李爽,郭肖杰,陈海博,陈思思,笪鑫,李峥辉,刘芹秀,王怡,邢新会,张翀.基于微流控技术的工程细胞高通量表型测试技术与装备研究进展[J].中国科学院院刊,2025,40(1):91-106.

基于微流控技术的工程细胞高通量表型测试技术与装备研究进展

Research progress in high-throughput phenotype testing technology and equipment for engineering cells based on microfluidics

李爽^1,2
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084
LI Shuang^1,2
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China
郭肖杰³
洛阳华清天木生物科技有限公司 洛阳 471023
GUO Xiaojie³
TMAXTREE Biotechnology Co. Ltd., Luoyang 471023, China
陈海博^1,2
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084
CHEN Haibo^1,2
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China
陈思思^1,2
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084
CHEN Sisi^1,2
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China
笪鑫^1,2
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084
DA Xin^1,2
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China
李峥辉⁴
北京联合大学 生物化学工程学院 生物质废弃物资源化利用北京市重点实验室 北京 100023
LI Zhenghui⁴
Beijing Key Laboratory of Biomass Waste Resource Utilization, College of Biochemical Engineering, Beijing Union University, Beijing 100023, China
刘芹秀^1,2
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084
LIU Qinxiu^1,2
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China
王怡^1,2
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084
WANG yi^1,2
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China
邢新会^1,2,5,6
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084;清华大学 合成与系统生物学中心 北京 100084;清华大学 深圳国际研究生院 生物医药与健康工程研究院 深圳 518055
XING Xinhui^1,2,5,6
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China;Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China;Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China
张翀^1,2,5*
清华大学 化学工程系 生物化工研究所 北京 100084;工业生物催化教育部重点实验室 北京 100084;清华大学 合成与系统生物学中心 北京 100084
ZHANG Chong^1,2,5*
Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China;Key Laboratory of Industrial Biocatalysts, Ministry of Education, Beijing 100084, China;Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China

         微流控;单细胞;高通量测试;合成生物学;生物制造

        microfluidics;single-cell;high-throughput testing;synthetic biology;biomanufacturing

        工程细胞是绿色生物制造的重要基础，如何高效测试并获得目标表型的工程细胞是影响生物制造应用的关键因素之一。近年来，基于微流控技术开发了非培养类型单细胞表型高通量测试装备，以及通过微液滴和微腔室等微型生物反应器实现单细胞生长代谢的培养类型高通量表型测试装备，实现了工程细胞表型的高通量、自动化、微型化和集成化测试，为工程细胞选育提供了强有力的工具。文章系统综述基于荧光信号、拉曼信号、图像信号、磁信号的非培养类型单细胞表型测试技术与装备，基于皮纳升、微升多尺度微型生物反应器的液滴、微腔室单细胞培养类型测试技术与装备研究进展，并探讨工程细胞高通量测试仪器创制发展趋势，为绿色生物制造工程细胞测试技术研究提供借鉴。

        Engineering cells are a core component of green bio-manufacturing. The efficient testing and acquisition of engineering cells with the desired phenotype is a critical factor in the successful implementation of bio-manufacturing. In recent years, based on microfluidics technologies, non-culture type single-cell phenotype high-throughput test equipment and culture type phenotype highthroughput test equipment for the growth and metabolism of single cell in a bioreactor have been developed such as microdroplet and microchamber, realizing high-throughput, automated, miniaturized, and integrated testing of the phenotypes of engineering cells and providing a powerful tool for the breeding of engineering cells. This review systematically compiles the research progress of nonculture type single-cell phenotype testing technologies and equipment based on fluorescence signals, Raman signals, image signals, and magnetic signals, as well as the droplet and microchamber culture type single-cell test technologies and equipment based on picoliter, nanoliter, and microliter multi-scale microbioreactors, and explores the development trend of the creation of high-throughput testing instruments for engineering cells, providing a reference for the research of green bio-manufacturing engineering cells testing technologies.