Optimization of Small Scale High-Throughput System for pH Sensitive CHO Cell Culture

For a CHO cell line of interest, productivity and cell counts in a small scale high-throughput system were significantly lower compared to bioreactor performance. A multivariate approach was applied to test methods of controlling pH and improving cell count measurements, including periodic pH adjustments, increasing bicarbonate levels in the media, eliminating CO2 overlay in the incubators, adding anti-clumping agent, and lowering batch feed volumes. The new small scale operating conditions developed significantly improved cell growth and cell count measurements and resulted in more comparable productivity to culture performance in bioreactors.