Automated cell culture to revolutionise drug discovery

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Related tags: Cell lines, Cell culture

Applying automation to tissue culture techniques can improve the
development, maintenance and expansion of mammalian cells,
increasing the efficiency of drug discovery efforts, reports Wai
Lang Chu.

Cell based assays are now the most important segment in drug discovery with 40-60 per cent of all assays concentrating on primary HTS screens and 50-60 per cent on selectivity screens.

According to market researchers, Front Line Strategic Market, the worldwide cellular assays market is projected to grow by more than 50 per cent to $700 million (€537 million) over the next five years. Currently, the US accounts for the lion's share of the market, at around 52 per cent of the total, with Europe following behind with 30 per cent and Japan in third with 15 per cent.

Speaking at the Lab Automation Europe show at London's Kensington Olympia, Tim Ward, cell culture business unit director at The Automation Partnership,​ stated that many successful implementations of automated cell culture in drug discovery have focused on automation of well-characterised cell lines. This has been because of the likelihood of an improved quality of output, healthier, consistent cells and improved assay data.

However the implementation of automation has proceeded slowly because of the challenging and specialised requirements of working with living systems and large variability of responses of cells to different conditions.

Reliable output from automated systems has required frequent manual intervention to make decisions effecting the action and timing of future process steps. Consequently, successful implementations has focussed on automation of these well-characterised cell lines and only limited parallel processing.

Ward outlined other areas in which automated cell culture could make an impact. As well as the earlier availability of protein and cell lines, earlier assay development leading to earlier structural data would result in shorter lead discovery, improving the lead quality entering clinical phase.

He recommended a series of steps designed to improve the process for producing new stable cell lines that included increasing the diversity in the initial number of clones, increase the number of projects working in parallel and documenting cell line history in greater detail.

Up until now, the process of producing viable cell lines has been a process that has required specialised labware, skilled operators and aseptic manipulation that has proved labour intensive.

The requirements, particularly for a working, viable automated system for clone selection, are numerous and while this may push up costs short term, the benefits are sure to be felt in the long term.

At an average price of $1,000 (€767) for assay systems and $250,000 (€192 000) for instrumentation, the high cost of cellular assay technology is expected to limit growth until economic recovery in the life sciences industry allows for the expansion of research. Front Line expected the market to expand around 7 per cent a year until accelerating to double-digit growth in 2007.

Ward stated that the maintenance and expansion of hundreds of cell lines would be a primary issue, as would the aseptic handling of adherent and non-adherent cells. Whilst not normally a big problem if handled manually by a researcher, the concept of automated cell lines could prove disastrous should contamination go undetected.

Compatibility is likely to remain key, as an automated system would need to work in conjunction with multiwell plates of 384, 96, 24 and 6 wells. Integrated imaging would need to be applied to each well to determine cell growth and clonality, enabling individual, customisable treatment.

Full integration with external data systems for automated selection of positives and recording of cell line history would be a compulsory requirement too.

Companies such as Amersham Biosciences (now GE) and PerkinElmer are currently dominating, with 24 and 17 per cent of the market, respectively. One company expected to gain market share is Invitrogen, with the maturation of its assay technologies, resulting from its acquisitions of Genicon Sciences, Molecular Probes and PanVera last year.

Other major companies in the cellular assay sector include BD Biosciences with 12 per cent of the market, Beckman Coulter with 10 per cent and Invitrogen and Molecular Devices, with 9 per cent each.

One specific driver of the market pinpointed the trend towards using primary cell lines. These are the growth of next generation cells taken directly from the living organism. Traditionally, immortalised cell lines have been used in drug discovery, but more researchers are turning to primary cells for their discovery efforts. Primary cells are more similar to the natural cell environment in the living body than immortalised cell lines.

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