Influence of Interfacial Force Models and Population Balance Models on the kLa Value in Stirred Bioreactors

Abstract

Optimal oxygen supply is vitally important for the cultivation of aerobically growing cells, as it has a direct influence on cell growth and product formation. A process engineering parameter directly related to oxygen supply is the volumetric oxygen mass transfer coefficient kLa. It is the influences on kLa and computing time of different interfacial force and population balance models in stirred bioreactors that have been evaluated in this study. For this investigation, the OpenFOAM 7 open-source toolbox was utilized. Firstly, the Euler–Euler model with a constant bubble diameter was applied to a 2L scale bioreactor to statistically examine the influence of different interfacial models on the kLa value. It was shown that the kL model and the constant bubble diameter have the greatest influence on the calculated kLa value. To eliminate the problem of a constant bubble diameter and to take effects such as bubble breakup and coalescence into account, the Euler–Euler model was coupled with population balance models (PBM). For this purpose, four coalescence and five bubble breakup models were examined. Ultimately, it was established that, for all of the models tested, coupling computational fluid dynamics (CFD) with PBM resulted in better agreement with the experimental data than using the Euler–Euler model. However, it should be noted that the higher accuracy of the PBM coupled models requires twice the computation time.

Scaling‐up of an Insect Cell‐based Virus Production Process in a Novel Single‐use Bioreactor with Flexible Agitation

“…Even though an increasing number of publications on multi‐phase CFD simulations became available over the last two decades 9, 10, 30–33, their practical use for scale‐up studies on bioreactors is still limited, especially when the required boundary conditions and model closures are unknown. Consequently, it was decided to maintain the maximum volumetric gas flow rate (in vvm) between the systems while using pure oxygen sparging for DO control, as proposed for a monoclonal antibody production process 34.…”

Computational Fluid Dynamics for Advanced Characterisation of Bioreactors Used in the Biopharmaceutical Industry – Part II: Case Studies

“…In contrast to the previous ones shown, which were single phase and steady state, the oxygen transfer in another 2 L stirred bioreactor (modified HyPerforma glass bioreactor from Thermo Fisher Scientific Inc.) was determined transiently via a twophase Euler-Euler simulation [7] (Figure 3 left). Besides the rotation of the stirrer which was realised via MRF, the aeration was defined by a gas inlet boundary condition at the sparger (a gas outlet is defined at the bioreactor lid).…”

“…The class method was used to model the gas bubbles and their size distribution with the population balance modelling approach in this example. 24 gas bubble size classes were used, which according to our own investigations and literature values proved to be a good compromise between accuracy and computation time (the computation time increases exponentially as the class number increases) [7,10,11]. The model of Laakkonen et al [12] with binary bubble breakup was used to model bubble…”

Laboratory-independent exploration of stirred bioreactors and their fluid dynamics

“…Turbulence was modeled by the Reynolds-averaged Navier-Stokes approach, using Launder and Spalding's standard k-ε-model (Launder and Spalding, 1974). The simulations were computed in parallel on the high-performance computing system described in Seidel and Eibl (2021). Post-processing was then required to make the flow visible to the students.…”

“…Bioreactors are used in numerous applications, including environmental biotechnology (biogas production Duarte et al (2021)), the production of plant cell culture extracts for the cosmetics industry (Georgiev et al, 2018), as well as the production of monoclonal antibodies, vaccines (Schirmer et al, 2020;Maschke et al, 2022) and cell therapeutics (Jossen et al, 2020). A variety of different mechanically, hydraulically and pneumatically driven bioreactor systems exist, with stirred bioreactors being the most widely used type (Seidel and Eibl, 2021;Jossen et al, 2019;Schirmer et al, 2021;Seidel et al, 2020). The design and components of stirred bioreactors differ depending on the production organism and the product they express.…”