Two-way Euler-Lagrange simulations are performed to characterize the hydrodynamics in the single-use bioreactor Mobius® CellReady 3 L. The hydrodynamics in stirred tank bioreactors are frequently modeled with the Euler–Euler approach, which cannot capture the trajectories of single bubbles. The present study employs the two-way coupled Euler–Lagrange approach, which accounts for the individual bubble trajectories through Langrangian equations and considers their impact on the Eulerian liquid phase equations. Hydrodynamic process characteristics that are relevant for cell cultivation including the oxygen mass transfer coefficient, the mixing time, and the hydrodynamic stress are evaluated for different working volumes, sparger types, impeller speeds, and sparging rates. A microporous sparger and an open pipe sparger are considered where bubbles of different sizes are generated, which has a pronounced impact on the bubble dispersion and the volumetric oxygen mass transfer coefficient. It is found that only the microporous sparger provides sufficiently high oxygen transfer to support typical suspended mammalian cell lines. The simulated mixing time and the volumetric oxygen mass transfer coefficient are successfully validated with experimental results. Due to the small reactor size, mixing times are below 25 s across all tested conditions. For the highest sparging rate of 100 mL min−1, the mixing time is found to be two seconds shorter than for a sparging rate of 50 mL min−1, which again, is 0.1 s longer than for a sparging rate of 10 mL min−1 at the same impeller speed of 100 rpm and the working volume of 1.7 L. The hydrodynamic stress in this bioreactor is found to be below critical levels for all investigated impeller speeds of up to 150 rpm, where the maximum levels are found in the region where the bubbles pass behind the impeller blades.
Understanding the hydrodynamic conditions in bioreactors is of utmost importance for the selection of operating conditions during cell culture process development. In the present study, the two-phase flow in the lab-scale single-use bioreactor XcellerexTM XDR-10 is characterized for working volumes from 4.5 L to 10 L, impeller speeds from 40 rpm to 360 rpm, and sparging with two different microporous spargers at rates from 0.02 L min−1 to 0.5 L min−1. The numerical simulations are performed with the one-way coupled Euler–Lagrange and the Euler–Euler models. The results of the agitated liquid height, the mixing time, and the volumetric oxygen mass transfer coefficient are compared to experiments. For the unbaffled XDR-10, strong surface vortex formation is found for the maximum impeller speed. To support the selection of suitable impeller speeds for cell cultivation, the surface vortex formation, the average turbulence energy dissipation rate, the hydrodynamic stress, and the mixing time are analyzed and discussed. Surface vortex formation is observed for the maximum impeller speed. Mixing times are below 30 s across all conditions, and volumetric oxygen mass transfer coefficients of up to 22.1 h−1 are found. The XDR-10 provides hydrodynamic conditions which are well suited for the cultivation of animal cells, despite the unusual design of a single bottom-mounted impeller and an unbaffled cultivation bioreactor.
The Xcellerex TM 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 2 /s 3 , 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.
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