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  1. Dinter C, Gumprecht A, Menze MA, Azizan A, Niehoff PJ, Hansen S, et al.
    Sci Rep, 2024 Feb 13;14(1):3658.
    PMID: 38351095 DOI: 10.1038/s41598-024-53980-7
    Computational fluid dynamics (CFD) has recently become a pivotal tool in the design and scale-up of bioprocesses. While CFD has been extensively utilized for stirred tank reactors (STRs), there exists a relatively limited body of literature focusing on CFD applications for shake flasks, almost exclusively concentrated on fluids at waterlike viscosity. The importance of CFD model validation cannot be overstated. While techniques to elucidate the internal flow field are necessary for model validation in STRs, the liquid distribution, caused by the orbital shaking motion of shake flasks, can be exploited for model validation. An OpenFOAM CFD model for shake flasks has been established. Calculated liquid distributions were compared to suitable, previously published experimental data. Across a broad range of shaking conditions, at waterlike and moderate viscosity (16.7 mPa∙s), the CFD model's liquid distributions align excellently with the experimental data, in terms of overall shape and position of the liquid relative to the direction of the centrifugal force. Additionally, the CFD model was used to calculate the volumetric power input, based on the energy dissipation. Depending on the shaking conditions, the computed volumetric power inputs range from 0.1 to 7 kW/m3 and differed on average by 0.01 kW/m3 from measured literature data.
  2. Dinter C, Gumprecht A, Menze MA, Azizan A, Hansen S, Büchs J
    Biotechnol Bioeng, 2024 Nov 30.
    PMID: 39614833 DOI: 10.1002/bit.28892
    Culture broth with secreted macromolecules and culture broth of filamentous fungi showing disperse growth exhibit elevated viscosity, usually with shear-thinning flow behavior. High viscosity, however, poses a serious challenge in the production and research of these compounds and organisms. It commonly causes insufficient mixing and oxygen transfer in large- and small-scale bioreactors. Computational Fluid dynamics (CFD) has been proven to be a valuable tool for the computation of important bioprocess parameters. The published literature for small-scale shaken bioreactors, especially shake flasks, however, almost exclusively focuses on water-like viscosity. In this paper, a previously published CFD model for 250 mL shake flasks was used to simulate experiments at high viscosities of up to 100 mPa·s. Compared to experimental data, the CFD model accurately predicted the liquid distribution and computed the volumetric power input with a deviation of less than 7% and the kLa value within a factor of two, compared to the kLa correlation from Henzler and Schedel. Furthermore, a novel approach to compute the shear rate was tested. Lastly, new insights into the out-of-phase phenomenon were gained. The presented data confirms the usefulness of the already established critical phase numbers of 0.91 and 1.26, while underlying the fundamentally smooth transition from in-phase to out-of-phase operating conditions.
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