HR001123S0027.pdf

Broad Agency Announcement

TELLUS

BIOLOGICAL TECHNOLOGIES OFFICE

HR001123S0027

April 21, 2023

TABLE OF CONTENTS

PART I: OVERVIEW INFORMATION

PART II: FULL TEXT OF ANNOUNCEMENT

1. Funding Opportunity Description

1.1. Program Overview

1.2. Background

1.3. Program Structure

1.4. Independent Verification and Validation (IV&V)

1.5. Schedule

1.6. Program Deliverables, Milestones and Metrics

1.7. General Requirements

2. Award Information

2.1. General Award Information

2.2. Fundamental Research

3. Eligibility Information

3.1. Eligible Applicants

3.2. Organizational Conflicts of Interest

3.3. Cost Sharing/Matching

4. Application and Submission Information

4.1. Address to Request Application Package

4.2. Contact and Form of Application Submission

4.3. Funding Restrictions

4.4. Other Submission Information

5. Application Review Information

5.1. Evaluation Criteria

5.2. Review of Proposals

5.2.4. Countering Foreign Influence Program (CFIP)

6. Award Administration Information

6.1. Submission Status Notifications

6.2. Administrative and National Policy Requirements

6.3. Reporting

6.4. Electronic Systems

7. Agency Contacts

8. Other Information

8.1. Proposers Day

8.2. University Funding

9. APPENDIX 1 – Volume II checklist

PART I: OVERVIEW INFORMATION

Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Biological Technologies Office (BTO)

Funding Opportunity Title – Tellus Announcement Type – Initial Announcement Funding Opportunity Number – HR001123S0027 North American Industry Classification System (NAICS) – 541714 Catalog of Federal Domestic Assistance Numbers (CFDA) – 12.910 Research and

Technology Development Dates o Posting Date: April 21, 2023 o Proposers’ Day: May 2, 2023 https://sam.gov/opp/05e7ca96007348e3904123d10f90fbfc/view o Proposal Abstract Due Date and Time: May 18, 2023, 4:00 PM ET o Full Proposal Due Date and Time: July 6, 2023, 4:00 PM ET o BAA Closing Date: July 6, 2023

Concise description of the funding opportunity – The goal of the DARPA Tellus program is to develop the Methodology to program microbial sense-and-respond devices to reliably detect a variety of chemical and physical stimuli, process this information and generate measurable output signals in DoD-relevant environments. Tellus will assess the feasibility of utilizing microbial devices for environmental monitoring.

Anticipated individual awards – Multiple awards are anticipated.

Types of instruments that may be awarded – Procurement contract, Cooperative

Agreement, or Other Transaction for Prototype agreements.

Agency contact

The BAA Coordinator for this effort may be reached at:

Tellus@darpa.mil

DARPA/BTO

ATTN: HR001123S0027

675 North Randolph Street Arlington, VA 22203-2114 https://sam.gov/opp/05e7ca96007348e3904123d10f90fbfc/view mailto:Tellus@darpa.mil

PART II: FULL TEXT OF ANNOUNCEMENT

1. Funding Opportunity Description

This publication constitutes a Broad Agency Announcement (BAA) as contemplated in Federal Acquisition Regulation (FAR) 6.102(d)(2) and 35.016 and 2 CFR § 200.203. Any resultant award negotiations will follow all pertinent laws and regulations, and any negotiations and/or awards for procurement contracts will use procedures under FAR 15.4, Contract Pricing, as specified in the BAA. Proposals received as a result of this BAA shall be evaluated in accordance with evaluation criteria specified herein through a scientific review process.

The Defense Advanced Research Project Agency (DARPA) is soliciting innovative proposals to develop agile, reliable sensing devices that leverage microbes for environmental monitoring.

Specifically, DARPA seeks to establish the range of chemical and physical stimuli that microbial “devices” can detect, environmental conditions they can tolerate, options for biologically-encoded information processing, types of output signals that can be generated, and theoretical stand-off or remote distances at which these signals could be detected. Tellus will focus on developing a Methodology that enables the reliable and reproducible design of agile, robust, and durable microbial sensors for environmental monitoring.

1.1. PROGRAM OVERVIEW

Tellus will explore the development of a platform Methodology for the rapid and modular design of microbe-based sensing systems to include tailoring of input stimuli and output signals, biologically-encoded signal processing, and response times. The microbial devices that are developed must be able to transduce detected stimuli into a variety of output signals (e.g., photons, colorimetric changes, chemicals, electric current, mechanical actuation) that are measurable by conventional “receiver” devices (e.g., optoelectronic, photonic, imaging, electrode). Classes of stimuli will include both chemical and physical, with emphasis on sensor functionality across many different environments and conditions. As remote environmental monitoring for existing and emerging threats, pollutants, or changing conditions is an area of DoD/national security interest, microbial sensing systems that are capable of detecting stimuli and/or relaying output signals at a distance and can operate unattended for long durations are desired. Tellus is a 2.5-year, single phase program focused on developing a Methodology that will enable rapid design, building, and testing of microbial sense-and-respond devices for environmental monitoring.

