I-Corps: Clinical Opportunities for Lens Free Holographic Urinalysis

I-Corps项目的更广泛影响/商业潜力是开发一种设备，用于改善医院环境中留置导尿管（IUC）的管理。在美国，每年有数千万个IUCs被植入，以缓解尿潴留、监测尿量和管理排尿。然而，导管相关性尿路感染（CA-UTI）是美国最常见的医院感染，它是由放置IUC后尿路细菌定植引起的。CA-UTI的一个重要危险因素是长期使用IUC，大多数病例被认为可以通过及时干预来预防。目前的做法标准是用肉眼检查尿液是否有问题，并间歇性地测量尿量。使用所提出的技术早期检测泌尿系统中的炎症生物标志物和细菌负荷，可以在CA-UTI发病前客观及时地取出IUC。除了能够开发基于证据的导管拔除触发器外，实时监测尿流还具有提高流体管理精度和检测急性变化的潜力。I-Corps项目的基础是开发一种无晶状体成像设备，该设备能够对尿液进行连续、无创分析，用于测量临床生物标志物，以检测导尿管相关性尿路感染（CA-UTI）的早期症状。该装置位于留置导尿管（IUC）和附带的尿引流袋之间，可在床边提供实时尿液分析。无透镜数字全息术用于获取尿液流过设备时的全息图。一种三维稀疏相位恢复重建算法将单个原始二维全息图像转换为重建的三维体。每个3D体积中的颗粒被分类和量化，以报告临床相关信息，包括细菌菌落形成单位（cfu）、白细胞计数和红细胞铸型的存在。一个台式原型系统已被验证，使用已知添加红细胞和白细胞和/或大肠杆菌的人类尿液。将台式系统的测量结果与常规方法的测量结果进行比较，证实该系统对用于诊断尿路感染的脓尿、血尿和细菌cfu的阈值高于或低于几个数量级的浓度敏感。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of a device for improving the management of indwelling urinary catheters (IUC) in the hospital setting. Tens of millions of IUCs are inserted each year in the United States to relieve urinary retention, monitor urine output, and manage urination. However, a significant problem occurs with catheter-associated urinary tract infections (CA-UTI) - the most common nosocomial infection in the United States – which are caused by bacterial colonization of the urinary tract following placement of an IUC. A significant risk factor for CA-UTI is prolonged use of an IUC, and a majority of these cases are believed to be preventable through timely intervention. Currently, the standard of practice is to examine urine with the naked eye for problems and measure volume intermittently. Early detection of inflammatory biomarkers and bacterial load in the urinary system using the proposed technology may enable objective and timely removal of the IUC before the onset of CA-UTI. In addition to enabling the development of evidence-based triggers for catheter removal, real-time monitoring of urine flow has the potential to increase fluid management precision and detect acute changes.This I-Corps project is based on the development of a lens-free imaging device capable of continuous, non-invasive analysis of urine for measuring clinical biomarkers to detect early signs of catheter-associated urinary tract infections (CA-UTI). The proposed device sits in-line between an indwelling urinary catheter (IUC) and an attached urine drainage bag, providing real-time urinalysis at the bedside. Lens-free digital holography is used to acquire holograms of the urine as it flows through the device. A 3D sparse phase recovery reconstruction algorithm transforms single raw 2D hologram images into reconstructed 3D volumes. Particulates in each 3D volume are classified and quantified for reporting clinically relevant information including bacteria colony forming units (CFUs), white blood cell count, and the presence of red blood cell casts. A benchtop prototype system has been validated using human urine with known additions of red and white blood cells and/or E. coli bacteria. Measurements made with the benchtop system were compared with measurements from conventional methods, and the system was confirmed to be sensitive to concentrations several orders of magnitude above and below thresholds of pyuria, hematuria, and bacterial CFUs used for the diagnosis of UTIs.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.