Hotspot增敏聚集体荧光生化传感器研究

Due to current technological difficulties, it is still very challenging to diagnose cancers through biomarkers at early stage. Here we propose to develope a microfluidics integrated hotspot-enhanced AIE fluorescence biosensor, to realize the diagonosis of cancers based on early-stage biomarkers detection with simultaneous multi-parameter mode, high sensitivity and reliability, fast and portable properties. The study will focus on the scientific problems including hotspot enhanced AIE fluorescence mechanism, the basic physics during the reliable fabrication process of micro-nano structures, and the coupling mechanism of multiple microchannels signals in biosensor. AIE molecule and probes would be designed, coupled and locally immobilized to capture target molecules with high specificity. It takes the advantages of two-dimensional materials and goden nanostructure to form plasmon in order to enhance the fluorescence signal. The integration of microfluidics and sensing units would greatly decrease sensing time. The study of this project would construct a theory frame of bio-information detection controlled by multiple interfaces including the intefaces between nano structure and probes, target molecules, and AIE fuorescence molecules. Finally through this project, valuable contributions would be made to new biosenser mode and theory, micro and nano fabrication technique of multiplex biosensor, bio-molecules detection, and data analysis.

项目针对现有技术对微量癌症早期标志物分子检测的困难，旨在研发集成微流控的hotspot增敏聚集体（AIE）荧光生化传感器，以满足癌症早期标志物分子（miRNA、蛋白等）多参数、高灵敏度、高重复性、快速、便捷检测的需求。围绕hotspot增敏AIE荧光的物理机制、高增敏微纳结构材料低成本、高重复性制备的基础物理问题、传感芯片多通道检测信号的耦合机理等关键科学问题，通过设计新型的AIE荧光-探针分子并进行局域组装实现生化分子捕获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，通过微流控技术与传感芯片的集成实现传感过程的时域增强。最终通过本项目的实施，将构建纳米结构表面与探针分子、目标生物分子和AIE荧光分子之间的多重界面控制的生物信息检测理论框架，在高增敏生物传感器新模式、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。

项目针对现有技术对微量癌症早期标志物分子检测的困难，研发集成微流控的高增敏荧光生物分子传感器件，以满足癌症早期标志物分子多参数高灵敏度检测的需求。设计新型的聚集体荧光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，通过微流道技术实现传感过程的时域增强。通过研究miRNA特异性捕捉、二维材料传感增强机制、AIE荧光“hot spot”增敏过程中的能量转移及荧光放大过程等关键科学问题，实现极低浓度miRNA的检测。通过本项目的实施，构建了纳米结构表面与探针分子、目标生物分制和聚集体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。.项目已经完成所有研究内容的指标。完成了血液前处理芯片—外泌体富集芯片的研发，进行了高效的外泌体富集。利用大面积转移的石墨烯和AAO纳米孔芯片掩膜，制备了高增敏金纳米结构的芯片基底。合成并测试了7中乳腺癌相关的miRNA和它们响应的探针分子。高增敏基底与微流控芯片集成，首先进行了医院乳腺癌样本中肿瘤标记物CEA和CA125的检测，检测灵敏度达到10pg/ml。.项目研究成果已经发表SCI论文8篇，申请发明专利6项。