DEFENSE HEALTH AGENCY (DHA)18.1 Small Business Innovation Research (SBIR)

Proposal Submission Instructions

The Defense Health Agency (DHA) SBIR Program seeks small businesses with strong research and development capabilities to pursue and commercialize medical technologies.

Broad Agency Announcement (BAA), topic, and general questions regarding the SBIR Program should be addressed according to the DoD SBIR Program BAA. For technical questions about a topic during the pre-release period, contact the Topic Author(s) listed for each topic in the BAA. To obtain answers to technical questions during the formal BAA period, visit https://sbir.defensebusiness.org/sitis.

Specific questions pertaining to the DHA SBIR Program should be submitted to the DHA SBIR Program Management Office (PMO) at:

E-mail - usarmy.detrick.medcom-usamrmc.mbx.dhpsbir@mail.milPhone - (301) 619-5047

The DHA Program participates in three DoD SBIR BAAs each year. Proposals not conforming to the terms of this BAA will not be considered. Only Government personnel will evaluate proposals.

PHASE I PROPOSAL SUBMISSION

Follow the instructions in the DoD SBIR Program BAA for program requirements and proposal submission instructions at http://www.acq.osd.mil/osbp/sbir/solicitations/index.shtml.

SBIR Phase I Proposals have four Volumes: Proposal Cover Sheets, Technical Volume, Cost Volume and Company Commercialization Report. The Technical Volume has a 20-page limit including: table of contents, pages intentionally left blank, references, letters of support, appendices, technical portions of subcontract documents (e.g., statements of work and resumes) and any other attachments. Do not duplicate the electronically generated Cover Sheets or put information normally associated with the Technical Volume in other sections of the proposal as these will count toward the 20-page limit.

Only the electronically generated Cover Sheets, Cost Volume and Company Commercialization Report (CCR) are excluded from the 20-page limit. The CCR is generated by the proposal submission website, based on information provided by small businesses through the Company Commercialization Report tool. Technical Volumes that exceed the 20-page limit will be reviewed only to the last word on the 20th page. Information beyond the 20th page will not be reviewed or considered in evaluating the offeror’s proposal. To the extent that mandatory technical content is not contained in the first 20 pages of the proposal, the evaluator may deem the proposal as non-responsive and score it accordingly.

Companies submitting a Phase I proposal under this BAA must complete the Cost Volume using the on-line form, within a total cost not to exceed $150,000 over a period of up to six months.

The DHA SBIR Program will evaluate and select Phase I proposals using the evaluation criteria in Section 6.0 of the DoD SBIR Program BAA. Due to limited funding, the DHA SBIR Program reserves

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the right to limit awards under any topic and only proposals considered to be of superior quality will be funded.

Proposals not conforming to the terms of this BAA, and unsolicited proposals, will not be considered. Awards are subject to the availability of funding and successful completion of contract negotiations.

PHASE II PROPOSAL SUBMISSION

Phase II is the demonstration of the technology found feasible in Phase I. All DHA SBIR Phase I awardees from this BAA will be allowed to submit a Phase II proposal for evaluation and possible selection. The details on the due date, content, and submission requirements of the Phase II proposal will be provided by the DHA SBIR PMO either in the Phase I award or by subsequent notification.

Small businesses submitting a Phase II Proposal must use the DoD SBIR electronic proposal submission system (https://sbir.defensebusiness.org/). This site contains step-by-step instructions for the preparation and submission of the Proposal Cover Sheets, the Company Commercialization Report, the Cost Volume, and how to upload the Technical Volume. For general inquiries or problems with proposal electronic submission, contact the DoD SBIR/STTR Help Desk at (1-800-348-0787) or Help Desk email at sbirhelp@bytecubed.com (9:00 am to 6:00 pm ET).

The DHA SBIR Program will evaluate and select Phase II proposals using the evaluation criteria in Section 8.0 of the DoD SBIR Program BAA. Due to limited funding, the DHA SBIR Program reserves the right to limit awards under any topic and only proposals considered to be of superior quality will be funded.

Small businesses submitting a proposal are required to develop and submit a technology transition and commercialization plan describing feasible approaches for transitioning and/or commercializing the developed technology in their Phase II proposal. DHA SBIR Phase II Cost Volumes must contain a budget for the entire 24-month Phase II period not to exceed the maximum dollar amount of $1,000,000. These costs must be submitted using the Cost Volume format (accessible electronically on the DoD submission site), and may be presented side-by-side on a single Cost Volume Sheet. The total proposed amount should be indicated on the Proposal Cover Sheet as the proposed cost. DHA SBIR Phase II Proposals have four Volumes: Proposal Cover Sheets, Technical Volume, Cost Volume and Company Commercialization Report. The Technical Volume has a 40-page limit including: table of contents, pages intentionally left blank, references, letters of support, appendices, technical portions of subcontract documents (e.g., statements of work and resumes) and any attachments. Do not include blank pages, duplicate the electronically generated Cover Sheets or put information normally associated with the Technical Volume in other sections of the proposal as these will count toward the 40-page limit.

Technical Volumes that exceed the 40-page limit will be reviewed only to the last word on the 40 th page. Information beyond the 40th page will not be reviewed or considered in evaluating the offeror’s proposal. To the extent that mandatory technical content is not contained in the first 40 pages of the proposal, the evaluator may deem the proposal as non-responsive and score it accordingly.

PHASE II ENHANCEMENTS

The DHA SBIR Program has a Phase II Enhancement Program which provides matching SBIR funds to expand an existing Phase II contract that attracts investment funds from a DoD Acquisition Program, a non-SBIR/non-STTR government program or private sector investments. Phase II Enhancements allow

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for an existing DHA SBIR Phase II contract to be extended for up to one year per Phase II Enhancement application, and perform additional research and development. Phase II Enhancement matching funds will be provided on a dollar-for-dollar basis up to a maximum $500,000 of SBIR funds. All Phase II Enhancement awards are subject to acceptance, review, and selection of candidate projects, are subject to availability of funding, and successful negotiation and award of a Phase II Enhancement contract modification.

DISCRETIONARY TECHNICAL ASSISTANCE

The DHA SBIR Program does not participate in the Discretionary Technical Assistance Program. Contractors should not submit proposals that include Discretionary Technical Assistance.

The DHA SBIR Program has a Technical Assistance Advocate (TAA) who provides technical and commercialization assistance to small businesses that have Phase I and Phase II projects.

