一种新型生物金属纳米簇探针的构建及其检测方法学研究

Bio-metal nanoclusters are a class of nanomaterials that templated by biomolecules, consist of several to hundreds of metal atoms, and with the size nearly Fermi wavelength. Compared to organic dyes and quantum dots, this new optical probe has attracted much attention in biomedicine recently owing to its advantages including high luminescent efficiency, resistance to photobleaching, tunable wavelength, biocompatibility, and so on. However, the current challenge is how to design and screening of biological template to control the electronic structure, surface properties and luminescent properties of the nanoclusters for developing related detection method and applying in practical clinical problems. The prescent proposal aims to synthesis of highly fluorescent bio-metal nanoclusters through rational design/selection of nucleic acid and protein as a template based on the green chemistry strategies. The effects of parameters such as the molecular structure, conformation, polarity, charge of the template and environmental medium on the structure and optical properties of the obtained nanoclusters will be further investigated. According to the actual needs of clinical inspection, we will combine the metal nanoclusters (signal report element) and aptamers which can bind target molecules via specific recognition (molecular recognition element), and use it as probe to develop ultrasensitive and highly selective method for the detection of low-content proteins (e.g., brain natriuretic peptide, BNP) in clinical blood samples. Moreover, the interactions between nanoclusters and the target molecules and the mechanisms responsible for the energy transfer happened in the recognition process will also be studied. This project is both worth studying in theory and promising for practical applications.

生物金属纳米簇是利用生物分子为模板合成的具有几到几百个金属原子、尺寸与费米波长相当的纳米团簇。相比有机染料及量子点等荧光探针，该新型探针具有高发光效率、抗光漂白、波长可调、生物相容等优势，已在生物医药领域备受关注。但如何设计与筛选生物模板调控纳米簇的电子结构、表面性质及发光性能，并建立相关检测方法用于解决临床检验中的实际问题，是目前研究中的瓶颈。本项目拟通过合理设计与筛选核酸、蛋白质为模板、采用绿色合成法制备金属纳米簇，深入探讨模板分子的结构、构象、极性、电荷及环境介质等参数对其结构和发光性能的影响，阐明作用规律及其机制。根据临床检验的实际需要，以金属纳米簇为探针（信号报告元件），结合核酸适配体对目标分子的特异性识别（分子识别元件），建立超灵敏、高特异性的检测新方法应用于临床血样中低丰度蛋白（如脑钠肽）的检测，并探索探针与目标分子间的相互作用及能量转移机制，既有理论价值又有应用前景。

生物金属纳米簇相比有机染料及量子点等荧光探针，具有高发光效率、抗光漂白、波长可调、生物相容性好等优势，已在生物医药领域备受关注。本项目以生物金属纳米探针为研究对象，设计与筛选生物模板来调控纳米探针的电子结构、表面性质及发光性能，通过热力学和动力学控制合成过程，制备了一系列高发光性能、高稳定的单一金属纳米簇、合金纳米簇等纳米探针，进一步基于其优异的性能构建了一系列高灵敏分析方法，并将其应用于药物、疾病相关小分子等检测分析及生物成像。本项目在理论上和应用中都取得了较好的成果，理论上深入探讨了模板分子的化学结构、三维构象、电荷性质及环境介质等参数对纳米探针结构和发光性能的影响，应用中开发了一系列高性能优异探针适用于生化高灵敏分析检测以及光学成像，具有较好的应用前景。