DEFENSE HEALTH AGENCY (DHA)17.1 Small Business Innovation Research (SBIR)

Proposal Submission Instructions

The Defense Health Agency (DHA) SBIR Program (previously known as the Defense Health Program 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.DHAsbir@mail.mil Phone - (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 with the exception of technical personnel from Geneva Foundation, and Capitol IT Solutions, will provide Advisory and Assistance Services to DHA, providing technical analysis in the evaluation of proposals submitted against DHA topic numbers:

DHA17-010 Point of Injury Device to Maintain and Stabilize Moderate-Severe Traumatic Brain Injury (TBI) Casualties

DHA17-011 Point of Injury Therapy to Maintain and Stabilize Moderate-Severe Traumatic Brain Injury (TBI) Casualties

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.

The electronically generated Cover Sheet, Cost Volume and Company Commercialization Report (CCR) do not have a 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 20 th page. Information beyond the 20th page will not be reviewed or considered in evaluating the offeror’s

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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 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.

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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 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 17.1 Topic Index

DHA17-001 Electro-Textile Medical SimulationDHA17-002 Self-Healing Elastomer for Medical Simulation & TrainingDHA17-003 Dynamics for Warfighter Avatars with Complete Articulated AnatomyDHA17-004 A Device to Rapidly Detect Coliform Bacteria and Escherichia Coli in Field Water SamplesDHA17-005 Compression Garment with Embedded Electronics for Ambulatory Health and Performance

MonitoringDHA17-006 Development of Thermal Desorption (TD) Tube Sequential SamplerDHA17-007 Noninvasive Monitor of Vascular Volume Fluid ShiftsDHA17-008 Self-Aligning Prosthetic ComponentsDHA17-009 Conformable Osteochondral Repair Platforms for Prevention of Post Traumatic

OsteoarthritisDHA17-010 Point of Injury Device to Maintain and Stabilize Moderate-Severe Traumatic Brain Injury

(TBI) CasualtiesDHA17-011 Point of Injury Therapy to Maintain and Stabilize Moderate-Severe Traumatic Brain Injury

(TBI) Casualties.

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DHA SBIR 17.1 Topic Descriptions

DHA17-001 TITLE: Electro-Textile Medical Simulation

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop a medical simulation to model the impacts to e-textiles that coincide with bodily injury. Once established, to use the e-textile impact to infer bodily damage. The model will be based on the e-textile work performed by the Services; in particular the Revolutionary Fibers and Textiles Institute located at US Army’s Natick Soldier Research Development and Engineering Center (NSRDEC).

DESCRIPTION: Conducting fibers and electro-textiles can be used to map damage. That is, a small signal passed along a conducting fiber results in a signal received at the other end or not. If no signal is received, we can infer the conducting fiber is broken. If at the same time, an expected signal along the opposite axis does not show up, we can infer a location where the damage occurred. For larger area damage, the number of conducting fibers not reporting a signal would increase.

However, not all impacts are direct and could be a glancing impact. In this case the damaged area might be more rectangular depending on the trajectory in relation to the impact area. With this simple example, the simulation explores other damage scenarios using different conducting fiber distances and different sampling times.

Another possible use is detecting directed energy damage such as laser beams. For instance, if a warfighter was subjected to a 3 mm diameter high energy beam, the damage would first appear like a 3 mm hole. However, as the beam cuts in different directions, the damage would appear as a slicing cut. In turn, the cutting speed velocity could be calculated. In cases where the beam cuts completely through the host and produces an exit hole; the calculated body mass of that area could be used to infer the amount of received energy.

Extending the concept, explosions can damage a much larger area of the e-textile. By calculating the time progression of damaged conducting fibers along the direction of the blast, it might be possible to calculate the explosive impact received and the explosive used. For instance, low explosives, such as black powder, could cut conductive fibers at a much slower rate than high explosives. Similarly, high explosives have characteristic velocities that might be determined by the rate of fibers cut. And importantly, the damage would indicate the direction of the blast. What’s more, if we know the strength of the conducting fiber, we may be able to calculate the blast energy received.

This research proposes to simulate various combat injuries on a combat uniform with embedded conductive fibers, in order to infer the cause of that damage. The simulator will be used to facilitate e-textile designs for capturing medical records at the time of injury. The research will prototype and test all of the different phases of the data collection, transfer, analysis, result, and relay.

At a minimum, the simulator will include variable values for the distance between conductive e-textile fibers and the period (time) for checking if a fiber still conducts. Then a number of damage conditions would be simulated thereby providing recommendations for e-textile design and signal design. The second part of the simulation is to take the simulated results and work backwards to infer the most likely cause of the results seen. This becomes challenging as multiple damage events occur.

In order to validate the observations, the vendor will need to construct a test fixture capable of providing low power signals to an 8cm by 8cm e-textile square. The test fixture should work with conductive fibers separated by at least 1 mm (80 fibers along the x-axis, 80 along the y-axis). The signal period passed through the conductive fibers should be selectable from 10 microseconds through 100 milliseconds. The time a signal degrades should be recorded in time units since the experiment star. For instance, if the period selected is 100 microseconds, the conductive fiber degraded and the number of time periods should be recorded. The connections to the e-textile should be along the edges and not obstruct the 8cm by 8cm test area. Laser, fire, and ballistics testing will be conducted at the Natick

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labs using the test fixture. The measured results will be used to calibrate the simulator.

To provide realism, the simulator should emulate a combat uniform consistent with the prototypes built by the Natick Soldier Research Development and Engineering Center [1].

PHASE I: During Phase I, the small business will emulate the effects of combat and environmental injuries on e-textile uniforms in order to determine what information can be inferred from conductive fiber damage. The damaging elements to be simulated will be selected based on their ability to break or damage conducting thread, as the characteristics. The injuries simulated should include bullet hits, shrapnel, directed energy weapons, explosive blasts, fire, and cold. The simulation will apply these varying conditions to the uniforms with conductive fiber in controlled environments. The impact on the e-textile clothing will be used to determine what medically important information could be harvested. The warfighter uniform will be modeled using the NSRDEC e-textile. The lab facilities at NSRDEC will be used to subject e-textile material to fire, laser, and ballistic damage.

PHASE II: During Phase II, the vendor will use the data models and algorithms developed in Phase I to infer the most likely cause of the signal loss. The small business will use the results of Phase I to update and test algorithms from Phase I to correctly determine the cause of damage, such as explosions, as well as key information about that damage, such as the number of fragment impacts and where the damage occurred in combat. It will also explore the resulting changes using different e-textile densities. This should help those involved in manufacturing and selecting optimum distances to infer bodily damage.

PHASE III DUAL USE APPLICATIONS: This R&D product development focuses on using conductive fibers as sensors to infer bodily injury. In contrast to dedicated medical systems, it builds on the R&D Product Development funded for other military applications. The simulations will provide the tools necessary for combining medical applications going forward. Embedded electronic sensors have endless uses for military combatants in both hazardous and everyday operational environments. This e-textile simulator research can support other similar research, offering both improved sensor technology and predictive algorithms to leverage recorded data. These developments will greatly improve our war-fighters’ uniforms to be more light-weight, affordable, and informative.

Workplace injury determination could be improved with wearable e-textiles. By recording damage at the time of injury, disability claims should be easier to approve (or disprove). Small business would be in a good position for developing tools or by providing consulting services for the larger manufacturing companies. Likewise, the simulator could be expanded by small business to accommodate other uses such as roof damage, tents, worn tires, worn belts, holes in aircraft skin, road holes, breaks in bridges, breaks in rail lines, breaks in pipelines, physical security alarms, broken cables, and many other uses. The small business would be in a position to provide tools or consulting services in determining optimum conductive fiber configuration.

REFERENCES:1. Electro-Textile Garments for Power and Data Distribution, Jeremiah R. Sladea, Carole Winterhalter, Infoscitex Corporation, 295 Foster Street, Littleton, MA, USA 01460; Natick Soldier Research Development and Engineering Center, 15 Kansas St., Natick, MA, USA 01760

2. Wearables at war: How smart textiles are lightening the load for soldiers, Trenholm, Richard; March 11, 2015; http://www.cnet.com/news/wearables-at-war-how-smart-textiles-are-lightening-the-load-for-soldiers/.

KEYWORDS: Smart Clothes, Electromagnetic Interference, Electromagnetic Fields, Wireless Sensor Networks, Electronic Textiles, Electronic Materials, Uniforms, Signal Detection

DHA17-002 TITLE: Self-Healing Elastomer for Medical Simulation & Training

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TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop lifelike synthetic self-healing material suitable for applications such as 3-D printing or continuous liquid interface production as examples for medical simulation physical trainer applications. It is desired that such simulated tissue enable self-sealing tissue such as vessels (e.g. veins, arteries, etc.) skin, or other simulated tissues/organs that may be punctured, cut (incision), and possibly even excised, to represent the simulation of wound closure and multiple additional uses.