RESEARCH INVOLVING ANIMAL OR HUMAN SUBJECTS

The DHA SBIR Program discourages offerors from proposing to conduct human subject or animal research during Phase I due to the significant lead time required to prepare regulatory documentation and secure approval, which will significantly delay the performance of the Phase I award.

The offeror is expressly forbidden to use or subcontract for the use of laboratory animals in any manner without the express written approval of the US Army Medical Research and Material Command's (USAMRMC) Animal Care and Use Review Office (ACURO). Written authorization to begin research under the applicable protocol(s) proposed for this award will be issued in the form of an approval letter from the USAMRMC ACURO to the recipient. Furthermore, modifications to already approved protocols require approval by ACURO prior to implementation.

Research under this award involving the use of human subjects, to include the use of human anatomical substances or human data, shall not begin until the USAMRMC’s Office of Research Protections (ORP) provides authorization that the research protocol may proceed. Written approval to begin research protocol will be issued from the USAMRMC ORP, under separate notification to the recipient. Written approval from the USAMRMC ORP is also required for any sub-recipient that will use funds from this award to conduct research involving human subjects.

Research involving human subjects shall be conducted in accordance with the protocol submitted to and approved by the USAMRMC ORP. Non-compliance with any provision may result in withholding of funds and or termination of the award.

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DHA SBIR 18.1 Topic Index

DHA18-001 In-Ear Monitoring for Hearing Protection Compliance and Noise Hazard ExposureDHA18-002 Broad Spectrum Envenomation TreatmentDHA18-003 Chronological Sweat Sensor Patch for Real-Time Human Molecular Biomarker MonitoringDHA18-004 Neural Stem Cell Therapy for Severe Traumatic Brain InjuryDHA18-005 Nanosecond Electrical Pulse (nsEP) Pain Inhibition DeviceDHA18-006 In-line, Non-invasive, Non-destructive Cell Monitoring in Dynamically Growing CulturesDHA18-007 Compact Speaker Array for Clinical Testing of Ear-level Devices

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DHA SBIR 18.1 Topic Descriptions

DHA18-001 TITLE: In-Ear Monitoring for Hearing Protection Compliance and Noise Hazard Exposure

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop and demonstrate a comprehensive solution for in-ear monitoring of noise exposure and auditory function that can be used in lieu of standard hearing protection for Service Members engaged in operational tasks to provide a better understanding of the relationship between noise exposures and hearing injury and better protect warfighter hearing.

DESCRIPTION: Hazardous noise exposure is a serious problem in the military, and hearing loss and tinnitus are the two most prevalent permanent injuries sustained by our service members. In order to address this problem, we need to improve our understanding of the relationship between noise exposure and hearing injury. Historically, research on the impact of noise exposure on hearing function has relied at least partially on prospective studies that have intentionally exposed listeners to calibrated levels of noise and then used careful laboratory measures to assess the resulting impact on the auditory system. However, recent research suggests that even modest noise exposures that result only in temporary shifts in absolute hearing thresholds may produce permanent degradation in hearing function as a result of auditory synaptopathy (Kujawa and Lieberman, 2009). This means that most future studies of noise exposure will have to rely on data collected from individuals who are unavoidably exposed to noise as a result of occupational requirements.

Consequently, there is a need to develop tools that can allow us to monitor the effective levels of noise that Service Members are being exposed to during the course of their assigned duties without in any way modifying the level of exposure that would ordinarily occur and without in any way interfering with the conduct of their duties. Additionally, while Service Members are often required to wear hearing protection, many do not comply. Thus, there is a need to objectively monitor how often Service Members are actually wearing the hearing protection devices that they are issued. No existing technology meets either of these needs.

A system that could meet these needs would be able to fit entirely within the form factor of a standard earplug (or possibly a modified earmuff) and could be issued to a service member in lieu of a standard hearing protection device for an extended time period (weeks or months) during their normal course of duty and then downloaded to provide some information about earplug use, exposure, and auditory function over that time period. Service members could also undergo further auditory testing in the clinic before and after this period to determine correlations between the measured noise exposure and any changes in auditory system function.

PHASE I: Phase I should identify a feasible technological approach (including sensors) for the in-ear monitoring system that can meet the necessary size, weight, and power requirements, develop a strategy for data collection and storage, and, if possible, demonstrate a bench-level prototype of the device.

PHASE II: In Phase II, the contractor should develop, test, and demonstrate at least four working prototype systems capable of being used in lieu of a standard hearing protector in the ear for a 2+ hour data collection effort. Real-ear attenuation at threshold testing (in accordance with ANSI S12.6) may be required to verify the attenuation performance of the device. At a minimum, the system must:

1) Look and feel like a standard hearing protection device2) Be compatible with all standard-issue Soldier Personal Protective Equipment3) Continuously monitor and record timestamped data about:a. Impulse and continuous noise levels both inside and outside the ear plugb. Earplug use (i.e. time history of when it is inserted in the ear)c. Some measure of auditory function (e.g., otoacoustic emissions, middle ear impedance, stapedius reflex activation)

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4) Provide ability to download stored data at end of test period5) Not contain any external wires or devices6) Have the ability to be combined with a passive earmuff to achieve double hearing protection

Other highly desirable system attributes are as follows:1) Can fit entirely in the ear2) Have attenuation performance (ANSI S12.6) thata. Can be modified to match an arbitrary hearing protector or,b. Matches the attenuation of a standard passive hearing protectorc. Possibly includes the ability to match attenuation of a nonlinear passive protector3) Potentially provide the ability to conduct behavioral auditory testing (i.e. threshold testing) or psychophysical testing4) Have an extremely minimal logistical tail (i.e., able be issued to service member for weeks or months of use)

PHASE III DUAL USE APPLICATIONS: Both the Army and Navy Public Health Centers have requirements to monitor occupational noise exposure as part of the Defense Occupational and Environmental Health Readiness System Industrial Hygiene (DOEHRS-IH) and have hearing conservation programs that focus on noise hazard identification, hearing protection, and monitoring audiometry. Thus, these systems would be well suited for Government use to monitor the noise exposure, hearing protection usage, and auditory function of Service Members and Civilian Employees who operate in noisy environments, and these centers are examples of potential Government funding sources for acquiring this type of technology. There is also great potential for commercial use in industrial hearing conservation programs. The hearing protection market is estimated to reach $1.9 Billion by 2021, reflecting the large number of individuals with occupational and recreational noise exposure. Furthermore, noise regulations continue to tighten, which will be a catalyst for companies to require increasingly accurate measures of true noise exposure for their workforce in order to avoid building in expensive safety margins to ensure they are in compliance with national and local noise regulations. We anticipate that Phase III has the potential to produce manufacturing demonstration run of useable devices for making in-ear measurements.

