基于微流控技术的多肿瘤标志物电化学免疫传感器

Combined detection of multiple cancer markers in the early diagnosis of lung cancer has important significance and clinical needs. However, the common analysis methods in the clinic are not conducive to clinical application of multi -site rapid detection indicators for relying on large equipment and complicated operation. In this project, CEA, CYFRA21-1, NSE and ProGRP are chosen as the target for research starting point according to the suggestions from the American Society of Clinical Biochemistry. Using the integration of such technologies as microfluidic, nanoscience and electrochemical detection, a novel immune sensing technology with high sensitivity and specificity is investigated for rapid detection of multiple lung cancer markers. Studies will be focused on the preparation of the multi-parameter paper-based microfluidic, the development of portable instrumentations, the integration of the systems and their clinical applications of verification. The in-depth analysis of the response mechanism will be included and the feasibility of biosensors for the early diagnosis and the assessment of therapeutic effecacy of the lung cancer will be explored. New theories are further established about the detection of multiple lung cancer markers using the paper-based microfluidic for rapid detection of lung cancer markers. This project could provide novel methods and technical sensor support for the research of the diagnosis and treatment of lung cancer, and promote the breakthrough of frontier technology about the combined rapid immunoassay in the field of medical detection. The implementation of this project will promote cooperation and resource sharing between biomedical and electronics research fields.

多肿瘤标志物联合快速检测对肺癌的早期诊断具有重要的研究意义和临床需求；目前临床主要采用中心实验室的大型分析仪器和试剂盒进行检测分析，需要专业人员操作、检测周期较长。本项目选择CEA、CYFRA21-1、NSE和ProGRP作为研究切入点，将生物传感器、微流控芯片、纳米科学与技术以及电化学检测等技术联用，开展用于现场快速检测的高灵敏、高特异、简便的多肿瘤标志物定量检测新方法研究。重点进行电化学免疫传感器制备、便携仪表研制、系统集成及其临床应用验证等研究，实现免疫分析的集成化和微型化，深入分析响应机理，并探索该传感器用于肺癌早期诊断的可行性；进而建立用于多肿瘤标志物快速检测的免疫传感器新理论和新方法，为肺癌早期诊断相关研究提供传感器理论和技术支撑，促进生物医学电子学、信息科学等多学科领域联合发展。

在国家自然科学基金等支持下，项目主要围绕电化学传感器制备、仪表研制、系统集成及其临床应用验证等方面开展了深入研究，完成了项目研究任务。在传感器技术方面，建立了无标记的直接电化学定量检测新方法，研制出纸芯片电化学免疫传感器和纸芯片电化学适配体传感器，可实现对CEA、NSE等的定量快速检测；在便携仪表研制方面，研制出基于差分脉冲伏安（DPV）检测的小型便携电化学检测仪，具有实时显示处理、高速USB通讯接口等功能，可与自制传感器纸芯片电化学集成用于对CEA、NSE的定量检测，其检出限达到10 pg/mL；在临床样本应用测试验证方面，自制的纸芯片电化学传感器检测结果与临床大型仪器结果之间相关性良好；该新方法还可进一步拓展用于如性激素参数等的定量检测，具有良好的实用价值和应用前景。在项目执行期间，发表相关论文29篇，其中，SCI/EI收录13篇；在纸芯片电化学传感器及传感器表面修饰、电化学检测仪方面获得国家发明专利授权3项、国家发明专利受理7项。在研究团队培养方面，培养副研究员3人，培养学术骨干5人进入中国科学院电子学研究所“优秀青年人才计划”；培养研究生获得研究生国家奖学金、中国科学院院长优秀奖、中国科学院电子学研究所顶秀奖等奖项4人次。