DARPA-BAA-12-33_IVN Dx_Final For Posting_15March12.pdf

Broad Agency Announcement

In vivo Nanoplatforms for Diagnostics (IVN:Dx)

Microsystems Technology Office (MTO)

DARPA-BAA-12-33

March 15, 2012

Table of Contents

Part I. Overview Information

Part II. Full Text of Announcement

Section I. FUNDING OPPORTUNITY

A. Background

B. Technical Areas of Interest

C. Program Metrics

Section II. AWARD INFORMATION

Section III. ELLIGIBILITY INFORMATION

A. Eligible Applicants

B. Procurement Integrity, Standards of Conduct, Ethical Considerations, and Organizational Conflicts of Interest

C. Cost Sharing/Matching

D. Other Eligibility Criteria

Section IV. APPLICATION AND SUBMISSION PACKAGE

A. Address to Request Application Package

B. Content and Form of Application Submission

Section V. APPLICATION REVIEW INFORMATION

A. Evaluation Criteria

B. Review and Selection Process

Section VI. AWARD ADMINISTRATION INFORMATION

A. Selection Notices

B. Administrative and National Policy Requirements

C. Reporting

D. Electronic Systems

Section VII. AGENCY CONTACTS

Section VIII. OTHER INFORMATION

A. Intellectual Property Procurement Contract Proposers

B. Non-Procurement Contract Proposers – Noncommercial and Commercial Items (Technical Data and Computer Software)

C. All Proposers – Patents

D. Other Transactions

Part I. Overview Information

Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Microsystems Technology Office (MTO)

Funding Announcement Type – Initial Broad Agency Announcement Funding Opportunity Number – DARPA-BAA-12-33 Opportunity Title – In vivo Nanosensors for Diagnostics (IVN:Dx) Catalog of Federal Domestic Assistance Numbers (CFDA) – 12.910 Research and Technology Development Dates o Posting Date March 15, 2012 o Proposal Abstract Due Date: April 18, 2012 at 3:00 PM Eastern Time o Proposal Due Date: June 28, 2012 at 3:00 PM Eastern Time

Concise description of the funding opportunity: The specific objective of the In vivo Nanoplatforms for Diagnostics (IVN:Dx) thrust of the In vivo Nanoplatforms (IVN) program is to develop biocompatible nanosensors that provide continuous, noninvasive, and highly accurate measurement of a variety of conditions and substances within the living tissue of animals, plants, and insects using non-toxic materials with limited immunogenicity. These sensors will permit qualitative and quantitative assessment over large concentration ranges of both small (e.g., glucose, lactate, and urea) and large molecules (e.g., proteins, oligonucleotides, infectious agents, and chemical/biological threat agents) in the organism and environment through optical, electronic, thermal or magnetic mechanisms.

Anticipated individual awards – Multiple awards are anticipated.

Anticipated available funding types – 6.2 and 6.3 Anticipated commencement of contract negotiations – October 1, 2012 Types of instruments that may be awarded – Procurement contract, grant, cooperative agreement or other transaction.

Any cost sharing requirements – No direct requirement in this BAA

PROPOSERS ARE CAUTIONED THAT EVALUATION RATINGS MAY BE LOWERED

AND/OR PROPOSALS REJECTED IF ALL PROPOSAL PREPARATION AND/OR

SUBMITTAL INSTRUCTIONS LISTED HEREIN ARE NOT FOLLOWED.

Agency contact

Dr. Timothy Broderick, Program Manager

DARPA/MTO

ATTN: DARPA-BAA-12-33

DARPA-BAA-12-33@darpa.mil

Part II. Full Text of Announcement

Section I. FUNDING OPPORTUNITY

The Defense Advanced Research Projects Agency (DARPA) often selects its research efforts through the Broad Agency Announcement (BAA) process. The BAA will appear on the FedBizOpps website (http://www.fedbizopps.gov/) and the Grants.gov website (http://www.grants.gov/). The following information is for those wishing to respond to the BAA.

The goal of the In vivo Nanoplatforms (IVN) program is to develop radically new classes of adaptable nanoparticles for persistent, distributed, unobtrusive physiologic and environmental sensing as well as the treatment of physiologic abnormalities, illness and infectious disease. Initially, DARPA is soliciting proposals to develop the nanoscale systems necessary for in vivo sensing and physiologic monitoring of warfighters as components of the In vivo Nanoplatforms for Diagnostics (IVN:Dx) thrust of the IVN program. A subsequent companion solicitation for the In vivo Nanoplatforms for Therapeutics (IVN:Tx) thrust is expected to be released in the first quarter of the government fiscal year 2013 (FY13 begins October 1, 2012). In these solicitations, DARPA seeks proposals that address diagnostic (this BAA) and therapeutic (subsequent BAA) objectives that will enable a versatile, rapidly adaptable system to provide medical and operational support to the warfighter in any location. The development of standalone diagnostic and therapeutic technologies within each thrust is strongly encouraged to optimize the technologies, capabilities, and applications developed within the IVN program. While not specifically encouraged, proposals that develop integrated “theragnostic” platforms are not excluded. The following information and guidance included in this solicitation addresses only those technical areas of interest relevant to the diagnostic and disease surveillance objectives of the IVN:Dx thrust.

