Modular systems automate the tissue culture process that is vital to the development of immortalised cell lines, providing a never-ending supply of DNA for extensive genetic studies
The University of Bristol is developing a growing reputation for its work in the growth of cell lines.
In part, this is because last year, an automated cell line system developed with RTS Life Science was installed, primarily for its work on the Avon Longitudinal Study of Parents and Children (Alspac).
After this system proved its success, a second system has been installed, this time for the 1958 British Birth Cohort Study, which is managed by St Georges Hospital, London, and the Institute of Child Health, with the growth of cell lines being outsourced to the team at Bristol.
Essentially both modular systems automate the tissue culture process that is vital to the development of immortalised cell lines, providing a never-ending supply of DNA for extensive genetic studies.
The technology behind the Bristol University systems comes from RTS's Assay Platform systems, which are primarily used by the pharmaceutical sector for high throughput and ultra high throughput screening.
Karen Allison, product manager for the Assay Platform family of products, explained: "The flexibility inherent in the Assay-Platform's physical layout and the Sprint scheduling software it uses, has translated into a proven application for fully automated cell manipulation in multi-well plates".
The 1958 British Birth Cohort Study has followed people born in that year from birth to the present time.
The studies have painted a detailed picture of how life in Britain has changed over the past 50 years and have been used by policymakers to assess the impact of government policies.
Once again, the university has received funding from the Wellcome Trust, as well as collaborative input from the ECCAC, the Europe-wide cell culture organisation.
Richard Wynn Jones, head of biological samples in both Alspac and the 1958 Cohort, explained: "RTS Life Science created a groundbreaking system to manage and carry out the cell manipulations crucial to the Alspac project.
"It was natural to turn to them when our first system came under strain from the sheer volume of work.
"As some of the cultures grown in the 1958 Cohort stay on the system for six weeks, we knew we had to have an even more highly defensive set-up than our first system.
"All the liquids entering the new system, including the sterile media, are run through a 0.1 micro filter, but other than that, there is very little difference between the new and the old systems.
"You could say we stuck with a winning formula".
Peripheral blood lymphocytes are isolated and transferred to a single well of a 24 well plate in which they are exposed to Epstein Barr Virus (EBV).
Once set up, the transforming cells are subjected to the automated refeeding and expansion process.
Cells are diluted and expanded progressively across the wells of the plate.
Plates are barcoded and strictly audited throughout their entire expansion process.
The barcode on the plate is read by the system and the appropriate refeeding or expansion protocol selected.
Either a proportion of the medium is removed and replaced, or the cells are diluted with medium and expanded into a larger number of wells.
The plate is returned by the system to its incubator prior to a further inspection after several days.
The growing cells move through the system until all 24 wells contain confluent cells.
In the second of the two systems, further expansion of the cultures for cryostorage and DNA extraction is facilitated by transfer of culture from 24 well plates to six well plates.
The RTS systems at Bristol University are capable of handling up to 600 cultures at any one time, with inspections taking place during office hours and expansion and cell feeding taking place overnight.
On average, there are now 2400 culture manipulations each week.
Both systems have the capacity for automated plating out, re-feeding, well assessment (via automated 'visual' assessment or Elisa assay) and cherry picking of wells for expansion.
Enclosing the system within a class II environment means that a range of applications such as Hybridoma production, vaccine development, DNA banking, Caco2 plate production and assaying may also be fully automated.
