Screening
Automating flow
cytometry for cell-based screening in drug discovery
Flow cytometry is a powerful tool for cell quantitation and analysis across a wide range of clinical and research applications. Most commonly used in the fields of immunology and haematology, recent improvements in instrument automation and throughput mean that the technique is now emerging as an increasingly attractive high-throughput screening (HTS) platform in drug discovery too.
F
low cytometry is a widely-used analytical method that uses light to count and charac- terise heterogeneous cell populations. Highly valued for its ability to measure multiple parameters simultaneously, the technique enables vast amounts of data on large, phenotypically- diverse cell populations to be rapidly collected. Coupled with the fact that it is a non-destructive method that can be performed on live cells allow- ing further processing and analysis, it has become well-established as an important tool for both investigatory and routine analysis across a wide range of applications.
Its ability to quickly generate a wide range of data on cell properties means flow cytometry has been widely used for a number of applications in drug discovery, from target identification and vali- dation, through to toxicological assessment1. As a screening tool, its ability to measure cell properties on a single-cell basis makes it highly useful when analysing highly heterogeneous cell populations. This powerful functionality is in contrast to the analysis of cell lysates on plate readers, for exam- ple, where phenotypic differences are averaged out and essentially lost during measurement. However, due to technical challenges around
Drug Discovery World Winter 2017/18
throughput and sample handling, its use has tradi- tionally been limited to relatively low volume applications such as small target-based assays. As a result, the screening of even small compound libraries has traditionally proven time-consuming and practically challenging.
Recent advances in instrument design, automa- tion and handling capacity are now enabling the wider use of flow cytometry for HTS applications. The commercial availability of instruments capable of handling micro-384 well plates and screening tens of thousands of cells per second are opening up a wide range of opportunities for HTS applica- tions in drug discovery. Coupled with novel auto- mated sample handling systems, these develop- ments are simplifying workflows, enhancing throughput and reducing cost associated with per- forming HTS assays. Indeed, the growing impor- tance of flow cytometry in drug discovery is high- lighted by the fact the technology will be a key focus of this year’s SLAS tradeshow2.
Flow cytometry basics
Flow cytometry works by analysing the way indi- vidual cells interact with light. In a typical experi- ment, cells suspended in solution are sprayed into
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By Paul Avery and Richard Massey
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