Multiplexed Paper-Based Blood Test for Early-Stage Colorectal Cancer Screening

项目摘要 预防服务被强调为医疗保健系统的重要组成部分。但 弱势群体的癌症发病率和死亡率的差异很明显， 结直肠癌（CRC）筛查。虽然社区卫生中心可以在解决 这些差异，他们目前的运作并没有建立，以确保每一个合格的病人得到及时的CRC 筛选目前的患者自我测试依赖于粪便免疫化学测试，该测试被低比率的 早期癌症识别阳性，难以排除肠出血的非肿瘤原因。直到 低成本，简单，和高度准确的诊断方法的开发，筛查率在少数民族，没有保险， 低收入人口可能会保持在低水平。该项目的长期目标是改善无障碍环境， 通过开发一种新的按需诊断方法， 在将测试发送到中央处理器后，在家中进行自我测试，然后进行信号开发和诊断 便利（例如邮寄）。当前R21应用程序的目标是预先验证一组5个CRC 通过在CRC中的3D纸基微流体装置上进行多重检测的癌抗原生物标志物 以及测试使用自再生光催化剂放大质谱的可能性 (MS)用于早期CRC检测的信号。该试验设计为稳定，可在环境温度下储存 条件，成功远程采样的关键条件。该测试也足够快速，以实现点- 在便携式质谱仪上进行检测。虽然所提出的检测策略是基于 在免疫测定中，使用光氧化还原催化剂来放大MS信号是新颖的。传统的免疫分析测试使用 通过酶扩增进行比色检测，需要冷藏和分析一次启动的 在规定的时间内检测比色信号，以确保测试的有效性。该研究计划将遵循三个 具体目的：（1）使用356个CRC患者生物储存库样品来验证五种选择的生物标志物CEA， CA 199、CA 242、CA 125、CA 153，并通过纸基免疫分析优化其多重检测，（2） 研究和选择质谱信号放大的光系统，（3）使用 在现场收集的一组独立的患者样本，以通过开发验证所提出的方法 用于全血样品中CRC检测的原型3D纸基微流体装置。该项目 创新，因为它结合了新的简单性和实用性水平，适度的成本水平，以及集中的 检测策略，这将重新定义准确CRC的应用范围和性能/成本比 在服务不足的社区进行检测。这项研究具有重要意义，因为它有潜力改善 所有人群的癌症护理，无论其种族，地理位置或收入。

Project Summary Preventive services have been emphasized as essential components of the medical care system. However, the disparities in cancer incidence and mortality rates experienced by vulnerable populations are evident in rates of screening for colorectal cancer (CRC). While community health centers can play an important role in addressing these disparities, their current operations are not set up to ensure that every eligible patient receives timely CRC screening. The current patient self-test relies on a fecal immunochemical test that is plagued with low rates of positive early cancer identification and difficulty in excluding non-neoplastic causes of intestinal bleed. Until a low-cost, simple, and highly accurate diagnostic method is developed, screening rates in minorities, uninsured, and low-income populations will likely remain low. The long-term goal of this project is to improve the accessibility of CRC screening through the development of a new, on-demand diagnostic approach that has potential to enable self-testing at home followed by signal development and diagnosis after sending the test to a central facility (for example by mail). The objective of the current R21 application is to pre-validate a set of five CRC cancer antigen biomarkers through their multiplexed detection on a 3D paper-based microfluidic device in CRC patients as well as to test the possibility of using a self-regenerative photo-catalyst to amplify mass spectrometry (MS) signals for early CRC detection. The test is designed to be stable enabling storage under ambient conditions, a condition critical for successful remote sampling. The test is also rapid enough to enable point-of- care testing on a portable mass spectrometer. Although the proposed detection strategy is based on immunoassay, the use of a photoredox catalyst to amplify MS signal is novel. Traditional immunoassay tests use colorimetric detection via enzyme amplification, necessitating both cold storage and analysis of the once-initiated colorimetric signal within a specified time to ensure the validity of the test. This research program will follow three specific aims: (1) using 356 CRC patient biorepository samples to validate the five selected biomarkers CEA, CA199, CA242, CA125, CA153 and to optimize their multiplexed detection via paper-based immunoassay, (2) investigation and selection of a photosystem for mass spectrometry signal amplification, and (3) using an independent set of patient samples collected in the field to validate proposed method through the development of a prototype 3D paper-based microfluidic device for CRC detection in whole blood samples. The project is innovative because it combines new levels of simplicity and practicality, modest levels of cost, and a centralized detection strategy, which will redefine the breadth of application and performance/cost ratio for accurate CRC detection in underserved communities. The proposed research is significant because it has potential to improve cancer care among all populations, irrespective of their race, geographic location, or income.