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

Abstract

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 CO(2) stripping. Particularly in large production reactors, CO(2) 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 CO(2)-stripping and O(2)-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.

Harmonization and characterization of different single‐use bioreactors adopting a new sparger design

“…bioreactor [29]. The improved k L a o2 in the 200/250 L scale at nearly the doubled power input values clearly indicate that the key parameter power input has a significant influence on the oxygen mass transfer rate, as reported by others [30][31][32].…”

The physical characterisation of a microscale parallel bioreactor platform with an industrial CHO cell line expressing an IgG4

“…Though the air sparge rate under normal conditions (0.15 mL/min) is similar to that used at the larger scale when expressed as vvm (0.01 vvm), it becomes higher with the additional oxygen flow required to give the desired driving force and hence dO 2 , which increases the flow rate to 0.45 mL/min (~ 0.03 vvm). This increased vvm flow helps carbon dioxide stripping [2] and pCO 2 control [33]. However, in terms of superficial air velocity (important for k L a), the flow is very low (maximum ~ 2 x 10 -5 m/s), which also encourages a significant contribution from the upper surface to the overall rate of mass transfer at this scale as can be seen in Table 2 and 3.…”

Equipment characterization to mitigate risks during transfers of cell culture manufacturing processes

“…While at lower volumetric gas throughput the rates of oxygen consumption and CO 2 production are comparable, the dissolved CO 2 may accumulate. More details about this stripping problem for large scale cell culture reactors can be found by Sieblist et al (2011a).…”