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

用于早期结直肠癌筛查的多重纸质血液检测

• 批准号: 10578142
• 负责人: Abraham Badu-Tawiah
• 金额: $ 21.55万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-26 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10578142
• 关键词: 3-Dimensional; Acids; Address; African American; Air; Antibodies; Biological Markers; Blood Tests; Blood specimen; CA-125 Antigen; Cancer Control; Carcinoma; Chemicals; Clinical; Collection; Colonoscopy; Colorectal Cancer; Cryopreservation; Detection; Development; Devices; Diagnosis; Diagnostic Procedure; Disease; Disparity; Early Diagnosis; Eligibility Determination; Ensure; Enzymes; Exclusion; Fecal occult blood; Feces; Fingers; Geographic Locations; Goals; Guaiac; Guidelines; Heme; Hemoglobin; Hemorrhage; Hispanic Populations; Home; Hygiene; Immunoassay; Incidence; Income; Intestines; Investigation; Life; Low Income Population; Low income; Malignant Neoplasms; Mass Spectrum Analysis; Medical; Methods; Microfluidic Microchips; Minority; Modernization; Monitor; Neighborhood Health Center; Neoplasms; Outcome; Paper; Pathology; Patients; Performance; Persons; Plasma; Play; Polymers; Population; Predisposition; Preventive; Preventive service; Proteins; Public Health; Race; Reaction; Recommendation; Reporting; Research; Research Project Grants; Role; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Signal Transduction; Specific qualifier value; Specificity; Statistical Algorithm; System; Techniques; Technology; Testing; Time; Tumor Antigens; Underserved Population; Uninsured; United States; Vulnerable Populations; Whole Blood; accurate diagnostics; biobank; biomarker selection; cancer biomarkers; cancer care; cancer health disparity; care systems; catalyst; colon cancer patients; colorectal cancer screening; cost; design; detection platform; diagnostic strategy; diagnostic value; experience; improved; innovation; interest; mass spectrometer; method development; minimally invasive; models and simulation; mortality; multiplex detection; novel; novel strategies; operation; outreach; outreach program; photosystem; point of care testing; polymerization; portability; programs; protein biomarkers; prototype; regenerative; screening; screening program; self testing; survival outcome; underserved community

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.

项目概要 预防服务被强调为医疗保健系统的重要组成部分。然而， 弱势群体的癌症发病率和死亡率存在明显差异 结直肠癌（CRC）筛查。虽然社区卫生中心可以在解决问题方面发挥重要作用 由于存在这些差异，他们目前的运作并不能确保每位符合条件的患者都能及时接受 CRC 筛选。目前的患者自检依赖于粪便免疫化学检测，但存在感染率低的问题。 积极的早期癌症识别和难以排除肠出血的非肿瘤原因。直到一个 开发了低成本、简单且高度准确的诊断方法，提高了少数族裔、无保险、 低收入人口的收入可能仍将保持在低水平。该项目的长期目标是提高可达性 通过开发一种新的按需诊断方法来进行结直肠癌筛查，该方法有潜力 在家中进行自我测试，然后将测试发送到中央后进行信号开发和诊断 设施（例如通过邮件）。当前 R21 应用程序的目标是预先验证一组五个 CRC 通过在 CRC 中的 3D 纸基微流体装置上进行多重检测来检测癌症抗原生物标志物 患者以及测试使用自再生光催化剂放大质谱的可能性 用于早期 CRC 检测的 (MS) 信号。该测试旨在稳定地实现环境下的存储 条件，这是成功远程采样的关键条件。该测试也足够快，可以实现点- 在便携式质谱仪上进行护理测试。尽管所提出的检测策略是基于 免疫分析中，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 规定时间内发出比色信号，保证测试的有效性。该研究计划将遵循三个 具体目标：(1) 使用 356 个 CRC 患者生物储存库样本来验证五种选定的生物标志物 CEA， CA199、CA242、CA125、CA153 并通过纸基免疫测定优化其多重检测，(2) 研究和选择用于质谱信号放大的光系统，以及（3）使用 在现场收集的独立患者样本集，以通过开发验证所提出的方法 用于全血样本中 CRC 检测的原型 3D 纸基微流体装置。该项目是 创新，因为它结合了新水平的简单性和实用性、适度的成本水平以及集中式 检测策略，将重新定义准确CRC的应用广度和性价比 在服务欠缺的社区进行检测。拟议的研究意义重大，因为它有可能改进 所有人群的癌症护理，无论其种族、地理位置或收入如何。