The interdisciplinary IVN:Dx program thrust envisioned by DARPA will develop and demonstrate the following: 1) implantable nanoplatforms using bio-compatible and non-toxic materials, 2) in vivo sensing of small and large molecules of biological interest, 3) multiplexed detection of analytes at clinically relevant concentrations, 4) external interrogation of the nanoplatform free from any implanted communications electronics, and 5) complete system demonstration in a large animal.

The resulting IVN:Dx sensing platform will need to provide long-term sensing capabilities for military-relevant analytes. Sensor read-out modality is a necessary component of the platform device and should be carefully considered with respect to parameters such as choice of tissue, analytes, repetitive non-contact signal acquisition, and signal-to-noise ratio. However, the primary objective of this thrust is to develop safe, biocompatible nanoparticles for in vivo multiplexed analyte sensing. Proposers are encouraged to focus on development of the implantable nanoparticles as opposed to development of read out hardware.

Literature suggests several technical approaches exist that may prove viable in meeting the challenging goals of the IVN:Dx thrust. Imperative to any new nanoplatform sensor concept is the overriding requirement to avoid harm to the host. The choice of size, shape and material to limit clearance by the reticuloendothelial system of the nanoparticles is an important design consideration, as is the selection of appropriate surface coatings that are non-fouling and biocompatible.

Although several such approaches are noted here, these should not be considered endorsements for the approach; proposers are specifically encouraged to submit the best solution to the problem. One potential approach is to use Surface Enhanced Raman Spectroscopy (SERS) nanoparticles within tissue to detect biologically relevant molecules at very low levels (e.g., femtomolar) whereby their optical response would be uniquely altered by analytes of interest. Related to this concept is the construction of a selective self-assembling monolayer (SAM) that has the ability to partition analytes of interest, thereby enhancing sensor specificity. Although a selective SAM has been demonstrated for glucose, each new analyte of interest will require a unique surface to exploit steric and energetic effects for enhanced selectivity. Mixed SAM coatings that include non-fouling components such as carboxybetaines could also improve sensor sensitivity and lifetime. Another potential optical approach uses “molecular beacons” that fluoresce upon binding to target analytes. Several researchers have demonstrated the use of background subtraction and ratiometric (or related) techniques to reduce obscurants while maintaining detector responsivity. The choice of wavelength is important to optimize tissue penetration and eye safety while limiting absorption by endogenous chromophores and water. These are a few potential approaches that could increase in vivo sensitivity, specificity, and lifetime of the sensor components, all of which are critical aspects of program success.

DARPA desires that performers will demonstrate an in vivo nanoplatform prototype at Technology Readiness Level (TRL) 5 by program end. The critical platform attributes are described below (see Table 1 under “Program Goals”). Performers shall include measurable platform performance metrics, and describe the test methodology, for as many attributes as possible based on the scope of the proposal and the best judgment of the team (see Table 2 “Relevant Attributes and Definitions”). The research and development program described below is expected to require the integration of multiple approaches and technologies across many basic and applied scientific disciplines (including but not limited to chemistry, molecular biology, theoretical and experimental engineering disciplines, biophysics, materials science, as well as clinical and laboratory medicine specialties). This program may require participation from multiple sectors of the scientific and technical community: academia, not-for-profit research institutes, and the private for-profit sector. The program may also require participation from organizations with expertise in system integration and device engineering.

This solicitation specifically calls for technologies that can be used in animals and ultimately in humans. Human use and testing, however, is specifically excluded from this solicitation. Clinical trials will not be funded under this program. Additionally, while DARPA envisions nanoplatforms that could be developed and used within diverse biologic systems, proposals to design sensors for use exclusively in plants or insects are discouraged.

A. Background

The leading cause of warfighter downtime is disease rather than battlefield injuries, as one might expect. The military has a compelling need to develop technologies that could dramatically improve soldier readiness, while also reducing healthcare costs and logistics burden. Current technologies and products for diagnosing disease are principally relegated to in vitro medical devices, which are often expensive, bulky, and fragile.

While there are some simple, inexpensive, and portable rapid diagnostic tests (RDTs), these too are in vitro devices and typically suffer from poor sensitivity and specificity;

they are almost always limited to the detection of a single analyte (or target). A diagnostic goal of this program is to develop a generalizable platform for in vivo sensing that removes the logistical burden of in vitro devices and provides continuous monitoring of warfighter physiology. Such a platform is not limited to single analyte detection, instead providing multiplexed monitoring in real time to the warfighter.

The IVN:Dx program thrust makes possible the opportunity for disruptive change to the traditional model for physiologic monitoring and healthcare delivery to the warfighter.

