SBIR Phase II: Universal electronic platform and system for rapid (direct from sample) phenotypic Antibiotic Susceptibility Testing (AST)

This SBIR Phase I project addresses the need to reduce the time associated with conducting tests currently used to establish targeted antibiotic (and dose) to treat infections. Sepsis and septic shock are one of the leading contributors to death in US Hospitals, responsible for 250,000 deaths annually (estimated at 30-50% of all hospital deaths). To combat these high death rates, time is of the essence. The administration of targeted (versus broad-spectrum) antibiotic therapy in the first five to six hours of septic shock increases the likelihood of survival by roughly fifty percent. This project combines electronics and microchannel fluidics to rapidly obtain results on antibiotic susceptibility. The project requires engineering, software development, and method development, resulting in an instrument that utilizes disposable cards to conduct the testing. The resulting product will allow transition from broad spectrum to targeted antibiotic therapy faster (1 day - weeks), leading to major benefits: (1) patient outcomes are greatly improved by faster transition to directed antibiotic therapy; (2) Reduced hospitalization stays (reduced intensive care stays), resulting in significant monetary saving for healthcare systems (estimated at a cost savings of at least $3.75B annually). (3) Reduced broad-spectrum antibiotic therapy reduces the current fostering of antibiotic resistance in healthcare settings globally. This project uses Microchannel Electrical Impedance Spectroscopy (m-EIS) to measure the "bulk capacitance" (Cb) of a suspension. Cb is a measure of the amount of charge transiently accumulated at the membranes of living cells in a suspension. Cell proliferation results in an increase in Cb, whereas cell death results in a decrease. Using m-EIS to measure bacteria in the presence of candidate antibiotics and doses, is robust, sensitive, and extremely fast, determining, in real time, cell growth, stasis, or death (in approximately 4 hrs). This project will develop a rapid, direct-from-sample, inexpensive commercial system. This is achieved by using commercial MNPs to isolate microorganisms from clinical samples such as blood culture broth, urine, sputum etc., and re-suspending the pathogens in specified volumes of growth media to obtain a suspension containing optimized concentrations of bacteria. Pathogen growth or death is then monitored using m-EIS in microfluidic cards where they are exposed to a range of antibiotic concentrations. The result is a phenotypic antibiotic susceptibility (AST) profile, yielding the minimal inhibitory concentration (MIC) of multiple candidate antibiotics within 4 hours of sample collection. The AST and MIC information is then used to treat infections with targeted therapeutic. The first products utilizing this system/method will focus on urine and positive blood culture broth 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.