SBIR Phase I: Ultra-Sensitive and Multiplexed Pathogen Profiling for Neonatal Sepsis Detection

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project lies in its potential to transform sepsis diagnostics and patient care, particularly for vulnerable newborns. Globally, sepsis is responsible for up to a third of neonatal deaths, with an increased burden in low- and middle- income countries. Current diagnostic methods rely heavily on blood cultures, which require substantial blood volumes, take 24+ hours to yield results, and frequently produce false negatives. The proposed DNA-based technology seeks to comprehensively identify and quantify pathogens in a few hours from small volumes of blood, critical capabilities for low-birthweight and immunocompromised newborns. The clinical impacts could include more targeted antibiotic therapy and guided therapy durations that could translate to thousands of lives saved annually, shortened hospital stays, and reduced readmission rates. This technology's compatibility with existing digital PCR hardware enables a very capital-efficient development path and reduces barriers to adoption in hospitals given the expanding use of digital PCR in clinical diagnostic laboratories. Enabling routine pathogen testing for sepsis in any community hospital represents a major opportunity. The core proposed technologies can build on a growing installed base of compatible hardware, adding new tests in other diverse applications. This Small Business Innovation Research (SBIR) Phase I project aims to develop a rapid diagnostic test for sepsis-causing pathogens in plasma samples with available digital PCR hardware that can scale to cover all critical pathogens. Pathogen identification tests must be very sensitive, fast, and able to detect a wide range of organisms. Specific innovations are proposed to make the test suitable for neonates with less than 1 mL of blood per test. Currently, digital PCR-based technologies achieve state-of-the-art sensitivity with results in a few hours but are limited in their panel breadth, typically detecting no more than a dozen analytes simultaneously. DNA sequencing can achieve comprehensive detection but is complex, costly for on-demand use, and much slower than PCR. The proposed technology combines advanced primer design with statistical algorithms to achieve critical features by targeting microbial cell-free DNA in plasma. The research objectives include developing an initial 17-target panel for common sepsis-causing pathogens and achieving analytical sensitivity below 5 genome copies/mL with turnaround time under 4 hours. Anticipated results include demonstration of clinically relevant analytical sensitivity and high analytical specificity in plasma samples. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.