基于信号转换的多目标物电致化学发光生物传感器研究

Electrochemiluminescence (ECL), as a new analytical technique, has strong controllability and high sensitivity. However, its reaction process is complicated and the cross-reaction between multiple luminescent reagents is very serious. It is difficult to detect multiple targets in the same ECL system. However, the sensitive detection of multiple (especially for different kind) disease markers or pathogenic factors could reflect more adequate disease information. Herein, in this project, a series of self-catalyzed ECL materials with high luminescence efficiency are prepared to construct ultrasensitive ECL biosensors based on signal conversion induced by multiple targets in assistance of a variety of novel DNA technology for signal amplification, which could realize multiple targets (such as different types of miRNAs, miRNAs and proteins, peptides and heavy metal ions) detection in the same ECL system. Then, the as-obtained ECL biosensors are applied for sensitive monitoring of the related targets in the serum or tumor cells, which provides a more comprehensive and accurate reference for the accurate diagnosis, the development of an effective treatment plan and timely prognosis evaluation. The construction of ECL biosensors for the ultrasensitive detection of multiple targets in the project also provides a new idea for the application of ECL technology in the analysis of science and clinical medicine.

电致化学发光作为一种新型分析技术，可控性强、灵敏度高，但其反应过程复杂，多个发光试剂之间交叉反应严重，很难在同一体系中实现对多个目标的检测。但实现对多个（特别是不同种类）疾病标志物及致病因子的灵敏检测可以反映更加充分的疾病信息。鉴于此，本项目拟合成一系列具有高发光效率的自催化电致化学发光材料作为发光物质，通过多种新型DNA技术实现信号放大，并基于多个目标物引发的信号转换，构建超灵敏的电致化学发光生物传感器，在同一体系中实现对多个不同种类目标物（如不同种类miRNA，miRNA和蛋白质及肽类和重金属离子）的检测。并将所制得的传感器应用到患者血清或肿瘤细胞内相关目标物含量的灵敏监测，为疾病的准确诊断、有效治疗方案的制定和及时的预后评估提供更加全面、准确的参考。项目中实现对多个目标物超灵敏检测的电致化学发光生物传感器的构建也为电致化学发光技术在分析科学及临床医学中的应用提供了新的思路。

本项目合成一系列具有高发光效率的电致化学发光材料（如近红外发光的SQDs、结构内自催化的钌配合物Ru-BNQDs及钌配合物纳米结构RuNDs等），通过多种技术实现信号放大（如基于三链体DNA的分子步行器、Zn2+驱动的DNA分子棘轮、多个CHA诱发的三维 DNA 网络结构及多种纳米催化等），并基于多种目标物引发的信号转换，构建具有不同信号输出模式的超灵敏的电致化学发光生物传感器，实现了对多个不同种类目标物（如miRNA-21、β2-微球蛋白（β2-M）、癌胚抗原（CEA）、Pb2+及谷胱甘肽（GSH）等）的检测。并将所制得的传感器初步应用到患者血清或肿瘤细胞内相关目标物含量的灵敏监测。项目中多种高性能发光材料的合成及实现对多个目标物超灵敏检测的电致化学发光生物传感器的构建也为电致化学发光技术更广泛的应用提供了新的思路。