SBIR Phase I: Multichannel Resonators Enabling A Phenotypic Point Of Care Infectious Disease Diagnostic

This SBIR Phase I project will build technology to reduce the time needed to identify effective antibiotics for urinary tract infections (UTIs) from 2 days to 2 hours. Every year in the US, 13 million UTIs are treated with a physician's best guess antibiotic, because antimicrobial susceptibility testing (AST) is too slow. Up to half of first guesses are wrong, opening up the possibility for infections to worsen into life-threatening sepsis and allowing antimicrobial resistance to evolve. One quarter of 1.5 million sepsis cases and at least 250,000 deaths every year begin as UTIs. Rapid AST using biophysical sensing can take guesswork out of UTI treatment, save lives, and avoid billions in unnecessary healthcare costs. By sensing bacterial cell fluctuations associated with the mechanically active processes of metabolism, motility, and growth, this novel and fundamentally different measurement concept for AST enables almost an order of magnitude increase in speed. This project will establish technical and commercial feasibility of developing the underlying sensor technology for point-of-care diagnostics that demand push-button technology operable in a hectic clinical environment. Translating innovative federally-funded technologies like this out of the laboratory and into medical clinics will build taxpayers' return on basic research investments. This project tackles a key technical hurdle for clinical implementation of rapid biophysical AST at a meaningful scale: demonstration that the demanding performance characteristics of the underlying resonating quartz sensor technology can be reproduced using low cost materials for a disposable resonator housing providing fluidic, thermal, and electrical control. The rapid biophysical AST method takes the pulse of bacterial cells. Changes in mechanical fluctuations of cells occur after exposure to an effective antibiotic, and can be sensed in real time by detecting phase noise generated by cells on a resonating crystal substrate. Key to the commercial success of this technology are multichannel resonators that can be manufactured in large quantities to perform with very low noise resonance characteristics. Best practices from low cost microfluidics studies will dovetail with those from high-tech resonator development to deliver the phase noise performance needed to pick up the biological signal. Rapid prototyping tools including 3D printing will be used for quick design iterations. If satisfactory, Phase II will optimize fabrication methodologies for both resonators and housing modules interfacing with a fully integrated clinical prototype instrument ready to support clinical trials of the technology. 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.