DESCRIPTION: The DOD has a need for synthetic vessels, skin (all layers), connective tissue and muscle with self-healing properties for practicing resuscitative fluid replacement and other procedures requiring lifelike simulation methods that require puncturing (e.g. percutaneous central lines), cutting (such as cricothyroidotomy incisions), and possibly even excisions. Part task physical trainers emphasize key parts of the procedure or skill. Emerging technologies can produce 3D anatomical models with minimal post processing, as well as offering the end user the capability to make changes and adjustments independent of medical simulation manufacturers. For example, multi-material 3D printing of synthetic tissues and sensors may play a significant role in increasing the realism and reducing the cost of the next generation of surgical training models. Similar to biologic systems evolving the capacity to heal and seal wounds, technologies that leverage biomimetic approaches to realize synthetic elastomers seek to achieve self-healing after damage or fatigue of components of simulation systems such as described by White, et. al.[1]. Additionally, other materials have been shown to exhibit biomimetic properties, such as, Slippery Liquid-Infused Porous Surfaces (SLIPS)[1], as well as synthetic materials based on coagulation have been investigated [2], [3], [4]. Recent work at Stanford has demonstrated crosslinking ligands enables bonds that can be readily broken and reformed after puncture [5]

Autonomous healing can be approached with a number of intrinsic or extrinsic processes [6], [7]. Microchannels can be used to facilitate replenishment of healing agents after breakage. Alternatively, reversible cross-linking, polymerization, bonding, and entanglement mechanisms can be employed. Ideally ‘healing’ can be achieved without the need for additional heat or other chemical agents to be added, but such additional methods may be considered. Strong consideration of materials, agents, catalysts, etc., must take into effect toxicity (inhalation, absorption, contact, etc.) during all aspects of production, use, and maintenance. Toxicity must be identified where applicable.

PHASE I: At the end of Phase I, it is expected that a proof of concept self-sealing material will be developed that is suitable from a rapid manufactured process such as 3-D printing, continuous liquid interface, or other such methods. The performer must demonstrate the feasibility of the approach to enable lifelike models fabricated with self-healing characteristics; this can be provided via video demonstration describing the capabilities and the stage of development. Provide detailed data on performance of the concept and identify anticipated performance of a more sophisticated working prototype. It is expected that appropriate simulants be created and tested for suitable skin and muscle tissues.

The Phase I proposal must include proposed concept, identify key component technological milestones, and have a preliminary methodology for the predicted performance of the tissue healing properties. In addition to a working hypothesis, research methodologies supporting the hypothesis, technical tasks, clinical impact, military impact, and statement of work must all be clearly addressed in the proposal. The Phase I proposal should also include a target end consumer cost for the self-healing material if it were to be successfully developed. Similar cost estimates, with practical examples, must be provided for consumables needed to produce anatomical sections. Anticipated resolution must be specified.

PHASE II: At the end of Phase II, it is expected that a working prototype will be demonstrated. The working prototype must demonstrate the self-healing properties of each material and evaluate the self-healing efficacy, healing time, maximum cycles, and degree of recovery. The report and demonstration must provide maximal distances (length, depth, width, etc.) that the respective material could represent, such as incisions or possibly even excisions. Material properties such as tensile modulus, elongation at break, and fatigue resistance need to be evaluated prior to and after puncture. Description of plans, if any, to colorize tissue simulant materials during printing need to be included in the deliverable. Furthermore, the report must provide information if different

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materials or polymers are needed to represent different tissue properties (such as skin, muscle, fascia) and respective corresponding information such as self-healing efficacy, healing time, maximum cycles, degree of recovery, and maximal distance (length, depth, and width) should be provided for each respective material provided.

Phase II must contain a validation study that examines simulated self-healing anatomy output for use in a medical training setting. A robust prototype must be delivered for independent testing. It is recommended that the prototype have various ‘tissues’ integrated such as skin (epidermis, dermis, and hypodermis), muscle, and vessels (Tunica intima, media, and adventitia) as components of the integrated prototype. Applicants are encouraged to consider independent testing of material properties and performance to provide some support for any future funding requests. Samples are welcomed to be provided to the government so that it may test and evaluate the materials independently. Summary and analysis of data needs to be provided as a Phase II deliverable. Material data properties and toxicities (if applicable) also need to be provided as a Phase II deliverable.

PHASE III DUAL USE APPLICATIONS: At the end of Phase III, it is expected that a fully robust, ergonomic, cost-effective, verified and validated product be ready for manufacturing and commercialization. Manufacturing capabilities and scale up plans shall be provided. Test results on robustness, shipping, safety testing, accuracy, consistency, and comparability to current existing methodologies are recommended. Detailed product cost and consumable cost information is necessary. Specifications of manufactured product, as well as manufacturing process, need to be prepared and finalized. List of materials, material properties, and conditions under which products may be shipped and stored are recommended.

It is anticipated that the final outcomes of this research and development will have both military and public purpose. Possibilities include military and nonmilitary medical end-users who have access to 3-D printers, continuous liquid interface production, or future technology that has yet to be developed could use the self-healing product for replacing simulation components or creating one’s own new simulation part task trainer. It could be used as medical training models that do not corrode and are able to withstand normal wear and tear from use and possible be incorporated into wearable electronics that could be used with standardized patients or mannequin-based training systems.

REFERENCES:1. S. White, et. al., "Autonomic Healing of Polymer Composites," Nature, pp. 794-797, 2000.

2. M. Nosonovsky, "Slippery When Wetted," Nature, vol. 477, no. 7365, pp. 412-413, 2011.

3. G. Bauer, "Restoration of tensile strength in bark samples of Ficus benjamina due to coagulatin of laxtex during fast self-healing of fissures," Annals of Botany, vol. 109, pp. 807-811, 2012.

4. G. Bauer, "Investigating the rheolgoical properties of native plant latex," Journal of the Royal Society Interface, vol. 11, no. 90, 2014.

5. G. Bauer, "Comparative study on latex particles and latex coagulation in Ficus benjamina, Campanula glomerata and three Euphorbia species," PLoS ONE, vol. 9, no. 11, 2014.

6. L. Cheng Hui, et. al., "A Highly Stretchable Autonomous Self-Healing Elastomer," Nature Chemistry, 2016.

7. Y. U. M. W. Yang, "Self-healing polymeric materials," Chemical Society Reviews, vol. 42, pp. 7446-7467, 2013.

KEYWORDS: Artificial simulated muscle, synthetic skin, medical simulation, autonomous healing, self-healing elastomer

DHA17-003 TITLE: Dynamics for Warfighter Avatars with Complete Articulated Anatomy

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TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Design, develop and demonstrate computer software and data structures for adding articulated joints and natural motions to the US Army Research Institute of Environmental Medicine (USARIEM) avatars and create a graphical user interface for planning and activating avatar physical movement. Complete anatomy avatars have a broad future role in advanced training environments providing, for example, ‘medically correct’ immersive experiences, performance-related physiological modeling studies, and in simulations for the purpose of designing protective armor.

DESCRIPTION: The US Army Research Institute of Environmental Medicine (USARIEM) is able to construct individualized avatars as 3-D tetrahedral Finite Element (FE) meshes with full labeled anatomy (see www.army.mil URL below). This is achieved by computer software deforming a 3-D tetrahedral mesh with labeled standard anatomy to fit within a body surface scan triangular FE mesh of an individual subject acquired from imagery. The current avatars are male, static and in the standing position.

There has been much progress in computer construction and manipulation of human models in recent years fueled by the acquisition of databases of large numbers of human body surface scans such as Civilian American and European Surface Anthropometry Resource Project (CAESAR) database and the U.S. Army Anthropometric Survey II (ANSUR II) 3D anthropometric database. Stimulating this research also has been the publishing of complete human imaging data for the male and female by the National Institute of Health’s National Library of Medicine Visible Human Project (see www.nlm.nih.gov URL below) and human body models with segmented anatomy by several other private organizations. A number of groups have made related developments of methods specifically to deform body surface meshes to fit closely to the shape of other specific body surface meshes, for reviews see [Cheng and Robinette, 2009][Cheng et al 2011]. Most prior research emphasis in this literature has been on movement of joints in order to reposition limbs and bodies and animate 3-D body surface meshes lacking internal structure or anatomy. Research strategies in these cases of surface mesh manipulations typically have an initial phase of skeletonization or rigging, then skinning or adding back FE mesh linked to the skeleton, and then repositioning. Several researchers have considered human movement through deformation that explicitly includes internal anatomy [Wilhelms and Gelder, 1997][Scheepers et al, 1997][Aubel and Thalmann, 2001]. Relevant openly available software tools that manipulate anatomy are Bender (Kitware Inc, Clifton Park NY) and OpenSim (National Center for Simulation in Rehabilitation Research, Stanford Univ., Stanford CA).

