复合SERS编码微球及其微阵列传感器对多组分肿瘤标志物高通量可视化检测

Cancer is one of the major diseases in today's society that endanger human health and life. The development of rapid, specific and sensitive tumor markers detection platform has become an urgent need for early diagnosis of cancer. Surface-enhanced Raman spectroscopy (SERS) has a great advantage in rapid detection of tumor markers, but there are problems such as poor reproducibility and difficulties in high-throughput and multiple detection. This project aims at combining Raman encoding, immunoassay and microarray to develop ultra-sensitive, high-throughput and simultaneous detection method and in vivo tissue imaging analysis for multiple tumor markers. The research process is as follows: (1) Design and fabricate composite SERS encoding microspheres with high density Raman hot spots to obtain highly enhanced and stable SERS coded probes. (2) According to the basic principles of Raman coding and immunoassay, rapid combined detection and micro Raman imaging of multiple tumor markers in serum, cell surface and tumor tissue can be achieved. (3) By combining with chemometrics, establish algorithm for SERS microarray data analysis and tumor markers quickly distinguish, and finally establish a new analytical platform for high-throughput visual detection of tumor markers. It is expected that our research results will provide a scientific basis and technical approach for combined detection and medical diagnosis of tumor markers.

癌症是当前危害人类健康的重大疾病之一，开发快速、特异性好、灵敏度高的肿瘤标志物检测平台，已成为癌症早期诊断的迫切需求。表面增强拉曼光谱（SERS）在肿瘤标志物快速灵敏检测方面具有巨大的优势，但存在重现性差及无法实现多组分高通量检测等问题。本项目拟将拉曼编码、免疫分析和微阵列生物芯片相结合，发展多组分肿瘤标志物的高通量同步检测与活体组织成像分析方法。（1）设计合成具有高密度拉曼热点的复合SERS编码微球，获得高增强和高稳定的SERS编码探针；（2）根据拉曼编码和免疫分析原理，实现对血清、肿瘤细胞和组织的多组分肿瘤标志物的同步检测与微区拉曼成像；（3）结合化学计量学算法，建立SERS微阵列芯片数据分析与肿瘤标志物快速区分算法，最终建立适合肿瘤标志物高通量可视化检测的新型分析平台。预期成果将为肿瘤标志物的联合检测和医学诊断提供科学依据与技术途径。

我们设计合成高密度和高稳定性的复合SERS编码探针的新原理和方法，获得拉曼增强因子高且分布窄的最佳复合SERS编码探针；构建了基于拉曼指纹识别的高灵敏和高选择性免疫分析检测模式，制备出具有多编码的SERS探针；根据拉曼编码和免疫分析基本原理，实现对肿瘤组织及细胞表面的多组分肿瘤标志物的快速联合检测；以复合SERS编码微球作为传感单元，并结合微阵列生物芯片，组合并构建出SERS可视化阵列传感器，最终发展出对肝癌等肿瘤标志物（miRNA）进行快速筛查的高灵敏、快速、高通量、可靠的可视化阵列传感器平台，成功实现对肝癌的早期筛查与诊断。发表有关免标记SERS微阵列芯片用于多组分癌症标志物和复杂样品实时高通量检测的SCI论文25篇，其中第一/通讯作者的22篇，IF>5的16篇，申请相应发明专利6项，获授权2项，培养研究生13名。