基于仿生分子识别及DNA循环放大技术的表面增强拉曼检测肿瘤细胞及单细胞分析

Early diagnosis of cancer is vital for the successful treatment of the disease. Hence, a rapid and sensitive diagnosis is essential before the cancer is spread out to the other body organs. Nowadays, surface enhanced Raman scattering (SERS) has received considerable attention owing to its high sensitivity, “fingerprinting” ability, resistance to photobleaching, minimal sample preparation, and ease of operation. In this work, a series of novel biosensing assay systems were developed for ultrasensitive SERS detection of cancer cell. The main researches include the design of biomimetic molecular recognition nanoprobe, the study of DNA circle amplification strategy based on aptamer recognition and the single-cell analysis based on SERS. The high amplification efficiency could be produced by nanoprobe enhancement and enzyme assisted multiple cycle amplification strategy. Excellent specificity and good performance in real sample assays could be achieved due to the high affinity and the specificity of the aptamer for the target cell, which is important for its application in biological or clinical analysis. The propsed methods may hold great promise for the broad applications in the field of medical research and early cancer diagnosis.

本项目以与人类健康密切相关的重大疾病（恶性肿瘤）的早期诊断为目标，以恶性肿瘤细胞为研究对象，结合分析化学、材料科学、纳米科学、光电子学和生物医学等交叉学科的前沿研究成果，基于适体的特异性识别作用，构建高选择性、高亲和性仿生分子纳米生物探针。设计新型、高效的DNA循环放大体系，采用表面增强拉曼分析技术，将构建的仿生分子纳米探针与循环放大技术相结合，协同增强检测信号，发展肿瘤细胞的高灵敏检测新方法，构建表面增强拉曼光谱单细胞分析技术平台，以期实现癌症的早期诊断，为揭示恶性肿瘤的致病机制、靶向治疗提供理论基础和技术支持。

恶性肿瘤严重威胁人类健康，本项目以癌症早期准确诊断为目标，以恶性肿瘤细胞及肿瘤标志物为研究对象，将纳米技术和多种分析检测方法相结合，实现对多种肿瘤标志物的生物传感分析。首先制备了多种稳定性强、光学效率高的多功能仿生分子纳米生物探针，在此基础上，利用适体对靶分子的特异性识别，构建了不同的分子机器及等温循环放大体系，实现了对DNA、DNA甲基化酶的高灵敏、高选择性检测。我们还进一步发展多种方法实现伴刀豆球蛋白和肿瘤细胞的高灵敏检测。在石英晶体微天平和表面等离子共振检测方面，我们对新型传感界面和新型信号放大方法进行了研究，拓宽了石英晶体微天平和表面等离子共振检测的适用范围。此外在细胞表面糖链的检测、光电化学传感器的设计以及纳米技术在肿瘤标志物检测中的应用都进行了细致的研究，为今后课题的开展打下了良好的基础。