The first high-payoff application of in vivo nanosensor technology is in the early sensing and detection of biologic exposure, long before the warfighter is contagious or symptoms are present. Persistent widespread diagnostics and surveillance could have significant operational impact, given that disease and illness have historically had a more deleterious impact on unit readiness than combat causalities. For military special forces the practical realization of implantable nanosensors capable of monitoring multiple indicators of physiological state could be a truly disruptive innovation. For example, if an isolated special operator is exposed to an infectious agent or pushed beyond optimum performance levels, the nanosensors could detect physiological distress and the operator could take corrective action. With an appropriate array of therapeutic nanoparticles (to be developed under the subsequent BAA), the warfighter could immediately administer effective therapy.

The commercial world would also benefit from continuous physiologic monitoring technology. One might reasonably expect IVN:Dx to have the same impact within the civilian healthcare system given concomitant economies of scale obtained for the military. The glucometer market alone is forecasted to reach $6B by 2015 as the total U.S. population that is diabetic or prediabetic exceeds 100M. A new in vivo nanoplatform could enable monitoring of metabolic and infectious disease of national significance via measurement of analytes such as glucose, urea, lactate, and cytokines.

B. Technical Areas of Interest

DARPA is soliciting proposals for the IVN:Dx thrust of the new IVN program.

Collaborative efforts and teaming are encouraged (see Section III.D for additional information). These teams should be self-organized (DARPA will specifically not assist in this regard during the solicitation phase), complementary, and comprehensive to achieve the challenging goals of the program.

The focus of this solicitation is the development of biocompatible nanosensors that provide continuous, noninvasive, and highly accurate measurement of a variety of conditions and substances within the living tissue of animals, plants, and insects using non-toxic materials with limited immunogenicity. There are two primary areas of interest, Technical Area 1: Development of safe and biocompatible nanoplatforms; and Technical Area 2: Development of implantable in vivo diagnostic nanoplatforms. Proposals that include revolutionary approaches in both technical areas are strongly encouraged; ideally teams will propose both, but if a team proposes an exceptionally good idea for technical area one that could be generalized for a number of approaches to technical area two (and the other way around) DARPA would like to see the idea. Proposals should address the key issues in each individual technical area and clearly describe the compatibility of the methods as well as any integration challenges. All proposers are encouraged to consider their ability to attain eventual clinical diagnostic and operational implementation as well as Food and Drug Administration (FDA) regulatory compliance when developing proposed efforts.

Technical Area 1: Development of safe and biocompatible nanoplatforms

Current implantable materials are limited by toxicity and immunogenic response.

Implanted nanomaterials may be rapidly cleared by the reticuloendothelial system or foul due to nonspecific binding of biologic material on the surface depending on size, shape and coating. Performers shall focus on new approaches to particle material, sizing, shaping and coating to limit platform toxicity and increase biocompatibility. New approaches to accomplishing this task could include, but are not limited to, polymer coatings; surface modifying additives; and new methods for creating non-toxic nanomaterials of narrow size distribution and tailored shape. End of program goals will require no observable adverse effects from the nanoplatform, as well as inflammation and immunological panels that confirm biocompatibility.

Technical Area 2: Development of implantable in vivo diagnostic nanoplatforms

Laboratory demonstrations and the few commercially available in vivo sensing platforms are limited to single small analytes at high concentrations. These systems are ineffective for use in monitoring a panel of molecules, or any biologic molecule with mass > 1 kDa. The need for internal calibration to account for sensor drift also limits the use of these devices for extended periods. Performers will focus on novel methods for enhancing sensitivity and lifetime of in vivo nanoplatforms. New approaches to accomplishing this task could include but are not limited to: mixed SAM coatings that include analyte selective and non-fouling components; self-calibrating multianalyte sensors; fluorescent molecular beacons; oligonucleotide modification enabling tissue targeting and nuclease resistance; and analyte/signal amplification via enzymatic or catalytic mechanisms. End of program goals will require 95% accuracy of multiple analytes over a large dynamic range and internal standards that enable an in vivo operating time of 12 months or greater.

C. Program Metrics

Proposed efforts should not exceed 42 months. Proposers should address all of the milestones and metrics listed below (Table 1) to which they are proposing. Continuation of funding over the 42-month period will be contingent on technical progress and availability of funding. Initial research should focus on the development of novel nanosensing technologies and techniques; after which the effort should focus on the refinement of these technologies and techniques needed to achieve targeted diagnostic goals. Specifically excluded are proposals that only incrementally advance the current state of practice, as well as those that propose clinical studies for regulatory submissions or any form of human use protocols. Proposals that aim to integrate existing technologies will be considered non-responsive.

Proposers should identify project-specific milestones that facilitate tracking of the research progress towards the overall program goals. Proposers should plan for the testing and evaluation of their components and/or constructs at each milestone and indicate the milestones and associated cost on the program schedule (Gantt chart).

Proposers may select analytes of interest within the broad biomarker categories of physiologic monitoring, infectious disease diagnostics/surveillance, and CBRN exposure.

Proposers are encouraged to select analytes that demonstrate platform capability to detect small molecules, proteins and nucleic acids across wide and clinically relevant concentrations. Sensing platforms developed in response to this solicitation should be flexible and have the ability to simultaneously test for the presence or absence of multiple analytes from the same sample.

