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

Stefan Seidel,Dieter Eibl

doi:10.3390/pr9071185

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.

Highlights

Due to the vast potential of biopharmaceuticals, the market is growing rapidly [1]
To examine the influence of different interfacial force models, the classical Euler–Euler model was used in the first step after the mesh analysis
This work aimed to investigate the influence of different interfacial force models and population balance models (PBM) on the calculation of the volumetric oxygen mass transfer coefficient in stirred and aerated bioreactors using computational fluid dynamics (CFD)

Summary

Introduction

Either cell cultures or microorganisms are used as production hosts, which, among other things, has an impact on bioreactor design and oxygen consumption [2]. As oxygen supply has a significant influence on cell growth and product yield, manufacturers are very interested in establishing how to achieve an optimal oxygen supply for specific organisms as early as the process development stage. The most commonly used bioreactors in both process development and commercial production are stirred bioreactors with forced aeration. Both computational fluid dynamics (CFD) and classical process engineering approaches are used for optimization and scaling-up of stirred bioreactor processes [3,4,5,6]. CFD is based on the laws of conservation of energy, mass, and momentum

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