
TTA-2TTA-2 I-A Phase I-BFeasibility Decision
Phase IIPDR
Phase IIILab Prototype EvaluationField Prototype CDR
Phase I-A Completion:• Detailed evaluation of RABIS feasability• Updated Phase I-B work plan
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
RABIS TTA-2
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 21
Possible Future HSARPA Directions
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).
Development of Family of Detection Technologies to Enable Detect-to-Protect
Trigger for Rapid Automated Detection
Trigger and Confirmation Detection System
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 22
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
BIAD BAA04-03
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 23
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
BIAD BAA04-03
27 May 2004Dr Steven Buchsbaum, NDIA Homeland Security Symposium 24
Schedule for BAA04-03
FY08FY06FY05FY04 FY07
Par
t I DemonstrationConcept & Strategy Development Assay FormulationTTA-2 Test & Eval. of Assays
Concept Development Test & Eval. of AssaysTTA-4 Transition to Customer
Assay formulation Assay OptimizationTTA-1 Transition to BaselineTest & Eval. of Assays
Evaluate Bioinformatics Tools New Tools Advocacy & DevelopmentTTA-3 Implement Tools Final Report
Par
t II
Re-open BAA
Phase I Phase II Phase IIILegend
TTA 1 - 5
Method & Concept Development Method Test & OptimizationTTA-5 Performance Analysis Final Report
Bidders are encouraged to provide accelerated schedule if possible
BIAD BAA04-03
27 May 2004Dr 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
27 May 2004
Top Related