OUSD (R&E) CRITICAL TECHNOLOGY AREA(S): Military Infectious Disease OBJECTIVE: To develop a self-contained, low-cost, and rapid detection system for use in large-scale combat operations. This system should enable medical personnel to quickly detect and identify clinically relevant microbial organisms from clinical isolates in situations where advanced assets or high-complexity techniques are unavailable or degraded. DESCRIPTION: Future combat operations are expected to involve intense, division-on-division conflicts, resulting in high casualty volumes and prolonged medical intervention times. In this environment, medical Providers at the point of injury or in forward-deployed medical facilities will face significant challenges in diagnosing and managing microbial-mediated diseases and wound infections. Current diagnostic tools are often too complex, requiring specialized training and expertise that may not be available in austere or resource-constrained settings. Furthermore, these devices often require regular maintenance, calibration, and resupply of reagents and consumables, which may be difficult or impossible to obtain in a contested logistics environment. The consequences of this capability gap would be severe, with delayed or incorrect diagnoses potentially resulting in increased morbidity, mortality, and long-term health consequences for Warfighters. The development of a portable and reliable backup diagnostic tool is critical to ensuring that medical Providers can detect microbial pathogens quickly and accurately, even in resource-constrained environments, and provide timely and effective treatment, ultimately saving lives and improving patient outcomes. This topic seeks innovative solutions for massively scalable and distributive (i.e., affordable) rapid diagnostic tools. Existing tools, such as biochemical test strips and sugar utilization testing reagents, are useful but have several limitations, including a short shelf life, cumbersome inventory, cold-chain requirements, poor limit of detection, and difficulty detecting antimicrobial resistance, which render them of limited utility as a reliable backup diagnostic tool for resource-limited clinical labs. Additionally, the proposed solution should be able to replace or supplement existing diagnostic tools and have a clear potential for civilian use and marketplace. The goal of this request is to develop a highly integrated, simplified inventory and quality control, cost-effective, and rapid paper-based (or similar matrix) microbial identification system suitable for use in medical support of large-scale combat operations at multiple rear echelons. The proposed solution should enable rapid detection and identification of clinically relevant microbial organisms from cultured isolates, providing broad and relevant results rapidly. The system should be designed to test cultured isolates, distinguishing between Gram-positive and Gram-negative bacteria and fungi, and provide unambiguous primary output (CLIA-Waived or Moderate Complexity designation). To support use in resource-constrained environments, the system should require minimal logistical support, have a minimum 12-month shelf life at room temperature (without refrigeration), and be compatible with extreme environments. By meeting these clinical and operational requirements, the proposed solution can provide a self-contained, low-cost, and compact detection system for use in large-scale combat operations. This proposal aims to replace traditional, labor-intensive, and often inaccurate methods of microbial identification, such as biochemical test strips and sugar utilization testing reagents, with a rapid, reliable, and user-friendly diagnostic system that can accurately identify pathogens in resource-constrained environments. Note: this proposal will exclude all technologies involving electronic components, batteries, complex interfaces, ...etc. PHASE I: Given the short duration of Phase I, this phase should focus on a feasibility study or proof of concept that is tested. The goal is to investigate the potential for a self-contained, low-cost, and rapid detection system for use in large-scale combat operations. The study should combine or merge relevant assays to address the identification requirement for clinically relevant isolates. For example, selecting one Gram-positive bacterium, one Gram-negative bacterium, and one fungus from one set of sample types for demonstration is an acceptable plan. The results of the study should demonstrate feasibility, ease of operation, and proof-of-concept, and establish reasonable qualitative pathogen signal identification and confirmation. The study should combine or merge relevant assays to address the identification requirement for clinically relevant isolates. The study should provide empirical confidence and accuracy data, including controls, false positive and negative rates, and an estimate of the feasible limit of detection (LOD). The results should indicate next steps and provide a clear plan for prototype