基于二维材料和金属纳米结构的集成微流控生化传感器研究

Because there are some difficulties for the existing sensing technology to detect the trace molecular cancer markers in early stage, we research and develop a new kind of biosensor based on two-dimensional material - metal nanostructures which is integrated with microfluidic to form LSPR - SERS "dual" sensing biochemical sensors. This kind of biosensor can meet the requirements of multi-parameters and high sensitivity detection for the cancer early markers. To design a new type of probing molecules was used to realize high specificity and high selectivity through local assembling target -biochemical molecules. To improve sensitivity was realized by using two-dimensional material cooperating with metal nanostructure plasmon. Meanwhile, time domain enhance of the biosensor came true through microfluidics. We investigate the miRNA specific capture, metal nanostructures SERS and LSPR sensing, two-dimensional material sensing mechanism, the "hot spot" produced by metal nanostructure in the process of energy transfer and key scientific problems, such as signal enhancement process for detecting low concentration of miRNA. And we eventually build detection theory framework of multiple interface among nanostructures, the probing molecules and target biological molecules. There are some innovation in the new pattern, new methods and new theory of high sensitivity two-dimensional material - metal nanostructures biosensor, micro/nano-fabrication technology of biosensor integrated with multi-channel, testing and data processing.

针对现有传感技术对微量癌症早期标志物分子检测的困难，研发基于二维材料-金属纳米结构的集成微流控LSPR-SERS“双”生化传感器，以满足癌症早期标志物分子多参数、高灵敏度检测的需求。设计新型的探针分子并进行局域组装实现生化分子的高特异性和高选择性，利用二维材料与金属增敏结构的等离激元协同增强作用提高灵敏度，通过微流控技术实现传感过程的时域增强。通过研究miRNA特异性捕捉、金属纳米结构SERS传感和LSPR传感、二维材料传感增强机制、金属纳米结构产生的“hot spot”增敏过程中的能量转移及信号增强过程等关键科学问题，实现极低浓度miRNA的检测。并最终构建纳米结构表面与探针分子、目标生物分子之间的多重界面控制的生物信息检测理论框架，在构建高增敏二维材料-金属纳米结构生物传感器新模式、新方法和新理论、多通道生物传感器的微纳加工技术、检测和数据处理技术方面获得创新成果。

针对当前患癌症的人数巨增，并且年轻化的现状，利用现有的生化检测技术，当病人被确诊为癌症时，通常错过了最佳治疗时。因此，目前迫切需要高灵敏度、极低浓度检测极限的新型传感器来满足医学检测的重大需求。.主要研究内容：.1. 设计了多款LSPR传感芯片，并与微流控芯片集成；.2. 开发了低成本微纳米结构LSPR传感芯片制备方法，并实现在石英、硅、柔性聚合物材料表面制备；.3. 开发了小型化LSPR传感检测系统；.4. 开展了癌症标物的传感检测验证。.重要结果：.1. 芯片：单通单点位，四通道四点位，九通道九点位，多种传感芯片。.2. 制备技术：开发了自吸纳压印技术，实现在四英寸晶圆不同基底上制备出纳米光栅或点阵，获得了自主知识产权。.3. 仪器：实现以了其于LSPR传感检测仪器达到商品化标准。.4. 应用：实现了癌症标记物（AFP，CEA，CA125，CA153，外泌体）的低浓度检测。.通过本项目研究，有效提高癌症标志物分子在低丰度情况下的有效吸附，实现快速检测，开辟了生物传感器新模式、新方法和新理论。在多通道生物传感器的微纳加工技术、检测和数据处理技术方面获得创新成果，可为癌症早期诊断提供依据。