Abstract COMBiNATi will work with Stanford University to bring the world’s first integrated ID+AST UTI diagnostic platform to the market by combining COMBiNATi’s “one-click” cost-effective dPCR platform with Stanford’s pathogen identification (ID) HRMA algorithm for broad detection, deep characterization and absolute quantification of UTI pathogens. By the end of the Phase 1 project, we will deliver the prototype instrument for ID and AST, scale-ready consumables for dPCR + HRM and culture + qPCR, machine-learning software algorithm for melt curve analysis, and prove the feasibility by identifying and quantifying the top two urinary tract infection bacteria. We will first develop two consumables: an 100k partition ID chip and a 32-lane, 10k partition per lane AST plate based on the micro-injection molding design rules established by COMBiNATi. An integrated system with thermal control and imaging capability will then be developed for HRM and qPCR processes. The prototype system will then be transferred to Stanford University where mock samples including both isolated bacteria and contrived urine samples will be tested on the platform for integrated pathogen ID and AST determination.

Narrative Urinary Tract Infection (UTI) is one of the most common community-acquired bacterial infection. However, like other bacterial infections, standard culture-based diagnosis of UTI requires at least 2-3 days from sample acquisition to result reporting. Despite technological advancements, the process remains time- consuming and requires significant technical expertise. Automated instruments remain bulky and still require clonal isolation of the pathogens from the body fluid samples prior to AST. Additionally, the lack of definitive microbiological diagnosis that is rapid enough to achieve evidence-based treatment has driven the over- and misuse of broad-spectrum antibiotics. We believe the proposed integrated ID + AST platform has the potential to enable deep genetic analyses of clinical samples to provide rapid precision UTI triage and MIC determination in a timely and cost-efficient manner to positively impact patient care as well as promote the use of narrow spectrum antibiotics to favorably impact antibiotic resistance profiles.