A novel model for the simulation of cell respiration in a mammalian cell culture process in an aerated stirred bioreactor

The cell respiration process of a Chinese Hamster Ovary (CHO) cell culture in a large-scale aerated and stirred bioreactor was modelled and simulated by using M-Star’s LES software. The simulation set-up was first validated with no cells present. The volume-averaged volumetric mass transfer coefficient ($k_{L}a$) and dissolved O₂ (DO, %) plots are in good agreement with experimental data. Then, the cells were added to the simulation hypothetically by defining a reaction that couples the O₂ consumption rate to the CO₂ production rate. A controller was set on the pure O₂ sparger to control the DO in the tank. Some simplifying assumptions were made such that only the CO₂ variations as a result of the cell respiration were modelled. The simulations were run on GPUs for almost one month to find how the dissolved O₂ and CO₂ concentrations evolve with time. The average rates of O₂ transfer and consumption as well as of CO₂ production and absorption look qualitatively correct and are in good agreement with the limited validation data available. The effect of varying the Viable Cell Density (VCD) was investigated as well. Finally, the local dissolved CO₂ concentration data were used to calculate local and averaged partial pressures of CO₂ (pCO₂) which remained well within the suggested range of 20–80 mmHg reported by Mostafa and Gu (2003) and Xing et al. (2017). Overall, the simulation approach showed great potential in capturing the local heterogeneities in dissolved O₂ and CO₂ concentrations.