REFERENCES:1. MIL-STD-1474D, U.S. Department of Defense Design Criteria Standard, Noise Limits, AMSC A7245, Washington, DC, (1997)

2. Gallagher, H. L., McKinley, R. L., Theis, M. A., & Bjorn, V. S. (2014). Calibration of an In-Ear Dosimeter for a Single Hearing Protection Device (No. AFRL-RH-WP-TP-2014-0002). AIR FORCE RESEARCH LAB WRIGHT-PATTERSON AFB OH HUMAN EFFECTIVENESS DIRECTORATE.

KEYWORDS: Hearing protection; Noise Dosimetry; Auditory Injury; Otoacoustic Emissions; Middle-Ear Reflex

DHA18-002 TITLE: Broad Spectrum Envenomation Treatment

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: This topic focuses on developing a broad spectrum venom mitigation and treatment that will be effective without identification of the venomous species and which can be used in the field without fear of significant adverse side-effects (such as serum sickness).

DESCRIPTION: Special Operations Forces (SOF) are deployed in austere areas within AFRICA Command (AFRICOM), Pacific Command (PACOM), and Southern Command (SOUTHCOM) that are associated with an increased risk of envenomation. Bites by venomous snakes cause: severe paralysis that may prevent breathing; bleeding disorders that can lead to fatal hemorrhage; irreversible kidney failure; and severe local tissue destruction that causes permanent disability and limb amputation.

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Traditional antivenins require correct identification of the venomous species to select the appropriate treatment and the risk is high for severe adverse reactions such as serum sickness and hypersensitivity. Identification of the specific species is frequently problematic or mistaken and treatment must be administered in in a higher echelon military treatment facility. Compounding this problem, reliable pharmaceutical companies no longer produce antivenins previously used in higher risk areas such as Africa.

However, current research into the enzymatic structure and function of venoms indicates that a new direction for antivenin is on the horizon. Broad spectrum venom inhibitors that use novel approaches such as nanoparticles and phage that target enzymatic classes such as Phospholipase A2 and Metalloproteinase are possible. Not only are the new approaches likely to treat a broad spectrum of envenomations, lyophilization and reagent stabilization will enable therapeutics to remain stable over a broad range of temperatures, allowing treatment at the point of envenomation.

The World Health Organization recently declared snake-bite a neglected tropical disease, with approximately 2.5 million poisonings from snake-bite occurring each year. Annually, snake bites result in at least 100,000 deaths and around three times as many amputations. While many antivenoms exist throughout the world, significant challenges exist in their manufacture and effective use. The majority of antivenoms are based on species-specific immune reaction to venom exposure. Very few antivenoms are approved for use by the Food and Drug Administration (FDA).

Successful proposals to develop broad spectrum envenomation treatment may include, but are not limited to, toxin and/or enzymatic inhibition technologies. Proposals should focus on broad applicability and ease of use in austere conditions. The regions of particular interest are AFRICOM and PACOM. Consideration should be given to the systemic neurotoxic, myotoxic, hemorrhagic, coagulant, and hypotensive effects of envenomation.

Proposals to improve existing polyvalent treatments that require high and/or repetitive dosing and/or require administration in a critical care facility are specifically excluded from this solicitation.

PHASE I: Define the component technologies needed to develop a broad spectrum envenomation treatment that can be used in austere conditions without concern of serious side-effects. Investigate major venom component toxins and potential therapeutics for combined toxin inhibition. Treatment categorization must determine use without relying on speciation. Define and develop FDA regulatory approval plan for any initial and follow-on therapies. Begin in vitro screening for proposed treatment methodology safety and efficacy. Future in vivo animal model should be planned and outlined.

Preliminary in vitro data should include cytotoxicity, binding affinities, and venom neutralization with proposed therapeutic and whole venoms including but not limited to Crotalus, Agkistrodon, Naja, Bungarua, and Dendroaspis, Where possible, available anti-venoms should be used as controls.

Phase I deliverables include (1) Opportunities and limitations of potential developed treatments with regards to safety, efficacy, and manufacturability, (2) PK/PD model of therapeutic mechanism of action, (3) Preliminary in vitro data (4) Any therapeutic categorization (if required) (5) Phase II in vivo animal model and animal use plan, and (6) FDA regulatory approval plan.

PHASE II: Synthesize and iteratively refine broad spectrum envenomation treatment with in vitro testing. Validate concept in a small animal model with unknown (or category) venom. Examine the PK/PD, biodistribution, safety, and efficacy of the concept. Demonstrate feasibility of GLP/GMP scale-up with appropriate yield efficiencies.

The overall objective is to develop and validate a venom inhibitor effective against a broad spectrum of envenomations that can be safely administered by SOF medics in the field without identification of the venomous species. The FDA approval pathway will be outlined and considered at each developmental stage. The goal is to receive Food and Drug Administration (FDA) clearance on the venom inhibiting solution.

Requirements:(1) Broad spectrum venom inhibitor

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a. Phospholipase, three-fingered toxins (cytotoxins, short-chain neurotoxins and long-chain neurotoxins), and metalloprotease classes (threshold)b. Other protease classes and toxins found within venoms (objective)(2) Administered by SOF medics in a field environment without immediate critical care facility availability (threshold)(3) Stable in ambient temperatures (threshold)(4) Two year shelf life (objective), one year shelf life (threshold)

Phase II deliverables will include: (1) Report detailing design, synthesis, and validation of envenomation treatment system, (2) Plan for regulatory approval. The offeror shall initiate contact with FDA representatives and provide a clear plan on how FDA clearance will be obtained.

PHASE III DUAL USE APPLICATIONS: Validate concept in large animal model and transition therapeutic to pharmaceutical company. A clear plan towards FDA approval for the therapeutic agent(s) and delivery platform will be in place, and additional testing to meet FDA requirements will be completed. Additionally, to expand the use of the device to medical diagnosis, FDA medical device certification will be pursued. Supplementary funding may be provided by DoD sources including, but not limited to US Special Operations Command and Air Force Medical Advanced Development. While additional funding may be provided for DoD applications, awardee should also look toward other Government to continue the process of translation and commercialization.

REFERENCES:1. Arias, Ana Silvia, Alexandra Rucavado, and Jose María Gutierrez. Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom. Toxicon 132 (2017) 40-49.

