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

这个PFI：AIR技术翻译项目专注于解决早期急性肾损伤（阿基）检测的技术。阿基发生在5 - 7%的住院患者中，导致约50%的死亡率。阿基的财务成本估计为每年80亿美元，或每挽救一个生命年约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用于连续监测肾功能的生物医学仪器系统。该项目将专注于原型工程，仪器和广泛的基准测试，旨在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，将开发一种用于阿基患者的近连续肌酐清除率测量的系统。该系统无与伦比的稳定性、灵敏度和再现性将允许收集这些数据用于临床分析和早期检测诸如脓毒症的状况。该传感器设计基于置于Kapton®管中的酶固定化藻酸盐珠，作为一种易于更换的一次性盒，代表了一种具有可行商业模式的有前途的临床诊断原型演示。该项目将开发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。差动式传感器的开发有望提高测量的灵敏度和精度。将使用尿样对测量系统的重现性、准确度和稳定性进行严格评价。将通过重复测量和统计方法，通过实验确定试验内和试验间变异性。通过比较HPLC（金标准）和石英谐振器测定的肌酐浓度，确定准确度。将通过Bland-Altman分析确定两种方法之间的一致性。通过在48小时内定期测量已知肌酐供试品溶液的肌酐浓度来确定系统的稳定性。将使用测得浓度与时间的曲线确定失效时间。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合作获得法规合规经验，该公司专注于通过将创新技术成功应用于医疗器械来改善患者的治疗效果。该团队还将参加多个商业化会议和活动，以建立技术转化和商业化的战略联盟和合作伙伴关系。

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.