基于毛细管尖端组装纳米多孔结构获取细胞微区分子信息的新方法

The cell is the basic unites of life, and most important life processes occur in the confined space of the cell. Therefore, acquiring molecular information from these micro/nano domains on the cell is fundamentally important. Based on the properties of cell, approaches for acquiring the molecular information from microdmains of a cell need to have high sensitivity, selectivity and the group identify ability, as well as modest spatial and temporal resolution. Nanopipette is easy to be pulled and manipulated. At the same time, assembly of nanoparticles has strong Raman/fluorescence enhancement activity toward the molecules on the surface of the nanoparticles. When combined with biorecognition molecules or spectral analysis, these structures can build analytical methods with high selectivity. In this application, we proposed the approach to assemble porous nanostructure at the end of a nanopipette. The porous nanostructure both act as the backbone of nanopores and as the substrate of enhanced spectrum and electrochemical signals. Based on such structure, a series of approaches for acquiring the information of biomolecules at the microdmain of a cell can be developed. Such type of sensors combined the high maneuverability of the nanopipette, the optical enhancement ability of the nanoassembly, special electrochemical and mass transportation properties of the nanopore, which will provide a methodological support for acquiring molecular information from microdmains of cells.

细胞是生命的基本单元，大部分重要的生命过程都发生在细胞微区内。获取这些微/纳米尺度内的分子信息对于深入认识生命过程具有重要意义。基于细胞自身特点，细胞微区分子信息获取方法必须具有高灵敏度、选择性与分子识别能力，同时具备一定的空间、时间分辨能力。纳米毛细管具有易于制备、方便进行空间操控等特点，而金属纳米粒子组装体的局域化表面等离子体共振特性使其对附着于其上的分子具有极高的拉曼散射、荧光增强活性。如结合生物标记和光谱分析，这些方法还具备高的选择性。本研究方案提出在纳米毛细管尖端自组装金属纳米颗粒形成孔径可控的纳米多孔结构，该纳米多孔结构同时作为纳米孔的组成单元和光谱、电化学信号增强基底，进而发展能够从细胞微区中直接获得生物分子电化学与光谱等多元信息的分析新方法。这一设计结合了纳米毛细管的高操控性、纳米组装体的光谱增强特性、纳米孔的电学和物质传输特性，将为原位获取细胞微区分子信息提供方法学支撑。

细胞是生命的基本单元，大部分重要的生命过程都发生在细胞微区内。获取这些微/纳米尺度内的分子信息对于深入认识生命过程具有重要意义。本项目提出在纳米毛细管尖端自组装金属纳米颗粒形成孔径可控的纳米多孔结构，该纳米多孔结构同时作为纳米孔的组成单元和光谱、电化学信号增强基底，进而发展能够从细胞微区中直接获得生物分子电化学与光谱等多元信息的分析新方法。在4年执行期内，我们利用金属有机骨架结构和金属纳米粒子分别在玻璃纳米管尖端构建了孔径高度可控和具有拉曼增强特性的纳米多孔结构。分别从孔结构、纳米孔物质传输特性、光谱增强特性、电流与分子过孔的关系等方面研究了纳米多孔结构的特性。进一步将筛选的纳米孔结构应用于单细胞中化学信息的采集。利用该结构获取细胞微区分子信息具有高灵敏度、高选择性与分子识别能力强等特点，同时具备一定的空间、时间分辨能力。所发展的方法不但为研究纳米孔特性提供了良好的实验平台，也为单细胞测量提供了新手段。本项目共发表SCI论文9篇，其中包含1篇Angew. Chem. Int. Ed.，1篇Adv. Func. Mater. 4篇Anal. Chem. 及1篇Chem. Commun.。