Flow Characterization in Wave Bioreactors Using Computational Fluid Dynamics

Abstract

Quantifying and optimizing the flow conditions in cultivation systems is essential for successful cell growth in major biotechnological applications, like vaccine production processes. Recently, disposable wave bioreactors have been proposed for manufacturing of biologics, leading to markedly different mixing properties compared to stirred tank reactors, i.e. lower shear stress. To describe accurately the conditions in wave bioreactors using numerical simulations, it is first necessary to compute the unsteady flow employing Computational Fluid Dynamics (CFD). Simultaneously, the Volume of Fluid (VOF) method is employed to simulate motion of the free liquid surface. Experimental measurements have been carried out in order to determine liquid surface height, flow velocity and shear stress, which are used as a validation of CFD simulations. The obtained results confirmed low shear stress levels, well below known threshold values leading to cell damage. Recent simulations take additionally into account microcarriers through Population Balance Model (PBM), needed for adherent cell growth. Nomenclature

A mechanistic model for gas–liquid mass transfer prediction in a rocking disposable bioreactor

“…The calculated Reynolds number, based on the definition presented in Equation , ranged from a low of 4,114 at 3L, 8° rocking angle and 10 rpm rocking speed to a high value of 27,435 at 10 L, 12° rocking angle and 40 rpm. This range was higher than in previously reported works due to the different definition used in this study, as well as a wider range of used experimental conditions (Eibl et al, ; Marsh et al, ; Öncül et al, ).…”

“…Though so far no experimental measurement of linear phase velocity in a wave bioreactor has been reported, there are some related works available for comparison which characterized either the averaged or temporal and spatial liquid velocity. Öncül et al () reported from their CFD simulation that the mean velocity fluctuated between 0.1 and 0.3 m/s (average approximately 0.2 m/s), passing through the center line of a 20 L bag (7 L liquid volume) at 15 rpm and a 7° angle. Kalmbach et al () later confirmed this value in their hot‐wire anenometry experiments.…”

“…For example, Eibl et al () examined the engineering characteristics of the rocking bioreactor including power input, flow pattern, mixing time, and gas–liquid mass transfer coefficient using a BioWave® bioreactor as a model. Kalmbach et al () investigated the hydrodynamic properties of the liquid flow in the bag using experiments as well as computational fluid dynamic (CFD) simulation tools (Öncül, Kalmbach, Genzel, Reichl, & Thévenin, ). Marsh et al () used phase‐resolved particle image velocimetry (PIV) to experimentally characterize the fluid flow in a 2 L hard plastic mimic of a disposable bag (Marsh et al, ).…”