1.2. BACKGROUND

Current approaches to environmental monitoring rely on both distributed sensor nodes (e.g., on the ground or in the water) and remote sensing using platforms, like satellites or unmanned systems, to collect information important for the protection of people and assets. Although available environmental sensing methods offer many benefits, additional improvements would further strengthen our capabilities. These include enabling more rapid development of sensors for new threats, increasing spatial resolution and confidence in the assessment, and reducing power and logistical burden. Further, some sensing devices currently used in the field require samples to be manually collected and processed (e.g., water quality monitors) or are hand-carried, putting operators at risk. To reduce potential risk to personnel, equipment and structures, sensors that are user-friendly, compact, can detect multiple threats, provide simple “yes/no” responses, and are compatible with many types of stand-off /remote “receiver” platforms would be impactful.

Microbial sense-and-respond devices offer promise for overcoming the challenges associated with environmental monitoring. There has been increased emphasis in recent years on expanding available options for input stimuli that can be detected and output signals that can be generated, as well as biologically-encoded information processing. Microbial sensors have been demonstrated for analytes such as heavy metals, organic pollutants, energetic compounds, chemical warfare agents, and gases, with sensitivities comparable to conventional sensors.

Microbes are able to detect and discriminate between multiple target chemicals as well as respond to distinct physical stimuli (e.g., ultraviolet to near infrared light, electrical potential, low frequency ultrasound, magnetic fields, temperature changes, microwaves/radio frequencies).

Some environmental microbes have demonstrated functionality in corrosive or high radiation conditions, and in the presence of terahertz electromagnetic radiation, which may be advantageous in certain settings. Microbial sensors capable of multiplexed stimuli detection with transduction to a single or multiple output signal types (e.g., chemical, mechanical, optical, gas, electrical, magnetic) using a variety of biologically-encoded signal processing circuits (e.g., digital, analog, neural network) have been developed. Microbial devices may offer endurance benefits over abiotic devices by harvesting energy to self-power and are readily sustained via encapsulation or within simple microfluidic systems.

While microbial sensing devices have been demonstrated, in general these utilized a bespoke approach with testing under ambient conditions in the lab. The ability to create agile, rapid, reliable, environmentally durable and deployable devices “on demand” will require additional development, which is the focus of the Tellus program. While synthetic biology tools are well-developed for model chassis organisms, and have been successful at demonstrating dynamic range and specificity in a lab-based setting, these approaches are underdeveloped for designing microbial “sense, process, and actuate” devices where stimuli and output signals can be customized and tested in realistic environmental conditions. Recent advances in microbial and biomolecular engineering with non-model chassis organisms and biological design automation could help address these limitations. The acquisition and employment of data to develop a microbial design Methodology tailored to environmental sensing applications will be paramount to overcoming the aforementioned challenges. This could be analogous to biological design automation tools that have been developed for metabolic synthesis of various products, but extend capabilities to allow for tailoring of stimulus sensing, specification of output signal type, and environmental conditions anticipated for operation.

1.3. PROGRAM STRUCTURE

This BAA solicits proposals which focus on developing (1) an interactive Methodology that enables rapid design of robust, reliable, user-specified microbial sense-and-respond devices in appropriate environments, and (2) fabrication and testing of several such microbial devices (“Tellus devices”). Proposers are required to address both Methodology Development with a user interface and Tellus Device Fabrication. Proposals must describe the technical approach planned to achieve the targeted improvements in Methodology Speed (reduction in time to design, build, and experimentally test devices) and Accuracy (increase in device success at meeting performance criteria), as well as how successive Tellus devices will be fabricated and tested on shortened intervals. Tellus is a 2.5-year, single phase program that will be guided by the SCHEDULE and PROGRAM DELIVERABLES, MILESTONES AND METRICS as described in Sections 1.5 and 1.6, below.

Tellus performers will develop multiple (≥ 6), unique, microbial sense-and-respond devices based on the parameters provided in Table 1. The Tellus program goals are to ascertain which of the parameters noted in Table 1 can be reliably incorporated to create “Tellus devices” that will function in a range of environments, and to develop the Methodology to enable more facile development of bespoke sensors based on different combinations of these parameters to be reliably designed, built, and tested. To achieve this goal, DARPA aims to “pressure test” the design-build-test-learn cycle for such devices. Note that while Tellus does not aim to have performers experimentally demonstrate stand-off or remote detection using microbial devices, it will be important to determine what is theoretically feasible based on sensitivity toward input stimuli, and/or output signal types and strengths that can be generated.

1.3.1. Tellus Methodology and Device Development

Performers will design, build and test a total of (at least) six unique Tellus devices using parameters selected from Table 1. Proposals should include designs for five unique Tellus devices (see Table 2 for notional examples) with at least two device designs per operational domain. DARPA will choose two initial designs from these five, which will be the first two Tellus devices that selected teams will fabricate (see Section 1.6, Table 4 for completion dates).

