Department of Bioengineering, University of Texas at Dallas, Richardson, Texas 75080, United States.
Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas 75080, United States.
ACS Sens. 2022 Jan 28;7(1):186-198. doi: 10.1021/acssensors.1c01951. Epub 2021 Dec 20.
Urine Prostaglandin E2 (PGE2) has been identified as an attractive diagnostic and prognostic biomarker for urinary tract infection (UTI). This work demonstrates the use of PGE2 as a biomarker for rapid and label-free testing for UTI. In this work, we have developed a novel electrofluidic capacitor-based biosensor that can used for home-based UTI management with high accuracy in less than 5 min for small volume urine samples (<60 μL). The PGE2 biosensor works on the principle of affinity capture using highly specific monoclonal PGE2 antibody and relies on non-faradaic electrical impedance spectroscopy (EIS) and Mott-Schottky (MS) for quantifying subtle variations in PGE2 levels expressed in human urine (pH 5-8). Dynamic light scattering experiments were performed to characterize surface charge properties and the impact of bulk interferents on the interfacial modulation of electrical properties due to binding and urine pH variations. Binding chemistry between the key elements of the immunosensor stack was validated using attenuated total reflectance-Fourier transform infrared spectroscopy and surface plasmon resonance studies. Linear calibration dose responses were obtained for PGE2 for both EIS and MS. The sensor reliably distinguished between UTI negative and UTI positive cases for both artificial (pH 5-8) and pooled human urine samples. The sensor was not found to cross-react with Prostaglandin D2, a structurally similar interferent, and other abundant urine interferents (urea and creatinine). Human subject studies confirmed the validity of the sensor for robust and accurate UTI diagnosis. This work can be extended to achieve easy, reliable, and rapid home-based UTI management, which can consequently help physicians with timely and appropriate administration of therapy to improve patient outcomes and treatment success.
尿前列腺素 E2（PGE2）已被确定为尿路感染（UTI）有吸引力的诊断和预后生物标志物。本工作证明了 PGE2 作为生物标志物用于快速和无标记的 UTI 检测。在这项工作中，我们开发了一种新颖的基于电流体电容器的生物传感器，可用于家庭 UTI 管理，对于小体积尿液样本（<60μL），其在不到 5 分钟内即可实现高精度检测。PGE2 生物传感器基于使用高度特异性单克隆 PGE2 抗体的亲和力捕获原理，依赖于非法拉第阻抗谱（EIS）和 Mott-Schottky（MS）来定量检测人尿中 PGE2 水平的细微变化（pH5-8）。进行动态光散射实验以表征表面电荷特性和体相干扰物对界面电特性调制的影响，这种调制是由于结合和尿液 pH 值变化引起的。使用衰减全反射-傅里叶变换红外光谱和表面等离子体共振研究验证了免疫传感器堆叠的关键元件之间的结合化学。对于 EIS 和 MS，均获得了 PGE2 的线性校准剂量响应。该传感器可可靠地区分 UTI 阴性和 UTI 阳性的人工（pH5-8）和混合人尿样本。该传感器未发现与结构相似的干扰物前列腺素 D2 以及其他丰富的尿液干扰物（尿素和肌酐）发生交叉反应。人体研究证实了该传感器用于稳健和准确的 UTI 诊断的有效性。这项工作可以扩展到实现简单，可靠和快速的家庭 UTI 管理，这可以帮助医生及时和适当地进行治疗，以改善患者的预后和治疗效果。