Proposers are encouraged to select a representative application to demonstrate the operational and medical relevance of their sensing technology. Proposers should define the application, target analytes, and the organism/tissue/cell in which they will be detected. The detection of multiple biomarkers (e.g., threat agent exposure, exogenous/pathogen, or endogenous/host-response) could provide the ability to detect pre-symptomatic infectious disease in military populations as well as address diagnostic specificity for a single disease in an individual warfighter. In vitro analytical performance of the sensor could be developed using model systems that mimic in vivo environments (e.g., spiked blood, interstitial fluids, cellular systems). Sensor biocompatibility and lifetime should initially be demonstrated in vitro in representative tissue/cells.

Subsequent milestone demonstrations should build on in vitro successes and be conducted in small and large animals. The animal and tissue must be relevant to the selected analytes and application. Platform scalability and flexibility are encouraged for widespread application.

THIS SECTION INTENTIONALLY LEFT BLANK; Table 1. On following page.

Common key elements are summarized below in Table 1.

TABLE 1. SUMMARY OF MILESTONES

MILESTONE DATE

(after award)

DESCRIPTION METRICS

Demonstration #1 12th month

Safely demonstrate in vivo nanoplatform sensor in a living tissue or biologic fluid with 1 analyte detection

Proposer specified limit of detection, dynamic range, and response time

75% AUC

1 month lifetime

Demonstration #2 24th month

Safely demonstrate nanoplatform sensor in a small animal with 2 analyte detection

Proposer specified limit of detection, dynamic range, and response time

Proposed specified inflammation and immunological panels

90% AUC

6 month lifetime

Demonstration #3 42nd month

Safely demonstrate nanoplatform sensor in a large animal with 5 analyte detection

Proposer specified limit of detection, dynamic range, and response time

Proposed specified inflammation and immunological panels

95% AUC

12 month lifetime

Goals for limit of detection, dynamic range, and response time should be included in each proposed milestone demonstration. Proposers should note that the metrics of limit of detection, dynamic range, and response time are highly dependent on the analyte of interest and the compartment in which the analyte is measured (e.g., tissue, fluid, cell, intracellular location). As such, proposers should suggest limits of detection, dynamic range, and response times for specific analytes in compartments that are clinically relevant and have high predictive value at a pre-symptomatic stage of disease progression. Proposers should also specify goals and methods for evaluating the inflammatory and immunological response at demonstrations 2 and 3. As with all other metrics, ample supporting information should be provided to justify the claims in predicted performance of the nanoplatform.

As an example of metrics, consider the pathogenesis of Bacillus anthracis (anthrax). This process begins with endospores introduced into the skin, lungs or intestines. The endospores are phagocytosed by macrophages and germinate into vegetative bacteria.

The bacteria multiply in the lymphatic system, and eventually enter the bloodstream to reach concentrations of 107 to 108 organisms per milliliter of blood. If untreated, sepsis and death occur within days to weeks post-exposure. Several biomarkers are present during disease progression, such as cytokines at ng/mL concentrations in macrophage and dendritic cells. However, this response is not specific to anthrax exposure and current methods to identify infection are often insensitive and/or have limited dynamic range. A preferred method of detection would be capable of identifying a pathogen-induced host response at low concentration levels in specific compartments prior to systemic release into the bloodstream. Potential strategies for in vivo monitoring could include, but are not limited to, a multiplexed intradermal tattoo that interrogates interstitial fluid or the cytosol of phagocytes to detect low levels of anthrax related cytokines, proteins and oligonucleotides. The proposed technology development could be justified by the operational and medical impact associated with the detection of specific analytes, in specific tissue, at specific times post anthrax exposure. Proposals would include limits of detection, dynamic range, and response time metrics for each of the three demonstrations with appropriate increases in targeted values at each stage.

As another example, a nanoplatform could interrogate central nervous system biomarkers, such as II-spectrin breakdown products (SBDP), in the cerebrospinal fluid (CSF) to diagnose traumatic brain injury. Research has shown that cerebrospinal fluid is transported with the olfactory nerve across the cribriform plate into extracranial lymphatics within the nasal mucosa. Nanoparticles could be functionalized for uptake and persistence in nasal olfactory or mucosal cells. With traumatic brain injury, SBDP would increase in the CSF and could be associated with an increased signal from optically interrogated nanosensors. Design considerations for the nanoplatform would include toxicity, biocompatibility, dwell time within target tissue, analytical sensitivity (at least pM limit of detection required in the case of SBDP), response time and specificity.

The above examples are illustrative and should not bias proposers towards specific technology, tissue, analyte, or application.

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TABLE 2. RELEVANT ATTRIBUTES AND DEFINITIONS

ATTRIBUTE DIMENSION DEFINITION

Analytical Sensitivity copies/mL

The ability of a test to detect a certain level of concentration of an analyte or target of interest. Not to be confused with “clinical sensitivity.” Also referred to as the limit-of-detection (LOD).

