I-Corps: Clinical Opportunities for Lens Free Holographic Urinalysis

这个i-Corps项目的更广泛的影响/商业潜力是开发一种设备，用于改进医院环境中留置尿管(IUC)的管理。在美国，每年有数以千万计的宫内节育器被植入，以缓解尿潴留，监测尿量，并管理排尿。然而，导管相关性尿路感染(CA-UTI)--美国最常见的医院感染--出现了一个重大问题，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，而这些病例中的大多数被认为可以通过及时的干预来预防。目前，实践的标准是用肉眼检查尿液是否有问题，并间歇性地测量尿量。使用所提出的技术及早检测泌尿系统中的炎性生物标志物和细菌负荷，可以在CA-UTI发生之前客观和及时地清除IUC。除了能够开发基于证据的导管拔除触发因素外，尿流实时监测还有可能提高液体管理的精确度和检测急性变化。这个i-Corps项目基于开发一种无透镜成像设备，能够连续、非侵入性地分析尿液，用于测量临床生物标记物，以检测导管相关性尿路感染的早期迹象(CA-UTI)。建议的设备位于留置尿管(IUC)和连接的尿液引流袋之间，在床边提供实时尿液分析。无透镜数字全息术被用来获取尿液流经该设备时的全息图。一种3D稀疏相位恢复重建算法将单个原始2D全息图图像转换为重建的3D体。对每个3D体积中的颗粒进行分类和量化，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经使用人类尿液进行了验证，已知添加了红细胞和白细胞和/或大肠杆菌。用台式系统进行的测量与传统方法的测量进行了比较，该系统被证实对用于诊断尿路感染的脓尿、血尿和细菌CFU阈值上下几个数量级的浓度敏感。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.