Subsequently, after the program commences, DARPA will select and provide to proposers the parameters for the next four devices at periodic intervals designed to “pressure-test” how quickly functional new devices can be designed, built, and tested. For this reason, it is likely that the DARPA-selected parameters for devices #3-#6 will NOT align with the proposer’s initial designs, and proposers should plan accordingly to be able to address a diverse set of parameters for devices #3-#6. This will allow the Tellus program to cover as many parameters in the table as possible.

For each completed device, it is expected that at least 10 complete ‘variants’ will be tested and made available to DARPA’s Independent Verification and Validation (IV&V) partners per scheduled deliverables (see Sections 1.4 and 1.5.3 for more details). This is to ensure sufficient data is collected to build a robust Methodology. “Variants” should differ from each other so as to attempt to optimize or vary functionality (e.g., increase range of activity, specificity, operating kinetics) or utilize different components (e.g., different ribosome binding sites, regulatory elements, environmental stress response genes, or information processing circuits). Performers should strive to optimize each of these devices in order to make a fair comparison.

Of equal importance to the actual microbial device fabrication and testing will be articulating the plan to use data obtained from these tests to inform the Methodology for designing robust and functional devices. The vision sought for the Methodology is to enable an end user to specify the kind of stimuli they’d like to detect; their preferred output signal; if they want to be able to distinguish between different stimuli or all possible combinations; and their anticipated environmental conditions. The Methodology would then provide guidance on the specific design needed for reliable operation: what chassis to use; which genetic circuits, biomolecular components or pathways to build; and what kind of signal output strength they might expect. It is expected that many iterations of the Tellus device design-build-test-learn cycle (i.e., >10 variants per device for each of six devices) will be necessary to realize the gains sought for Speed and Accuracy of the Methodology. Performers will be encouraged to cooperate/collaborate with each other and DARPA’s IV&V partners to develop an optimized Methodology for Tellus devices.

Proposals should include plans for data sharing with IV&V partners and DARPA. Proposals should also describe all necessary positive and negative controls, and identify anticipated technical challenges and associated risk mitigation strategies.

Key technical challenges that will need to be overcome by the Tellus program:

Sensing and discriminating between different combinations of multiple stimuli.

Lowering limits-of-detection without increasing background.

Employing more sensitive receptors which have inherently smaller dynamic ranges that suffer from saturation at higher concentrations.

Difficulty of use in realistic environmental conditions.

Integration with “receiver” device(s) to collect/measure output signals.

Overcoming genetic burden of added pathways/circuits on cells/efficacy.

Determining whether to use single cells vs. multiple cells or consortia.

Difficulties associated with robust circuitry design and high throughput testing.

Response time needed for processing stimuli.

Developing strategies to record and store stimulus detection events for retrieval at a later time.

Multiplexing sensing modalities.

Operating discriminately in the presence of confounders.

The proposed technical approach is expected to be multidisciplinary in order to address the development of the Methodology for designing the Tellus device, genetic and/or biomolecular engineering of the organism(s), bio-based energy harvesting to enable long endurance, and generation of output signals detectable via a “receiver” (that can potentially translate to stand-off or remote detection). Strategies for optimizing, integrating, and expanding capabilities should be elaborated throughout. Proposals should also discuss mitigation of technical challenges that may arise. Specifically excluded from this opportunity is research that: (1) proposes the use of plants (although microalgae are acceptable); (2) proposes use of well-established chemical stimuli such as antibiotics, quorum-sensing molecules, inducers like isopropyl β-D-1-thiogalactopyranoside (IPTG) or Β-galactose; (3) proposes only the use of fluorescent or luminescent proteins for output signals; or (4) proposes a subset of the parameters in Table 1 as described (i.e., selection of an Environmental Domain, Environmental Condition, at least three Stimuli to be Sensed, at least one Biologically-encoded Information Processing step and at least one Output Signal/Communication Method for each proposed Tellus microbial device) – proposals that omit any of these parameter selections will be considered non-conforming and will not undergo further evaluation.

Each Tellus device must incorporate parameters from each section of Table 1 as noted:

Reliable function in a selected Environmental Domain, coupled with an

Environmental Condition.

Detect and distinguish between at least three stimuli with at least one of these being a physical stimulus. Note that quantitative measurement of stimuli is not anticipated; rather the device should indicate that a detected stimulus is above or below a target threshold based on the potential risk to human health or potential to cause damage to equipment or other assets. Notional thresholds for stimuli are provided in Table 3, but proposers will need to provide justification for threshold values for the stimuli they select.

Employ at least 1 information processing step.

Generate one or more output signals in response to detected stimuli (individual stimuli or all combinations thereof).

