A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery

被引:22
|
作者
Joslin, John [1 ]
Gilligan, James [1 ]
Anderson, Paul [1 ]
Garcia, Catherine [1 ]
Sharif, Orzala [1 ]
Hampton, Janice [1 ]
Cohen, Steven [1 ]
King, Miranda [1 ]
Zhou, Bin [1 ]
Jiang, Shumei [1 ]
Trussell, Christopher [1 ]
Dunn, Robert [1 ]
Fathman, John W. [1 ]
Snead, Jennifer L. [1 ]
Boitano, Anthony E. [1 ]
Nguyen, Tommy [1 ]
Conner, Michael [1 ]
Cooke, Mike [1 ]
Harris, Jennifer [1 ]
Ainscow, Ed [1 ]
Zhou, Yingyao [1 ]
Shaw, Chris [1 ]
Sipes, Dan [1 ]
Mainquist, James [1 ]
Lesley, Scott [1 ]
机构
[1] Genom Inst Novartis Res Fdn, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA
关键词
high-throughput flow cytometry; phenotypic screening; high-throughput screening; drug discovery; REGULATORY T-CELLS; HEMATOPOIETIC STEM-CELLS; DATA-COLLECTION; IN-VITRO; ACTIVATION; DISEASES;
D O I
10.1177/2472555218773086
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.
引用
收藏
页码:697 / 707
页数:11
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