(147e) High Throughput Cell Culture Process Optimization By Using Green Fluorescence Protein (Gfp) To Simultaneously Monitor Cell Growth And Protein Production In Microbioreactor Array And Perfusion Bioreactor

A real-time three-dimensional (3-D) cell culture microbioreactor array was developed for high-throughput cell culture process development for antibody production by CHO cells in a fibrous bed bioreactor (FBB). A fast simple method was used to obtain recombinant CHO cells expressing GFP without antibiotic selection. The transgenic cells produced by this method were stable in producing the recombinant antibody. The effect of sodium butyrate treatment on the MAb productivity was studied as an example for the optimization of the cell culture process using the microbioreactor array. Finally, an online fluorescence probe was developed and used for spinner flasks and lab-scale perfusion FBB to quantify cell growth non-invasively and MAb productivity with the optimized sodium butyrate treatment. The result from this study showed that GFP fluorescence could be reliably used to indicate the recombinant protein production and thus provide a convenient method for cell culture process development to optimize target protein productivity without cell counting or protein analysis.