真菌感染的日趋严重以及耐药菌株的不断出现对抗真菌新药需求日趋增长。传统孔板法已经不能满足抗真菌药物活性分析的高通量和高内涵。微型化和集成化的微流控芯片技术已逐渐应用于药物活性研究并凸显优势，很有可能取代孔板，成为下一代主流的药物活性筛选平台。本课题拟以具有良好研究基础的抗真菌药物为研究对象，以微流控芯片为载体，从细胞（白念珠菌）和模式生物（线虫模型）两个层面，构建白念珠菌和感染白念珠菌线虫模型的液滴微流控芯片系统，将液滴生成、融合和在线荧光检测等功能集成，实现高通量的抗真菌药物活性在线分析；进而结合多维液质联用技术，将培养、浓度梯度生成、在线荧光检测、生理指标检测、前处理等功能集成，对以上高通量分析获得的新化合物进行活性的定量表征，实现高内涵分析。本项目旨在探索抗真菌药物活性分析的创新方法，建立优于传统孔板法并能实现活性定量表征的微流控芯片系统，为抗真菌新药研究提供新的思路和技术借鉴。

There is an urgent need for anti-fungal new drugs due to the more serious mycotic infection and the increasing drug-resistant strains. The anti-fungal activity screening using 96-well plates cannot meet the requirement of the high-throughput and high content assays. Recently, the miniaturized and integrated microfluidics has shown great potential in drug activity analysis that it might be a promising substitute for 96-well plates. This project aims to develop the micro-droplet microfluidic chip system in view of Candida albicans and C.elegans. The microdroplet generation,merge and online fluorescent detection were integrated in the device,which would be used for high-throughput activity assay of anti-fungal candidate compounds. Morever, the multiple gradient generator followed by an array of microscale cell or worms culture chambers and on-chip solid-phase extraction columns for sample pretreatment prior to mass analysis was integrated in the device which was fabricated in one single step. The quantitative characterization of the anti-fungal activity and high content screening are to be obtained using an integrated microfluidic device coupled to a mass spectrometer. All work attempts to develop a feasible new methodology for high-throughput activity analysis of anti-fungal candidate compounds, which would be better than the screening with 96-well plates and quantify the activity. This project will provide new measure and technical support for the research and development of anti-fungal new drugs.