2. Fox, J.W., Serrano, S.M.T., 2005. Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases. Toxicon 45, 969-985.

3. Laustsen, A.H., Engmark, M., Milbo, C., Johanneses, J., Lomonte, B., Gutierrez, J.M., Lohse, B., 2016. From fangs to Pharmacology: the future of snakebite envenoming therapy. Curr. Pharm. Des. 22, 5270-5293.

4. Lewin, M., Samuel, M., Merkel, J., Bickler, P., 2016. Varespladib (LY315920) appears to be a potent, broad-spectrum, inhibitor of snake venom phospholipase A2 and a possible pre-referral treatment for envenomation. Toxins 8, 248.

5. World Health Organization, Snake antivenoms Fact sheet N° 337, 2010; http://www.who.int/mediacentre/factsheets/fs337/en/

KEYWORDS: Venom Inhibitor, Phospholipase A2 Inhibitor, Metalloproteinase Inhibitor, Envenomation, Toxin, Neglected Tropical Disease

DHA18-003 TITLE: Chronological Sweat Sensor Patch for Real-Time Human Molecular Biomarker Monitoring

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Human performance monitoring by developing a non-invasive system that chronologically captures sweat, measures sweat rate, blocks contaminants, conforms to skin, and continuously reports sweat biomarkers.

DESCRIPTION: The consequence of degraded human performance is of critical importance not only to the department of defense (DoD) missions but also to the general population as well. For example, fatigue, both

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physical and mental, is a recurrent problem costing businesses an estimated $150 billion annually in loss of productivity (Institute of Medicine of the National Academies 2006). Caused by many factors such as sleep deprivation, persistent mental activity, and prolonged physical exertion, fatigue can have negative effects on a large range of individuals across many walks of life. Heat-injuries for Tri-Service trainees impose great risks as well. In the Air Force alone, more than 200 trainees per year experience a significant level of heat injury, resulting in substantial losses in training time, potential injury, decreased mission effectiveness, and loss of life. Therefore, the ability to non-invasively detect and mitigate the risks associated with individuals who are facing the challenges in physiological and cognitive performance without interfering their job duties is of grave importance.

Sweat is an information-abundant medium. Earlier human subject studies on the levels of molecular biomarkers such as interleukin-6, neuropeptide-Y (NPY),[1] cortisol,[1] and brain-derived neurotrophic factor,[2] showed that their physiological concentrations can be related to the human cognitive levels. The mass spectrometry study performed to perspiration samples collected using commercial sweat patches on major depressive disorder and healthy human subjects indicates that the concentration of secreted cytokines and neuropeptides are possible indicators for the human cognition level.[3] Collectively, a sweat sensor patch metering sweat rate and detecting molecular targets including, but not limited to, peptides, small molecules, and/or volatile organic compounds, in the human perspiration can be a game changer to achieve an ultimate direct and minimally invasive human protection and performance monitoring.

Obtaining days of continuous sampling of sweat from an identical dermal spot has proved challenging using conventional sweat collectors, resulting in inconsistencies of sample quantity, contaminants, and exact time stamping. Thus identical volumes of chronologically collected sweat sampling hardware is in great demand for the continuous monitoring of sweating and sweat biomarkers. This work seeks to develop a modular wearable sweat patch system that incorporates chronological sample collection and real-time sensor technologies for molecular biomarkers into a single device containing sweat sampling well, electronic sensor, transducer, and communication via wired/wireless power for successful operation. This system will be used to establish and monitor the frequency, magnitude, and chemical make-up of sweat and sweat molecular biomarkers in order to noninvasively monitor human performance. Accomplishing these goals can ultimately lead to development of a real-time, wearable sweat monitoring device that correlates human performance with threshold biomarker concentrations established to indicate physiological health and cognitive levels in the training and operational environment.

PHASE I: The temporal collection of sweat will allow for monitoring changes in the sweat metabolome and proteome biomarkers as a test subject sweating progresses over time. The chronologically obtained sweat sample from a body/skin-conformal sweat patch enables one not only to analyze the biomarker profiles without intermittent sampling gaps, but also to provide an effective real-time sweat sensing platform that paces its response to the more precisely time-stamped samples. The chronological sweat sampling patch is to be developed and demonstrated in this Phase I. The objective is to develop microfluidic sweat patch system that 1) capture discrete volumes of sweat in a time-stamped chronological manner for at least 72hrs, 2) scale from 100s of nL to 100s µL total collected sweat volume per patch, 3) flexible to conform to the body, 4) leakage-free in both static and dynamic dermal setting, 5) expandable to construct a robust electrical/electrochemical/optical epidermal sensor platform, and 6) integrate the wireless power and communication means for the sweat data acquisition and log. 7) The sweat patch performance has to be evaluated with simulated sweat or its equivalents using the proposer’s own or commercially available testbeds that are strictly NOT involved with any human or animal subjects.

PHASE II: Phase II should demonstrate, evaluate, and deliver repeatable and reproducible microfluidic sweat patch system that satisfy Phase I 1-7 requirements, and 1) contain multiple wells each collecting 50-100 uL sweat which can be removed from the device to facilitate laboratory-based sweat analysis 2) sized to fit within a disk dimension of 2 in diameter and 1/8 in thickness, 3) measure sweat rate per unit area of skin, 4) display real-time log of collected sweat in each well, 5) demonstrate capturing of biomarker targets including, but not limited to, peptides, small molecules, and/or volatile organic compounds using analytical instruments, such as mass spectroscopy, 6) block potential skin or non-skin contaminants by analyzing chromatograms, 7) use material that emits less than 1ppb of analytical contaminants during the 8hr or longer exposure to the sweat, 8) designed to perform without cross-contaminating from the chronologically collected sweat samples, and 9) integrate robust electrical/electrochemical/optical epidermal biomarker sensors that monitor one or more sweat biomarker levels (e.g. sodium, chloride, cortisol, or NPY). The offeror shall initiate contact with FDA representatives and provide a

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clear plan on how FDA clearance will be obtained.

PHASE III DUAL USE APPLICATIONS: Phase III should demonstrate the manufacturing of real-time sweat and sweat-biomarker monitoring epidermal patches. The developed sweat patch tech is planned transitioning to a product used by Tri-Service members to obtain the biomarker signifying his/her cognitive levels, individual level chemical exposure data, hydration, and/or physiological status. Air Education and Training Command (AETC) and Air Combat Command (ACC) can be the potential near-term customer fielding the technology for trainee health and cognitive stress monitoring. Air Force Medical Support Agency/SG5M (AFMSA/SG5M) will be the vehicle to develop the acquisition strategy to continue the work and identify manufacturing capability of current technology developers and/or their partners who can handle the manufacturing of same depending on required number of devices. The end product can be dual/multiple use item of interest from both other non-DoD government agencies and private sectors like sports, biomedical, and personal care industry. Additionally, to expand the use of the device to medical diagnosis FDA medical device certification will be pursued by the offeror.

