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 (k_La), an index of oxygen supply efficiency, by scale-up roughly in proportion to the depth of the water. A corresponding increase in k_La was found in a real cell culture of Chinese hamster ovary cells. dCO₂ stripping efficiency was evaluated in water tests using changes in k_La^co2, an index defined in relation to k_La. k_La^co2 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.