Culture scale-up studies as seen from the viewpoint of oxygen supply and dissolved carbon dioxide stripping

Oxygen supply and dissolved carbon dioxide (dCO2) stripping are two of the most important control parameters in cell culture. In this study, we investigated the effect of scale-up on the volumetric gas transfer coefficient with bioreactors of different sizes (working volume: 80 L, 500 L, 2000 L, and 10,000 L; aspect ratio: 1.0–1.6). Sparging air into water increased the volumetric oxygen transfer coefficient (kLa), an index of oxygen supply efficiency, by scale-up roughly in proportion to the depth of the water. A corresponding increase in kLa was found in a real cell culture of Chinese hamster ovary cells. dCO2 stripping efficiency was evaluated in water tests using changes in kLaco2, an index defined in relation to kLa. kLaco2 increased following surface aeration, but the rate of increase was reduced by scale-up, which was attributed to a decrease in the liquid surface-to-volume ratio. A similar decrease in efficiency was observed in a 2000 L bioreactor by increasing the liquid volume at constant liquid surface area. The observed scale-up effects are discussed based on a simple theoretical consideration.