外泌体在肿瘤诊疗中具有极高的应用价值，但临床中缺乏高效的分选和检测技术。微流控芯片是极具前景的检测方法，但现有的制造技术难以实现高精度微纳结构的有序调控，导致芯片存在微观结构单一、比表面积低、无法介导或增敏光学信号等缺陷，因而未能实现对外泌体的高效分选和检测。针对上述技术难题，本项目重点研究高精度微纳结构的调控方法。在前期工作基础上，具体探索微纳电喷印技术联合纳米合成技术调控贵金属三维基底微纳结构的规律和机制，并研究高精度微纳结构对表面增强拉曼光谱（SERS）的增强机制。进而通过调控芯片的加工精度，探索外泌体高效分选和鉴定所需的微纳结构类型及影响因素，构建出基于确定性侧向位移原理的尺寸分选芯片和基于SERS信号的定量检测芯片，将其用于肺癌EGFR突变型外泌体的检测。本课题有望研发出新的微纳制造工艺，并据此提升微流控芯片分选富集和定量检测外泌体的效率，对推动肺癌的临床诊疗具有重要意义。

Exosomes are of great value in the diagnosis and treatment of tumors. However, there is a lack of efficient separation and quantitative detection techniques in clinical practice. Microfluidic chip is a promising detection technology. But the existing manufacturing technology can not achieve precise control of micro-nano structure. As a result, the microstructure of the chip is single, the specific surface area of the chip is low, and the optical signal can not be mediated or sensitized by the chip. Thus, microfluidic chip have not achieved efficient separation and detection for exosomes. In view of the above technical problems, this project focuses on the research of high-precision regulation methods for micro-nano structure. Based on the applicant's previous work, this study mainly explores the rule and mechanism of the combined regulation on micro-nano structure of precious metals using electrohydrodynamic jet printing and nano-synthesis technology. And then the enhancement mechanism of high-precision micro-nano structure on surface-enhanced Raman spectroscopy (SERS) is studied. By regulating the micro-nano structure of the substrate, the types of micro-nano structures for the efficient detection of exosomes are explored. The exosome size sorting chip based on deterministic lateral displacement and quantitative detection chip based on SERS signals were constructed to detect EGFR mutant exosomes in lung cancer. This subject is expected to develop novel micro-nano manufacturing technology. The efficiency of microfluidic microarray in separation and quantitative detection of exosomes was improved. It is of great significance to promote the clinical diagnosis and treatment of lung cancer.