Cyto-Mine transforms cell line development at FUJIFILM Diosynth Biotechnologies

Scientists at FUJIFILM Diosynth Biotechnologies have transformed their cell line development processes through the incorporation of Cyto-Mine, a next-generation single-cell analysis system developed by Sphere Fluidics. The new processes are streamlined, compared with previous workflows, and productivity has been enhanced. Projects are now able to swiftly transition from the initial transfection phase through to development of highly productive cell lines within approximately 10 weeks.

Cell line development: critical objectives and challenges

Specialist contract development and manufacturing organisations (CDMOs) offer technical expertise and capacity in cell line and process development to optimise production of biological medicines for biotherapeutic manufacturers. In this commercially competitive field, CDMOs are under increasing pressure to deliver robust and productive stable cell lines within shortened timeframes, to drive faster transfer of therapeutic molecules into clinical development. This must be achieved while maintaining excellence concerning biological product quality.

Technologies that provide better predictive screening capabilities and higher throughputs than those traditionally used in cell line development laboratories have been sought to meet the growing urgency and demand for unique biotherapeutic molecules. Conventional manual screening techniques, such as colony picking and limiting dilution cloning, are time-consuming, laborious and restricted concerning the number of cells that can be processed or analysed within a given period. Industry regulators, such as the Food and Drug Administration (FDA), require evidence of monoclonality regarding cell lines used in the production of biological medicines. Traditional approaches do not allow visualisation of individual cells upon initial seeding, making demonstration of monoclonality difficult or impossible in certain cases.

Cyto-Mine in practice: improving efficiency and ensuring quality

Cyto-Mine enables individual cells to be encapsulated within picolitre-sized aqueous droplets in a biocompatible carrier oil (picodroplets). FUJIFILM Diosynth Biotechnologies has harnessed this technology to develop a single-step cloning process, which removes bottlenecks in the cell development process and improves both accuracy and efficiency. Each picodroplet provides a controlled, defined and adjustable environment that maintains cell viability. Single cells may be screened with speed and precision while secreted proteins are trapped within the picodroplets, making them easily accessible for characterisation.

Multiple procedures and assays within the cell line development pathway are miniaturised and integrated within Cyto-Mine (Figure 1), allowing tasks that would previously have taken weeks to complete to be undertaken within one day. Approximately 200,000 individual cells can be screened in a matter of hours using this approach, compared with around 10,000 cells with manual analysis techniques.

Figure 1: Integration of productivity assay screening, sorting, isolation and verification using a fully automated picodroplet microfluidic process. For a larger version, click here.

Quality and quantity of molecular product are enhanced as screening is now conducted at an early stage so that only cells expressing the protein of interest, and the best-performing cells within this pool, are taken forward in the development process. Workflows have been significantly shortened, from around 25 weeks to approximately 10 weeks (Figure 2). Importantly, single cells may be visualised using Cyto-Mine and monoclonality data can be provided to support regulatory submissions.

Figure 2: Example timeline highlighting the streamlining of workflows using Cyto-Mine. For a larger version, click here.

Overall efficiency and productivity in the cell line and process development team at FUJIFILM Diosynth Biotechnologies has been enhanced through the application of Cyto-Mine. Scientists spend less time conducting laborious manual procedures and are able to complete a greater number of projects within a given timeframe. This allows them to apply their specialist skills and expertise to other important aspects of their work. Motivated by the possibilities of Cyto-Mine, the scientists are now exploring further applications using this technology platform.

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