突破衍射与颜色双重极限的SERS显微成像新技术研究

Surface-enhanced Raman scattering (SERS) possesses two major characters of near field energy enhancement and molecular fingerprint identification, and it will provide a distinguished super-multiplex optical imaging technique with super high spatial resolution under the control of light field, which has not been reported till now. On the basis of our previous researches involved in Raman imaging and ‘Click’ SERS spectroscopy, this project aims to sharpen the excitation laser spot and finally realizes an assumption that “allowing a single irradiation, only at most one illuminant glows”. The main researches contain: synthesis and screen of alkyne coded noble metal nanoparticles (light-emitting elements) and photo deformable nanomaterials (photo switch); constructing of light ‘clicked’ SERS illuminant by assembling two light-emitting elements on both sides of photo switch along its deformation direction. Afterwards, a single SERS illuminant will glow because the photo switch may mediate the degree of coupling that exists between two sides of light-emitting elements under the ‘Click’ irradiation of the linearly polarized focusing Gauss beam. Of course, there are some prerequisites to really decrease the size of airy disk that the polarization direction, power density and irradiation time of the focusing Gauss beam need to be adjusted. On this basis, after the optimization of the size of light-emitting elements and photo switch, and further the development of software for simulating the signals of ‘Click’ SERS spectra, a novel SERS imaging technique beyond diffraction and color limits would be facilely developed on a popular Raman microscopy.

表面增强拉曼散射（surface-enhanced Raman scattering, SERS）具有近场能量增强和分子指纹识别两大特性，在光场调控下有望成为一种高空间分辨、超多色的细胞成像手段，尚未见文献报道。本项目拟在课题组前期细胞成像与“点击”SERS光谱工作基础上，制备和筛选炔烃编码的贵金属纳米颗粒（发光元件）和光致变形纳米材料（光开关），沿光开关形变方向在其两端连接发光元件以构筑光点击SERS发光体，在线偏振的高斯光束点击辐照下，光开关将沿着偏振方向改变发光元件的耦合程度从而控制发光体发光，通过调控点击光束的偏振方向、功率密度和照射时间来缩小艾里斑的尺寸，最终实现“一次照射，仅允许至多一个发光体发光”的设想。在此基础上，优化发光元件和光开关的尺寸、形状并丰富炔烃的分子结构，开发点击SERS光谱的伪彩色模拟软件，可在普通拉曼谱仪上开发出突破衍射和颜色双重极限的SERS成像新技术。

本项目开展了增强基底材料和三键类拉曼信号分子的合成、表征与筛选，光开关纳米材料靶向的筛选和测试，以及点击SERS发光体的组装及其用于细胞凋亡过程活细胞超多色、高分辨成像应用。此外，在三键SERS 编码，等离激元纳米复合材料用于抗菌/肿瘤治疗，超多因子单分子免疫荧光分析方法的构建，2D/3D 防伪油墨开发，细菌检测，光镊拉曼等多个领域全面开展了拓展研究。本项目共发表SCI论文23篇，中文核心论文2篇，项目批准号第一标注11篇，第二标注12篇。影响因子大于5的SCI论文17篇，其中Angewandte Chemie International Edition 1篇，Analytical Chemistry 4篇，Chemical Engineering Journal 1篇，Small 1篇，Applied Materials Today 2篇，Advanced Healthcare Materials 1篇，Nanoscale 3篇。在本项目的支持下，课题组“单个聚合物纳米粒子上的叁键编码及其用于多重SRS成像”的原创工作继点击SERS发表于JACS之后再次获得顶级化学类期刊Angewandte Chemie International Edition的青睐，论文发表数量和质量远远超过预期研究成果。在研究生培养上，共计培养博士研究生和硕士研究生18名，博士后1名。