U'S' Department of Homeland Security

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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_at_dhs.gov
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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

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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

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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
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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

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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

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TTA-1 Goals Performance Targets
BAND TTA-1

• Continuous, Fully Autonomous Operation with 3
  Hour Sample Intervals and 1 Hour Latency (2920
  Samples per Year)
• Broad Agent Coverage gt 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

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TTA-1 Goals Cost System Requirements
BAND TTA-1

• 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)

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Key Technical Challenges
BAND TTA-1

• Very High Sensitivity in Cluttered Background
• 100 Organisms in a Backgound of gt 18,000 liters
  of air
• Extending Breadth of Threat Coverage (gt20)
• 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)

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Requirements Additional Thoughts
BAND TTA-1

• 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 105 in DoD Speak
• Toxin Detection
• Drives Complexity and Cost
• Possibly Detectable from Residual DNA
• Cost Targets Extremely Aggressive at this
  Performance

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Notional Program Schedule
BAND TTA-1
FY06
FY05
FY04
FY08
FY07
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
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Programmatic Strategy
BAND TTA-1

• 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

• MFSI
• Next generation reusable microfluidic platform
• Modular components - decreased size, increased
  longevity, increased functionality

Diversify Risk in Two Dimensions

• 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

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USGenomics Broadband Approach for Detection
BAND TTA-1
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MFSI Technical Approach
BAND TTA-1

• 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

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Northrop GrummanBroadband Approaches for
Detection
BAND TTA-1

• 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

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BAND TTA-1
Broadband Approach for Detection
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Rapid Automated Biological Identification System
(RABIS) TTA-2
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 (lt 2 Minutes)
• Very Low False Alarm Rates
• Broad and Sensitive Threat Coverage
• TTA-2 Will Require Significant Innovation
• Extraordinarily Challenging Technical Goals

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TTA-2 Goals Performance Cost Targets
RABIS TTA-2

• Continuous, Fully Autonomous Operation with 2
  Minute or Shorter Sample Intervals Including
  Latency
• 250K Samples per Year
• Broad Agent Coverage gt 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 lt 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.

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Key Technical Challenges
RABIS TTA-2

• 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

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Notional Program Schedule
RABIS TTA-2
Bidders are encouraged to provide accelerated
schedule if possible
FY06
FY05
FY04
FY08
FY07
TTA-2
I-A
Phase I-B
Phase II
Phase III

• 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

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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

• 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).

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BIAD Program Technical Topic Areas
BIAD BAA04-03

• 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

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BAA04-03 BIAD Program Goals
BIAD BAA04-03

• 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

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Schedule for BAA04-03
BIAD BAA04-03
Bidders are encouraged to provide accelerated
schedule if possible
FY08
FY06
FY05
FY04
FY07
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
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• For HSARPA RD funding opportunities, please
  monitor
• www.dhs.gov, www.hsarpasbir.com,
  www.hsarpabaa.com, and www.fedbizopps.gov

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