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Item type:Publication, Access status: with files , Modeling and validating of oxygen transport in wave bioreactors: optimized experimental mass transfer method and novel Lattice-Boltzmann CFD approach(Frontiers Media S.A., 2026-01-21); ; ; Wave bioreactors are commonly used in biopharmaceutical upstream processes as an intermediate stage between shake flasks and stirred tanks within the seed train. They offer a controlled environment for cell cultivation while minimizing shear stress. Accurate characterization of these systems is essential for optimizing cell culture performance, particularly as state of the art cell lines require higher volumetric mass transfer coefficients k<inf>L</inf>a. This study aims to determine the volumetric mass transfer coefficient through experiments and computational fluid dynamics (CFD) simulations. An improved experimental method for the measurements of the volumetric mass transfer is presented, with results correlated to key process parameters: rocking angle, rocking rate, and filling volume. In addition, CFD simulations were caried out using M-Star CFD by means of a Lattice-Boltzmann Method-based solver. The mass transfer was calculated using Higbie’s penetration theory, incorporating the Kolmogorov scale to define contact time. The analysis also integrates concepts from Friedl and the surface renewal model, introducing the surface normal velocity as an additional parameter in the mass transfer coefficient k<inf>L</inf> calculation. Analyzes were carried out for 10 and 50 L wave bioreactors, with one degree of freedom movement. Optimized process parameters were identified and validated in biological cultivations, resulting in increased dissolved oxygen levels in the medium. These findings contribute to improved characterization and control of wave bioreactors, enabling more accurate prediction of process parameter effects.Publicationtype: Journal Article30 14 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Study of hydrodynamic stress in cell culture bioreactors via lattice-Boltzmann CFD simulations supported by micro-probe shear stress method(Elsevier, 2024-08-01); ; ; Mammalian cell cultivation in pharmaceutical industry can last up to units of weeks and requires proper transport of nutrients and oxygen for cell growth and production. Given the long time period, cells experience flow fields from all bioreactor's zones, where the energy dissipation rate (ε) varies substantially. Shear sensitive micro-probes with size comparable to cells and Kolmogorov eddies are used for the determination of the maximum hydrodynamic stress (τmax) in bioreactors. For the very first time, the micro-probe method is applied successfully not only to laboratory (3 L) and pilot scale (80 L and 200 L), but also to industrial production scale bioreactor (12,500 L) with Rushton turbine and pitched-blade (RT-PB) impeller configuration. Experimentally obtained data are used for the validation of comprehensive CFD scale-up study, using the Lattice-Boltzmann large eddy simulation (LB-LES) method. Besides τmax, this work also focuses on the study of mixing time and flow field attributes.Publicationtype: Journal Article28 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Lagrangian sensors in a stirred tank reactor: comparing trajectories from 4D-Particle Tracking Velocimetry and Lattice-Boltzmann simulations(Elsevier, 2022-06-17); ; ; ; In this study, three-dimensional flow measurements by means of 4D-Particle Tracking Velocimetry (4D-PTV) are carried out in a laboratory-scale 3 L stirred tank reactor in order to investigate the flow-following behavior of two different inertial particle types, Polyethylene (PE) particles and alginate beads, at different impeller frequencies. Applied particles mimic Lagrangian sensor particles, which are intended to determine process parameters such as oxygen concentration at their corresponding position inside a bioreactor. Accompanying Lattice-Boltzmann Large Eddy Simulations (LB LES) provide additional information about the fluid flow and the difference in the trajectories between inertial and non-inertial particles. The data acquired from LB LES is validated with the experimental data by means of a Lagrangian and a Eulerian approach. In their tail, the probability distributions show higher Lagrangian velocities and accelerations for 4D-PTV data compared to LB LES data. Time-averaged Eulerian data is utilized to determine particle Reynolds numbers lower than 200. The Stokes number distributions show 10-fold higher values for the alginate beads than for PE particles, however, both particle types do not sufficiently meet the criterion of a flow-following Stokes number of St≤0.01. Generally, time-averaged results from LB LES are in good accordance to the 4D-PTV data. From the LB LES, a theoretical, maximum particle diameter of approx. 20 μm is determined, which meets the criterion of St≤0.01 throughout the reactor. This result implies that with current sensor particle technology it is not possible to meet the flow-following behavior and depict the lifelines of cells during a cultivation process. Therefore, further research is necessary to understand particle trajectories and to translate them into lifelines of cells.Publicationtype: Journal ArticleScopus© Citations 13 101 628