Table 1: Tellus Microbial Device Parameters

Environmental Domain (Choose 1)

Environmental Conditions (Choose 1)

Stimuli to be Sensed (Choose ≥3, m u s t i n c l u d e ≥ 1 Physical)

Biologically-encoded Information Processing (Choose ≥1)

Output Signal/Communication Method (Choose ≥ 1)

- Terrestrial

- Maritime

- Hyperbaric

- Corrosive

- Foliated

- Biofouled

- Swamp

- Murky

- EM-cluttered/ noisy

- Snow

- Dusty/smoky

Chemical

- Organic

- Metals

- Gases

- Radionuclides

Physical

- Magnetic field

- Electric (current, voltage)

- Electromagnetic

(UV/Vis→ microwave/RF)

- Temperature

- Ionizing radiation

- Electronic circuit equivalents

- Neural networks

- Analog or digital

- Event recording

- Control systems

- Electric (current, voltage)

- Optical/multispectral

- Chemicals/polymers

- Magnetic particles

- Mechanical actuation

Table 2: Examples of device configurations that are considered “unique.” Note that these are representative examples, and solutions are not limited to those listed. All device configurations must select the required number of elements from each column in Table 1.

Ex Domain Environmental Conditions (Choose 1)

Stimuli to be Sensed (Choose ≥3, must include ≥ 1 Physical)

Biologically-encoded Information Processing (Choose ≥1)

Output Signal/ Communication Method (Choose ≥1)

1 Terrestrial Snow - Acrylonitrile

- Heavy metal

- Temperature

Electronic circuit equivalents

Electric (current, voltage)

2 Terrestrial Foliated - Pesticide

- Copper

- Radioactivity

Neural networks Optical

3 Maritime Corrosive - Copper

- Zinc

- Electric fields

Event recording

Magnetic particles

Tellus Microbial Device Parameters (Description of Table 1):

Environmental Domain. Tellus devices developed for the Maritime domain will need to function in a submerged (i.e., not floating, unless in “swamp” conditions), aqueous environment.

For the Terrestrial domain, Tellus devices may be tested on soil, other land features, or on object surfaces. Performers will need to establish device performance and reliability over the range of temperatures expected for the selected domain, as well as determine overall device endurance.

For the Terrestrial domain effects of varying relative humidity should also be determined. For both domains, proposers will need to consider how output signals generated by their Tellus devices can be transmitted to a “receiver” device for collection and measurement that also functions in that domain.

Although Tellus seeks to understand how well microbial sensors can function in realistic environments and conditions, actual environmental release of organisms is not within scope. All experiments must be conducted in controlled, contained settings where any unintentional release of the engineered microbial components can be safely managed (e.g., environmental chambers).

Environmental Conditions.

“Hyperbaric” experiments should assess functionality of the Tellus device at a minimum of 20 atm.

“Corrosive” conditions of interest include those that cause chemical corrosion to electronic components such as salt water, sulfidic, acidic or basic conditions.

“Foliated” conditions could include dense grasses, bushes, and/or trees.

“Biofouled” could include surfaces covered by microbial biofilms; or macroscopic organisms.

If “swamp” is selected, proposers should imagine a scenario where it is important to test water quality; in this case it is possible for the device to be deployed on the surface of the water.

“Murky” conditions should be considered in the context of visible light penetration of less than 1 meter. A range of suspended particulate matter concentrations should be tested to understand the maximum density that can be tolerated and how this may affect stand-off detection.

If “EM-cluttered/noisy” condition is selected, Tellus microbes should be shown to be functional in the presence of EM radiation typical of a cell phone tower or near a radio station.

If the “snow” condition is chosen either real snow or ice particles (“artificial snow”) at temperatures below 0°C should be utilized.

“Dusty/smoky” conditions should examine fine particles, ash, or actual smoke that may settle on or remain suspended around the Tellus device.

Stimuli to be Sensed (notional thresholds for stimuli detection provided in Table 3).

Chemicals, inorganics, gases: Detection of organic chemicals such as fuel components, toxic industrial chemicals, synthetic opioids, herbicides, pesticides, or organophosphates are of interest. Metal elements such as copper, zinc, arsenic, lead, and radionuclides (e.g., uranium, thorium, iodine 131, cesium 137, strontium 90) are also of interest. Mock stimuli such as quorum sensing molecules, IPTG, galactose, and antibiotics, are ineligible as stimuli and proposing their use will be considered non-conforming.

Physical stimuli:

o Detection of magnetic or electrical stimuli should move beyond organism-level response (e.g., taxis by a magnetotactic bacterium toward a magnet) to approaches that directly couple the detection event to an intra- or inter-cellular signaling pathway.

o Electromagnetic radiation detection should be tested against a range of wavelengths/frequencies in order to determine specificity (see Table 3).

o Detection or response to discrete temperature changes should account for the likely ambient temperatures that will be found in the Environmental Domain. This parameter might also be addressed by using the Tellus device to monitor changes in temperature of an object located in the Environmental Domain.

o Detection of radioactivity could involve detection of particles or photons associated with radioactive decay (e.g., alpha/beta particles, gamma rays). Heat and oxidative stress responses must be assessed in order to demonstrate that the microbial sensor response is specific to radiation. Because of technical challenges in applying ionizing radiation, it is acceptable to expose the microbial Tellus device to the radiation source, and then separately assess the signal processing and transduction components in a radiation-free setting.