REFERENCES:1. Morgan Iii, C.A., Rasmusson, A.M., Wang, S., Hoyt, G., Hauger, R.L., and Hazlett, G.: ‘Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report’, Biological Psychiatry, 2002, 52, (2), pp. 136-142

2. Rojas Vega, S., Strüder, H.K., Vera Wahrmann, B., Schmidt, A., Bloch, W., and Hollmann, W.: ‘Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans’, Brain Research, 2006, 1121, (1), pp. 59-65

3. Cizza, G., Marques, A.H., Eskandari, F., Christie, I.C., Torvik, S., Silverman, M.N., Phillips, T.M., and Sternberg, E.M.: ‘Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission: The POWER Study’, Biological Psychiatry, 2008, 64, (10), pp. 907-911

KEYWORDS: sweat, chronological sampling, sweat collection, epidermal sensor, sweat biomarker monitor, sensor

DHA18-004 TITLE: Neural Stem Cell Therapy for Severe Traumatic Brain Injury

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop and demonstrate a neural stem cell transplantation treatment protocol using human neural stem cells that will satisfy FDA mandated requirements for a Phase I/II, open-label, neural stem cell transplantation trial for the treatment of severe traumatic brain injury (TBI). Investigate the safety and effectiveness of this product as a neurorestorative therapy in promoting wound healing and recovery to injured brain.

DESCRIPTION: The Department of Defense (DoD) and the military services require solutions to fill the capability gap to treat traumatic brain injury (TBI) which affects not only soldiers during wartime, but during training exercises as well. Currently, there are no clinically proven and FDA-approved pharmacological therapies for traumatic brain injury (TBI). Severe TBI results in widespread delayed focal and global neuronal loss causing significant disability or persistent vegetative state of the effected individual. Since these processes have proven resistant to numerous therapies, there is renewed interest in strategies to replace or endogenously regenerate these lost neurons following TBI. This interest has been driven by the realization that neural stem cells (NSC) possess a remarkable ability to integrate into the injured brain in either a targeted or widespread manner. In the central nervous system, they are capable of forming both neuronal and glial phenotypes, dependent largely upon the micro milieu of the host environment.

In support of the concept of cellular transplantation for severe TBI, numerous studies have been performed to prove the concept that precursor cells of embryonic, fetal or mesenchymal origin can be transplanted into the brain, can

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integrate with the host brain architecture, and improve functional outcome in various animal models of stroke, neurodegenerative diseases and TBI. However, mesenchymal origin stem cells (MSC), though able to differentiate and express some neural markers, have not been shown to form synaptic connections, or integrate well with host tissues and are assumed to exert their beneficial effect through trophic factor modulation (1-2). Moreover, cells delivered via intravenous administration lose the majority (~95%) of the cells during lung passage (3). Intra-arterial injection carries the risk of causing embolic brain infarction and fails to deliver sufficient cells across the vascular wall barrier to the brain parenchyma (4). Thus, the choice of cell type, injection dose and technique of injection is clearly critical to success.

To meet the objective of this topic, the company will evaluate existing human stem cell lines that give rise to a neuronal phenotype; these cell lines must not be on the Federal moratorium list for funding, must be ultimately be produced under good manufacturing practice (GMP) conditions, and must ultimately meet FDA guidelines for cellular therapies. This topic asks for an innovative approach to develop a human neural stem cell product that is capable of being delivered directly to the injured brain. The transplanted cells need to target brain tissue; the cells should survive and integrate into the host brain and be maintained for a sufficient duration of time to reach the desired efficacy. The desired end product would consist of a human neural stem cell replacement therapy that complies with the FDA regulatory pathway. Early FDA consideration is encouraged.

PHASE I: The SBIR Performer must identify a human neural stem cell line that can address the technical challenges on this topic. The effort should clearly analyze and define the properties of any materials used for culturing the stem cells and define methods for intraparenchymal delivery of the cells in a rodent model of traumatic brain injury. If immunosuppression is required, the composite immunosuppressant therapy and treatment regimen should be defined.

PHASE II: The SBIR Performer will design and perform pre-clinical in vivo studies to demonstrate and validate safety and therapeutic efficacy of neural stem cell transplantation in a rat model of TBI. The small business will develop, demonstrate, validate, and show feasibility of the selected stem cell therapy in an established animal model of severe TBI. Additionally, the small business will provide details regarding delivery of the cells and any required immunosuppressant regimen. TBI rodent models should demonstrate reduction in neurological deficits; including motor and cognitive deficits. The Performer will provide evidence of product safety by testing for long-term tumorigenicity of the stem cell transplants in immune-compromised athymic nude rats, who undergo TBI. For this purpose, athymic nude (rnu-/rnu-) rats represent an FDA-approved animal model of choice for general, pre-clinical tumorigenicity studies and are recommended by regulatory agencies specifically for the evaluation of tumorigenicity. All research involving animals, shall comply with the applicable federal and state laws and agency policy/guidelines for animal protection. The U. S. Army Medical Materiel Development Activity, Division of Regulated Activities & Compliance (USAMMDA/DRAC) may provide regulatory assistance. The FDA approval pathway will be outlined and considered at each developmental stage. The offeror shall initiate contact with FDA representatives and provide a clear plan on how FDA clearance will be obtained.

PHASE III DUAL USE APPLICATIONS: Once the product successfully completes Phase II, the small business can seek partnership with a commercial entity for the production of prototypes using Good Manufacturing Practice (GMP) processes. Dose escalation studies using clinical grade GMP cells in swine or non-human primate TBI models may be recommended. A detailed analysis of the predicted performance pertaining to engraftment, survival and safety indications including, but not limited to bioavailability, bio-distribution, phenotypic differentiation, formation should be provided. It is recommended, although not required, to establish an independent advisory committee to review protocols and clinical trial design, planned endpoints, and statistical analysis. Ideally, the small business will sponsor the clinical studies necessary to demonstrate selective, targeted delivery to the brain, as well as clinical safety and efficacy. The small business should have a plan to continue to systematically collect and report data on safety, efficacy and utility after clinical use; therefore, plans to conduct long-term monitoring should be included in study protocols. The small business should seek FDA approval for the validation of the human neural stem cell delivery platform and tests conducted with it.