The goal of this solicitation is to develop the software and user interface in order to manipulate the USARIEM avatars in 3-D so that the original standing avatar pose can be changed to any desired position by the user. All internal and superficial anatomy must accommodate the movement in as natural and medically accurate a fashion as possible. The software must accommodate avatars of all sizes and shapes and both male and female genders. The movements expected to be enabled in the software tool of this project include neck and head rotation and bending, arm rotation and bending at the shoulder, elbow rotation and bending, leg rotation and bending at the pelvis, rotation at the pelvis, knee bending, cervical and lumbar vertebrae bending. Movement abilities must comply with standard human range of motion for the specified anatomy.

Respondents should have expertise in and prior experience in medical modeling using finite elements, 3-D surface FE meshes, medical image processing, computer science particularly software engineering, algorithm development, MATLAB programming, graphics display. Programming experience with models represented as tetrahedral FE meshes is additionally favorable. The software produced in this project is forecasted to be complex, yet should be developed for operation on a commercially available workstation exclusively using the MATLAB (MathWorks Inc., Natick MA) software language.

Development and deployment of such a framework of data structures and software modules to simulate joint motion will require collaboration between private and/or academic engineers/scientists and government engineers/scientists and may need to accommodate both open source and commercial software components. Therefore it is envisioned that this project will produce a software product that is specifically designed to accommodate USARIEM avatars, possibly include open source/open access components, and add newly created algorithms and newly programmed software modules to provide the desired functionality.

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Medical areas of interest that can be served by simulations with USARIEM avatars with motion capability include thermoregulation, stress on joints and bones and the protection of internal anatomy when in different body positions. Knowledge gained from individual’s future physical and physiological monitoring, and medical imaging can be imposed within the representation of their avatars. This project aims to lead to an advanced simulation platform for warfighter health in many environments without human subject risk, at lower cost and yet with greater flexibility of circumstances, and limitless ability for repetition. This answers a military need for strategies within smaller budgets to provide greater capabilities that enhance personalized healthcare and safety.

PHASE I: Design and produce a demonstration of prototype software, using MATLAB that adds joint articulation and movement to USARIEM avatars, using a set of USARIEM avatars provided. Create a prototype graphical user interface (GUI) to activate computation of basic movement functionality of a USARIEM avatar. The MATLAB software should have the capability of taking movement commands from the screen or from the GUI produced in Phase I. Create a standard human joint-skeleton framework of data structures and software modules, based upon and possibly expanding the USARIEM avatar data structures, to simulate simultaneous joint motion while incorporating realistic joint range of motion constraints. The joints that must be flexible in the implementation include at a minimum: the knees, hips, shoulders, elbows, cervical spine, and lumbar spine. Identify open source tools, methods, algorithms and software modules developed by academia and/or government that could be utilized in this effort. Prepare the Phase I final report describing the details and diagrams of the proposed software and GUI, describing and assessing preliminary results based on the test set of avatars provided, and providing detailed plans for further development. A video proof-of-concept must be prepared that demonstrates the functionality of the software and describes the software design and implementation details.

PHASE II: Develop and demonstrate a functional version of software providing articulated joints, natural appendage movement of the USARIEM avatars. The minimum software configuration should allow for manual screen command operation, enabling the repositioning of all avatar limbs, head and neck, and torso bend and twist, with the full human range of motion, as well as translation and rotation of the entire avatar. Repositioning must minimally be able to mimic those encountered when sitting, couching, prone, walking up or down a steep slope, and reaching out. The software would be required to perform one or more movements as if occurring simultaneously. Software would need to be able to perform movements and repositioning with all of the male USARIEM avatars provided, which may be of differing element sizes. Minimally, there must be provisions made within the software to reposition female avatars with the same functionality as the male avatar manipulations. At the juncture when the minimal software package is available it will be demonstrated to the USARIEM modeling division for a critique.

Using functions of the minimal software set described, a fully functional GUI is to be created that can retrieve both male and female avatars from storage directories, and reposition all arms, legs, head/neck and torso with the full range of human motion. The software would be required to add other finite element-encoded objects into the scene and store images of the scene. More advanced goals would include storing the body motion commands to simulate complete human movements involving several or all body parts: moving from standing to sitting; entering a vehicle and sitting; exiting a vehicle; running; walking; climbing stairs; crawling; crawling through an opening; kneeling; and, crouching. The complete avatar movement software package and GUI will be demonstrated to the military medicine stakeholders.

PHASE III DUAL USE APPLICATIONS: The end solution of this solicitation will represent a software suite that takes, as input, a human full anatomy tetrahedral FE mesh, and repositions its body in a medically realistic fashion. The end product software can be sold as a functional product both in the military and private sectors. In the military sector, when coupled with the USARIEM avatars, the end product software will provide the capability of dynamic movement to the avatars, therefore providing the models that a user can manipulate for many current and future military physical testing applications and medical applications, particularly physiological modeling. The target users may include military groups that test and develop clothing and gear, transiting in and out of vehicles and planes, and design realistic physical and physiological simulations. Other target users include those that research physiological aspects of performance, blast and injury trauma. In the commercial sector, the end product software can be packaged with existing or newly developed human models to provide a tetrahedral FE mesh representation of a human in a user-determined body position, which can be used for any further simulations as may be desired. This feature indicates the value in the end product software, in that it has the ability to produce the starting model for a

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host of existing and future commercial models. These undoubtedly will lead to future models and simulation software of potentially high value to the military’s ongoing simulation efforts.

REFERENCES:1. Aubel A and D Thalmann, Interactive modeling of the human musculature, in Proc of Computer Animation, 2001.

2. Cheng Z and K Robinette, Static and Dynamic Human Shape Modeling – A Review of the Literature and State of the Art, Technical Report, Air Force Research Laboratory, AFRL-RH-WP-TR-2010-0023, 2009.

3. Cheng Z, J Parakkat, M Darby, K Robinette, Static and Dynamic Human Shape Modeling – Concept Formation and Technology Development, Technical Report, Air Force Research Laboratory, AFRL-RH-WP-TR-2011-0023, 2011.

4. Scheepers F, RE Parent, WE Carlson, SF May, Anatomy-based modeling of the human musculature, Proc ACM SIGGRAPH 97, T Whitted, Ed, Annual Conf Ser ACM, 163-172, 1997.

5. Wilhelms J and AV Gelder, Anatomically based modeling, Proc ACM SIGGRAPH 97, T Whitted, Ed, Annual Conf Ser ACM, 173-180, 1997.

6. https://www.army.mil/article/165340/Research_Institute_of_Environmental_Medicine_creating_3_D_Soldier_Avatars/

7. https://www.nlm.nih.gov/research/visible/visible_human.html

KEYWORDS: human body model, finite element mesh, physiology, animation, body protection, modeling and simulation, joint articulation

DHA17-004 TITLE: A Device to Rapidly Detect Coliform Bacteria and Escherichia Coli in Field Water Samples

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop a field-portable device to rapidly detect viable coliform bacteria and Escherichia coli (E. coli) in water samples.

DESCRIPTION: Waterborne diseases are a threat to deployed personnel, and monitoring of field water supplies is an essential element in minimizing disease outbreaks. Army Preventive Medicine personnel conduct surveillance of drinking water used in field operations by testing for indicator organisms of fecal contamination – coliform bacteria and E. coli - to help ensure that the water is safe. Testing for total coliform bacteria and E. coli uses procedures approved by the U.S. Environmental Protection Agency (USEPA), as described in the Revised Total Coliform Rule (USEPA, 2013). Although available USEPA-approved tests take a minimum of 16 hours to complete, causing significant delays in the evaluation of field drinking water supplies, new research offers possible avenues to rapid detection (e.g., Gopinath et al., 2014; Amini and Kraatz, 2015). The goal of this effort is to develop an innovative field-portable device that can rapidly detect both coliform bacteria and E. coli in less than 8 hours while being capable of meeting USEPA approval under the Alternative Test Procedure (ATP) rule (USEPA, 2010). A key performance aspect is rapid detection of viable coliform bacteria and E. coli. Preference will be given to technologies that can rapidly detect viable bacteria, even if they are growth-delayed due to chlorination or other stressors, but that will not detect non-viable bacteria. Detection success will be judged based on comparability to the results of testing with USEPA-approved reference methods for enumeration of coliform bacteria and E. coli

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(USEPA, 2010). The detection method should not be susceptible to interferences by non-target bacteria.

PHASE I: Develop a breadboard test system for rapid detection of coliform bacteria and E. coli (Technology Readiness Level 4). Demonstrate that the system can meet the desired detection level (1 CFU/100 mL) within the time frame required (less than 8 hours); test systems with more rapid detection times are preferred. Design and describe in detail a fully-developed system that meets the USEPA ATP testing requirements and other requested performance elements (interferences, size, battery operation, consumables, automated operation, training, processing steps, stable reagents).