Confounders o At least 5 confounders per stimulus should be tested; enough confounders should be tested in order to determine the specificity limits and what dictates sensing specificity. For instance, chemical confounders should only vary slightly from the target compound. The environmental lifecycle of a chemical should also be considered, for example pesticide degradation products that still act as a pesticide, or indicate past use of the pesticide, may still be considered as the chemical target.

Non-targeted stimuli: Off-target responses of the device should also be tested, to assess potential effects of other stimuli (e.g., effects of heat stress on detection of organic chemical targets) or leakiness of genetic circuits.

Table 3: Tellus Notional Stimuli Thresholds. Performers should justify the threshold levels for the stimuli they propose based on risk or other rationale.

Source Sub-class Stimulus Threshold Organic (fuel components, pollutants, toxic chemicals, synthetic opioids)

0.1 ppbChemical

Inorganics 1 ppb Visible/near-IR Visible → near IR 0.1 lux EMF Microwaves, radio waves **

Magnetic Not applicable 2 milli Tesla (mT) Radioactive decay All 3 rads (0.03 Grays)

**See https://www.govinfo.gov/content/pkg/CFR-2021-title47-vol1/xml/CFR-2021-title47-vol1-sec1-1310.xml for detailed information.

Biological Encoded Information Processing. This category addresses stimuli processing and transduction within the Tellus device. Once stimuli (chemical or physical) are detected that information should be biologically processed to render it interpretable by a “receiver” platform.

It is important that for each stimulus detected by the Tellus device, a distinguishable output signal be generated. It is anticipated that for some output signals, electronic circuit-equivalent operations such as signal amplification, switching, oscillation, or control systems such as feed-forward or feed-back loops, or timers may be useful. Implementation of genetically or biomolecularly-encoded Boolean logic operations, neural network, or analog processing may also be utilized to facilitate discrimination between different stimuli (or combinations thereof), setting of thresholds, expansion of dynamic range, influencing of response times, or other device operations. A particularly challenging end point that is sought by Tellus is to temporally record and subsequently read out when detection events have occurred without requiring laboratory sequencing of the microbe’s DNA or RNA. Whichever information processing steps are incorporated, laboratory measurements should confirm that each step is working as anticipated.

Output Signal/Communication Method. Output signal methods must be theoretically strong enough to communicate with a receiver platform at stand-off as shown in the metrics table (Section 1.6.2, Table 5). Performers are not required to experimentally test their microbial device at these stand-off distances but should theoretically calculate what is possible based upon measured output signal strength. Tellus devices may be interfaced with a signal measuring system (i.e., a “receiver”) either through a direct connection (i.e., output signals leave the cells and are immediately collected by the receiver) or an indirect connection (output signals generated by the cells are detected by a receiver located some distance away). Although a minimum of one output signal is specified in Table 1, it is important to be able to distinguish between the three or more stimuli the Tellus device is programmed to detect, by virtue of the information processing routines that are developed, and output signals that are generated. This could mean tailoring the single output signal (e.g., electric currents produced at different voltage potentials; different pigments or fluorophores), or could entail different output signals aligned to each stimulus detected. Output signal may be amplified or diversified with the addition of abiotic components such as carbon nanotubes, quantum dots, dyes, or other nanomaterials; however, these modifications should not be the dominant element in the process of detecting, processing, or outputting the signal. Collection and processing of signals generated by Tellus devices can be accomplished using standard instrumentation (e.g., photodetectors, cameras, spectrometers, magnetometers) in laboratory settings or, if desired, may be accomplished using detectors mounted on unmanned systems or hand-held devices. [Note: it is expected that all experiments will be performed in a contained environment; no environmental release or outdoor testing is envisioned].

Electric (current-voltage) – production of electric current or voltage as an output signal should be detectable via an electrode array, voltmeter, or other means.

Optical/multispectral signal(s) – production of photons detectable using a camera, photodiode, or comparable imaging system.

https://www.govinfo.gov/content/pkg/CFR-2021-title47-vol1/xml/CFR-2021-title47-vol1-sec1-1310.xml https://www.govinfo.gov/content/pkg/CFR-2021-title47-vol1/xml/CFR-2021-title47-vol1-sec1-1310.xml

Chemicals/polymers/pigments – production of a detectable non-toxic chemical, such as a gas, polymer or pigment. Detection could occur via optical, spectral or mechanical means.

Magnetic particles – this form of output signal would be expected to render the Tellus device to be detectable by a magnetic sensor or to physically migrate to a magnetized object.

Mechanical actuation – this output signal type could affect motion or operation of another system component (e.g., gears, switches, levers, microrobots).

1.3.2. Eligible Organisms

Microbial organisms that are appropriate include non-pathogenic bacteria, archaea, spores, or single cell eukaryotes (algae, fungi), that ideally have demonstrated functionality in the selected Environmental Domains and Environmental Conditions described in Table 1. Performers will need to understand growth rates, managing biomass (without environmental release of genetically modified organisms) and how this affects sensor function in different Tellus device configurations. While integrating detection of multiple stimuli, information processing and output signal generation into a single organism could achieve Tellus program goals, use of a microbial consortia approach would also be responsive to this BAA. Should a consortial approach be proposed, it should be clear how the organisms selected work in concert with each other in regard to multiplexed stimuli detection and response (times, output signals).