Area Under the Curve (AUC) %

This is the total area under the receiver operating characteristic curve (see below ROC definition); it is the mathematical definition of clinical accuracy of a dichotomous test. A perfect ROC curve would be “L” shaped and have an area of 1.0 (or 100%). The proverbial “coin toss” is a diagonal and has an area of 0.5 (or 50-50 chance).

Clinical Sensitivity %

Test positivity in disease; the true positive fraction;

ability of a test to correctly identify disease at a particular decision threshold. It tells us something about the relative frequency of “false negative” results from a given diagnostic test. This term is often confused with or misused as synonymous with “analytical sensitivity” or “limit-of-detection.”

Sometimes referred to as “diagnostic sensitivity.”

Dynamic Range logs

The range of analyte concentration over which the detector is capable of providing an accurate quantitative measure within a certain statistical confidence.

Multiplex Level # The ability to simultaneously test for the presence or absence of multiple analytes from the same sample.

Operational Lifetime days

Duration of the system without any downtime.

Sensor performance (e.g., sensitivity, specificity) must be maintained during the operational lifetime.

There should be no observable adverse effects.

Receiver Operating Characteristic (ROC) Curve

N/A

A graphical description of test performance representing the relationship between the two adversarial variables of clinical sensitivity and specificity. Clinical accuracy of the dichotomous test is therefore displayed for the entire spectrum of decision levels.

Response Time minutes A time interval that encompasses the entire testing process to obtain an analytical result.

Section II. AWARD INFORMATION

Multiple awards are anticipated. The amount of resources made available under this BAA will depend on the quality of the proposals received and the availability of funds.

The Government reserves the right to select for negotiation all, some, one, or none of the proposals received in response to this solicitation, and to make awards without discussions with proposers. The Government also reserves the right to conduct discussions if it is later determined to be necessary. If warranted, portions of resulting awards may be segregated into pre-priced options. Additionally, DARPA reserves the right to accept proposals in their entirety or to select only portions of proposals for award.

In the event that DARPA desires to award only portions of a proposal, negotiations may be opened with that proposer. The Government reserves the right to fund proposals in phases with options for continued work at the end of one or more of the phases.

Awards under this BAA will be made to proposers on the basis of the evaluation criteria listed below (see section labeled “Application Review Information”, Sec. V.), and program balance to provide overall value to the Government. Proposals identified for negotiation may result in a procurement contract, grant, cooperative agreement, or other transaction depending upon the nature of the work proposed, the required degree of interaction between parties, and other factors. The Government reserves the right to request any additional, necessary documentation once it makes the award instrument determination. Such additional information may include but is not limited to Representations and Certifications. The Government reserves the right to remove proposers from award consideration should the parties fail to reach agreement on award terms, conditions and cost/price within a reasonable time or the proposer fails to timely provide requested additional information.

As of the date of publication of this BAA, DARPA expects to fund efforts with 6.2 and

6.3 dollars. It is possible that responses to Technical Area 1 could be considered ‘fundamental research’ i.e., basic and applied research in science and engineering, the results of which ordinarily are published and shared broadly within the scientific community, as distinguished from proprietary research and from industrial development, design, production, and product utilization the results of which ordinarily are restricted for proprietary or national security reasons. Technical Area 2 would not be fundamental research. DARPA will do its best to provide the ideal type of funding to each performer but is constrained by availability of funds. Therefore, DARPA anticipates restrictions on the resultant research. Notwithstanding this statement of expectation, DARPA recognizes that proposed research solutions could be of either a fundamental or restricted nature.

Proposers should indicate in their proposal whether they believe the nature of the research included in their proposal is fundamental or restricted, with the understanding that in all cases, the DARPA selected contracting officer shall have sole discretion to select award instrument type and to negotiate all instrument provisions with selectees.

See Section VI.B.4 for further information on fundamental, non-fundamental and restricted research.

Section III. ELLIGIBILITY INFORMATION

A. Eligible Applicants

All responsible sources capable of satisfying the Government's needs may submit a proposal that shall be considered by DARPA. Historically Black Colleges and Universities (HBCUs), Small Businesses, Small Disadvantaged Businesses and Minority Institutions (MIs) are encouraged to submit proposals and join others in submitting proposals; however, no portion of this announcement will be set aside for these organizations’ participation due to the impracticality of reserving discrete or severable areas of this research for exclusive competition among these entities.

Federally Funded Research and Development Centers (FFRDCs) and Government entities (Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they address the following conditions. FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector AND must also provide a letter on letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to government solicitations and compete with industry, and compliance with the associated FFRDC sponsor agreement and terms and conditions. This information is required for FFRDCs proposing to be prime or subcontractors. Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority (as well as, where relevant, contractual authority) establishing their ability to propose to Government solicitations. At the present time, DARPA does not consider 15 U.S.C. 3710a to be sufficient legal authority to show eligibility. While 10 U.S.C. 2539b may be the appropriate statutory starting point for some entities, specific supporting regulatory guidance, together with evidence of agency approval, will still be required to fully establish eligibility. DARPA will consider eligibility submissions on a case-by-case basis; however, the burden to prove eligibility for all team members rests solely with the Proposer.

