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高通量流式细胞术在早期药物发现中的应用:阿斯利康视角。

Application of High-Throughput Flow Cytometry in Early Drug Discovery: An AstraZeneca Perspective.

机构信息

1 Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

2 Discovery Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, UK.

出版信息

SLAS Discov. 2018 Aug;23(7):719-731. doi: 10.1177/2472555218775074. Epub 2018 May 22.

Abstract

Flow cytometry is a powerful tool providing multiparametric analysis of single cells or particles. The introduction of faster plate-based sampling technologies on flow cytometers has transformed the technology into one that has become attractive for higher throughput drug discovery screening. This article describes AstraZeneca's perspectives on the deployment and application of high-throughput flow cytometry (HTFC) platforms for small-molecule high-throughput screening (HTS), structure-activity relationship (SAR) and phenotypic screening, and antibody screening. We describe the overarching HTFC workflow, including the associated automation and data analysis, along with a high-level overview of our HTFC assay portfolio. We go on to discuss the practical challenges encountered and solutions adopted in the course of our deployment of HTFC, as well as future enhancements and expansion of the technology to new areas of drug discovery.

摘要

流式细胞术是一种强大的工具,可对单细胞或粒子进行多参数分析。在流式细胞仪上引入更快的基于平板的采样技术,已经将该技术转变为一种对高通量药物发现筛选具有吸引力的技术。本文介绍了阿斯利康(AstraZeneca)在小分子高通量筛选(HTS)、结构-活性关系(SAR)和表型筛选以及抗体筛选中部署和应用高通量流式细胞术(HTFC)平台的观点。我们描述了总体的 HTFC 工作流程,包括相关的自动化和数据分析,以及我们的 HTFC 检测组合的高级概述。我们接着讨论了在部署 HTFC 过程中遇到的实际挑战和采用的解决方案,以及该技术在药物发现新领域的未来增强和扩展。

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