1.4. INDEPENDENT VERIFICATION AND VALIDATION (IV&V)

Throughout the program, the performers will work with an IV&V team established by DARPA.

The IV&V team will consist of subject matter experts from the Government, to include Federally Funded Research and Development Centers (FFRDCs). The IV&V team will test and validate the ability of performer-generated Tellus sensing devices to function as described by the performer and may also compare them to conventional sensing systems. The IV&V partners may also assess and consolidate performer methodologies into a unified methodology using performer-provided data and algorithms. Table 4 below describes the schedule for delivery of performer-developed strains and protocols to the IV&V team for testing and evaluation. To avoid potential conflicts of interest, performers for HR001123S0027 will not be allowed to compete for the IV&V contract. HR001123S0027 is not soliciting proposals for IV&V.

1.5. SCHEDULE

The Tellus program will last 2.5 years, across a single phase. Progress towards the stated goals will be assessed throughout the program against the provided milestones and metrics tables (Section 1.6, Tables 4 and 5) as well as performer-defined milestones in the Statement of Work

(SOW).

1.6. PROGRAM DELIVERABLES, MILESTONES AND METRICS

1.6.1. Tellus Deliverables, Milestones and Specifications

Table 4 below describes the expected deliverables for Tellus, the completion due dates and specifications for the performance of the Tellus devices. Deliverables for both the Tellus Methodology and Device Fabrication and testing are included. As noted in Section 1.3.1 above, the first 2 Tellus devices will be selected from the proposal’s five submitted designs; these will be due at Months 6 and 10. DARPA will subsequently provide device parameters for Tellus devices 3-6; these parameters will be provided at Months 12, 15, 18 and 21 with each due 3 months later (i.e., at Months 15, 18, 21 and 24, respectively). In order to best test their Methodology development to assess Speed and Accuracy, performers should plan on making and testing at least 10 variants of each device. The specifications provided in Table 4 articulate expected device performance characteristics typically expected of sensors, such as being able to specifically respond to target stimuli and not confounders, and to generate output signals that (theoretically) can be detected at stand-off. Although specific ranges are not provided, performers will be expected to establish the temperature and relative humidity ranges over which their devices can reliably function, as well as establish their endurance. The latter includes determining how long the Tellus devices remain functional and reliable, which may include assessing microbial viability, biomass management, provision of nutrients/energy sources, and any loss in performance over time. Performers are expected to provide Tellus Devices and their final Methodology to DARPA’s IV&V partners for comparative testing and evaluation (see Table 4).

Table 4: Tellus Milestones, Deliverables and Specifications

Month Milestones and Deliverables Specifications 3 Draft Methodology - Establish program start baselines for Speed and Accuracy.

6 Complete fabrication and testing of Tellus Device #1 (Performer specs).

Deliver Tellus Device #1 to IV&V partner.

10 Complete fabrication and testing of Tellus Device #2 (Performer specs).

Deliver Tellus Device #2 to IV&V partner.

12 Report on Interim Methodology.

DARPA provides parameters for Tellus Device #3.

15 Complete fabrication and testing of Tellus Device #3.

Deliver Tellus Device #3 to IV&V partner.

DARPA provides parameters for Tellus Device #4.

18 Complete fabrication and testing of Tellus Device #4 Deliver Tellus Device #4 to IV&V partner.

DARPA provides parameters for Tellus Device #5.

Methodology - a user interface such as a web application, standalone design tool or program code that can be downloaded.

Devices must:

• Detect and distinguish between selected input stimuli:

• At relevant thresholds.

• In presence of at least five confounding signals.

• Insensitive to non-targeted stimuli.

• Reliably execute information processing.

• Generate selected output signal(s) at levels sufficient for detection at stand-off distance (theoretical

21 Complete fabrication and testing of Tellus Device #5.

Deliver Tellus Device #5 to IV&V partner.

DARPA provides parameters for Tellus Device #6.

24 Complete fabrication and testing of Tellus Device #6.

Deliver Tellus Device #6 to IV&V partner.

Report on Interim Methodology.

30 Complete endurance test of top designs (to be selected by DARPA) of all devices.

Report on Final Methodology.

Deliver Final Methodology to IV&V partner.

calculation).

Performers will also establish:

• Environmental tolerances (T°, rel.

humidity, pH).

• Device endurance.

1.6.2. Tellus Program Metrics

The specific metrics for development of both Tellus Methodology and Devices expected at various timepoints across the 2.5-year, single phase program are given in Table 5, Metrics for Tellus Devices. More detail on what each metric is seeking is provided below:

Methodology Development: The key deliverable for the Tellus program will be the Methodology that defines how reliable and robust microbial sense-and-response devices can be designed, built and tested. The final Methodology could be a user-friendly dashboard that enables the operator to select specific environments, conditions, stimuli and output signals for their desired configuration, and then provides a design specifying chassis type, circuits/parts, and type of “receiver” system needed for reliable and robust performance. Key metrics for assessing progress in Tellus Methodology development will be Speed (defined as a reduction in the time required to design, build and experimentally test Tellus devices) and Accuracy (defined as the increase in device success at meeting the performance criteria, such as Sensitivity and Specificity).