PHASE II: Develop, demonstrate, and validate the Phase I test system. Determine the detection levels of the system and show that the performance of the prototype system is comparable to USEPA-recommended methods using diluted chlorinated sewage (USEPA, 2010). At a minimum, presence/absence of target bacteria must be determined at the level of at least 1 colony forming unit (CFU) in 100 milliliters (mL) of water; quantitation is desirable. Demonstrate that the test system does not respond to non-coliform bacteria. Optimize shelf life of reagents. To be useful as a field-portable device, the proposed technology must be suitable for use in a compact, light-weight format (less than 20 pounds) and to function on a rechargeable battery for at least 8 hours. Consumables required should be minimal and cost less than $10 per test. Other important performance elements include automated operation, use with minimal training, minimal processing of water samples, and the use of reagents that do not require refrigeration and are stable for at least one year.

PHASE III DUAL USE APPLICATIONS: In this phase, a test plan would be submitted to the USEPA for completion under the ATP process. The actual ATP testing would be conducted by an independent laboratory. A rapid detection technique for coliform bacteria and E. coli meeting the performance requirements of this effort and successfully completing ATP testing would be useful both for the military and in multiple commercial applications. The Army has an approved Capability Production Document (CARDS # 14065) for a Coliform Analyzer that requires that USEPA ATP testing requirements are met, and successful completion of this SBIR topic would provide an ideal candidate to meet this high priority requirement. Further; Army, Air Force and Navy preventive medicine personnel all have similar water testing requirements per joint document TB MED 577/ NAVMED P-5010-10/AFMAN 48-138 IP (Departments of the Army, Navy and Air Force, 2010). Other technologies approved by the USEPA under the ATP are used by municipalities for drinking water testing as well as for evaluating the suitability of recreational waters, but, as noted above, take at least 16 hours to complete. A rapid test method that also meets USEPA standards would have a wide market for water utilities and other industries where rapid testing of drinking or process water for bacterial contamination is critical. For example, rapid evaluation of beach water quality would facilitate early decisions that would ensure public health while avoiding unnecessary beach closures. At public water utilities, rapid detection technology would allow better monitoring of water production and distribution systems so that microbial contamination events could be more quickly identified and resolved, thus providing improved protection of public health, potentially at lower cost per sample than current approaches.

REFERENCES:1. U.S. Environmental Protection Agency. 2013. Revised Total Coliform Rule (RTCR). 78 FR 10269, February 13, 2013, Vol. 78 No. 30, https://www.gpo.gov/fdsys/pkg/FR-2013-02-13/pdf/2012-31205.pdf

2. U.S. Environmental Protection Agency. 2010. EPA Microbiological Alternate Test Procedure (ATP) Protocol for Drinking Water, Ambient Water, Wastewater, and Sewage Sludge Monitoring Methods, EPA 821-B-10-001, September 2010, https://www.epa.gov/sites/production/files/2015-09/documents/micro_atp_p

3. Gopinath, S.C.B. et al. 2014. Bacterial detection: From microscope to smartphone. Biosens. Bioelectron. 60: 332-342, http://www.ncbi.nlm.nih.gov/pubmed/24836016

4. Amini, K. and H.-B. Kraatz. 2015. Recent advances and developments in monitoring biological agents in water samples. Rev. Environ. Sci. Biotechnol. 14:23-48, http://link.springer.com/article/10.1007/s11157-014-9351-5

5. Departments of the Army, Navy and Air Force. 2010. Sanitary Control and Surveillance of Field Water Supplies. TB MED 577/ NAVMED P-5010-10/AFMAN 48-138 IP, Washington, DC,

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http://armypubs.army.mil/med/DR_pubs/dr_a/pdf/tbmed577.pdf

KEYWORDS: Coliform bacteria, Escherichia coli, rapid detection, pathogens, drinking water

DHA17-005 TITLE: Compression Garment with Embedded Electronics for Ambulatory Health and Performance Monitoring

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop and demonstrate a functional compression shirt with embedded electronics capable of physiological monitoring. The prototype e-garment should be both comfortable for the user as well as capable of collecting, storing and wirelessly transmitting acquired data with minimal distortion. This system will provide physiological health and performance state information allowing for improved safety and sustained work capacity. The focus of this topic is primarily on the integration necessary to exploit extant and emerging state of the art ultra-low power electronics and other government furnished technologies to produce a functional physiological monitoring system.

DESCRIPTION: Health maintenance and performance monitoring are just two of the many benefits of continuous ambulatory monitoring. Uninterrupted monitoring can record performance and/or alter a pending event, e.g. overheating. Traditional ambulatory monitoring systems collect data for offline processing, not meeting needs for real-time observation. Currently, wrist worn systems are comfortable to wear and highly acceptable to users, however they lack data accuracy. Alternatively, chest worn systems can provide accurate data but compromise comfort. When the data being collected involve the use of multiple sensors, the system can become very bulky, causing discomfort to the user and potentially influencing the data being collected. When transmitting the signal wirelessly, interference may also create security concerns when the communication channel is communal to multiple sources. System integration may be a challenge when multiple sensor types are being used; and the power required for the system as a whole must be minimized.

With recent breakthroughs in areas including smart fabrics, flex circuitry, ultra-low power microcontrollers, wireless capabilities, and Internet of Things (IoT) applications, it brings forward the possibility for a new generation of sensors that could function in a continuous yet concealed fashion. Over the last decade, significant exploration in the area of sensors embedded within garments has been made in an attempt to circumvent these issues. Broad interest exists in the development of a compression shirt as an integrated monitoring platform that may be used by service men/women. This integrated e-garment will enable the collection and storage of continuous physiological data and provide real-time off-body secure wireless transmission and on-device storage. The ability to monitor service members both during their routine tasks and in combat settings will allow for early intervention and precautionary observance as well as for situational awareness and mission planning purposes.

PHASE I: In Phase I, the contractor should deliver a detailed plan that outlines the scientific, technical, and commercial feasibility of producing a functional e-wearable compression garment as well as providing an outline of success criteria to reach this goal. Phase I should demonstrate non-integrated functional elements of the desired system, e.g. compression garment with conductive electrodes, options for embedded electronics and communications elements, envisioned data collection and transfer routines, user interfaces, strategies for system initiation and setup that require minimal user interaction, and a plan for final system integration. The approach must be based on an architecture open to third party developers; and utilize and extend as needed previous Government work with the Open Body Area Network, OBAN.

The report should illustrate the feasibility of all desired system attributes. A variety of technical concerns should be considered as detailed in the Phase II section below. Numerous technical approaches may be proposed with accompanying pros and cons for each solution.

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PHASE II: During Phase II, the contractor will use the results from Phase I to fabricate and validate a prototype garment with embedded sensors. Apparel characteristics: must be lightweight, comfortable, cool (minimal insulation), highly permeable to water vapor/sweat. It is desired that this environmental 3D, seamless garment tolerate numerous washes in a standard washing machine on a gentle cycle without compromising operational capability. Sensors to collect heart rate, skin temperature, respiration and accelerometry must be incorporated. The integrated sensors should be anchored sufficiently such that motion artifact related disturbance is negligible (i.e. disturbance of the integrated system is less than that of the sensors alone, prior to integration). Proposed electronics must function on ultra-low power (approximate overall total average system power requirements including communications of 1mW (threshold), reducing or eliminating the need to change or recharge batteries. Electronics must accommodate government-furnished algorithms that estimate core temperature from heart rate, and other third party algorithms that recognize apparent sleep; identify upright and supine postures, unstructured activity, and basic walk/run activities. Garment must have ruggedized electronics packaging and full integration between apparel and sensors. The study should also detail the wireless architecture to be included for this “smart” apparel. The ideal system would incorporate a Texas Instruments tunable narrow-band (TNB) chip (government furnished firmware), and BLE (Bluetooth low energy) connecting though the appropriate antennas to a BLE-capable, and TNB dongled Android handheld device. The tunable transceiver should operate on military frequencies under 400 MHz. On-device storage should also be feasible, with the ability to store data collected continuously over the span of days. The resulting prototype should be a well-defined deliverable, meeting the requirements detailed in this paragraph and which can be made commercially viable. Subcontractor support may be leveraged to develop the desired garment. Contractor should provide a specifications sheet and benchmark test results with prototype. Phase II will also include testing and validation of function and comfort by the Government using human subjects, flat plate and mannequin systems of textiles and garments to ensure that goals are met. Innovative techniques should be used to accommodate various body morphologies and body types for both male and female users. A strategy for semi-custom fitting and individualization should also be included. In addition, a future plan for fire retardant textiles to be incorporated into the design should also be explored. The final architecture should allow the ability to connect multiple garment based systems to a single Android device.

PHASE III DUAL USE APPLICATIONS: Phase III will explore in detail the commercialization strategy for the Electronic Embedded Wearable Compression Garment. A commercialization plan should be described including sourcing of materials and resources, affordability of the end product, manufacturability, intellectual property and other considerations. An evaluation of possibilities for transition of a viable product both within the government as well as in private sector markets will be further explored. The desired end product would be a user validated garment with the ability to collect and store physiological data of interest. Potential commercial applications include those in athlete performance, and physical strain recovery, operation in hazardous environments and other situations that would require personnel to be monitored over an extended period of time (e.g., over the span of days or weeks). This technology is relevant to the mission needs of a variety of military entities including the National Guard Bureau, US Marines, Special Forced Command, PEO Solider and other organizations. Successful Phase III partnership with these groups would include detailed conversations with their management and adaptation of the system to meet specific organizational needs and mission requirements for successful transition.

