CFD-based Characterization of the Single-use BioreactorXcellerexTM XDR-10 for Cell Culture Process Optimization

The Xcellerex XDR-10 is a cylindrical stirred tank single-use bioreactor with a flat bottom and a maximum working volume of 10 L. Computational fluid dynamics (CFD) simulations with both Euler-Euler and Euler-Lagrange approaches are used to characterize the hydrodynamic conditions inside the vessel for different operating conditions. They include the full range of recommended working volume (4.5 L to 10 L), impeller speeds from 40 rpm to 360 rpm, and sparging rates from 0.02 L/min to 0.5 L/min. The evaluated parameters include the specific oxygen mass transfer coefficient (kLa), mixing time, vortex formation, energy dissipation rate, and shear stress. To evaluate the experimentally observed vortex formation the change in agitated liquid height is measured and used for validation. Additionally, kLa and mixing time are determined experimentally and used for validation. The lowest mixing time and a high kLa are observed at the maximum stirrer speed with both approaches as well as in experiments. However, analysis of the volume-average energy dissipation rate for this condition violates the upper limit of 0.4 m/s, which has been observed to have negative impact on mammalian cell culture performance. This indicates that, while a high stirrer speed seems recommendable to improve oxygen transfer and reduce mixing time, going up to the maximum level will lead to high hydrodynamic stress on the cultivated cells and should be avoided. The present study shows how CFD can provide in-depth understanding of a bioreactor with non-standard geometry. Furthermore, despite their differences, both modeling approaches lead to similar results and perform similarly well with respect to experimental validation. Thus, for the considered operating conditions the effect of bubbles on the liquid flow, which is mainly driven by the mechanical agitation of the stirrer, is small and the computationally less expensive one-way coupled Euler-Lagrange approach can characterize the process well.