B. Procurement Integrity, Standards of Conduct, Ethical Considerations, and Organizational Conflicts of Interest

Current federal employees are prohibited from participating in particular matters involving conflicting financial, employment, and representational interests (18 USC 203, 205, and 208). The DARPA Program Manager for this BAA is Dr. Timothy Broderick.

Once the proposals have been received, and prior to the start of proposal evaluations, the Government will assess potential conflicts of interest and will promptly notify the Proposer if any appear to exist. (Please note, the Government assessment does NOT affect, offset, or mitigate the Proposer’s own duty to give full notice and planned mitigation for all potential organizational conflicts, as discussed below.)

Without prior approval or a waiver from the DARPA Director, in accordance with FAR 9.503, a Contractor cannot simultaneously provide scientific, engineering, technical assistance (SETA) or similar support and also be a technical performer. Therefore, all Proposers as well as proposed subcontractors and consultants must affirm whether they

(their organizations and individual team members) are providing SETA or similar support to any DARPA technical office(s) through an active contract or subcontract. All affirmations must state which office(s) the Proposer, subcontractor, consultant, or individual supports and identify the prime contract number(s). Affirmations shall be furnished at the time of proposal submission. All facts relevant to the existence or potential existence of organizational conflicts of interest (FAR 9.5) must be disclosed.

The disclosure must include a description of the action the Proposer has taken or proposes to take to avoid, neutralize, or mitigate such conflict. If in the sole opinion of the Government after full consideration of the circumstances, a proposal fails to fully disclose potential conflicts of interest and/or any identified conflict situation cannot be effectively mitigated, the proposal will be rejected without technical evaluation and withdrawn from further consideration for award.

If a prospective Proposer believes that any conflict of interest exists or may exist (whether organizational or otherwise) or has questions on what constitutes a conflict of interest, the Proposer should promptly raise the issue with DARPA by sending his/her contact information and a summary of the potential conflict to the BAA mailbox (DARPA-BAA-12-33@darpa.mil) before time and effort are expended in preparing a proposal and mitigation plan.

C. Cost Sharing/Matching

Cost sharing is not required for this particular program; however, cost sharing will be carefully considered where there is an applicable statutory condition relating to the selected funding instrument (e.g., for any Other Transactions under the authority of 10 U.S.C. § 2371). Cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

D. Other Eligibility Criteria

Collaborative Efforts

Collaborative efforts/teaming are encouraged. A teaming website, http://teaming.sysplan.com/BAA-12-33/, has been established to facilitate the formation of teaming arrangements between interested parties. Specific content, communications, networking, and team formation are the sole responsibility of the participants. Neither DARPA nor the Department of Defense (DOD) endorses the destination web site or the information and organizations contained therein, nor does DARPA or the DOD exercise any responsibility at the destination. This website is provided consistent with the stated purpose of this BAA.

Section IV. APPLICATION AND SUBMISSION PACKAGE

A. Address to Request Application Package

This solicitation contains all information required to submit a proposal. No additional forms, kits, or other materials are needed. This notice constitutes the total BAA. No additional information is available, nor will a formal Request for Proposal (RFP) or additional solicitation regarding this announcement be issued. Requests for same will be disregarded.

B. Content and Form of Application Submission

1. Security and Proprietary Issues

NOTE: If proposals are classified, the proposals must indicate the classification level of not only the proposal itself, but also the anticipated award document classification level.

The Government anticipates proposals submitted under this BAA will be unclassified.

However, if a proposal is submitted as “Classified National Security Information” as defined by Executive Order 13526, then the information must be marked and protected as though classified at the appropriate classification level and then submitted to DARPA for a final classification determination.

Security classification guidance via a DD Form 254, “DoD Contract Security Classification Specification,” will not be provided at this time, since DARPA is soliciting ideas only. After reviewing the incoming proposals, if a determination is made that the award instrument may result in access to classified information, a DD Form 254 will be issued and attached as part of the award.

Proposers choosing to submit a classified proposal from other classified sources must first receive permission from the respective Original Classification Authority in order to use their information in replying to this BAA. Applicable classification guide(s) should also be submitted to ensure the proposal is protected at the appropriate classification level.

Although the Government anticipates proposals submitted under this BAA will be unclassified, classified submissions shall be appropriately and conspicuously marked with the proposed classification level and declassification date. Submissions requiring DARPA to make a final classification determination shall be marked as follows:

CLASSIFICATION DETERMINATION PENDING. Protect as though classified (insert the recommended classification level: (e.g., Top Secret, Secret or Confidential)

Classified submissions shall be in accordance with the following guidance:

Confidential and Secret Collateral Information: Use classification and marking guidance provided by previously issued security classification guides, the Information Security Regulation (DoD Manual 5200.01, Volume 1-4, dated 24 February 2012), and the National Industrial Security Program Operating Manual (DoD 5220.22-M) when marking and transmitting information previously classified by another Original Classification Authority. Classified information at the Confidential and Secret level may be submitted via ONE of the two following methods:

1. Hand-carried by an appropriately cleared and authorized courier to the DARPA CDR. Prior to traveling, the courier shall contact the DARPA CDR at 703-526-4052 to coordinate arrival and delivery.