REFERENCES:

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1. Xiong Y, Mahmood A, Chopp M. Neurorestorative treatments for traumatic brain injury. Discovery medicine 2010; 10(54): 434-42.

2. Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. Journal of neurosurgery 2015; 122(4): 856-67.

3. Pendharkar AV, Chua JY, Andres RH, Wang N, Gaeta X, Wang H et al. Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia. Stroke; a journal of cerebral circulation 2010; 41(9): 2064-70. 54.

4. Yavagal DR, Lin B, Raval AP, Garza PS, Dong C, Zhao W et al. Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model. PloS one 2014; 9(5): e93735.55. NCT01273337. Study of ALD-401 Via Intracarotid Infusion in Ischemic Stroke Subjects. In, 2014. 56.

5. Giusto E, Donega M, Cossetti C, Pluchino S. Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials. Experimental neurology 2014; 260: 19-32.

KEYWORDS: neural stem cells, traumatic brain injury, TBI, neurotransplantation, cellular replacement, neurorestorative

DHA18-005 TITLE: Nanosecond Electrical Pulse (nsEP) Pain Inhibition Device

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: To develop a high voltage nanosecond electrical pulse generator for the use in pain inhibition techniques.

DESCRIPTION: raumatic injury in the battlefield provides a severe complication both short term and long term for the warfighter. Studies suggest that pain intervention very early on provides preliminary improvements in pain, safety, and complications.

A device that can relieve pain after quick attachment by a fellow Airman will enable more rapid stabilization and extraction of injured personnel. In addition, such technology can reduce the amount of drugs carried, handled, or administered. It can also help reduce any complications due to side effects, overdose, or allergic reaction typically seen with drug use. Similar to validated nerve block technology, this treatment at the site of the wound allows the injured to remain conscious and may help to alleviate pain. It has been shown that secondary issues such as phantom limb syndrome and chronic pain occur regardless of the use of whole body analgesics, which block the perception of pain but not the sensory signals that reach the brain. Therefore, the cognitive effects of lasting and persistent pain are still “felt” by the brain. Localized pain treatment has been shown to reduce these secondary complications by blocking the signal from reaching the brain, resulting in fewer secondary complications following severe injury. This proposed technology maintains this advantage while also removing the need for localized administration of pain killers.

nsEPs are generally ultra-short electric pulses that have durations typically between 0.1 and 10000 nanoseconds, and amplitude in thousands of volts. Applications using high-powered nsEP range from instrument sterilization to in vivo treatment of superficial melanomas. Schoenbach et al. first applied nsEP to cells using a microscopic parallel plate setup and showed dramatic bioeffects, including nuclear granulation, calcium influx into cytoplasm (reported to be from internal stores), permeabilization of intracellular granules, cell apoptosis, and damage to the nuclear DNA. It is hypothesized that “nanopores” are formed within the plasma membrane, allowing for the influx of ions and water into the cell, but still restricting the influx of larger molecules like propidium iodide. Pakhomov et al. further verified this finding using patch clamp technique to measure the plasma membrane integrity following nsEP exposure.

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Low-intensity nsEP exposures have also generated action potentials (APs), leading to muscle contractions and neural stimulation. Modeling work suggests that at higher voltages (100 kV/cm at 10 ns or 2 kV/cm at 600 ns) nsEPs can cause the inhibition of APs by forming a conductance block.

It is anticipated that a man portable device (less than 5 pounds and less than 10000 cm3 in volume) is feasible because the repetition rate to maintain nerve block is anticipated to be less than 0.1 Hertz, requiring minimal power supply volume and cooling capability.

PHASE I: In Phase I, a prototype design concept will be developed for use in a laboratory setting. The developed “breadboard” should meet basic requirements for repeated nanosecond electrical pulse generation. Generic requirements for the pain inhibition device are:- Adjustable high voltage: 10-80kV- Pulse width: 900-10000 nanoseconds- Rise time: 10 nanoseconds- Pulse repetition frequency: 0.1Hz to 0.003Hz- Load: 200 ohm- Electrode/tissue interface that will allow delivery of maximum current to tissue with no arcing

PHASE II: The developed breadboard from Phase I will be implemented into a final design solution, a laboratory-use prototype developed, and optimized output validated.

Based on the Phase I design parameters, construct and demonstrate a functional prototype of the device. The technical feasibility of the device should be validated through voltage and current measurements into a biologically relevant load for high voltage delivery (such as an aqueous-electrolyte resistor). Specifically, the prototype should address the general requirements of Phase I, as well as the method for electrical delivery control and attachment to patient.The SBIR company may propose to do joint testing with 711 HPW/RHDR of the final prototype using RHDR’s electrical measurement capabilities.

PHASE III DUAL USE APPLICATIONS: Phase III will transition the device, developed in Phase II, into a clinically acceptable prototype for use during en-route care and in a hospital setting, for use both in military and commercial applications. The SBIR company should propose partnership with an organization (commercial, university, or military), with experience at animal and human research, clinical trials, and FDA coordination of medical devices in order to successfully transition the device to medical end users. In addition, the company should explore airworthiness requirements for airevac scenarios. The translation of the technology can also be explored into the commercial sector for chronic pain therapy.

The objective system should be suitable to allow man-portable transport to the field by Independent Duty Medical Technicians (IDMTs). It is anticipated that the IDMTs will be in field conditions for a number of days without access to battery-charging power, therefore, the package should be able to maintain a usable charge for several weeks in a storage condition, then operate for up to 24 hours when attached to a patient. It is anticipated that the electrode assembly will be placed on the patient by the IDMT and remain with the patient until they are delivered to a higher echelon of care or airlifted out of theater. The electronics package should be interchangeable so the electrodes can stay on the patient and the electronics (to include the power supply) can be changed out by treatment providers at the higher echelon of care.

REFERENCES:1. Roth CC, Payne JA, Tolstykh GP, Kuipers MA, Thompson GL, Wilmink GJ, Ibey BL, Nanosecond pulsed electric field thresholds for nanopore formation in neural cells, Journal of Biomedical Optics, 2013, 18(3): 035005-1-10

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2. Joshi RP, Mishra A, Song J, Pakhomov A, Schoenbach K. 2008. Simulation Studies of Ultrashort, High-Intensity Electric Pulse Induced Action Potential Block in Whole-Animal Nerves. IEEE Trans Biomed Eng. 55:1391-1398.

