大环分子功能化量子点的超分子组装与光电生物传感

Focusing the issues of quantum dots-based photoelectrochemical biosensing such as low photoconversion efficiency and difficult to modify, this project will synthesis macrocyclic molecules functionalized quantum dots as photoelectrochemical active materials, and immobilize them uniformly on modified electrode surface via Langmuir-Blodgett or self-assembly technology. The quantum dots-DNA supramolecular conjugates can be established by sequential assembly of guest molecule-labeled DNA probe with controllable structures and excellent properties. The effect of macrocyclic molecules, assembly methods and the dimension of quantum dots on film structure and film quality are investigated to effectively prevent its aggregation and abscission, resulting in the significant improvement of photoconversion efficiency. The synergy between macrocyclic molecules and quantum dots is studied in order to expand their applications, and perfect the theoretical basis of photoelectrochemical methods. The ordered array of quantum dots on electrode surface is employed to obtain the desirable structural orientations and biological activities as well as the enhancement of the stability and reproducibility of biosensors. Moreover, the biological recognition mechanism of target molecules with functionalized quantum dots is revised. The DNA assembly-based signal amplifications and regulating methods of photoelectrochemical process are designed to develop a series of photoelectrochemical biosensors for rapid detection of many biological markers of diseases, showing important applied value in clinical diagnosis and bioanalysis.

针对量子点光电传感中存在的光电效率低和修饰难于控制的问题，本项目拟合成大环分子功能化量子点作为光电活性材料，利用LB或自组装技术将其均匀分布在修饰电极表面，并与客体分子标记的DNA探针偶联，制备结构可控、性能优异的量子点-DNA超分子组装体。通过考察大环分子、组装方式、量子点尺寸对成膜结构和成膜质量的影响，极大减少量子点的团聚和脱落现象，有效提高其光电转换效率。研究大环分子与量子点的协同效应，拓展量子点的应用范围，完善其在光电分析中的基本理论。利用功能化量子点在电极表面的有序组装，优化量子点-DNA超分子组装体的结构取向和生物活性，增强光电检测的稳定性和操作重现性。揭示功能化量子点与靶分子间的识别机制，设计DNA组装诱导的信号放大和光电调控策略，发展超高灵敏、高通量的光电分析新方法，构建多种光电生物传感平台并实现对疾病标志物的快速检测，在临床诊断与生物分析中呈现出重要的应用价值。

本项目面向我国社会发展中提高人类健康的国家需求，以建立与人类健康密切相关的重大疾病早期诊断新方法为目标，采用大环分子功能化半导体作为光电活性材料，特定生物探针分子作为识别单元，利用自组装技术将其均匀分布在修饰电极表面，制备了一系列新型光电生物传感平台，实现对疾病标志物的快速检测。本项目有效解决了光电传感中存在的光电效率低和生物探针修饰难于控制等关键科学问题，研究特色和创新点在于将主-客体分子的识别作用引入到光电传感领域，既简化光电活性材料和探针分子的修饰过程，增强光电检测的稳定性和操作重现性，又可与DNA组装关联的信号转导机制相结合，发展超高灵敏度、快速可靠的光电分析新方法，丰富了光电分析的理论基础，为重大疾病早期诊断与预警提供新原理和新思路。例如，我们采用水热法首次合成了β-CD@CdS纳米棒，有效增强了CdS纳米棒的稳定性与水溶性，而且为组装生物分子提供大量的活性位点，从而能够快速构建可调控、高度有序的光电生物传感器件，具有较宽的线性范围和较低的检测限。同时，利用模拟酶抑制CdS量子点的原位生成，设计了分体式的光电免疫传感平台，有效降低长期储存后的CdS颗粒聚集和光致腐蚀，避免了生物分子与光电化学检测之间的相互干扰。随后，我们发现过渡金属二硫化物纳米材料（如MoS2量子点、WS2纳米片）能够显著提高CdS的光电流响应，进一步改善生物传感器的检测灵敏度和准确性。研究成果将为临床诊断、疾病标志物的检测提供新的重要资源，有助于解决当前重大疾病诊疗的瓶颈问题。