OR

2. Mailed via appropriate U.S. Postal Service methods (e.g., (USPS) Registered Mail or USPS Express Mail). All classified information will be enclosed in opaque inner and outer covers and double wrapped. The inner envelope shall be sealed and plainly marked with the assigned classification and addresses of both sender and addressee.

The inner envelope shall be addressed to:

Defense Advanced Research Projects Agency

ATTN: (MTO)

Reference: (DARPA-BAA-12-33) 675 North Randolph Street

Arlington, VA 22203-2114

The outer envelope shall be sealed with no identification as to the classification of its contents and addressed to:

Defense Advanced Research Projects Agency Security & Intelligence Directorate, Attn: CDR 675 North Randolph Street

Arlington, VA 22203-2114

All Top Secret materials: Top Secret information should be hand carried by an appropriately cleared and authorized courier to the DARPA CDR. Prior to traveling, the courier shall contact the DARPA CDR at 703-526-4052 to coordinate arrival and delivery.

Special Access Program (SAP) Information: SAP information must be transmitted via approved methods. Prior to transmitting SAP information, contact the DARPA SAPCO at 703-526-4052 for instructions.

Sensitive Compartmented Information (SCI): SCI must be transmitted via approved methods. Prior to transmitting SCI, contact the DARPA Special Security Office (SSO) at 703-526-4052 for instructions.

Proprietary Data: All proposals containing proprietary data should have the cover page and each page containing proprietary data clearly marked as containing proprietary data. It is the Proposer’s responsibility to clearly define to the Government what is considered proprietary data.

Proposers must have existing and in-place prior to execution of an award, approved capabilities (personnel and facilities) to perform research and development at the classification level they propose. It is the policy of DARPA to treat all proposals as competitive information, and to disclose their contents only for the purpose of evaluation. Proposals will not be returned. The original of each proposal received will be retained at DARPA and all other non-required copies destroyed. A certification of destruction may be requested, provided the formal request is received at this office within 5 days after unsuccessful notification.

For All Proposers:

All administrative correspondence and questions on this solicitation, including requests for information on how to submit an abstract or full proposal to this BAA, should be directed to the administrative address below; e-mail is preferred. DARPA-BAA-12- 33@darpa.mil. DARPA intends to use electronic mail for correspondence regarding DARPA-BAA-12-33. Abstracts will not be submitted by fax or e-mail; any so sent will be disregarded. DARPA encourages use of the Internet for retrieving the BAA and any other related information that may subsequently be provided.

2. Abstract Submission Information

Proposers are strongly encouraged to submit a proposal abstract in advance of a full proposal. This informal procedure is intended to minimize unnecessary effort in proposal preparation and review; no funding will be awarded for proposal abstract submissions.

The time and date for submission of abstracts is specified in Section 6 (page 28) below.

DARPA will acknowledge receipt of the submission and assign a control number that should be used in all further correspondence regarding the abstract.

Proposal abstracts sent in response to DARPA-BAA-12-33 shall be submitted through T-

FIMS. DO NOT SUBMIT PROPOSAL ABSTRACTS TO GRANTS.GOV OR VIA

MAIL. See http://baat.darpa.mil for more information on how to request an account, upload proposal abstracts, and use the T-FIMS tool. Because proposers using T-FIMS may encounter heavy traffic on the web server, and T-FIMS requires a registration and certificate installation for all proposers, proposers should not wait until the day the proposal abstract is due to create an account in T-FIMS and submit the proposal.

Upon review of the proposal abstract, DARPA will provide written feedback on the likelihood of a full proposal being selected and the time and date for submission of a full proposal, which may differ from the originally published date below.

3. Abstract Format

Abstracts are strongly encouraged in advance of full proposals in order to provide potential proposers with a rapid response to minimize unnecessary effort. Abstracts should follow the same general format as described for Volume I under PROPOSAL FORMAT (see below), but include ONLY Sections I and II with significant focus on technical approach, key personnel, program metrics, and milestones. Abstracts should include enough detail to provide a representative overview of the proposed effort. The cover sheet should be clearly marked “ABSTRACT” and the total length should not exceed 10 pages, excluding cover page. All pages shall be printed on 8-1/2 by 11 inch paper with type not smaller than 12 point. Smaller font may be used for figures, tables and charts. The page limitation for abstracts includes all figures, tables, and charts. No formal transmittal letter is required for proposal abstracts. All abstracts must be written in English.

DARPA will respond to abstracts with a statement as to whether DARPA is interested in the idea. DARPA will attempt to reply to abstracts via letter within thirty (30) calendar days of receipt. Should a proposer be discouraged from submitting a full proposal, the letter must contain feedback for the proposer regarding the rationale for the decision not to recommend a full proposal be submitted. Abstracts will be reviewed in the order they are received. Early submissions of abstracts and full proposals are strongly encouraged because selections may be made at any time during the period of solicitation. Regardless of DARPA’s response to an abstract, proposers may submit a full proposal. DARPA will review all full proposals submitted using the published evaluation criteria and without regard to any comments resulting from the review of an abstract.

