Characterization of flow conditions in 2 L and 20 L wave bioreactors® using computational fluid dynamics

Abstract

Characterization of flow conditions is of great importance to control cell growth and cell damage in animal cell culture because cell viability is influenced by the flow properties in bioreactors. Alternative reactor types like Wave Bioreactors have been proposed in recent years, leading to markedly different results in cell growth and product formation. An advantage of Wave Bioreactors is the disposability of the Polyethylenterephthalet-bags after one single use (fast setup of new production facilities). Another expected advantage is a lower shear stress compared to classical stirred-tank reactors, due to the gentle liquid motion in the rocking cellbag. This property would considerably reduce possible cell damage. The purpose of the present study is to investigate in a quantitative manner the key flow properties in Wave Bioreactors, both numerically and experimentally. To describe accurately flow conditions and shear stress in Wave Bioreactors using numerical simulations, it is necessary to compute the unsteady flow applying Computational Fluid Dynamics (CFD). Corresponding computations for two reactor scales (2 L and 20 L cellbags) are presented using the CFD code ANSYS-FLUENT. To describe correctly the free liquid surface, the present simulations employ the Volume of Fluid (VOF) method. Additionally, experimental measurements have been carried out to determine liquid level, flow velocity and liquid shear stress, which are used as a validation of the present CFD simulations. It is shown that the obtained flows stay in the laminar regime. Furthermore, the obtained shear stress levels are well below known threshold values leading to damage of animal cells.