基于碳基纳米材料和荧光信号放大策略的多功能纳米传感器的设计、构建及应用

The project aims to prepare carbon quantum dots with highly efficient and tunable fluorescence and to build highly biocompatible and multifunctional nanosensors with amplified fluorescence signal based on as-prepared carbon quantum dots and graphene oxide (carbon nanotubes). Through the strategy of fluorescence resonance energy transfer between the conjugated polymer and fluorescent probes, sequential fluorescence signal amplification of constructed nanosensors will be achieved, and applied to trace detection of intracellular multiple targets or in vivo. The relationship and rules between the surface modification or doping of carbon quantum dots and fluorescence performance will be studied, a series of multi-colored fluorescent probes based on carbon quantum dots for different detection targets with different recognition mechanisms will be prepared. The highly selective and sensitive detection of biological markers will be achieved through turn-on and turn-off of fluorescence, which correspondingly resulted from the fluorescence quenching due to fluorescence resonance energy transfer between probe and graphene oxide (carbon nanotubes), and fluorescence recovery owing to the specific interaction between target molecules and probes. The goal is to construct nanosensors with multiple fluorescent probes for recognition of multiple targets, and to realize simultaneously online identification and detection of multiple species. The general regulation of amplification of fluorescence signal will be studied and used to achieve trace detection of complex samples with high sensitivity. The detection performance for multiple species and biological evaluation of constructed multifunctional nanosensor inside the cell will be explored. Through the targeted groups connected to the surface of carbon quantum dots and graphene oxide (carbon nanotubes) and their drug-carrying function to achieve the detection of intracellular species and in vivo, fluorescent tracing and drug delivery.

本项目拟制备具有高量子产率、荧光颜色可调变的碳量子点，构建基于碳量子点和氧化石墨烯（碳纳米管）的高生物相容性的多功能纳米传感器，通过与共轭聚合物之间荧光共振能量转移策略实现荧光信号的逐级放大，并将其用于细胞内多物种的靶向痕量检测。研究碳量子点表面修饰或掺杂与量子产率及荧光颜色之间的关系和规律，基于不同的识别机制制备系列适于不同目标分子的多颜色荧光碳量子点探针。利用碳量子点与氧化石墨烯（碳纳米管）之间的荧光共振能量转移来实现荧光的猝灭和恢复，通过荧光“开”和“关”来实现高选择性、高灵敏度、方便快捷的生物分子检测。建立多荧光颜色和多目标识别功能的荧光传感器，实现多物种或多目标生物标记物的同时在线检测。研究其荧光信号放大的一般方法和规律，实现荧光信号的放大和调控应用于复杂样品的痕量检测。在此基础上，通过连接靶向基团的靶向作用以及表面的载药性能来实现细胞内及活体物种的靶向检测、荧光示踪和药物传输。

本项目开发了基于碳基纳米材料用于生物分子的荧光检测新策略，构建了基于碳量子点和氧化石墨烯（氧化纳米管）的高生物相容性、稳定性及灵敏度的荧光传感器，并用于对细胞内外多物种的检测。发展了一系列有机官能团修饰的碳量子点，对碳量子点的荧光调变及荧光增强性能进行了系统研究；基于适配体修饰的碳量子点荧光探针实现了对铅离子、DNA、凝血酶等物种的高灵敏高选择性的检测，并发展了多物种的同时在线检测方法；采用功能化的碳量子点，基于聚集分散机制和光诱导电子转移机制实现了对碱性磷酸酶、酸性磷酸酶、酪氨酸酶、半乳糖苷酶、葡萄糖苷酶和乙酰胆碱酯酶的活性检测。同时将制备得到的荧光碳量子点探针成功用于细胞毒性、生物成像及细胞内的生物标记物的在线检测。设计合成了长寿命室温磷光金属纳米簇，并将其应用于生物化学传感器的设计及应用。设计合成了系列小分子巯基化合物稳定的、具有红色磷光的铜纳米簇，并用于常见有机溶剂中的痕量水分检测以及酸性磷酸酶活性的检测；首次发现了谷胱甘肽包含的银纳米簇具有显著的聚集诱导发光增强性质，并基于该性质实现了对无机焦磷酸酶的发光增强模式的定量测定。本项目的完成在发光纳米材料的可控制备、性能调控、生物成像和化学与生物传感研究方面取得了一定研究成果，相关研究成果发表在《Analytical Chemistry》、《ACS Applied Materials & Interfaces》、《Biosensors & Bioelectronics》、《Sensors and Actutators B: Chemical》、《Journal of Materials Chemistry B》、《Nanotechnology》、《Journal of Materials Chemsitry C》、《Analytica Chimica Acta》和《Talanta》等国际学术刊物上，共发表学术论文25篇。