3. Schoenbach, KH, Beebe SJ, Buescher ES. 2001. Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics. 22:440-448.

4. Pakhomov AG, Kolb JF, White JA, Joshi, RP, Xiao, X, Schoenbach, KH. 2007. Long-lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF). Bioelectromagnetics. 28:655-663.

5. Joshi RP, Mishra A, Song J, Pakhomov AG, Schoenbach KH. 2008. Simulation Studies of Ultrashort, High-Intensity Electric Pulse Induced Action Potential Block in Whole-Animal Nerves. Biomedical Engineering, IEEE Transactions on, 55:1391-1398

KEYWORDS: Pulse Generation, Generator, nanosecond pulsers, pulsed power applications, high voltage, electrical pulse generation

DHA18-006 TITLE: In-line, Non-invasive, Non-destructive Cell Monitoring in Dynamically Growing Cultures

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: To develop, design, and demonstrate a material product or device that will allow non-invasive, non-destructive, real-time, in-line monitoring of dynamically cultured cell viability and proliferation for GLP/GMP processes.

DESCRIPTION: The Department of Defense has an urgent need for material products or devices that can operate in GLP/GMP processes that will allow for assessment of dynamically cultured cell viability and proliferation in ways that do not require invasive introduction of sampling equipment into the in-line production process or require extraction and destruction of samples.

Cellular and tissue engineered therapies for regenerative medicine applications that do not derive from autologous sources must be processed in accordance with Good Manufacturing Practices prior to introduction into the body. This requires monitoring processes to assess various characteristics about the culture, e.g. cell viability, cell differentiation, and microbial contamination. In standard laboratory processes this would involve extraction of a sample for visual inspection, metabolic testing, or cell/tissue staining. From a GLP/GMP perspective, however, this is not an ideal methodology for several reasons. First, it introduces a foreign object into the production line (invasive), which increases the opportunity for contamination. Second, it terminally removes part of the product from the production line (destructive). Third, sample testing operates under the assumption that the region sampled is representative of the culture as a whole. However, while this assumption may be acceptable for 2D cultures, in 3D cultures, different regions may exhibit differential accumulations of metabolites or waste products.

The currently available methods for monitoring the health of cultures in bioreactors typically involve indirect measurements of cell metabolism. Metabolic assays can evaluate cytotoxicity and drug effects [1], biocompatibility [2], viability [3], and proliferation. Some existing methodologies are already used for these assessments, and although they correlate reasonably well with many 2D cultures, they don’t correlate well with 3D cultures [4]. There is also some concern that they may be cytotoxic to some cell types [5]. Ultimately, direct measurements of cell health would be preferred.

Another factor that influences the utility of a given measurement technique is whether or not it is suitable for cultures growing dynamically in a bioreactor. Standard cell culturing technique involves growing cells in flasks with a static overlaying medium containing the nutrients. This medium must be changed periodically as nutrients are used up and waste products accumulate. In a dynamically growing culture, media is flowed through a

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bioreactor, continually providing fresh nutrients and removing waste products. Although dynamically growing cultures do not necessarily preclude the use of a particular type of measurement, they will influence the applicability of a given method.

The ultimate goal of this topic is to develop new material products that will allow direct assessment of dynamically growing cultured cell viability and proliferation without introducing an external sampling device (and the concomitant possibility of contamination) or the requisite destruction of the cells being measured.

PHASE I: In the Phase I effort, innovative efforts for monitoring cell viability and proliferation will be conceptualized and designed. Such solutions may include visualization technologies, bioassays or other measuring devices. Solutions directed toward evaluation of 3D cultures are preferred, but exceptional studies that improve on the ability to non-invasively and non-destructively assess 2D cultures will be considered. Phase I efforts can support early concept work, or efforts necessary to support a regulatory submission. Proposed technologies or bioassays should be designed, and the development, fabrication or production procedures should be developed for a representative product. Cell types used should be obtained from a validated cell source such as Production Assistance for Cellular Therapies (PACT) at the National Heart, Lung, and Blood Institute. It is also recommended that in Phase 1 efforts offerors consider which measurement parameters are meaningful to industries, clinicians and regulatory bodies such as by conferring with the Standards Coordinating Body (https://www.standardscoordinatingbody.org/). The Phase I effort should also include any fabrication experiments and benchmarking that demonstrate an adequate capability for meeting the expected challenges in fabricating or producing the proposed solution. Bioassays should be able to demonstrate lack of cytotoxicity and utility for the majority of cell types, particularly primary cells and adult stem cells. Specific milestones include the absence of cytotoxicity, the ability to show real-time changes to cell viability and proliferation, and any necessary algorithms for interpreting readouts.

PHASE II: In the Phase II effort, a prototype technology should be fabricated and demonstrated. The performance of the technology or assay should be fully evaluated in terms of sensitivity, selectivity, dynamic range and limit of detection. Phase II results should demonstrate understanding of requirements to successfully enter Phase III, including how Phase II testing andvalidation will support independent user testing and qualification to lead towards use in a GLP/GMP environment.. Phase II studies may include work necessary to support a regulatory submission, to include, but not limited to: manufacturing development, qualification, packaging, stability, or sterility studies, etc. The researcher shall also describe in detail the transition plan for the Phase III effort.

PHASE III DUAL USE APPLICATIONS: During phase III, it is envisioned that requirements to support a commercially available end item for use in a GMP manufacturing suite or for research will be completed. As part of that, scalability, repeatability and reliability of the proposed technology should be demonstrated. Devices should be fabricated using standard fabrication technologies and reliability. The proposal should include a commercialization or technology transition plan for the product that demonstrates how these requirements will be addressed including GMP manufacturing sufficient materials for evaluation. It is envisioned that this technology will be used in advanced regenerative medicine manufacturing efforts. Thus potential funding sources may be collaborative efforts with academia, other industries manufacturing consortia.

This technology is envisioned for use in GLP/GMP facilities producing products for medical application. As such, the technology should have both military and civilian applications. Procurement of such technology would be at the discretion of the medical treatment facility.

REFERENCES:1. O'Brien J. Wilson I. Orton T. Pognan F. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem. 2000;267:5421.

2. Finch D.S. Oreskovic T. Ramadurai K. Herrmann C.F. George S.M. Mahajan R.L. Biocompatibility of atomic layer-deposited alumina thin films. J Biomed Mater Res Part A. 2008;87A:100.

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3. Al-Nasiry S. Geusens N. Hanssens M. Luyten C. Pijnenborg R. The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells. Hum Reprod. 2007;22:1304.

