高质量硒化镉核壳量子点荧光特性调控和生物检测应用研究

Spectrofluorimetry has become an essential tool of diagnosing, monitoring and pathogenesis of many diseases. The low sensitivity due to the weak fluorescence intensity is the major obstacle of the spectrofluorimetry towards early accurate diagnosis of dangerous disease such as cancer. In this project, CdSe based core/shell quantum dots with high stability and high quantum yield (> 90%) are firstly prepared by using the self-owned “phosphine-free”, “low temperature injection and high temperature growth” technology. On ground of localized surface plasmon resonance of metal nanostructure, maximum fluorescence enhancement signal will be obtained through controlling the shell thickness via a layer-by-layer growth method in order to accurately control the distance between quantum dot and gold nanoparticles, and through the optimization of the morphologies of gold nanoparticles. This will also enrich the driving mechanism of fluorescence enhancement in the course of distance and morphology manipulation. This strong fluorescence intensity will experience a second-time amplification via a hybridization chain reaction. Finally, a highly sensitive detection method of univariate and multivariate tumor markers will be constructed to meet the needs of high sensitivity biological detection and even single molecule detection. This project will be of significant importance for realizing high sensitivity, early and accurate diagnosis of dangerous diseases such as cancer.

荧光分析技术已成为当今癌症等重大疾病诊断、监控和发病机制探究必不可少的研究工具。由于荧光亮度偏低而造成的灵敏度不够是限制荧光分析技术应用于重大疾病早期即时精确诊断的主要障碍。本项目拟基于金属表面等离子体共振效应，采用具有完全自主知识产权的“无膦”，“低温成核，高温长壳”技术可控制备高稳定性，高量子产率（>90%）的硒化镉核壳量子点，在金纳米颗粒形貌优化的基础上，通过逐层生长的方法调控壳层厚度以达到量子点-金纳米颗粒之间距离的精准控制，实现荧光信号的最大化增强。通过距离和形貌的调控研究，丰富金属增强量子点荧光的物理图像。在此基础上，基于杂交链式反应，实现荧光强度的再次放大，进而构建肿瘤标志物的一元、多元分析高灵敏检测方法，满足高灵敏度生物检测甚至单分子检测需求。本项目对实现癌症等重大疾病的高灵敏度早期即时精准诊断有着重要应用价值。

荧光分析技术已成为当今癌症等重大疾病诊断、监控和发病机制探究必不可少的研究工具。由于荧光亮度偏低而造成的灵敏度不够是限制荧光分析技术应用于重大疾病早期即时精确诊断的主要障碍。本项目首先采用具有完全自主知识产权的“无膦”，“低温成核，高温长壳”技术，结合逐层生长壳层的方法，可控制备了高稳定性、高量子产率（>90%）的壳层厚度可控的超大尺寸（>24 nm）硒化镉核壳量子点。设计制备了形貌可控的金纳米颗粒，构建了金纳米颗粒-超大量子点复合体系，通过壳层厚度及聚合物包覆的方法实现了距离的精准化控制，解决了复合体系的生物相容性问题。基于复合体系构筑了生物传感器，可达到荧光约3倍的增强效果，C-反应蛋白的检测灵敏度提高了17倍（检测限达0.056 ng/mL）。其次，提出了金属离子增强量子点荧光的策略，实现了量子点荧光4倍的增强；基于高荧光亮度的量子点构筑了生物探针，将C-反应蛋白的检测灵敏度提高了4倍（检测限达0.23 ng/mL）。在此基础上，结合激发态动力学表征，探明金纳米材料增强量子点荧光性能的物理机制，丰富金属增强荧光特性机理。最后，研究了环境友好型量子点（硒化锌、磷化镓等）的发光特性，提出尺寸工程和壳层工程的新型荧光调控策略。本项目经认真执行，在Nano Letters等国际知名期刊发表论文3篇，培养博/硕研究生共5名，成果有望为癌症等重大疾病的高灵敏度早期即时精准诊断提供物质基础与理论依据。