REFERENCES:1. Friedl, K.E., Buller, M.J., Tharion, W.J., Potter, A.W., Manglapus, G.L., and Hoyt, R.W. (2016). Real time physiological status monitoring (RT-PSM): accomplishments, requirements, and research roadmap. (Technical Note TN-16-2). Natick, MA: United States Army Research Institute of Environmental Medicine.

2. Tharion, W.J., Buller, M.J., Potter, A.W., Karis, A.J., Goetz, V., & Hoyt, R.W. (2013). Acceptability and usability of an ambulatory health monitoring system for use by military personnel. IIE Transactions on Occupational Ergonomic and Human Factors, 1(4), 204-214.[https://www.researchgate.net/publication/263312379_Acceptability_and_Usability_of_an_Ambulatory_Health_Monitoring_System_for_Use_by_Military_Personnel] (Uploaded in SITIS on 01/23/17)

3. Patel, S., Park, H., Bonato, P., Chan, L., & Rodgers, M. (2012). A review of wearable sensors and systems with application in rehabilitation. Journal of Neuroengineering and Rehabilitation, 9(21), 1-17.

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[https://jneuroengrehab.biomedcentral.com/articles/10.1186/1743-0003-9-21] (Uploaded in SITIS on 01/23/17)

KEYWORDS: Physiological status monitoring, Compression shirt, Embedded monitoring, Wearable sensors, Heart rate, Core temperature, Skin temperature, Accelerometry

DHA17-006 TITLE: Development of Thermal Desorption (TD) Tube Sequential Sampler

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop a thermal desorption (TD) tube sequential sampler to aid in accomplishing comprehensive air sampling on predetermined or automatically initiated timelines to improve the identification of contaminant concentrations at a certain point of time.

DESCRIPTION: Current air sampling methods that measure chemical contaminants, specifically volatile organic compounds (VOCs), over a period of time provide results in the form of time weighted averages (TWAs). These TWAs cannot identify the point in time where a concentration peak or valley may have occurred. However, the use of Thermal Desorption (TD) tubes as collection media with sequential air samplers have been used as a sampling method for conducting interval based sampling and has been accepted by the Environmental Protection Agency (EPA) (1). Commercial off the shelf (COTS) sequential samplers are no longer in production and older models utilized by the United States Air Force School of Aerospace Medicine (USAFSAM) are not adequate for future research initiatives such as, but not limited to: 1) quantifying occupational exposures during an industrial operation to identify exposures at a specific point in time during the work process, 2) sampling environmental atmosphere after a chemical weapon attack, and 3) collecting fighter aircraft pilot breathing air during the course of his/her flight.

The problem is current sequential samplers provide many limitations that hinder future research and use under true operational parameters. Current sequential samplers can only sample VOCs using one flow rate for each of the tubes during the sampling session within each bank. Also, the minimum flow time for each tube can only go as low as one minute. In addition, the sequential sampler must be manually started by either pressing a button or setting a timer and has no ability to remotely start a sampling sequence. Once the sampling sequence starts, it cannot be stopped. There is no ability to add additional tubes during the sampling to extend the sampling sequence without having to start over. The required deliverable is a device that, by supporting the use of TD tubes, can aid in obtaining chemical exposures from a specific point in time from a sampling event.

PHASE I: Design a concept for a TD tube sequential sampler detection that can be the cornerstone device for VOC sampling in the workplace, environment, and aircraft cockpit. Determine the technical feasibility of developing a device that, through the use of TD tubes as sampling media, can collect data rich VOC air samples that are time splices of an entire sampling event. Data rich samples are those that encompass all of the potential air contaminants in a sampling period and not limited to one specific compound such as through traditional cassette air sampling.

PHASE II: Based on Phase I design parameters, construct and demonstrate a functional prototype of a TD tube VOC sequential sampler that adequately collects personal worker chemical exposures from an industrial operation event. The sampler should be large enough to hold all necessary components (no bigger than shoe box size) but have the capability to conduct breathing zone air sampling on an industrial worker. Specifically, the prototype sequential air sampler should address the following problems/requirements related to successfully obtain an occupational worker exposure utilizing this sampling method:

- The sampling times for each tube should have the ability to be set as small as possible (30 seconds/tube). - Each tube should be capable of being programmed to run at a desired flow rate and sample time independent of other tubes in the sample bank. The simple cascade mode of running the series of tubes at the same flow rate and sample time should be maintained.- The device should have multiple banks (more than two) and the tubes within each bank should have the capability

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to run at the same time. For example, a device with four banks should have four tubes running at the same time, possibly at different sample times and flow rates.- The device should have indicator lights to show when it is on, off and running. Ideally, there would be an exterior screen to identify which tubes are running and at what flow rates.- The ability to manually start and stop the sequence using a remote is desired.- The device should have the ability to contain at least 30 sample tubes.- The device should have the ability to switch manifolds during sequential sampling. In other words, a user should be able to remove tubes used and replace with new tubes during the sampling process. This could eliminate the need for additional tube storage in the device.- The ability to add a PID type instrument to enable the device to automatically begin sampling once a contaminant of interest is detected. This same approach can be applied to additional sensors of interest.- The ability to, going forward, be placed on an individual to obtain personal exposures.

Validate that the device can be used in occupational, environmental, and aircraft settings. Validate, through laboratory analysis, that the TD tubes successfully collected chemical contaminants.

PHASE III DUAL USE APPLICATIONS: The TD tube sequential sampler suite will have numerous military specific, government, and commercial applications outside of purposes for medical research. For the military, the device will provide a method of identifying and quantifying contaminants in pilot and aircrew breathing air systems spanning multiple aircraft systems. In addition, this device will extend into other service branches that require monitoring of breathing air in unique operational environments such as Army tanks and hummers and Navy submarines. This translates into expanding industrial hygiene surveillance beyond the typical industrial workplace into unique military operating conditions and environments. For government applications, the device will be used for environmental sampling of hazardous material to support emergency responses from applicable government agencies. For commercial applications, the device will be used by any industry to conduct advanced occupational worker monitoring in that identifies when peaks in exposures occur. This will provide industrial hygienists improved workplace process knowledge to provide specific control measures that either reduces or eliminates exposures. The future extension of this product is the ability to provide real time analysis of VOCs.

REFERENCES:1. Woolfenden, E.A. and W.A. McClenny, “Method TO-17, Determination of Volatile Organic Compounds in Ambient Air using Active Sampling onto Sorbent Tubes, EPA/625/R-96/010b,” US Environmental Protection Agency, Research Triangle Park, NC, 1997.

KEYWORDS: aircraft aircrew breathing air, Air Force, Army, chemical exposure, emergency response, environment, industrial hygiene, Navy, thermal desorption (TD) tubes, sequential air sampling

DHA17-007 TITLE: Noninvasive Monitor of Vascular Volume Fluid Shifts

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: The envisioned monitor is a working device that quantifies serial/continuous measurements of vascular volume components to detect shifts of 2% in less than 1 hour.

DESCRIPTION: The clinical evaluation of hemorrhage, which is the single most treatable cause of mortality in trauma patients remains problematic (1,2). Vital signs measurement is a routine aspect of clinical practice and research protocols. Although it is known that transient variability and measurement error can, in principle, affect the accuracy of vital signs. Vital signs fluctuate through time because of transient perturbations (e.g. medication boluses, bouts of pain, anxiety, coughing etc.) as well as natural state variability. In addition, the accuracy of vital sign data is affected by clinicians’ technique. While meticulous attention to these factors results in improvement (3), direct measures of physiology are needed in real time to optimize therapeutic/clinical response. The ideal prototype would quantify an analyte(s) such as blood volume, plasma volume/hemoglobin ratio, red cell volume or mass and

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intestinal volume as well as the equilibrium and shifts among these compartments. While sudden blood loss is catastrophic, slower losses can also be problematic especially during prolonged transport or observation (i.e. intra-abdominal/ non- compressible hemorrhage). Thus the rate of change and the frequency of sampling with defined limits for precision and accuracy of the measurements require strict attention and interpretation.

The movement of water and water borne/soluble materials within and between the vascular system and other compartments within the body is a fundamental requirement for homeostasis and constant physiological regulation. (4). The precise, real time quantification of these variables has proven difficult to measure. Current technologies obtain signals from red blood cells and water that cannot be distinguished as intra or extra vascular fluid, and their movement and overall disposition follows the movement of the plasma component, a variable essentially unobservable noninvasively until recently. The Advanced Trauma Life Support (ATLS) manual offers a procedure for estimating blood loss in a trauma patient based on vital signs that is at best, semi-quantitative and subjective often leading to overestimation or underestimation. This SBIR topic seeks new solutions to this problem that utilize spectroscopic technology, physics, chemistry, algorithmic concepts, wearable wireless sensing, and integrative information technology solutions. It has been almost 15 years since the commercial introduction of real time noninvasive hematocrit measurement into extra-corporeal circulatory environments (5). The current solicitation looks to the next generation of these types of measurements for an innovative solution that is robust with capability to function in environmental extremes, deployable, and requiring minimal training.