Theoretical System Stand-off: The sum of the “target to biological sensor” and “biological sensor to receiver” distances. Experimental measurement of stand-off or remote detection distance is not a required outcome, however, based on experimental measurements of sensitivity to input stimuli and/or strength of output signal that is generated, a theoretical calculation of these distances should be conducted. Target distances for both “Terrestrial” and “Maritime” domains are provided in Table 5. Performers may utilize conventional laboratory instruments/equipment to collect and measure the output signal(s) generated by their Tellus devices, using either direct contact or interfaces that involve physical separation of the microbe and signal measurement system.

Device Sensitivity and Specificity: As for other environmental monitoring systems, two key performance parameters are sensitivity and specificity, which aim to reduce false positive and negative detection events.

Sensitivity is defined as the number of true positive detection events (i.e., stimuli accurately detected, TP) divided by the total number of positive detection events (P):

Sensitivity = TP/P

Specificity is defined as the number of true negative events (confounders identified as confounders, confounders ignored, or confounders not detected; TN) divided by the total number of negative events (N):

Specificity = TN/N

Device Endurance and Response Time: Performers will have to address endurance and response time goals for their Tellus devices as requested in Table 5. These will ideally be tunable to allow maximum flexibility to adapt to various environmental monitoring applications. It is anticipated that strategies to help the microbes remain fully functional for long periods may include environmental energy or nutrient scavenging; encapsulation; use of microbial consortia; and stimulus detection modes that reduce reliance on transcription/translation approaches.

Containment of genetically-modified microbes: Containment is defined as the number of escaped microbes divided by the total number of microbes. Although release of genetically modified microbes (GMM) into the environment is not a component of the Tellus program, it is important that proposers incorporate safeguards to mitigate this risk. Physical and/or genetic strategies to ensure containment must be included in the proposal. It is the responsibility of the performer to obtain any necessary permits and to comply with institutional/local/state/Federal regulations applicable to the proposed research.

Table 5: Metrics for Tellus Devices

Metric Month 3 Month 6 Month 12 Month 18 Month 24 Month 30

Methodology – Speed

Establish baseline

3-fold decrease relative to baseline

5-fold decrease relative to baseline

8-fold decrease relative to baseline

Methodology – Accuracy

Establish baseline

2-fold increase relative to baseline

3-fold increase relative to baseline

5-fold increase relative to baseline

Theoretical system stand-off

>5 m (terrestrial)

>0.3m (maritime)

>10 m (terrestrial)

>1.0 m (maritime)

Sensitivity (TP/P) 0.75 0.75 0.80 0.90 0.95

Specificity (TN/N) 0.75 0.75 0.80 0.90 0.95

1.7. GENERAL REQUIREMENTS

1.7.1. Proposing Teams

Proposer teams must address the Tellus Program Schedule, Deliverables, Milestones and Metrics as described above in Sections 1.5 and 1.6. Consequently, it is expected that the teams will include experts from the multiple disciplines related to the program challenges and goals (e.g., synthetic biology, environmental microbiology, signal processing, biological design automation, environmental monitoring, remote sensing). Because several different technologies must ultimately work together to prototype a functional sensing system, teams must identify one or more members as project integrators who will ensure those team members focused on a specific supporting technology are also appropriately working towards the overall project goal.

The project integrator should also address all risks specifically associated with integration.

Specific content, communications, networking, and team formation are the sole responsibility of the proposer teams. Proposer teams must submit a single, integrated proposal led by a Prime Contractor or Lead research institution.

1.7.2. Controlled Unclassified Information (CUI)

Given the aim of Tellus to develop a new sensing paradigm for use in environmental monitoring, it is possible that detection of certain proposed stimuli, when coupled with output signal types and/or specific environmental conditions, may require protection as CUI. Proprietary or other sensitive technical information will also require safeguarding or dissemination controls pursuant to and consistent with applicable law, regulations, and Government-wide policies. Proposers should review the attached Tellus CUI guide and the Tellus Science and Technology Protection Plan (S&T P2), provided by BTO Security upon request (BTO_Security@darpa.mil), and, if relevant to the work proposed, should include a draft Science and Technology Protection Implementation Plan (S&T PIP) with their proposal to DARPA [see Section 4.2.2.A. Volume I, Technical and Management Proposal, Section III; Attachment 1 - CUI Guide;

Attachment 2 – Science & Technology Protection Implementation Plan (S&T PIP) Template]. Performers must partition potentially sensitive/CUI tasks from non-sensitive research efforts, and are asked to identify sensitive/CUI tasks within their Statement of Work (Attachment 3 – Statement of Work Template). All performers (prime contractor and subcontractors) supporting efforts with sensitive/CUI tasks that desire public release of project information will be required to submit a request for public release from DARPA in accordance with their contractual requirements. As such, organizations that can comply with DoD CUI requirements as described in Attachment 1 must be part of the proposed team.