development in Phase II, including a plan for pilot clinical validation and testing with several select organisms to demonstrate the scientific principles behind the detection mechanisms. This phase will down-select promising designs for expansion in Phase II. PHASE II: During this phase, the prototype should be developed and tested to demonstrate earlier and more robust detection of diverse sets of microbes from diverse sample types and reduce the downstream need for incubators or specialized equipment in analysis. The technology should provide broad and relevant results in less than 24 hours without requiring additional steps, such as coagulation tests, urease activity, sugar utilization, catalase, etc. The testing should be conducted in controlled and rigorous conditions, evaluating the qualitative and quantitative outcomes of the product with regards to quantification, identification of pathogenic organisms, and characteristics such as reagent reactivity and antibiotic resistance. The system's design should also prioritize compactness, with dimensions not exceeding 4 x 9 inches and a thickness of less than 0.15 inches, and ease of use, with minimal training required. The results of the testing should indicate next steps and provide a clear plan for further development and commercialization. The company should focus on optimizing the design for manufacturability, with an emphasis on affordability, to influence the Government's ability to become a future customer. The offeror should consider early interactions through Q-submission (Q-SUB) process with FDA for guidance on planned pre-clinical testing. The offeror should provide a comprehensive regulatory strategy outlining details of proposed pre-clinical & pivotal testing along with specific regulatory plans, as well as a CLIA designation letter. PHASE III DUAL USE APPLICATIONS: The ultimate goal of this phase is to secure FDA approval and commercialize the technology. The company should develop partnerships that adhere to Quality Management System (QMS) requirements to demonstrate and commercialize the technology in civilian-relevant settings, such as disaster response and rural or low-resource healthcare, where there is a significant need for rapid and accurate diagnostic capabilities. The point-of-care diagnostics market is a large and growing market, with a potential value of over $72 billion, and the company should provide evidence of customer pull and interest in this technology. The company should also investigate potential opportunities with other government agencies, such as Congressionally Directed Medical Research Programs (CDMRP) and Joint Warfighter Medical Research Programs (JWMRP), that may be interested in supporting the development and commercialization of this technology. If the technology is successful, it may be considered for future acquisition programs, and the company should be prepared to work with the Government to explore potential transition paths. The company should develop a plan for making the product available to potential military and civilian users and should be aware of the potential for future government funding opportunities to support the technology's development and deployment. REFERENCES: 1. Murray, C. K. (2017). "Field Wound Care: Prophylactic Antibiotics." Wilderness Environ Med 28(2S): S90-S102. 2. Emergency and Disaster Response Market - Companies & Size. (n.d.). Www.mordorintelligence.com. https://www.mordorintelligence.com/industry-reports/emergency-and-disaster-response-market 3. Drancourt, Michel, et al. "The point-of-care laboratory in clinical microbiology." Clinical microbiology reviews 29.3 (2016): 429-447. 4. Hansen, Glen T. "Point-of-care testing in microbiology: A mechanism for improving patient outcomes." Clinical Chemistry 66.1 (2020): 124-137. 5. Ozer, Tugba, and Charles S. Henry. "based analytical devices for virus detection: Recent strategies for current and future pandemics." TrAC Trends in Analytical Chemistry 144 (2021): 116424. 6. Benjamin, S.R.; de Lima, F.; Nascimento, V.A.d.; de Andrade, G.M.; Ori , R.B. Advancement in Paper-Based Electrochemical Biosensing and Emerging Diagnostic Methods. Biosensors 2023, 13, 689. https://doi.org/10.3390/bios13070689 7. Brazaca, La s Canniatti, et al. "The use of biological fluids in microfluidic paper-based analytical devices ( PADs): Recent advances, challenges and future perspectives." Biosensors and Bioelectronics (2023): 115846. 8. Kozel, Thomas R., and Amanda R. Burnham-Marusich. "Point-of-care testing for infectious diseases: past, present, and future." Journal of clinical microbiology 55.8 (2017): 2313-2320. 9. TechSci Research, https://www.techsciresearch.com. (2024). Point of Care Diagnostics Market By Size, Share & Forecast 2029F | TechSci Research. Techsciresearch.com. https://www.techsciresearch.com/report/point-of-care-diagnostics-market/23497.html 10. U.S. Army. TRADOC. First Aid (Technical Circular 4-02.1) 01/21/2016 KEYWORDS: MDO, Infectious disease, Microbiology, diagnosis, monitoring, trauma, prolonged care
