量子点多色电化学发光机制研究及其在急性心肌梗死标志物同时检测中的应用

Rapid and accurate detection of myocardial markers plays an important role in early diagnosis and treatment of acute myocardial infarction (AMI). Developing sensitive, selective and high-throughput techniques for the simultaneous detection of multiple biomarkers is highly desired. Spectrum-resolved (namely multicolor) electrochemiluminescence (ECL) is indeed a powerful tool for multiplex bioassay. This project will focus on the controlled synthesis of high-quality semiconductor quantum dots (QDs) and their ECL applications in multiplexed detection of AMI biomarkers. We plan to passivate efficiently the surface-defect states of QDs using appropriate functional capping ligands or inorganic shell layers, thus achieving ECL generation from the intrinsic states. The exact characteristics of excitons (such as single exciton, biexcitons or charged excitons) involved in the ECL generation of QDs will be rationalized by electrochemistry-coupled time-correlated single photon counting system. By further tuning the composition and/or size of QDs, we expect to achieve ECL at different spectrum ranges. Then the multicolor ECL can be employed to fabricate biosensors, in conjunction with appropriate biorecognition elements, for the simulation detection of multiple biomarkers of AMI.

多种心肌损伤标志物的快速精准检测对于急性心肌梗死的早诊早治至关重要，发展高灵敏度、高选择性、高通量的标志物同时检测技术是临床诊断的迫切需求，光谱分辨（即多色）电化学发光是一种颇具潜力的方法和技术。本项目立足高光学质量的半导体量子点的可控合成，利用有机配体或无机半导体壳层对量子点表面态进行高度钝化，研究量子点本征态电化学发光，通过电化学耦合时间相关单光子计数联用系统揭示量子点电化学发光激子态（如单激子态、多激子态和带电激子态等）来源。进一步通过调节量子点组成或尺寸，实现量子点电化学发光波长可调，构建多色电化学发光体系。最终结合生物识别单元，设计并制备电化学发光生化分析传感器，用于多种急性心肌梗死生物标志物的同时检测。

电化学发光是一种由电化学触发的化学发光，具有背景低、灵敏度高、时空可控、表面敏感等特点与优势，在体外诊断、环境监测和食品安全等领域均有重要应用。对电化学发光反应机理的深入理解，有利于发展新型的电化学发光分析原理、方法和技术，进一步拓展电化学发光在生化分析和生物传感等方面的应用。本项目基于电化学发光显微成像与测量技术，结合金微米管电极，实现了溶液相电化学发光层厚度测量，证实了“催化反应路径”对电化学发光信号的空间延展作用。提出了基于一维分子晶体的电化学发光波导成像分析新方法，将电化学发光信号从电极表面拓展至非导电表面。基于上述研究，实现了单/亚细胞水平的细胞-基质黏着蛋白的非标记动态成像和细胞-基质黏着蛋白和细胞-细胞间连接蛋白的顺次成像，以及单细胞释放的过氧化氢、多巴胺等重要化学物质的成分分析。项目执行期内，发表标注论文9篇，其中包括4篇Angew. Chem. Int. Ed.。