PHASE I: In Phase I of the development of the Noninvasive Monitor of Vascular Volume Fluid Shifts, the successful applicant should identify a suitable technological approach and design for a prototype that is robust and feasible. After establishing detailed performance goals and measurements, a benchtop breadboard prototype is expected and constructed to demonstrate that the performance is within the goals previously set. Required Phase I deliverable will include a live demonstration of the prototype performance, the measurement of several diagnostic analytes, and a proposed algorithmic solution.

PHASE II: In Phase II of the development of a Noninvasive Monitor of Vascular Volume Fluid Shifts, performers will develop, demonstrate and validate the operation of a field-deployable, diagnostic device, suitable for operation in an extreme environment in animal and/or human subjects. Upon completion of Phase II, the offeror must produce sufficient hardware and software ready field-deployable prototypes that are suitable for third party testing and evaluation; deliver a plan for the FDA clearance process, and a clear mature manufacturing plan. The performer will deliver data supporting the performance characteristics of the device to include consistency, reliability, reproducibility, and user instructions. Data will be provided on performance (sensitivity, specificity, positive predictive value, negative predictive value, and limit of detection in several analytes to be specified in Phase II.

PHASE III DUAL USE APPLICATIONS: In Phase III of the development of a Noninvasive Monitor of Vascular Volume Fluid Shifts, the monitor/device design will be refined from third party testing, operational testing and evaluation. Execution of the manufacturing plan at low rate production will commence after FDA approvals and move to scale up and commercial off the shelf (COTS) availability for DoD and public sector acquisition. The end state device would be commercially available and provide clinical information critical to the management of quantification of blood loss and fluid shifts from point of injury to definitive clinical care.

REFERENCES:1. Peng R, Chang C, Gilmore D, et al. Epidemiology of immediate and early trauma deaths at an urban level I trauma center. Am Surg1998;64:950-4.http://www.ncbi.nlm.nih.gov/pubmed/9764699

2. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma deaths: a reassessment. J Trauma 1995;38:185-93.http://www.ncbi.nlm.nih.gov/pubmed/7869433

3. Reisner AT.Chen L, Reifman J. The association between vital signs and major hemorrhagic injury is significantly improved after controlling for sources of measurement variability. J. Critical Care2012: 27, 533e1-533e10.

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https://www.researchgate.net/publication/221708006

4. “Optimal hematocrit: theory, regulation and implications,” G. F. Birchard, Amer. Zool.1997 37, 65-72.https://www.researchgate.net/publication/249287118_

5. A new optical technique for monitoring hematocrit and circulating blood volume: Its application in renal dialysis”, R.R. Steuer, David H. Harris, James M. Conis, Dialysis and Transplantation,1993 22, 2http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291932-6920

KEYWORDS: blood volume, plasma volume, red cell volume or mass, interstitial volume, noninvasive

DHA17-008 TITLE: Self-Aligning Prosthetic Components

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop and demonstrate an automatic alignment tool for a prosthetic leg. This tool will generate objective measures to determine optimal alignment of the prosthesis and will provide real time feedback to the care provider and patient.

DESCRIPTION: Musculoskeletal injury is the leading cause of health problems for the military. It can be caused by traumatic combat injuries and physically straining risk factors such as military training, repeated combat deployment, carrying heavy loads, standing for extended periods of time, walking long distances and participating in sports [1]. There have been over 1600 major limb amputations from the current conflicts with most of those affecting the lower extremity.

Traditionally prosthetic legs are built by a prosthetist and then properly aligned while the patient is wearing the device. This process is iterative and time consuming for the patient and prosthetist. The alignment process can also lead to some variability in the biomechanics of the patient depending on the prosthetist and the patient adapting to an abnormal gait. It has been shown that poor alignment accounts for increased oxygen consumption in amputees for the short term [2] and can lead to chronic injuries such as tendonitis and lower back pain in the long term. Improper alignment could also be detrimental in prosthetics research. When a group is comparing different prosthetic legs, alignment cannot be quantitatively controlled for. As a result there could be confounding results even when the prescribing prosthetist is the same.

A solution to this problem would still need to account for patient input and prosthetist expertise. These changes could be qualitative in nature such as patient comfort, or prosthetist recommendations after monitoring the gait of the patient. An ideal solution would quantify these deviations from the self-alignment process and track them over time to inform care providers if a rehabilitation intervention, such as physical therapy or gait training, is needed. It is important that the data captured in this area is handled and stored properly either by populating a patient medical record or stored securely by the prosthetist.

The solution to this problem can come in a number of forms, whether it’s a prosthetist’s tool, a component of the prosthesis, or some other technological intervention. It should be noted however an addition to the prosthesis has a barrier to market of either needing new insurance codes or conforming to existing codes.

PHASE I: During this phase, the performer will demonstrate the feasibility of producing an alignment tool, and will outline demonstration success criteria. Additionally, the performer will design and simulate a method for achieving perfect alignment for an amputee. During this phase the performer may simplify the problem and consider only quantitative measures for alignment (i.e. perfect biomechanics rather than comfort). Designs should be able to interface with current prosthetic components (i.e. easily implemented into the user’s current device(s)). The required Phase I deliverables will include: 1) a research design for engineering the device, and 2) a preliminary prototype to demonstrate proof-of-concept evidence that demonstrates the ability to achieve alignment. Some way to

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quantify this alignment is also desired. Other supportive data may also be provided during this 6-month Phase I, $150K (max) effort.

Human subjects testing in Phase I is not allowed due to the short duration of the period of performance. The proposed solution to the requirements identified in the announcement should be demonstrated without the use of human subjects.

PHASE II: The performer shall design, develop, test, finalize and validate the practical implementation of the prototype system that implements the Phase I methodology for achieving proper prosthesis alignment, over this 2-year, $1.0M (max) effort. The testing and practical implementation of the prototype system should be relevant to Service members who have experienced limb trauma requiring the use of a prosthesis. These patients are often young and have previously demonstrated the need to perform Return to Duty, occupation, and other life activities which cannot be completed with a passive device. The device should dynamically align the prosthesis in the sagittal, frontal, and transverse planes. The demonstration of prototype should show applicability to a number of different prosthetic legs whether those legs are passive or microprocessor controlled. The device should also account for different activity specific prosthetic devices such as a running foot.

PHASE III DUAL USE APPLICATIONS: The performer is encouraged to work with commercial partners and military clinics (for example, a military treatment facility that treats patients with amputation. The three main centers include Walter Reed National Military Medical Center, San Antonio Military Medical Center, and the Naval Medical Center – San Diego) to develop a final commercial product that will allow prosthetists to quickly align a prosthetic leg, and allow researchers to consistently achieve the same alignment across multiple prosthetic legs.

REFERENCES:1. Yancosek, K. E., Roy, T., & Erickson, M. (2012). Rehabilitation programs for musculoskeletal injuries in military personnel. Current Opinion in Rheumatology, 24(2), 232–236. doi:10.1097/BOR.0b013e3283503406

2. Schmalz, Thomas, Siegmar Blumentritt, and Rolf Jarasch. "Energy expenditure and biomechanical characteristics of lower limb amputee gait: The influence of prosthetic alignment and different prosthetic components." Gait & posture 16.3 (2002): 255-263.

KEYWORDS: Prosthetics, Rehabilitation, Alignment, Pylon, Pyramid Adapter, Prosthetic Leg

DHA17-009 TITLE: Conformable Osteochondral Repair Platforms for Prevention of Post Traumatic Osteoarthritis

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop an osteochondral repair platform that is conformable to a wide variety of injury geometries without the need for pre-operative customization, that does not rely on any autologous tissue, and that is amenable to scalable manufacturing methods.

DESCRIPTION: Adult articular cartilage exhibits very little capacity for intrinsic repair. Relatively minor injuries that result in small cartilage lesions may lead to progressive cartilage degeneration and eventually to osteoarthritis. This kind of post-traumatic osteoarthritis (PTOA) can result in significant pain and disability early in life. While there have been many attempts to develop grafts to repair early focal chondral and osteochondral defects, these have demonstrated limited efficacy. Significant challenges remain in the development and clinical application of osteochondral repair platforms.

