Insights into large-scale cell-culture reactors: II. Gas-phase mixing and CO2 stripping

Most discussions about stirred tank bioreactors for cell cultures focus on liquid-phase motions and neglect the importance of the gas phase for mixing, power input and especially CO2 stripping. Particularly in large production reactors, CO2 removal from the culture is known to be a major problem. Here, we show that stripping is mainly affected by the change of the gas composition during the movement of the gas phase through the bioreactor from the sparger system towards the headspace. A mathematical model for CO2-stripping and O2-mass transfer is presented taking gas-residence times into account. The gas phase is not moving through the reactor in form of a plug flow as often assumed. The model is validated by measurement data. Further measurement results are presented that show how the gas is partly recirculated by the impellers, thus increasing the gas-residence time. The gas-residence times can be measured easily with stimulus-response techniques. The results offer further insights on the gas-residence time distributions in stirred tank reactors.