High-throughput cell culture process development using 3-D microbioreactors and online quantifications of cell growth and GFP expression

BIOT 156

Xudong Zhang, zhangx@chbmeng.ohio-state.edu, Department of Chemical and Biomolecular Engineering, The Ohio State University, 140 West 19th Ave., Columbus, OH 43210, Yuan Wen, wen.33@osu.edu, Chemical and Biomolecular Engineering, The Ohio State University, 125A Koffolt Labs, 140 West 19th Avenue, Columbus, OH 43210, and Shang-tian Yang, yang.15@osu.edu, Dept. of Chemical Engineering, Ohio State University, 140 W.19th Ave, Columbus, OH 43210.
A high-throughput, real-time, bioactivity assay based on three-dimensional (3D) cultures of GFP-expressing cells can provide accurate, parallel, non-invasive, and long-term cell bioactivity assays. The 3D culture assays were developed on two different microbioreactor platforms for high-throughput cell culture process development. The first platform contained 40 batch microbioreactors on a 384-well plate, which was used to optimize media components for antibody production by CHO cells. The second platform contained 4 x 4 microfluidic bioreactors with the capability of continuous perfusion. This scaled-down perfusion system can be used to quickly optimize a bioprocess with minimal reagent consumption. Finally, an online fluorescence probe was developed and used for monitoring and quantifying cell growth and antibody production in the FBB. A strong correlation between fluorescence signals and antibody production was observed, which can be used to study the effects of external stimuli on antibody production, and to guide process operation and optimize its productivity.