Current treatment strategies to address chondral injuries are limited; and include: observation, debridement (chondroplasty) to remove irregular edges, microfracture, osteochondral autograft or allograft transplantation, and

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autologous chondrocyte implantation (ACI). Traditionally, microfracture has been the treatment of choice for chondral lesions, especially those with smaller diameters (<2cm2). Microfracture is quick, inexpensive, and easy to perform at the time of identification of a chondral injury. However, long term data now available demonstrates that microfracture may not be as durable or effective as previously thought [1, 2]. Osteochondral autograft transplant (OATS) has been considered a gold standard treatment as it replaces an area of chondral loss with native hyaline cartilage and it has been demonstrated that OATS is superior to microfracture in terms of functional outcomes and return to pre-injury activity [3, 4]; however this comes at the expense of harvesting native cartilage from a normal site within the knee. ACI requires a two stage surgery for harvest and then implantation, but the procedure is limited in practicality in many private practice settings by high costs [4]. Outcomes after ACI are promising in comparative studies with OATS; however histological follow-up typically demonstrates a preponderance of fibrocartilage rather than native hyaline cartilage [5].

This SBIR is seeking development of an innovative osteochondral repair platform that allows for intra-operative manipulation of a device or combination product (the platform) to render it suitable for use in a wide range of osteochondral repair geometries. It is desired that the platform will not rely on any pre-operative customization methods such as autologous cell expansion or custom machining of hardware components, as such approaches increase costs and impose barriers to manufacturing scalability. It is desired that the platform will allow the surgeon to manually manipulate the product intra-operatively to fit any geometry and to perform this procedure using minimally-invasive surgical techniques. It is also desired that the platform does not require the use of any autologous cells, to include the use of debrided material, to perform its function or to achieve clinical outcomes. It is envisioned that the platform shall be intra-operatively adaptable to either chondral-only or to osteochondral repairs. Proposals in which the induction of osteogenesis or chondrogenesis is reliant on the use of processed allograft tissue will need to propose combination approaches in which processed allograft tissue is co-implanted with inductive chondrogenic and osteogenic agents (drugs and/or biologics) that are released into the injury site over timescales exceeding a minimum of three months. This requirement is intended to stimulate novel approaches and to limit those that are merely incremental over the current state of the art.

PHASE I: The performer will develop a prototype of the osteochondral repair platform and demonstrate its suitability for implantation using minimally invasive surgical techniques, as well as demonstrate osteochondral repair potential using a suitable in-vitro or ex-vivo testing method. Actual animal testing should be planned for Phase II instead where there is more time conducive to executing such research because of the additional DoD Animal Care and Use Review Office involvement in approving such research. Feasibility will be established through demonstration of intra-operative manipulability suitable to treat a variety of osteochondral defects, and through the demonstration of both chondral and osteogenic induction in a suitable in-vitro or ex-vivo system. Inclusion of subject matter experts such as surgeons and rehabilitative clinicians working in the field is encouraged in the design and development of proposed solution.

PHASE II: The performer will advance the Phase I prototype through evaluation of the performance of the proposed technology platform using a suitable animal model, ideally a weight-bearing model and make appropriate design refinements. Preclinical endpoints should include functional, radiologic, and histomorphometric assessments of osteochondral repair. The animal model selected should permit the use of minimally invasive surgical techniques in order to fully assess the performance of the technology platform. The end goal at the completion of Phase II is an osteochondral repair platform that is near finalized and well-tested in a relevant animal model that also allows for intra-operative manipulation of a device or combination product and suitable for use in a wide range of osteochondral repair geometries (through application of minimally-invasive surgical techniques). The design shall be cost effective to produce, allow for easy manufacturing scalability, require minimal training for surgeons for widespread implementation and consistency in application, and avoid additional medical/laboratory monitoring of implants or specialized surgical equipment. Additional required deliverable includes an early stage FDA regulatory plan, developed with experts who have successfully transitioned similar medical devices from conception to FDA approval.

PHASE III DUAL USE APPLICATIONS: Osteochondral repair platforms address the needs of both military and civilian populations with exceptionally large market potential. The economic impact of preventing or delaying the onset of PTOA, as well as effective treatment of it, is an addressable public health concern and is of particular importance to the DoD and the VA. The Phase III plan shall describe strategies for transitioning the Phase II

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developed and tested technology towards commercialization, to include strategies for entry into a viable FDA regulatory pathway(s) for approval and leading to commercialization with identified and ideally committed strategic partners. In addition, the final performance metrics and cost plan are to be included.

REFERENCES:1. Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc. 2014 Sep;22(9):1986-96.

2. Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med. 2009 Oct;37(10):2053-63.

3. Clar C, Cummins E, McIntyre L, Thomas S, Lamb J, Bain L, Jobanputra P, Waugh N. Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation. Health Technology Assess. 2005 Dec;9(47):iii-iv, ix-x, 1-82.

4. Cameron KL, Hsiao MS, Owens BD, Burks R, Svoboda SJ. Incidence of physician-diagnosed osteoarthritis among active duty United States military service members. Arthritis Rheum. 2011 Oct;63(10):2974-82.

KEYWORDS: post-traumatic osteoarthritis (PTOA), osteochondral defects, osteochondral repair platform, intra-operative manipulability, manufacturing scalability, inductive chondrogenic and osteogenic agents, minimally invasive.

DHA17-010 TITLE: Point of Injury Device to Maintain and Stabilize Moderate-Severe Traumatic Brain Injury (TBI) Casualties

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Development of a novel device for the stabilization of moderate to severe brain injury at point of injury/point of need that can be used by first responders in the deployed environment (medics and corpsmen).

DESCRIPTION: TBI is the signature injury of Iraq and Afghanistan conflicts, accounting for approximately 20-25% of the Joint Theater Trauma Registry (JTTR) reviewed combat casualties [1]. Between 2000 and Q3FY15, 37,147 service members sustained a moderate/severe brain injury [2].

Neurological damage from TBI is a consequence of both the moment of impact or injury as well as the secondary injury that evolves over the hours and days post-injury. To maximize outcomes, TBI care should begin as soon as possible after injury and be targeted to prevent or mitigate the secondary, delayed insults [3]. Improved TBI outcomes reflect cumulative care delivered throughout the casualty care continuum including (1) battlefield first responder care, (2) tactical field and tactical evacuation care, and (3) subsequent care across the global military care system. Early resuscitative attempts by the Medics include hemorrhage control, hypertonic saline, prehospital endotracheal intubation, and hyperventilation [4]. The “Golden Hour” is based upon the movement of the injured to a fixed location within 60 minutes. During the OIF/OEF conflicts casualties were moved rapidly and efficiently through echelons of care. Force 2025 however predicts complex combat scenarios where evacuation time is expected to be significantly longer. This requires bringing the advanced capabilities forward for Prolonged Field Care (PFC) by medics/corpsmen [5]. Military medical research, advanced development, testing, and evaluation (RDT&E) are part of a vital national security strategy to prepare for future combat scenarios. [6]

In this solicitation we are requesting proposals addressing the mitigation/prevention of secondary brain injury from moderate, severe, and penetrating TBI. Specifically this solicitation is seeking a device for use during PFC to stabilize casualties who sustain a moderate-severe TBI. The proposal shall address not only preliminary data to

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support the therapeutic claims, but it should also provide a plan for an effective, logistically supportable deployment during PFC.

The outcome for this proposal is the development of a battlefield therapeutic device for moderate-severe TBI. It is expected that this intervention will enable the Medic/Corpsman to administer interventions earlier, ultimately resulting in improved outcomes. The device will be ruggedized, portable, field deployable and be able to withstand extreme conditions such as cold, heat, and high altitude, and fit into a Medic or Corpsman bag. If capability requires power it must be battery powered with appropriate battery life.

PHASE I: Design/develop an innovative device to prevent or reduce secondary brain injury for use point of injury/Role1. The effort should clearly describe the scientific, technical feasibility, and commercial merit of developing a low-cost medical device to be used by medical providers of all levels in Combat Medical Programs. The submitter shall define the proposed concept(s) and develop key component of milestones; technical risks to the approach; costs, benefits, and schedule associated with the development and demonstration of the prototype. It is expected that the submitter analyze, assess and verify the Technological Readiness Level (TRL) of the proposed device at the conclusion of phase 1. The offeror may consider initiating discussions with the Food and Drug Administration (FDA) regarding requirements and end points necessary to obtain FDA approval. The final report shall include the design of the device, including performance goals, associated metrics, and conceptual validation through simulation or other means.

Example approaches, include, but are not limited to; medical device to allow for surgical interventions in the far forward environment; devices to decrease intracranial pressure; devices to stop intracranial bleeding; solutions to sanitize an open skull injury and prevent infection; interventions that in the past were performed at higher level of care. The device will be ruggedized, portable, field deployable and be able to withstand extreme conditions such as cold, heat, and high altitude. If capability requires power it must be battery powered with appropriate battery life.

PHASE II: Based on the Phase I design and development feasibility report, the offeror shall produce a prototype device demonstrating medical efficacy large animal (ex. sheep or swine) or non-human preclinical model of moderate-severe TBI according to the criteria and milestones developed in Phase I. The offeror will deliver the prototype for DoD evaluation. The offeror shall deliver a report describing the design and standard operation procedures (SOP) of the prototype as well as a comprehensive instruction manual for use.

It is expected that the submitter analyze, assess and verify the Technological Readiness Level (TRL) of the proposed device at the conclusion of Phase II.

