大分子复合印迹自组装体的制备及其对疾病标记物的特异性识别与检测

This project aims to develop a novel multifuntional molecular imprinted self-assembled system with molecular recognition and signal response of disease markers via macromolecular self-assembly of amphiphilic copolymer in combination with molecular imprinting technique using disease markers as template and inorganic nanomaterials (quantum dot, carbon nanotube) as signal (photo or electric) response center. Firstly, a series of amphiphilic random copolymer containing special units which have interaction with inorganic nanomaterials or template was designed and synthesized. The obtained amphiphilic copolymer was then co-assembled with disease marker (template) and inorganic nanomaterials in aqueous solution. The disease marker and inorganic nanomaterials were imbedded in the self-assembled system through the interactions between disease marker, inorganic nanomaterials and copolymer chain. Subsequent photocrosslinking and the extraction of disease marker lead to the generation of molecular imprinted self-assembled system, which integrate the specific recognition property of imprinted polymer and the signal response of inorganic nanomaterials. The influence of copolymer structure and assembly conditions as well as the interaction between the assembly components on the molecular recognition, response and detection of the self-assembled system will be systematically investigated, based on which the multicomponent self-assembly mechanism and its recognition and response mechanism will be clarified. Finally, the molecular imprinted self-assembled system was finally coupled with transducer and the relationship between copolymer structure, assembly microstructure and the sensing behavior will be established to realize the recognition and highly sensitive detection of disease marker.

本申请拟将大分子自组装、无机纳米材料（量子点、碳纳米管）与分子印迹技术进行有效结合，制备一种集分子识别与响应于一体的智能型大分子复合印迹自组装体。设计合成一系列含有特定基元（可与无机纳米材料或模板分子发生作用）的双亲共聚物，将其与疾病标记物（模板分子）和无机纳米材料进行复合自组装，通过光交联来固定印迹位点，洗脱模板分子得到大分子复合印迹自组装体。对组装体的分子识别与响应功能进行考察；并将其与器件基底结合，使感应信号被提取和转换，实现对疾病标记物的识别与检测。研究双亲聚合物结构和组装环境对大分子复合组装体制备的影响因素；探索组装基元间的相互作用对组装体内识别点位以及光电响应中心构建与分布的影响，阐明大分子复合印迹组装体的组装机理和识别响应机制，实现大分子复合组装体对疾病标记物的识别与光电响应的有效调控。并致力于拓展大分子复合组装体在生物识别与传感领域的新应用，促进大分子自组装的进一步发展。

本项目将大分子自组装的可调控性、分子印迹材料的分子识别特性和光电基元的信号传递特性结合起来，实现具有集分子识别功能和光电响应功能于一体的大分子复合印迹自组装体的设计及可控制备，获得了一系列能够在水体系中识别生物分子并给出光电信号的胶体粒子，并将其用于构筑分子印迹传感器。系统研究了双亲聚合物结构参数、组装条件对所得组装体的识别响应性能以及所构建传感器性能的影响，阐述了组装体对模板分子的识别响应机制，实现了对多种生物分子（蛋白质、药物、葡萄糖等）的高选择性与高灵敏性检测，对于模拟天然的识别系统和在生物分子的识别检测方面提供一种新的思路与方法。研究结果如下：.1.电活性大分子复合印迹自组装体的制备及其在传感器中的应用。设计合成了含有乙烯基咔唑的电活性双亲大分子，所制备得到的电活性分子印迹纳米粒子，将其固载在电极表面形成分子印迹膜。结果显示咔唑基元的引入提升了电化学传感器的灵敏性，实现了对扑热息痛的选择性与高灵敏度检测。.2.金纳米粒子复合印迹自组装体的制备及其在传感器中的应用。设计合成了含有亚氨基的双亲聚合物，利用亚氨基的弱还原性原位还原氯金酸得到含有金纳米粒子的大分子复合印迹自组装体，结果显示金纳米粒子的引入有效提高了传感涂层的检测性能。.3.碳纳米管复合印迹自组装体的制备及其在传感器中的应用。通过对聚合物结构的设计与自组装环境的精细调控，得到了以碳纳米管为“线”、分子印迹纳米粒子为“珠”的“项链状”分子印迹复合组装体，形成了立体网状微结构传感涂层，增大了涂层的比表面积，碳纳米管的引入能有效提高涂层的导电性，进而提高了传感电极的检测性能。.4.分子印迹荧光纳米粒子的制备及其应用。设计合成了含有荧光基元的可光交联双亲聚合物，通过其与交联剂、模板分子的共组装以及原位光交联，得到了一系列分子印迹荧光纳米粒子。进一步向大分子链上引入硼酸酯基元，获得了能够识别糖蛋白并发出荧光信号的荧光组装体.