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

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 sc...

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Autores principales: Joslin, John, Gilligan, James, Anderson, Paul, Garcia, Catherine, Sharif, Orzala, Hampton, Janice, Cohen, Steven, King, Miranda, Zhou, Bin, Jiang, Shumei, Trussell, Christopher, Dunn, Robert, Fathman, John W., Snead, Jennifer L., Boitano, Anthony E., Nguyen, Tommy, Conner, Michael, Cooke, Mike, Harris, Jennifer, Ainscow, Ed, Zhou, Yingyao, Shaw, Chris, Sipes, Dan, Mainquist, James, Lesley, Scott
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055113/
https://www.ncbi.nlm.nih.gov/pubmed/29843542
http://dx.doi.org/10.1177/2472555218773086
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author Joslin, John
Gilligan, James
Anderson, Paul
Garcia, Catherine
Sharif, Orzala
Hampton, Janice
Cohen, Steven
King, Miranda
Zhou, Bin
Jiang, Shumei
Trussell, Christopher
Dunn, Robert
Fathman, John W.
Snead, Jennifer L.
Boitano, Anthony E.
Nguyen, Tommy
Conner, Michael
Cooke, Mike
Harris, Jennifer
Ainscow, Ed
Zhou, Yingyao
Shaw, Chris
Sipes, Dan
Mainquist, James
Lesley, Scott
author_facet Joslin, John
Gilligan, James
Anderson, Paul
Garcia, Catherine
Sharif, Orzala
Hampton, Janice
Cohen, Steven
King, Miranda
Zhou, Bin
Jiang, Shumei
Trussell, Christopher
Dunn, Robert
Fathman, John W.
Snead, Jennifer L.
Boitano, Anthony E.
Nguyen, Tommy
Conner, Michael
Cooke, Mike
Harris, Jennifer
Ainscow, Ed
Zhou, Yingyao
Shaw, Chris
Sipes, Dan
Mainquist, James
Lesley, Scott
author_sort Joslin, John
collection PubMed
description 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.
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spelling pubmed-60551132018-08-10 A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery Joslin, John Gilligan, James Anderson, Paul Garcia, Catherine Sharif, Orzala Hampton, Janice Cohen, Steven King, Miranda Zhou, Bin Jiang, Shumei Trussell, Christopher Dunn, Robert Fathman, John W. Snead, Jennifer L. Boitano, Anthony E. Nguyen, Tommy Conner, Michael Cooke, Mike Harris, Jennifer Ainscow, Ed Zhou, Yingyao Shaw, Chris Sipes, Dan Mainquist, James Lesley, Scott SLAS Discov Original Research 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. SAGE Publications 2018-05-29 2018-08 /pmc/articles/PMC6055113/ /pubmed/29843542 http://dx.doi.org/10.1177/2472555218773086 Text en © 2018 Society for Laboratory Automation and Screening http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Joslin, John
Gilligan, James
Anderson, Paul
Garcia, Catherine
Sharif, Orzala
Hampton, Janice
Cohen, Steven
King, Miranda
Zhou, Bin
Jiang, Shumei
Trussell, Christopher
Dunn, Robert
Fathman, John W.
Snead, Jennifer L.
Boitano, Anthony E.
Nguyen, Tommy
Conner, Michael
Cooke, Mike
Harris, Jennifer
Ainscow, Ed
Zhou, Yingyao
Shaw, Chris
Sipes, Dan
Mainquist, James
Lesley, Scott
A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery
title A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery
title_full A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery
title_fullStr A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery
title_full_unstemmed A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery
title_short A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery
title_sort fully automated high-throughput flow cytometry screening system enabling phenotypic drug discovery
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055113/
https://www.ncbi.nlm.nih.gov/pubmed/29843542
http://dx.doi.org/10.1177/2472555218773086
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