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

项目摘要 预防服务一直被强调为医疗保健系统的基本组成部分。然而， 脆弱人群在癌症发病率和死亡率方面的差异明显体现在 结直肠癌筛查(CRC)。虽然社区卫生中心可以发挥重要作用，以解决 这些差异，他们目前的手术并不是为了确保每个符合条件的患者都能及时收到CRC 放映。目前的患者自我测试依赖于粪便免疫化学测试，该测试存在低发病率 早期癌症诊断阳性，难以排除肠道出血的非肿瘤性原因。直到一个 开发了低成本、简单、高精度的诊断方法，在少数族裔、未参保的、 而低收入人口可能会保持在较低水平。这个项目的长期目标是改善无障碍 通过开发一种新的按需诊断方法来进行结直肠癌筛查，这种方法有可能 在家中启用自检，然后在将测试发送到中心后进行信号开发和诊断 设施(例如通过邮寄)。当前R21应用程序的目标是预先验证一组五个CRC 肿瘤抗原生物标志物在三维纸基微流控装置上的多重检测 以及测试使用自再生光催化剂放大质谱学的可能性 (Ms)用于早期CRC检测的信号。该测试设计稳定，可在常温下进行存储 条件，这是成功远程采样的关键条件。测试速度也足够快，可以实现点对点 在便携式质谱仪上进行谨慎测试。尽管建议的检测策略基于 在免疫分析中，使用光氧化还原催化剂放大MS信号是一种新颖的方法。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 在规定的时间内发出比色信号，以确保测试的有效性。这项研究计划将遵循三个 具体目的：(1)使用356例结直肠癌患者生物库样本来验证所选择的五个生物标志物CEA， CA199、CA242、CA125、CA153并通过纸质免疫分析优化其多重检测，(2) 用于质谱信号放大的光系统的研究和选择，以及(3)使用 现场采集的一组独立的患者样本，以通过开发验证所提出的方法 一种用于全血样本中CRC检测的3D纸基微流控设备的原型。该项目是 创新，因为它结合了新级别的简单性和实用性、适中的成本和集中的 检测策略，它将重新定义应用范围和性能/成本比，以实现准确的CRC 在服务不足的社区进行检测。这项拟议的研究意义重大，因为它有改进的潜力 所有人群的癌症护理，不分种族、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.