文献类型：期刊文献

英文题名：Fish Capsules: A System for High-Throughput Screening of Combinatorial Drugs

作者：Tang, Minghui[1];Duan, Xin[1];Yang, Anqi[1];He, Shijie[1];Zhou, Yajing[1];Liu, Yuxin[1];Zhang, Lu[1];Luo, Xuan[2,3];Shi, Peng[2,3];Li, Honglin[4];Lin, Xudong[1]

机构：[1]Sun Yat Sen Univ, Sch Biomed Engn, Guangdong Prov Key Lab Sensor Technol & Biomed In, Guangzhou 510006, Peoples R China;[2]City Univ Hong Kong, Dept Biomed Engn, Kowloon, Hong Kong 999077, Peoples R China;[3]City Univ Hong Kong, Shenzhen Res Inst, Shenzhen 523808, Guangdong, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2022

卷号：9

期号：9

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20220511566703);WOS:【SCI-EXPANDED(收录号:WOS:000747555600001)】；

基金：This work was supported by the National Science Foundation of China (81901837, 81871452, and 81825020), the National Science Foundation of Guangdong Province (2021A1515010266, 2020B1212060077), the Science Technology and Innovation Committee of Shenzhen Municipality (JCYJ20180507181624871), the General Research Fund from RGC Hong Kong SAR (11215920, 11203017), and the Health and Medical Research Fund from the Food and Health Bureau of Hong Kong SAR HMRF (06172336). The authors thank Prof. Jiulin Du (Institute of Neuroscience, Center for Excellence in Brain Science & Intelligence Technology, Chinese Academy of Sciences) for kindly providing the transgenic line elavl3:H2B-GCaMP6f.

语种：英文

外文关键词：drug combination; high-throughput screening; microdroplet array; microfluidics; zebrafish

摘要：Large-scale screening of molecules heavily relies on phenotyping of small living organisms during preclinical development. However, deep profiling candidate therapeutics on whole animals typically requires laborious manipulations and anesthetic treatment using traditional techniques or automated tools. Here, a novel fish capsule system that combines automated zebrafish encapsulating technology and droplet microarray strategy for in vivo functional screening of mono/polytherapies is described. This platform enables automated, rapid zebrafish orientation and immobilization in agarose to generate large-scale fish capsules by using a microfluidic device. Based on the effect of discontinuous dewetting, the prompt trapping of fish capsules in the aqueous arrays is successfully demonstrate. This system provides the capability to integrate pharmaceutical treatments with real-time multispectral microscopic imaging in a simple, pipetting-free and highly parallel manner. Coupling with machine learning algorithms, a small library of compounds is screened and analyzed, and clues about how to exploit compound combinations as therapeutic candidates are obtained. It is believed that this proposed strategy can be readily applied to multiple fields and is especially useful in the exploration of combinatorial drugs with limited amounts of samples and resources to accelerate the identification of novel therapeutics for precision medicines.