PFI:AIR - TT: Continuous Urine Assay Instrumentation for Monitoring Kidney Function

This PFI: AIR Technology Translation project focuses on a technology to address the detection of early acute kidney injury (AKI). AKI occurs in 5 - 7% of hospitalized patients and results in a mortality rate of about 50%. The financial costs of AKI are estimated to be 8 billion dollars per year, or about $130,000 per life-year saved. It is unlikely that this high mortality and associated cost will be reduced until there are better tools for the early diagnosis of renal injury. This project translates a quartz resonator based thermal biosensor concept into a biomedical instrumentation system for continuous monitoring of kidney function. The project will focus on prototype engineering, instrumentation, and extensive benchmarking with the aim to provide accurate and automated measurements of urine creatinine. Coupled with in-line urine flow, and periodic serum creatinine concentration measurements, a system for near-continuous creatinine clearance measurement in AKI patients will be developed. The unmatched stability, sensitivity, and reproducibility of this system will allow for collection of such data for clinical analysis and early detection of conditions such as sepsis. The sensor design based on enzyme immobilized alginate beads placed in a Kapton® tubing, as an easy to swap disposable cartridge represents a promising clinical diagnostic prototype demonstration with a viable business model.This project will develop a calorimetric biosensor prototype based upon differential measurement as a way to compensate for background thermal effects. Development of a differential sensor is expected to improve both the sensitivity and the precision of measurement. The reproducibility, accuracy, and stability of the measurement system will be critically evaluated using urine samples. Intra-assay and inter-assay variability will be experimentally determined by repeated measurements and statistical methods. Accuracy will be determined by comparison of the creatinine concentrations determined by HPLC (the gold standard) and the quartz resonator. Agreement between the two methods will be determined by Bland-Altman analysis. Stability of the system will be determined by measuring the creatinine concentration of known creatinine test solutions at regular intervals over a period of 48 hours. The plot of measured concentration vs time will be used to determine the time to failure. In addition, personnel involved in this project, one graduate and one undergraduate student, will receive regulatory compliance experiences through collaboration with our partner company focused on improving patient outcomes through the successful implementation of innovative technology into medical devices. The team will be also participate in several commercialization conferences and events to establish strategic alliances and partnerships for the technology translation and commercialization.