离子液体功能化光敏MOFs和限阈生长贵金属纳米晶增强光电化学免疫传感及机制研究

Photoelectrochemical immunosensing system was commonly developed based on photoactive materials and antibody, in which the light is served as excitation source and the photocurrent variation before and after the specific recognition of antigen is served as signal readout. The total separation of excitation source (light) and detection signal (photocurrent) provides photoelectrochemical immunosensor with superior characteristics including low background signal, desirable sensitivity and high selectivity etc., and thus enables to fulfill the immunoassay of target biomolecules with high performances. Unfortunately, the common photoactive species with wide band gap require UV light to generate photocurrent, often leading to deactivating effects on biomolecules; meanwhile, the low photo-conversion efficiency of photoactive materials and the unclear signaling mechanisms are also the major obstacles for promoting photoelectrochemical immunosensors in practical applications. Based on the aforementioned key points, macrocyclic ionic liquids functionalized with aromatic carboxylic acid group will be designed and synthesized, and used as ligands to react with transition metal ions (Ru and Cu etc.) and rare earth metal ions (Sm or Tm ect.) to prepare metal organic frameworks (IL-MOFs). The photoelectric conversion efficiency in visible (or near-infrared) region, pore structure and size will be optimized by regulating conjugated π-bond, molecular structure and the experimental conditions for fabrication. The porous structure of IL-MOFs will be used as template for spatial confinement growth of noble metal (such as gold and silver etc.) nanocrystals (NMNCs) by in situ reducing, and thus to improve the photoelecrtochemical response significantly due to the superior characteristics of ionic liquid for charge transfer, and the high conductivity and plasma resonance effect of NMNCs. Furthermore, antibody for tumor marker protein can be efficiently immobilized onto the NMNCs@IL-MOFs based interface due to the high specific surface area and porosity factor of IL-MOFs. As a result, a photoelectrochemical immunosensing platform can be successfully fabricated for tumor marker protein. The proposal will mainly concentrate on some key points such as the mechanism for the photoelectric conversion and the enhanced effects, efficiency regulation, and the relationship between the photoelectrochemical immunosensing performances and the physical characteristics of IL-MOFs and NMNCs, electron transfer and dynamic parameters in the photoelectric conversion process. Based on NMNCs@IL-MOFs nanocomposites, novel photoelectrochemical immunosensing systems will be developed for tumor marker proteins. Finally, the developed photoelectrochemical immunosensor will be employed for assaying the target protein in clinical samples.

光电化学免疫传感器基于光敏介质耦合抗体构建，以光激发，依据特异性识别抗原前后光电流变化，实现高效传感检测。通用光敏材料需高能激发、光电转换效率低、信号转导机制不明等是限制传感性能提升的关键问题。拟设计合成大共轭芳香羧酸类离子液体配体，制备过渡或稀土离子的金属有机框架化合物(MOFs)，通过调控共轭度、分子结构及制备条件，优化MOFs在可见(或近红外)光区的光电转换性能、孔隙结构及尺寸；以MOFs的孔隙为模板，原位限阈生长贵金属纳米晶(NMNCs)。基于离子液体优异的电荷传输特性、NMNCs的高导电性和等离子共振效应增强MOFs光电响应性能；基于MOFs的大比表面积、高孔隙率实现肿瘤标志蛋白抗体高效负载，搭建光电化学免疫传感平台，研究光电转换及增敏机制、效率调控、传感性能与MOFs和NMNCs物性特征间的内在关联，获取光生电荷传输及反应动力学参数，建立光电化学免疫传感新体系，实现临床样品分析

高能激发、光电转换效率低、信号转导机制不明等是限制光电传感性能提升的关键问题。课题设计合成光敏离子液体功能化MOFs框架化合物(IL-MOFs)，通过配体结构、金属离子种类、制备策略调控IL-MOFs能带间隙、形貌及孔隙结构，并限阈生长贵金属纳米粒子，增强光电免疫传感效能，阐明响应原理、增敏规律及内在关联。以邻二氮杂菲、芘环、萘环、菲环、联吡啶、硫代碳菁、联-二萘、SCy7等为共轭母体，成功合成系列不同共轭结构的离子液体类有机单体，调控其光吸收特性，并以其为有机配体，以Zn2+、Eu3+、Yb3+、Nd3+、Er3+等为中心金属离子，基于水热或溶剂热等，制备出系列IL-MOFs，系统考察离子液体共轭度、分子结构及制备条件对IL-MOFs纳米材料的物理特性(空隙结构、形貌、尺寸等)的影响，获取系列具有可见(或近红外)光电转换效能的IL-MOFs。以所制备的IL-MOFs的多孔结构为模板，基于真空负压效应，引入氯金酸，在IL-MOFs孔隙结构内限阈、原位还原生成金纳米晶，获取IL-MOFs/AuNPs纳米复合材料体系，基于离子液体优良特性、纳米金的优异电子传输及局域表面等离子共振效应增强IL-MOFs的光电转换效能，获取具有较好光电响应特性的传感界面，并以其为载体，负载肿瘤标志物抗体、适配体等特异性识别生物元件，构建鳞状细胞癌抗原、癌胚抗原、α-甲胎蛋白、血清糖类抗原153、血管内皮生长因子165、ctDNA、循环肿瘤细胞、磷脂酰肌醇蛋白聚糖3等肿瘤标志物的光电免疫传感体系，阐明基于离子液体功能化MOFs耦合限阈生长纳米金复合纳米材料体系的光电转换及增敏机制、效率调控、传感性能与两者物性特征间的内在关联，探究基于IL-MOFs的光电免疫传感平台构筑策略、信号放大策略、分析性能提升策略，获取可实现高效能分析的光电化学免疫传感体系，实现临床血清样品准确检测。研究成果阐明了离子液体功能单体及中心金属离子调控IL-MOFs物性特征的策略及规律、限阈生长贵金属纳米晶增强光电响应效能的原理及机制，免疫传感效能增强策略，有助于发展光电生物传感新体系，对医学诊断具有重要价值。