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

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Oxygen supply and dissolved carbon dioxide (dCO_2) 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: 80L, 500L, 2000L, and 10,000L; 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. dCO_2 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 2000L bioreactor by increasing the liquid volume at constant liquid surface area. The observed scale-up effects are discussed based on a simple theoretical consideration.
社団法人日本生物工学会の論文