微流控通道表面拉曼增强纳米可控结构建立和芯片原位液体光波导检测研究

The integration of Optofluidic technology and microfluidic controlling has become an important trend in the field of microfluidic chip biochemical analysis. Surface enhanced Raman scattering (SERS) spectroscopy has the advantages of fast detection, no need for sample pretreatment, high sensitivity, ignorable influence from water background, and the ability of multiple sample detection, etc. However, the qualitative and quantitative analyzing with the combination of SERS and microfluidic technology are still in their infant. There are still lots of unsolved problems, such as low SERS gain efficiency, poor repeatability, difficulties in on-chip integration and low sensitivity. Based on the Micro-nano processing technology，microfluidic chip analysis，nano- preparation methodology and Optofluidic technology, a new type of in-suit bio-chemical testing chip which integrates both liquid waveguide and micro-channel is proposed in this proposal, which would improve the SERS detection sensitivity and repeatability. Orderly Raman enhanced nano-medium structure will be fabricated on the surface of microchannal. In order to realize an microfluidic biochemical sensing chip analysis system based on integrated SERS detector on the chip, the structure-activity relationship between nano-surface and response signals, response mechanism and the detection principle will be studied. The breakthrough of several key techniques including high efficient SERS metrix, the integration of optical testing and mciro-fluidic controlling, and qualitative/quantitative analyzing will be focused on. Applied fundamental research will also be conducted to build up a SERS based on-chip microfluidic biochemical analyzing system, and pave the way for the future development of a portable Raman spectrometer and on-chip bio-chemical testing with high efficiency.

微光学检测技术与微流体控制的结合已经成为微流控生化芯片分析的重要发展趋势。表面拉曼增强散射光谱（SERS）技术具有检测速度快、无需样品预处理、探测灵敏度高、水基干扰小等优点。SERS与微流控分析技术相结合的高效定性和定量分析方法与技术尚处于初级阶段，仍存在实际拉曼增强系数较小，信号重复性差，芯片集成难度大，检测灵敏度低等瓶颈问题。课题基于微纳加工技术和微流控分析技术，将纳米制备和微纳光学有机结合，在微流控芯片微管道中的表面制备多种有序纳米拉曼增强介质结构；提出一种液体光波导与微样品通道相结合的SERS原位检测芯片新型结构，以提高SERS检测灵敏度和可重复性；研究其构效关系、响应机制和检测原理；重点研究并突破高效增强拉曼光谱技术、光学检测与微流体控制的一体化集成技术和定性定量分析方法与技术；开展表面增强拉曼光谱在生化检测中的应用基础研究，实现一种基于增强拉曼光谱的微流控生化传感芯片分析系统。

本项目将纳米制备技术和微流控分析技术有机结合，通过对纳米表面拉曼增强的电磁增强和化学增强机制分析，提出在微流控芯片上纳米基底的结构设计和增强效应评价指标，建立了样品分子在金属表面亚单层分布下的SSEF计算模型，并应用于后续的纳米基底SERS效应评价；研究了基于MEMS技术、化学自组装法和双点位计时电沉积法等不同途径的SERS基底设计和制备方法，在微流控芯片微管道中成功获得Ag@nanoAu、Au/Ag NCs、ITO-Ag@Au、Au@Ag/TiO2 NTs、Ti-Au@Ag/TiO2 NTs、Ag film@nanoAu和阵列式银纳米碗等多种有序纳米拉曼增强介质结构；开展了集成微流控SERS芯片的设计和研制，获得系列不同功能结构的微流控SERS芯片，对罗丹明6G和系列生化样本的测试发现，其在检测灵敏度、选择性和稳定性方面具有明显优势；利用长程等离子波导强大的局域场来提高探测灵敏度，并增加光的传输距离，结合微流体通道长距离探测的平均效应，成功研制出集成液体光波导与微样品通道的SERS原位检测芯片新型结构，突破高效增强拉曼光谱技术、光学检测与微流体控制的一体化集成技术和定性定量分析方法与技术，有效提高了SERS检测灵敏度和可重复性；针对三聚氰胺、血清肌酐、腺嘌呤、大肠杆菌、血液等系列生化样本，构建了微流控SERS芯片分析微系统，开展SERS芯片的测试应用研究，成功实现了相关样本的快速高效检测。相关研究所构建的基于增强拉曼光谱的微流控生化传感芯片分析系统和相应的测试方法，为表面增强拉曼光谱在生化检测中的理论研究和实际应用奠定了理论和技术基础，为其在环境监测、食品安全监测、临床检验等多方面的拓展应用提供了新思路和新途径。另外，本项目研究过程中共发表论文24篇（其中SCI论文19篇，会议论文4篇），获得发明专利3项，培养研究生6名（其中，博士生3名，硕士生3名）。