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LabAutomation


SAFETY FIRST automating cell line development


Developing and maintaining cell cultures in a stable and sterile environment is of paramount importance to protect samples and increase overall success of drug discovery pipelines.Cell lines are extremely fragile and susceptible to contamination which can be catastrophic in terms of both time and money. Therefore, adequate environmental protection must be provided at all times in automation system enclosures.Here we examine what to look out for to ensure safe and successful automated cell line development.


By Jon Newman- Smith


A


utomation in drug discovery has become a fundamental driver of progress, enabling increased throughput and reduced reliance


on labour-intensive workflows. One of the main drivers behind this is the need for increased ‘speed to clinic’ – investors and CROs are placing height- ened importance on shorter cell line development times and the production of consistently high-qual- ity recombinant products. As a result, many com- panies are developing automation strategies in order to meet these demands. There are various processes in cell line develop-


ment that are particularly labour-intensive. For example, transfection (gene knock in or knock out), which is a random process, can often create a major bottleneck. This is because multiple screens and selection panels are needed to ensure the best clones are identified. Cell maintenance and cell line stability are also time-consuming, involving selec- tion of high-performing clones and culture and expansion over a range of volumes to achieve yields that can be moved on to systems for further development. Of course, well-designed, comprehensive enclosed


automation systems can accurately perform a wide range of tasks covering the entire cell line develop- ment workflow (Figure 1):


●Cell seeding ❍ Dispensing cells into primary culture plates ❍ Maintaining cell lines in water baths to


40


avoid temperature shocking


❍ Dilutions to required cell concentration with fresh media


●Addition of growth supplements or inhibitors ●Automated incubation ❍ Controlled CO2 and temperature


●Confluence measurement ❍ Assess cell growth and clones ❍ Automatic clone selection based on operator-set growth parameters


●Clone selection and cell maintenance ●Transfection of cells ❍ Both chemical and viral transfection


●Clone selection ❍ Stripping of adherent cell lines ❍ Cell centrifugation ❍ Transfer to expansion plates and fresh media


●Lead optimisation and target identification ●Phenotypic screening of suspension cells ●Clone selection for antibody production ●Hit picking


These automation solutions normally consist of


robotic plate handlers, microplate stores, incuba- tors and laboratory instruments controlled by scheduling software. These are housed in an enclosed system also known as a workcell or an enclosure that importantly monitors and controls the internal sterile environment. Automating these processes significantly streamlines the workflow,


Drug DiscoveryWorld Summer 2019


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