基于“双共振”和“频率位移”表面增强拉曼光谱的高灵敏度和高重复性的无标记检测技术

Surface-enhanced Raman spectroscopy (SERS) is highly favorable for the development of the highly-sensitive and portable real-time biosensing application, which has a significant impact on the fields including clinical diagnosis, criminal investigation and food safety. But SERS also has some issues including the decreased enhancement factor in the near-infrared (NIR) region and the low reproducibility. In this project, we propose to design a novel type of double-resonance and frequency-shifts SERS for the label-free biosensing to improve the sensitivity in the NIR region and the reproducibility. The double resonances can be realized with the strong plasmon coupling between the localized surface plasmon resonance (LSPR) of the nanostructures and the cavity mode of the Fabry-Pérot cavity to avoid using very fine nanostructures (e.g. narrow gaps and sharp tips) on the SERS substrate. This strategy will improve the SERS enhancement factor in the NIR region and will keep a very uniform structural morphology on the substrate, which leads to a good reproducibility and low fabrication cost. Moreover, based on the vibrational frequency shifts in quantitative correlation with the concentration of the targeted molecules in SERS, a much better reproducibility is predicted compared to those based on the intensity variation with the change of molecular concentration. Finally, we believe that the double-resonance and frequency-shifts SERS technique in the project will pay the way to further development of the SERS in the application of the quantitatively reproducible molecular detection.

表面增强拉曼光谱非常适合应用于高灵敏度和微型化的即时检测技术，尤其对临床诊断、公安刑侦和食品安全等关系国计民生的领域有重大影响，但是目前存在重复性差和近红外区增强效应减弱的问题。课题拟通过全新的思路来设计一种基于"双共振"和"频率位移"表面增强拉曼光谱的高灵敏度和高重复性的无标记检测技术。通过"局域表面等离激元"和"空腔谐振模"的耦合作用，来达到"双振动表面增强拉曼"的效应，有效避免了使用极细微的纳米结构，实现了近红外区极大拉曼增强因子（高灵敏度）的同时，保持了芯片结构的均一性和可重复性，又降低对芯片制造工艺的要求和成本。通过比较待测分子与芯片结合前后增强拉曼光谱的"频率位移"而避免了运用其强烈依赖于增强因子的"强度变化"来识别待测分子的浓度，从而显著提高表面增强拉曼光谱的可重复性和实用性，尤其是在定量检测范围的应用，为构建新一类基于表面增强拉曼光谱的高灵敏度和微型快速的检测技术奠定基础。

本项目通过设计一种基于“双共振”和“频率位移”表面增强拉曼光谱的高灵敏度和高重复性的无标记检测技术，实现了近红外区极大拉曼增强因子（高灵敏度）的同时，保持了芯片结构的均一性和可重复性，从而显著提高表面增强拉曼光谱的可重复性和实用性，尤其是在定量检测范围的应用，为构建新一类基于表面增强拉曼光谱的高灵敏度和微型快速的检测技术奠定基础。另外开发了基于缝隙增强拉曼探针的新理论研究、材料制备和生物医学应用。以第一或通讯作者共发表SCI文章17 篇，总影响因子>90分，影响因子大于10 的1 篇（以通讯作者发表在本领域top 5%期刊，Nano Letters，IF: 13.779），影响因子大于7 的7 篇，已申请中国发明专利3 项，培养5位研究生（1位博士，4位硕士），申请人本人也获得了国家自然科学基金优秀青年基金项目的支持。