Prior to conducting human studies, the offeror, using an appropriate animal model of moderate to severe TBI, must show effective stabilization and/or prevention of secondary injury to the brain. Only after such studies can the product be translated into human studies.

Based on the Phase I design and development feasibility report, the performer shall produce a prototype demonstrating potential medical utility in accordance with the success criteria developed in Phase I. The performer will then deliver the prototype for DoD evaluation. The performer shall deliver a report describing the design and operation of the prototype. The intent of this phase is for the developer to deliver a well-defined prototype (i.e., a technology or product) meeting the requirements of the original solicitation topic and which can be made commercially viable. The prototype should slow or mitigate secondary brain injury. The offeror shall provide a clear plan on how FDA clearance will be obtained.

PHASE III DUAL USE APPLICATIONS: Follow-on activities shall include a demonstration of the application of this system to the Military Health System in deployed and non-deployed environments, paramedics, civilian air evacuation transport, civilian hospitals, residency training programs, and other military medical personnel. The offeror shall focus on transitioning the device technology from research to operational capability and shall demonstrate that this system could be used in a broad range of military and civilian settings by paramedics, physicians and mid level providers in austere medical environments. The offeror shall provide a clear plan on how FDA clearance will be obtained.

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REFERENCES:1. Owens, B.D., et al., Combat wounds in operation Iraqi Freedom and operation Enduring Freedom. J Trauma, 2008. 64(2): p. 295-9.

2. Armed Forces Health Surveillance, C., Deployment-Related Conditions of Special Surveillance Interest, U.S. Armed Forces, by Month and Service, January 2003-August 2012. MSMR, 2012. 19(9): p. 20.

3. Joint Theatre Trauma System: Management of Patients with Severe Head Trauma Clinical Practice Guideline. 16 JUN 2014.

4. Fang, R., et al., Early in-theater management of combat-related traumatic brain injury: A prospective, observational study to identify opportunities for performance improvement. J Trauma Acute Care Surg. 2015. 79(4 Suppl 2): S181-7

5. Rasmussen T., et al., In the “Golden Hour”, Army AL&T, January-March 2015, 80-85

6. Rasmussen T., et al., Why Military Medical Research?, Military Medicine, 179, 8:1, 2014.

KEYWORDS: Traumatic brain injury, intracranial hypotension, intracranial hypertension, elevated intracranial pressure (ICP), cerebral vasospasm, hypoxemia, respiratory ventilation, device

DHA17-011 TITLE: Point of Injury Therapy to Maintain and Stabilize Moderate-Severe Traumatic Brain Injury (TBI) Casualties.

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Development of a novel treatment for the stabilization of moderate to severe brain injury at point of injury/point of need that can be used by first responders in the deployed environment (medics and corpsmen).

DESCRIPTION: TBI is the signature injury of Iraq and Afghanistan conflicts, accounting for approximately 20-25% of the Joint Theater Trauma Registry (JTTR) reviewed combat casualties [1]. Between 2000 and Q3FY15, 37,147 service members sustained a moderate/severe brain injury [2].Neurological damage from TBI is a consequence of both the moment of impact or injury as well as the secondary injury that evolves over the hours and days post-injury. To maximize outcomes, TBI care should begin as soon as possible after injury and be targeted to prevent or mitigate the secondary, delayed insults [3]. Improved TBI outcomes reflect cumulative care delivered throughout the casualty care continuum including (1) battlefield first responder care, (2) tactical field and tactical evacuation care, and (3) subsequent care across the global military care system. Early resuscitative attempts by the Medics include hemorrhage control, hypertonic saline, prehospital endotracheal intubation, and hyperventilation [4]. The “Golden Hour” is based upon the movement of the injured to a fixed location within 60 minutes. During the OIF/OEF conflicts casualties were moved rapidly and efficiently through echelons of care. Force 2025 however predicts complex combat scenarios where evacuation time is expected to be significantly longer. This requires bringing the advanced capabilities forward for Prolonged Field Care (PFC) by medics/corpsmen [5]. Military medical research, advanced development, testing, and evaluation (RDT&E) are part of a vital national security strategy to prepare for future combat scenarios. [6]

In this solicitation we are requesting proposals addressing the mitigation/prevention of secondary brain injury from moderate, severe, and penetrating TBI. Specifically this solicitation is seeking a drug or therapy for use during PFC to stabilize casualties who sustain a moderate-severe TBI. The proposal shall address not only preliminary data to support the therapeutic claims, but it should also provide a plan for an effective, logistically supportable deployment during PFC.

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The outcome for this proposal is the development of a battlefield therapeutic treatment for moderate-severe TBI. It is expected that this intervention will enable the Medic/Corpsman to administer interventions earlier, ultimately resulting in improved outcomes. The treatment will be field deployable and be able to withstand extreme conditions such as cold, heat, and high altitude, and fit into a Medic or Corpsman bag.

Though early studies and proof of concept may be performed in small animals, to facilitate rapid translation from preclinical study to clinical application in human population, this work is will target a gyrencephalic animal model of TBI as an end point for translation to human studies.

PHASE I: Test a promising and innovative drug to prevent or reduce secondary brain injury for use point of injury/Role1. The effort should clearly describe the scientific, technical feasibility, and commercial merit of developing a low-cost drug for use by medical providers of all levels in Combat Medical Programs. The submitter shall define the proposed concept(s) and develop key component of milestones; technical risks to the approach; costs, benefits, and schedule associated with the development and demonstration of the safety and efficacy of the treatment. It is expected that the submitter analyze, assess and verify the Technological Readiness Level (TRL) of the proposed treatment at the conclusion of phase 1. The offeror is encouraged to engage in early discussions with the Food and Drug Administration (FDA) regarding requirements and end points necessary to obtain FDA approval. The final report shall include the composition of the treatment, including performance goals, associated metrics, and conceptual validation through simulation or other means, and status of FDA communications.

Example approaches, include, but are not limited to; pharmaceutical treatment to mitigate the progression of secondary brain injury by targeting the Blood Brain Barrier, Brain Blood Barrier, inflammatory response, or resuscitative adjunct. The treatment will be field deployable and be able to withstand extreme conditions such as cold, heat, and high altitude.

PHASE II: Based on the Phase I preclinical evidence of drug efficacy to treat and/or prevent secondary brain injury following moderate- severe TBI, the offeror shall provide a treatment protocol to demonstrate drug safety/ dose escalation in a large animal (ex. sheep or swine) or non-human preclinical model of moderate-severe TBI. The offeror will deliver the treatment to the DoD for evaluation. The offeror shall deliver a report describing the design and standard operation procedures (SOP) of the treatment.

It is expected that the submitter analyze, assess and verify the Technological Readiness Level (TRL) of the proposed therapeutic drug at the conclusion of Phase II.

Prior to conducting human studies, the offeror, using an appropriate animal model of moderate to severe TBI, must show effective stabilization and/or prevention of secondary injury to the brain. Only after such studies can the project be translated into human studies. These safety studies shall be concluded in Phase III of this SBIR.

PHASE III DUAL USE APPLICATIONS: The performer shall produce a protocol (dosage, route of administration, timing of intervention) demonstrating potential medical utility in accordance with the success criteria developed in Phase II. The performer will then deliver the drug and protocol for DoD evaluation. The performer shall deliver a protocol describing the therapeutic drug dose escalation and safety testing administration. The intent of this phase is for the developer to deliver a well-described intervention meeting the requirements of the original solicitation topic and which can be made commercially viable. The offeror will provide a clear plan on how FDA clearance will be obtained.

Follow-on activities shall include the necessary studies requested by the FDA to gain clearance of the drug for use in severe TBI population. The offeror shall focus on working towards getting the therapy FDA approved for the indication to treat severe TBI. The offeror shall provide a clear plan on how FDA clearance will be obtained.

REFERENCES:1. Owens, B.D., et al., Combat wounds in operation Iraqi Freedom and operation Enduring Freedom. J Trauma, 2008. 64(2): p. 295-9.

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2. Armed Forces Health Surveillance, C., Deployment-Related Conditions of Special Surveillance Interest, U.S. Armed Forces, by Month and Service, January 2003-August 2012. MSMR, 2012. 19(9): p. 20.

3. Joint Theatre Trauma System: Management of Patients with Severe Head Trauma Clinical Practice Guideline. 16 JUN 2014.

4. Fang, R., et al., Early in-theater management of combat-related traumatic brain injury: A prospective, observational study to identify opportunities for performance improvement. J Trauma Acute Care Surg. 2015. 79(4 Suppl 2): S181-7

5. Rasmussen T., et al., In the “Golden Hour”, Army AL&T, January-March 2015, 80-85

6. Rasmussen T., et al., Why Military Medical Research?, Military Medicine, 179, 8:1, 2014.

KEYWORDS: Traumatic brain injury, intracranial hypotension, intracranial hypertension, elevated intracranial pressure (ICP), cerebral vasospasm, hypoxemia, respiratory ventilation; therapy, drug. Blood Brain Barrier, therapeutic intervention, inflammation

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