DoD STTR Program Solicitation FY15.B

Demand for plasma-based therapies continues to rise. In the US alone, there were ~29 million donations of plasma in 20131. Plasma-based therapies are also in high demand in the military. Warfighters with combat casualties often require massive plasma transfusions for trauma, shock, burn injury, and emergency surgery. Today, only Type AB blood donors, who account for only 4% of the overall donor population, are considered universal plasma donors. This greatly limits the overall plasma donor pool, and necessitates time-consuming and costly screening of non-AB plasma. The restricted donor pool poses additional logistic challenges to already complicated blood transfusion practices in the far-forward setting.2 Anti-A and anti-B (IgG and IgM antibodies) found in plasma from Type A, B or O donors can mediate blood cell hemolysis if not appropriately matched. These antibodies bind to A and B blood group antigens found on the surfaces of red blood cells, lymphocytes, endothelial cells and platelets in a recipient, triggering potentially dangerous hemolytic transfusion reactions. Plasma from Type AB blood donors lack these antibodies and do not cause hemolytic reactions. Therefore, blood purification/extraction technologies that selectively remove anti-A and anti-B antibodies from plasma can potentially produce universal plasma and significantly expand the plasma donor pool. One potential solution is the passage of plasma through a small, portable, biocompatible filter that can efficiently and selectively remove anti-A and anti-B (IgG and IgM antibodies) from plasma while sparing beneficial substances in plasma such as coagulation factors and albumin. Such a filter should ideally be: • Easy to implement with little to no supervision • Capable of being used at the point of plasma collection or transfusion, using gravity alone with no change in standard transfusion times • Easily stored at ambient temperature without the need of refrigeration, with a shelf-life of more than 2 years • Devoid of biologics, antibodies or ligands that can leach or degrade over time • Simple to manufacture and gamma sterilizable • Easy to use and not cost prohibitive. PHASE I: The contractor will develop and screen various chemical / synthetic modifications of the base filtration technology, optimizing anti-A and anti-B antibody removal capacity as a proof-of-concept. As the feasibility criteria for Phase I, the contractor is required to demonstrate at least 70% selective removal of anti-A and/or anti-B (IgG and IgM antibodies) from plasma, while avoiding the removal of no more than 25% of coagulation factors and beneficial substances. Beneficial substances include albumin, total IgG, certain coagulation factors, and electrolytes (Na+, K+, and Ca2+). The research plan should include a R&D concept and in vitro screening methods to support the investigation. PHASE II: The contractor will down select the optimal filtration technology developed in Phase I and target anti-A and anti-B (IgG and IgM antibodies) removal of >90%, while removing no more than 10% of coagulation factors and beneficial substances. The Phase II research plan should incorporate a detailed product design specification and plan for custom tooling, manufacturing, and final delivery of a prototype DHP - 7 filtration/extraction device. The contractor shall furthermore demonstrate device compatibility with gamma sterilization. PHASE III: The contractor will conduct an animal safety and efficacy study. The device should be tested for ISO 10993 biocompatibility and immunohematological compatibility testing and be compatible with standard hospital transfusion and blood filtration equipment. The contractor will be required to apply for IDE approval from the FDA to run a small human pilot trial. This device could expand the plasma donor pool and alleviate substantial donor transfusion restrictions in definitive care, combat casualty care, and austere environments globally.

