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

这个PFI：空气技术转换项目专注于解决早期急性肾损伤(AKI)检测的技术。AKI发生在5-7%的住院患者中，导致约50%的死亡率。据估计，AKI每年的财务成本为80亿美元，或者说每个节省下来的生命年大约13万美元。在有更好的工具来早期诊断肾损伤之前，这种高死亡率和相关成本不太可能降低。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。该项目将专注于原型工程、仪器仪表和广泛的基准测试，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肌酐浓度测量，将开发一种几乎连续测量AKI患者内生肌酐清除量的系统。该系统无与伦比的稳定性、敏感性和重复性将使收集此类数据用于临床分析和早期检测脓毒症等情况成为可能。该传感器设计基于酶固定化海藻酸盐珠，放置在Kapton®管道中，作为一种易于更换的一次性墨盒，代表了一种有前景的临床诊断原型演示和可行的商业模式。该项目将开发一种基于差示测量的量热生物传感器原型，以补偿背景热效应。差动传感器的研制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复性、准确性和稳定性进行严格评估。试剂盒内和试剂盒间的可变性将通过重复测量和统计方法进行实验确定。准确度将通过比较高效液相色谱仪(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由Bland-Altman分析确定。该系统的稳定性将通过在48小时内定期测量已知肌酐测试溶液的肌酐浓度来确定。测量的浓度与时间的关系图将被用来确定故障时间。此外，参与该项目的人员，一名毕业生和一名本科生，将通过与我们的合作伙伴公司合作，获得监管合规经验，重点是通过在医疗设备中成功实施创新技术来改善患者结果。该小组还将参加几个商业化会议和活动，以建立技术翻译和商业化的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.