4. Proposal Submission Information

Proposers are required to submit proposals by the time and date specified in the BAA in order to be considered during selections. Proposals shall not be submitted by fax or e-mail; any so sent will be disregarded. Proposals received after the date and time specified in the BAA will be considered late, and as such, will not be evaluated.

The typical proposal should express a consolidated effort in support of one or more related technical concepts or ideas. Disjointed efforts should not be included into a single proposal.

Restrictive notices notwithstanding, proposals may be handled, for administrative purposes only, by a support contractor. This support contractor is prohibited from competition in DARPA technical research and is bound by appropriate nondisclosure requirements.

Proposals not meeting the format described in this BAA may not be reviewed.

For Proposer’s Requesting a Contract or Other Transaction Award Instrument

Proposals sent in response to DARPA-BAA-12-33 must be submitted through T-FIMS (not including those who require a Grant). See http://baat.darpa.mil for more information on how to request an account, upload proposals, and use the T-FIMS tool. Because proposers using T-FIMS may encounter heavy traffic on the web server, and T-FIMS requires a registration and certificate installation for all proposers, proposers should not wait until the day the proposal is due to create an account in T-FIMS and submit the proposal.

For Proposers Requesting an Assistance Instrument (Grant or Cooperative Agreement):

Grant or cooperative agreement proposals may only be submitted to DARPA through Grants.gov or in hard-copy. Grant or cooperative agreement proposals will not be submitted through any other means (including T-FIMS and other comparable systems). If proposers intend to use Grants.gov as their means of submission, then they must submit their entire proposal through Grants.gov; applications cannot be submitted in part to Grants.gov and in part as a hard-copy. Proposers using the Grants.gov APPLY do not submit paper proposals in addition to the Grants.gov APPLY electronic submission.

Proposers must complete the following steps in the order listed below before submitting proposals on Grants.gov (these steps are also detailed at www.grants.gov/applicants/get_registered.jsp):

Proposers must obtain a DUNS number Proposers must register their organization in the Central Contractor Registration

(CCR): https://www.bpn.gov/ccr/default.aspx Proposers must register the Authorized Organization Representative (AOR) in

Grants.gov Proposers must have the organization’s E-BIZ point of contact authorize the AOR to submit applications.

Once Grants.gov has received a proposal submission, Grants.gov will send two email messages to advise proposers as to whether or not their proposals have been validated or rejected by the system; IT MAY TAKE UP TO TWO DAYS TO RECEIVE THESE EMAILS. The first email will confirm receipt of the proposal by the Grants.gov system;

this email only confirms receipt, not acceptance, of the proposal. The second will indicate that the application has been successfully validated by the system prior to transmission to the grantor agency or has been rejected due to errors. If the proposal is validated, then the proposer has successfully submitted their proposal. If the proposal is rejected, the proposer will have to resubmit their proposal. Once the proposal is retrieved by DARPA, the proposer will receive a third email from Grants.gov. To avoid missing deadlines, proposers should submit their proposals in advance of the final proposal due date with sufficient time to receive confirmations and correct any errors in the submission process through Grants.gov. For more information on submitting proposals to Grants.gov, visit the Grants.gov submissions page at: http://grants.gov/applicants/apply_for_grants.jsp.

Proposers electing to submit grant or cooperative agreement proposals via grants.gov must complete the SF 424 R&R form (Application for Federal Assistance, Research and Related) and the SF-LLL (if required). Please use the Attachments Form and upload, as two separate documents, Volume I, Technical and Management Proposal and Volume II, the Cost Proposal, as well as any other documents require by the BAA (i.e., subcontract proposals). No other Grants.gov forms are required. Please note that Grants.gov does not accept zipped or encrypted documents uploaded at attachments. Please follow the document made available on grants.gov as part of the solicitation entitled “Instructions for Using Grants.gov to Apply for a Grant or Agreement from DARPA (Short Form),” dated 20 October 2011, for more information.

If submitting hard-copy, an original and (4) copies of the proposal and (4) electronic copies of the proposal on a CD-ROM shall be submitted to DARPA/MTO, 675 North Randolph Street, Arlington, VA 22203-2114 (Attn: DARPA-BAA-12-33) no later than time and date specified in Section IV.7 Submission Dates and Times.

Technical support for Grants.gov submissions may be reached at 1-800-518-4726 or support@grants.gov.

5. Full Proposal Format

All full proposals must be in the format given below. Nonconforming proposals may be rejected without review. Proposals shall consist of only two volumes; additional files will not be reviewed. All pages shall be printed on 8-1/2 by 11 inch paper with type not smaller than 12 point. Smaller font may be used for figures, tables and charts. The page limitation for full proposals includes all figures, tables, and charts. Volume I, Technical and Management Proposal, may include an attached bibliography of relevant technical papers or research notes (published and unpublished) which document the technical ideas and approach upon which the proposal is based.