Application of High Throughput Bioreactors for Subclone Selection
Date
2008-10-22Type of Work
application/pdfText
theses
Department
Chemical, Biochemical & Environmental EngineeringProgram
EngineeringRights
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Subjects
Engineering, Chemical(0542)subcloning
mammalian cell culture
improved protein productivity
miniature bioreactors
limiting dilution cloning
Abstract
The demand for monoclonal antibodies in pharmaceutical drug production requires the highest technology be invested in obtaining a stable, high producing cell line. Currently the most common method of selection is by limiting dilution cloning, done in well plates. The highest producing cell is chosen after samples from the stationary plates have been analyzed for antibody production. The selection is based on stationary culture, even though after scale-up cells will grow in a stirred environment. This research investigates a way to test multiple clones in a stirred environment by using high throughput bioreactors (HTBRs) in the early stages of clone selection. It has been found that simply selecting subclones based on results from stationary culture could result in the chance of missing even higher producing clones. Instead, choosing a clone after analyzing its performance in a stirred environment is an improved method to select a cell line for further scale-up.