Since 8 December 2007, the war in the Middle East has seen over 30,000 soldiers injured in combat with the majority of these injuries occurring the last few years [1]. Despite the type of the injury, the majority of the wounded have suffered some degree of soft tissue injury which needs to be addressed. Since these soldiers endure harsh conditions and their wounds are much more likely to become infected while in the field, early treatment is critical. Many colonized wounds harbor bacterial loads that can eventually lead to infections that not only can result in significant delays in healing (affecting troop deployment) but also increase rates of morbidity and mortality. Furthermore, wound healing is a complex process that involves a series of events including initial clotting, inflammation, granulation tissue formation, epithelialization, collagen synthesis, and finally tissue remodeling. Finding the optimal treatment for various types of wounds would also save time and money by allowing Warfighters to return to service as quickly as possible. Treatments that may be effective at stimulating one type of injury may not be effective on a different type of injury. For example, a diabetic wound ulcer not healing because of dead necrotic tissue and lack of blood flow may benefit significantly from a stimulatory laser or lightwave treatment rather than a standard antimicrobial wound care dressing treatment. Laser and lightwave therapies have been used as an adjunctive treatment in acute wound healing at military treatment facilities (MTFs) in treating superficial epidermal injuries such as contractures or for reducing scarring in DHP - 7 Warfighters. Typically, a laser or lightwave technology is placed over a wounded area, and the photon energy from the light stimulates the healing process. The heat brings blood to the wound and increases circulation, which expedites recovery. Several MTFs currently use pulsed dye lasers (PDL) and excimer lasers for epidermal treatments. PDLs typically use a concentrated beam of light while an excimer laser uses a combination of a noble gas (argon, krypton, or xenon) and a reactive gas (fluorine or chlorine) to excite molecules at various wavelengths. Compared to gases and most solid state lasing media, a dye can generally be used for a much wider range of wavelengths. There are a number of other commercial lasers and lightwave devices on the market today which have potential for wound healing application. Furthermore, several researchers continue to work on various novel developmental device efforts for process optimization and alterative treatment modalities [2]. Animal modeling studies have suggested laser and lightwave therapy can be beneficial in treating more invasive wounds such as acute burns, partial thickness, full thickness, musculoskeletal injuries, degenerative damage, and chronic wounds [3, 4]. Very few controlled studies have explored the idea of using lasers or light wave therapies for dermis or subcutanenous thickness injuries in humans [5, 6]. It is the goal of this topic to explore the feasibility of developing or adapting an existing device that can meet the military need of accelerating the wound healing process for deep dermal injuries (dermis, subcutaneous, and muscular). The device should function by means of laser or lightwave energy. The device should be accessible by trained medical personnel in a military treatment facility. Finally, the device should demonstrate a clear improvement in wound healing as compared to the control therapy. Design of such a system to accelerate wound healing injuries using up-to-date computer, laser, and mechanical engineering technologies is expected to be technically challenging, and will require innovative and creative approaches to meet the technical goals. Significant flexibility in formulating an approach will be considered. PHASE I: Develop design of an automated laser or lightwave wound healing system. Electronic engineering plans should be generated that allow 3-dimensional, rotational views of all components of the proposed system. A document describing the proposed operation and functionality of the system should also be generated. Furthermore, this phase should include a plan for development, clinical validation, regulatory strategy, concept of the proposed device, and a literature search to support feasibility. PHASE II: Develop and demonstrate efficacy of a working prototype based on Phase I work suitable for FDA clinical trials. Conduct in-depth statistically significant testing in an appropriate animal model to show functionality, safety, toxicity, effectiveness, for deep dermal wounds (eg, second degree burns, partial thickness injuries, full thickness injuries, ulcers, etc.). Identify clinical sites for validation and primary investigators and have preliminary talks with FDA regarding regulatory path (at least pre-IDE, preferably IDE). Finalize plans pivotal trial protocol. PHASE III: Design, develop, and conduct a pivotal clinical trial. The purpose is to create further indications, establish human safety and effectiveness in a clinical setting with the goal of gaining additional FDA clearance for the use of the device in wound management. Expanding the indications would pave the way for future uses in the healing of all types of tissue to include muscle, tendon and bone. In addition, emphasis on the treatment of deep pain would be addressed. The device indication would be expanded to include not just definitive care but to combat casualty care and austere environments.

Rapid Integrated Circuit (IC) inspection using x-ray microscopy requires novel x-ray scintillating materials with high efficiency and high spatial resolution. Current scintillator materials, such as Cesium Iodide (CsI), suffer from a trade-off between efficiency and spatial resolution. Novel materials with higher stopping power and light yields are necessary to address the stringent requirements of fast, high resolution x-ray microscopy. PHASE I: Perform a study to compare the novel scintillator materials to existing commercially available scintillators. Develop a plan to produce an x-ray scintillator that meets the following characteristics: ● Transparent to visible light (particularly at the scintillating frequency) ● At least 5% efficient for 9keV photons ● 0.5 micrometer spatial resolution ● Afterglow decays to less than 0.0001% of the signal, 0.5s after exposure is removed ● Defect free (no dark spots or imperfections larger than 0.25um) ● Homogeneous across a 5mm diameter active area ● No browning (the transparency of the scintillator should not vary over time) The required manufacturing apparatus must be identified and detailed in the production plan. Deliver a report of research that presents tradeoffs between the new scintillator and existing, commercially available scintillators (in all the above mentioned characteristics). If any of the constraints cannot be adhered to, the report must include relevant research and rationale. Offerors may provide alternative parameters that are both attainable and consistent with the goals summarized above. The report must also include all generated files (e.g., CAD drawings), an explanation of feasibility, a program plan for manufacture, a demonstration of the capability and test results for the chosen material. PHASE II: Based on the aforementioned research make a full size, high quality prototype of the scintillator detailed in Phase I. Test and deliver the sample, characterization results, and all generated files (e.g., final CAD drawings, test results, etc.). PHASE III: There may be opportunities for further development of this scintillator for use in a specific military or commercial application. During a Phase III program, offerors may refine the performance of the design and produce pre-production quantities for evaluation by the Government. POTENTIAL DUAL USE APPLICATIONS: The scintillator would be applicable to fast, high-resolution microscopy for both commercial and government use. It is a critical component of x-ray microscopes routinely used in the fields of semiconductors, failure analysis, energy generation and storage. High duty cycle scintillators can help optimize processes like fuel injection, cells charging and discharging, graphite nuclear radiation damage analysis, crack formation, and many other novel material research projects. Government applications include failure analysis and characterization of advanced semiconductor fabrication processes.