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

这个PFI: AIR技术翻译项目的重点是一项技术，以解决早期急性肾损伤（AKI）的检测。AKI发生在5 - 7%的住院患者中，其死亡率约为50%。AKI的财务成本估计为每年80亿美元，或每个生命年节省约13万美元。在有更好的早期诊断肾损伤的工具之前，这种高死亡率和相关费用不太可能降低。该项目将基于石英谐振器的热生物传感器概念转化为生物医学仪器系统，用于连续监测肾功能。该项目将侧重于原型工程、仪器和广泛的基准测试，目的是提供准确和自动化的尿肌酐测量。结合在线尿流和定期血清肌酐浓度测量，将开发一种用于AKI患者近连续肌酐清除率测量的系统。该系统无与伦比的稳定性、灵敏度和可重复性将允许收集此类数据用于临床分析和脓毒症等疾病的早期检测。传感器设计基于酶固定化海藻酸珠放置在Kapton®管，作为一个易于交换的一次性药筒代表了一个有前途的临床诊断原型演示与可行的商业模式。该项目将开发一个基于差分测量的量热生物传感器原型，作为补偿背景热效应的一种方式。差分传感器的开发有望提高测量的灵敏度和精度。将使用尿液样本对测量系统的再现性、准确性和稳定性进行严格评估。测定内和测定间的变异性将通过重复测量和统计方法实验确定。准确度将通过比较HPLC（金标准）和石英谐振器测定的肌酐浓度来确定。两种方法之间的一致性将通过Bland-Altman分析来确定。系统的稳定性将通过测量已知肌酸酐测试溶液的肌酸酐浓度在48小时内定期间隔来确定。测量浓度与时间的关系图将用于确定失效时间。此外，参与该项目的人员，一名研究生和一名本科生，将通过与我们的合作伙伴公司的合作获得监管合规经验，重点是通过成功地将创新技术应用于医疗设备来改善患者的治疗效果。该团队还将参加若干商业化会议和活动，为技术翻译和商业化建立战略联盟和伙伴关系。

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.