RUI: Chronometric Biosensors

及早发现和经常监测传染病和化学威胁物质对维护国家健康和安全至关重要。快速护理点(POC)生物传感器在允许在家庭和现场进行广泛测试方面发挥了关键作用，但目前的设备在其应用中受到限制，因为它们是定性的，不够灵敏，无法检测非常低浓度的感兴趣的分析物，或者太昂贵而无法广泛部署。该项目旨在开发一种新型的定量POC生物传感器，该传感器使用时间作为检测的信号，并具有更复杂的实验室测试的灵敏度。对于POC生物传感器来说，时间是一个理想的信号，因为它可以通过简单的手表进行精确测量，这将减少设备的成本和占地面积，并且时间不像颜色变化那样主观。这项拟议的工作可能导致一种新的低成本POC生物传感器，能够满足对疾病标记物、环境污染物和安全威胁的即时检测的迫切需求。该项目还将为加州大学保利分校的本科生提供一个从事具有现实世界应用的基础科学和工程研究的非同寻常的机会，并将鼓励这一新一代科学家在STEM领域追求职业生涯。该项目的目标是开发一种新的纸基计时生物传感器，使其能够以横向流动免疫分析(LFA)的简单和低成本以及酶联免疫吸附分析(ELISA)的检测极限对分析物进行定量检测。大多数生物传感器依赖于光学或电化学信号，这需要复杂的仪器才能准确测量。所提出的生物传感器将使用时间作为检测的信号，可以通过简单的手表精确地测量，并可广泛应用于现场生物分析物的定量检测。拟议的生物传感器将包括一个纸基通道，一个由可生物降解聚合物制成的屏障，它将减缓或阻止毛细管在通道中的芯吸，以及一个简单的计时器，用于测量液体样本穿过聚合物屏障所需的时间量。通过利用聚合物降解酶(PDE)的催化活性，生物传感器将能够达到其他酶信号放大技术所特有的低检测限。该项目将优化不同的聚合物-PDE对，以使生物传感器能够与各种样品兼容，干扰最小。通过将传感器与特定识别感兴趣的生物标记物的选择步骤相结合，可以开发针对各种分析物的护理点诊断测试。该项目的模型分析物将包括蛋白质、核酸和小分子靶标。这项技术将有助于解决对定量和快速护理点诊断的迫切和未得到满足的需求，这种诊断可以快速调整，以应对新出现的威胁，如新型传染病病原体。该奖项反映了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。

Early detection and frequent monitoring of infectious disease and chemical threat agents are critical to safeguarding national health and security. Rapid point-of-care (POC) biosensors play a critical role in allowing widespread testing at home and in the field, but current devices are limited in their applications because they are qualitative, not sensitive enough to detect very low concentrations of the analytes of interest, or too expensive to be deployed widely. This project aims to develop a new class of quantitative POC biosensor that uses time as the signal for the assay and has the sensitivity of more sophisticated laboratory-based tests. Time is an ideal signal for a POC biosensor because it can be measured accurately with a simple watch, which will reduce the cost and footprint of the device, and time is not subjective the way color changes can be. The proposed work could lead to a new class of low-cost POC biosensors capable of addressing the urgent need for point-of-care detection of disease markers, environmental contaminants, and security threats. The project will also provide an extraordinary opportunity for undergraduate students at Cal Poly to engage in basic science and engineering research with real-world applications and will encourage this next generation of scientists to pursue careers in STEM fields.The objective of this project is to develop a new class of paper-based chronometric biosensors that will enable quantitative detection of analytes with the simplicity and low cost of lateral-flow immunoassays (LFAs) and the limits of detection of enzyme-linked immunosorbent assays (ELISAs). Most biosensors rely on optical or electrochemical signals, which require sophisticated instrumentation to be measured accurately. The proposed biosensors will use time as the signal for the assay, which can be measured accurately with a simple watch, and could be applied broadly for the quantitative detection of biological analytes in the field. The proposed biosensors will consist of a paper-based channel, a barrier made from a biodegradable polymer that will slow or stop capillary wicking in the channel, and a simple timer for measuring the amount of time it takes for a liquid sample to wick across the polymer barrier. By harnessing the catalytic activity of polymer degrading enzymes (PDEs), the biosensors will be able to achieve the low limits of detection that are characteristic of other enzymatic signal amplification techniques. The project will optimize different polymer-PDE pairs to enable biosensors that are compatible with a wide variety of samples with minimal interferences. By coupling the sensor with a selection step to specifically identify biomarkers of interest, point-of-care diagnostic tests for a wide variety of analytes can be developed. Model analytes for the project will include protein, nucleic acid, and small molecule targets. The technology will help address the urgent and unmet need for quantitative and rapid point-of-care diagnostics that can be adapted rapidly to address emerging threats such as novel infectious agents.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.