4. Zhou X, Holsbeeks I, Impens S, Sonnaert M, Bloemen V, Luyten F, Schrooten J.Noninvasive real-time monitoring by alamarBlue(®) during in vitro culture of three-dimensional tissue-engineered bone constructs. Tissue Eng Part C Methods. 2013 Sep;19(9):720-9.

5. Mueller D. Tasher G. Damm G. Nüssler A.K. Heinzle E. Noor F. Real-time in situ viability assessment in a 3D bioreactor with liver cells using resazurin assay. Cytotechnology. 2013;65:297.

KEYWORDS: Viability, proliferation, in-line, non-destructive, non-invasive, real-time

DHA18-007 TITLE: Compact Speaker Array for Clinical Testing of Ear-level Devices

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop and demonstrate a speaker array system with a minimal profile that can easily be installed and used to obtain consistent sound field performance measurements of hearing devices in multiple clinical environments for the purposes of determining the functional effects of hearing devices on Warfighter spatial hearing ability and situational awareness.

DESCRIPTION: Clinical audiometry is most often conducted over headphones, which provides very consistent results across a wide variety of clinical environments as long as the background noise levels do not exceed the Maximum Permissible Ambient Noise Levels outlined in ANSI S3.1. However, there are certain cases where regulations require the functional performance of hearing impaired listeners to be evaluated while they are wearing hearing devices, such as hearing aids. For example, AR190-56 specifies the use of a sound field hearing in noise test for the evaluation of candidates for civilian security guard positions in the Army who wish to have their hearing tested with amplification. There are many practical cases where it may be desirable to measure the hearing performance of listeners wearing hearing aids, hearing protection devices, or implantable hearing prosthetics, both for evaluating fitness for duty and for evaluating outcome measures of clinical interventions. Traditional sound-field audiometry is generally limited to two speakers attached to an audiometer, with very little standardization in terms of where those speakers are placed. Consequently, there is no reason to believe that functional hearing measures conducted with these sound field speakers will be consistent across different audiological test booths, even within the same clinic. Conversely, large speaker-arrays, which can easily evaluate the hearing performance of Warfighters with hearing devices, are currently reserved for research facilities and cannot easily be deployed into clinical settings; as such, the development of standardized tests using larger systems is impractical. As the DOD Hearing Center of Excellence builds its DOD-wide hearing registry, it will become increasingly important to have a standardized method for conducting audiological sound-field testing that is compact and affordable enough to be deployed in a large number of DOD Clinics and will produce results that are consistent and reliable enough to allow direct comparisons of data across multiple facilities. A survey of commercially available systems has revealed that no systems currently exist that are compact enough to be permanently installed in a clinical sound booth (without severely limiting the usability of the booth) and flexible enough to allow independent control of the individual sound channels (commercial 5.1 and 7.1 sound bars incorporate multichannel processing that does not allow the channels to be controlled independently). Also, no current systems have been validated to allow comparable spatial hearing performance in multiple sound booths: they typically require the collection of normative data that is specific to each individual sound booth. The ideal system would:1) Be compact enough to be retrofitted in most clinical sound booths with minimal interference with current clinical operations.2) Take advantage of commercial multichannel formats like HDMI or ADAT to provide a multichannel sound field solution (5-8 channels) that can be controlled from a single wire from a PC sound card or Android Tablet.3) Be capable of simulating both discrete, spatially separated sound sources and simulated room reverberation.4) Be completely self-contained in terms of amplification and decoding

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5) Provide a method for controlling/maintaining the location of the subject’s head in the center of the array6) Provide a method for reliably calibrating the system7) Develop some novel methodologies for improving the robustness and consistency of auditory testing across multiple rooms with different acoustic environments.

PHASE I: Phase I should identify a feasible technological approach for the speaker array system that addresses all of the major requirements for consistent clinical testing across a wide range of test environments, demonstrate a bench-level prototype that meets these requirements and all applicable ANSI standards, and develop a plan for implementing a compact version of the prototype suitable for integration into clinical sound booths at a minimal cost. The system should be able to connect to various tablets and PCs sound cards which are equipped with tests that evaluate speech perception in noise and localization. The system should have the ability to accommodate single and multisource sound localization including front-back confusions, separation and perception of multi-talker speech, and spatial hearing from masking for speech perception in noise. A feasibility study should be completed using the Knowles Electronics Mannequin for Acoustical Research (KEMAR).

PHASE II: By the end of Phase II, the contractor should deliver at least 10 viable prototypes for pilot testing in DOD Audiology Clinics. The products should have demonstrated success in a small sample of human subjects demonstrating repeatable spatial hearing and speech perception performance across a variety of typical sound booth acoustic environments for: 1) normal hearing listeners with and without hearing protection devices and 2) hearing impaired listeners with and without hearing protection devices and with hearing rehabilitative devices (i.e., hearing aids and auditory implantable devices). Tests should include tasks of spatial hearing (i.e., localization and speech perception in noise). Other deliverables include technical reports document the appropriate performance measurements for the device, specifications with diagrams on setup of the equipment, and proposed roadmap addressing additional research activities, cost, and time required to make the technology commercially available.

PHASE III DUAL USE APPLICATIONS: Phase III the contractor should develop a plan for medium-rate production of the systems for integration into clinical audiological booths both within the US Government (DoD and VA) and in the commercial sector. Customers would include hearing conservation and clinical audiology settings in the DOD for use in auditory fitness for duty evaluations for hearing impaired Warfighters with hearing rehabilitative devices. It is likely that the HCE would support deployment of the system at major MTFs where audiological implants and cochlear implants in order to increase the accuracy. In clinical audiology settings in the VA and DOD, the units could be used for evaluation of outcomes with auditory rehabilitative devices. Commercially, the department of labor estimates that there were 13,000 audiologists in the US in 2014, suggesting a potential market size of at least several thousand units if an affordable and reliable solution could be developed.

REFERENCES:1. American National Standards Institute. (1991). American national standard maximum permissible ambient noise levels for audiometric test rooms. Standards Secretariat, Acoustical Society of America.

2. Army Regulation 190-56. (Effective: 15 March 2013). Military Police: The Army Civilian Police and Security Guard Program. Headquarters: Department of the Army; Appendix C:8(30-31). http://www.apd.army.mil/epubs/DR_pubs/DR_a/pdf/web/r190_56.pdf

KEYWORDS: Audiological Testing; Sound-field testing; Spatial Audiometry; Auditory Fitness-for-duty Testing; Speaker Array; Hearing Loss

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