1.7.3. Other Requirements

Performers are expected to attend semi-annual program reviews to provide updates to the

Response time 120 min 90 min 60 min 30 min 20 min

Endurance Hours Hours to days

Days Days to weeks

Weeks

Containment 1 x 10-6 1 x 10-7 1 x 10-8 mailto:BTO_Security@darpa.mil

DARPA program management team, IV&V partners, Government stakeholders and other Tellus performers on progress towards their milestones and scientific goals on the Tellus program.

Performers will also summarize outstanding challenges and limitations that must still be overcome to achieve the overarching goals of the program. Cooperation and collaboration between Tellus performers and IV&V partners to develop an optimized final Tellus Methodology are also expected. This may involve sharing of raw and/or processed data with DARPA and/or IV&V partners. DARPA and IV&V personnel may also conduct periodic site visits.

2. Award Information

2.1. General Award Information

Multiple awards are possible. 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, as applicable.

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 (see Section VI.B.2., “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/or cost/price within a reasonable time, and the proposer fails to timely provide requested additional information. Proposals identified for negotiation may result in a procurement contract, cooperative agreement, or other transaction, depending upon the nature of the work proposed, the required degree of interaction between parties, whether or not the research is classified as Fundamental Research, and other factors.

Proposers looking for innovative, commercial-like contractual arrangements are encouraged to consider requesting Other Transactions. To understand the flexibility and options associated with Other Transactions, consult http://www.darpa.mil/work-with-us/contract-management#OtherTransactions.

In accordance with 10 U.S.C. § 4022(f), the Government may award a follow-on production contract or Other Transaction (OT) for any OT awarded under this solicitation if: (1) that participant in the OT, or a recognized successor in interest to the OT, successfully completed the entire prototype project provided for in the OT, as modified; and (2) the OT provides for the award of a follow-on production contract or OT to the participant, or a recognized successor in interest to the OT.

http://www.darpa.mil/work-with-us/contract-management#OtherTransactions

In all cases, the Government contracting officer shall have sole discretion to select award instrument type, regardless of instrument type proposed, and to negotiate all instrument terms and conditions with selectees. DARPA will apply publication or other restrictions, as necessary, if it determines that the research resulting from the proposed effort will present a high likelihood of disclosing performance characteristics of military systems or manufacturing technologies that are unique and critical to defense. Any award resulting from such a determination will include a requirement for DARPA permission before publishing any information or results on the program. For more information on publication restrictions, see the section below on Fundamental Research

2.2. FUNDAMENTAL RESEARCH

It is DoD policy that the publication of products of fundamental research will remain unrestricted to the maximum extent possible. National Security Decision Directive (NSDD) 189 defines fundamental research as follows:

‘Fundamental research’ means 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.

As of the date of publication of this solicitation, the Government expects that program goals as described herein may be met by proposed efforts for fundamental research and non-fundamental research. Some proposed research may present a high likelihood of disclosing performance characteristics of military systems or manufacturing technologies that are unique and critical to defense. Based on the anticipated type of proposer (e.g., university or industry) and the nature of the solicited work, the Government expects that some awards will include restrictions on the resultant research that will require the awardee to seek DARPA permission before publishing any information or results relative to the program.

University or non-profit research institution performance under this solicitation may include effort categorized as fundamental research. In addition to Government support for free and open scientific exchanges and dissemination of research results in a broad and unrestricted manner, the academic or non-profit research performer or recipient, regardless of tier, acknowledges that such research may have implications that are important to U.S. national interests and must be protected against foreign influence and exploitation. As such, the academic or non-profit research performer or recipient agrees to comply with the following requirements:

(a) The University or non-profit research institution performer or recipient must establish and maintain an internal process or procedure to address foreign talent programs, conflicts of commitment, conflicts of interest, and research integrity. The academic or non-profit research performer or recipient must also utilize due diligence to identify Foreign Components or participation by Senior/Key Personnel in Foreign Government Talent Recruitment Programs and agree to share such information with the Government upon request.

i. The above described information will be provided to the Government as part of the proposal response to the solicitation and will be reviewed and assessed prior to award. Generally, this information will be included in the Research and Related Senior/Key Personnel Profile (Expanded) form (SF-424) required as part the proposer’s submission through Grants.gov.

1. Instructions regarding how to fill out the SF-424 and its biographical sketch can be found through Grants.gov.

ii. In accordance with USD(R&E) direction to mitigate undue foreign influence in DoD-funded science and technology, DARPA will assess all Senior/Key Personnel proposed to support DARPA grants and cooperative agreements for potential undue foreign influence risk factors relating to professional and financial activities. This will be done by evaluating information provided via the SF-424, and any accompanying or referenced documents, in order to identify and assess any associations or affiliations the Senior/Key Personnel may have with foreign strategic competitors or countries that have a history of intellectual property theft, research misconduct, or history of targeting U.S. technology for unauthorized transfer.