活性染料-半导体纳米复合物的组装与硫醇等生物小分子的光电传感

This project aims to develop novel photochemical sensors for the sensitive and selective discrimination of biothiols (such as cysteine, homocysteine and gluthoine) in biological systems based on the nanocomposite of thiol fluorescent probe and semiconductor nanomaterial. Herein, fluorescent probes which could specifically recognize biothiol is designed and synthesized to substite ordinary dyes for the construction of photochemical sensors. The discrimination of biothiol is based on the decrease of photochemical amperometric response originated from the decrease of photoelectron tranfer ability of fluorescent probe after their interactions with biothiol. Semiconductor nanomaterials with both large surface area and improved photoelectron transfer ability, such as TiO2 nanoparticle, TiO2 nanotube, ZnO nanoparticle, ZnO nanotube, and their nanocomposites with either carbon nanomaterial or nobel metal nanomaterial, will also be prepared and introduced for the construction of photochemical sensors. The integration of highly specific fluorescent probes with semiconductor nanomaterials with both good photoelectron transfer ability and large surface area is believed to be able to solve the conflict between sensitivity and selectivity. Therefore, novel photochemical sensor with both good selectivity and high sensitivity could be fabricated based on this strategy, which may have great prospective in the in vivo analysis of biothiol in pysiological fluids such as serum and blood after their combination with microelectrode, thus may provide essential data to unravel the rationship between biothiols and malignant disease. In addition,to further understand the photoelectron transfer mechanism between dye and semiconductor, several factors such as the structure and composition of the fluorescent probe, the dimension, morphology, and composition of the semiconductor, and the strategy to modify the functional interface of the sensor, will also be detailly investigated, which may provide essential information for the construction of other kinds of highly efficient photochemical sensors.

硫醇等活性小分子是生物体的重要成分，它们参与了许多重要的生理反应，其浓度的异常与肿瘤等重大疾病有着直接的关联。然而由于硫醇分子种类的繁多和结构的相似性，现有的检测技术远不能满足对其进行原位和选择性检测的需要。本项目将光电分析方法与荧光探针（活性染料）技术、纳米技术相结合，利用光电分析方法特有的高灵敏度、荧光探针的高选择性和纳米结构的进一步信号放大，提出一系列特异性强、灵敏、快速的可原位检测生物硫醇含量的光电传感新方法；本项目将深入研究荧光探针的结构和组成，半导体纳米材料的组成、形貌和尺寸，以及光电传感界面组装方式等因素对光电子转移效率的影响，发展可显著提高光电效率和光电传感器灵敏度的有效方法；并将结合纳米导电光纤，研制微型光电传感器，推进硫醇光电传感器在在线及活体分析中的应用，为肿瘤等重大疾病的临床诊断和日常监测提供方便快捷的有效工具。

在该项目的资助下，我们成功设计了多种探针分子（活性染料），包括系列三苯胺染料、系列钌联吡啶染料和一种方酸菁染料；并制备了多种纳米材料，包括TiO2纳米颗粒和纳米管阵列、Mn2+杂化的CdS纳米晶、银纳米簇、石墨烯和CdTe的纳米复合物等；通过将活性染料和TiO2纳米功能界面复合，构筑了多种活性染料-TiO2纳米功能界面。在光激发下，基于识别反应前后电信号的变化，发展了多种光电传感方法，成功实现了对半胱氨酸、谷胱甘肽、抗坏血酸、多巴胺等生物小分子的高灵敏选择性检测，并实现了对小鼠脑内抗坏血酸的原位检测。此外，基于光电材料的高光电活性，结合生物识别反应，如抗原抗体间的免疫反应等，我们还发展了一系列高灵敏的光电传感方法，实现了对癌胚抗原等肿瘤标志物的高灵敏检测。这些工作的取得一定程度上推进了光电分析技术在生命分析化学和临床诊断中的应用，基本达到预期目标。