CFD for Characterizing Standard and Single-use Stirred Cell Culture Bioreactors

Kaiser, Stefan; Löffelholz, Christian; Werner, Sören; Eibl, Dieter

doi:10.5772/23496

Cited by 13 publications

(3 citation statements)

References 63 publications

(68 reference statements)

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“…The turbulence model used here is the k -

shear stress transport (SST) model of Menter [ 45 ] (

corresponds to the turbulent specific dissipation rate), as it can also be directly used as a model for low Reynolds numbers (a detailed derivation can be found in Appendix B ). The rotation of the stirrer was handled by the multiple reference frame (MRF) approach as it is a steady-state analysis [ 46 , 47 , 48 ]. The relatively low speeds and axial pumping (less vortex formation compared with radial pumping stirrers) allow for the assumption of a non-free surface.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, a symmetry plane was used as boundary conditions for the liquid surface, as is usual for single-phase stirred bioreactor simulations [ 48 , 49 , 50 ]. A no-slip wall boundary condition was used for the bioreactor wall, stirrer, and internals [ 46 , 47 ]. The OpenFOAM solver simpleFOAM was employed, which uses the Semi-Implicit Method for Pressure-Linked Equations (SIMPLE) algorithm for the pressure-velocity coupling [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

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Improvement of HEK293 Cell Growth by Adapting Hydrodynamic Stress and Predicting Cell Aggregate Size Distribution

et al. 2023

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HEK293 is a widely used cell line in the fields of research and industry. It is assumed that these cells are sensitive to hydrodynamic stress. The aim of this research was to use particle image velocimetry validated computational fluid dynamics (CFD) to determine the hydrodynamic stress in both shake flasks, with and without baffles, and in stirred Minifors 2 bioreactors to evaluate its effect on the growth and aggregate size distribution of HEK293 suspension cells. The HEK FreeStyleTM 293-F cell line was cultivated in batch mode at different specific power inputs (from 63W/m3–451W/m3), whereby ≈60W/m3 corresponds to the upper limit, which is what has been typically described in published experiments. In addition to the specific growth rate and maximum viable cell density VCDmax, the cell size distribution over time and cluster size distribution were investigated. The VCDmax of 5.77±0.02e6cells/mL was reached at a specific power input of 233W/m3 and was 23.8% higher than the value obtained at 63W/m3 and 7.2% higher than the value obtained at 451W/m3. No significant change in the cell size distribution could be measured in the investigated range. It was shown that the cell cluster size distribution follows a strict geometric distribution whose free parameter p is linearly dependent on the mean Kolmogorov length scale. Based on the performed experiments, it has been shown that by using CFD-characterised bioreactors, the VCDmax can be increased and the cell aggregate rate can be precisely controlled.

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“…The turbulence model used here is the k -

shear stress transport (SST) model of Menter [ 45 ] (

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Improvement of HEK293 Cell Growth by Adapting Hydrodynamic Stress and Predicting Cell Aggregate Size Distribution

et al. 2023

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“…In this method the average velocity direction is selected as the frame of reference and the normal and shear components are calculated by rotating the stress tensor on this frame of reference. Kaiser et al 31 and Wollny 21 refer to Langer and Deppe 32 in order to argue how and why these components need to be separated for a better assessment of stress on cells. In short, the frame of reference is transformed so that the first axis is aligned with the average velocity direction.…”

Section: Normal and Shear Stresses In The Average Velocity Frame Of R...mentioning

confidence: 99%

Quantifying the hydrodynamic stress for bioprocesses

Kaya

Gopireddy

Urbanetz

et al. 2023

Biotechnology Progress

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Hydrodynamic stress is an influential physical parameter for various bioprocesses, affecting the performance and viability of the living organisms. However, different approaches are in use in various computational and experimental studies to calculate this parameter (including its normal and shear subcomponents) from velocity fields without a consensus on which one is the most representative of its effect on living cells. In this letter, we investigate these different methods with clear definitions and provide our suggested approach which relies on the principal stress values providing a maximal distinction between the shear and normal components. Furthermore, a numerical comparison is presented using the computational fluid dynamics simulation of a stirred and sparged bioreactor. It is demonstrated that for this specific bioreactor, some of these methods exhibit quite similar patterns throughout the bioreactor—therefore can be considered equivalent—whereas some of them differ significantly.

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Development of the Travelling Wave Bioreactor. Part II: Engineering Characteristics and Cultivation Results

Kaiser¹,

Perepelitsa

Kraume

et al. 2015

Chemie Ingenieur Technik

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The innovative travelling wave bioreactor (TWB), an orbitally shaken system, developed specifically for cell culture applications, is investigated. In this study, engineering parameters covering power input, mixing time and oxygen mass transfer obtained in two TWB prototypes are presented for the first time. Based on the results, cultivation parameters for CHO suspension cell cultivations were defined. Cell growth and substrate consumption were comparable with a wave‐mixed reference bioreactor, which demonstrates the bioreactor's applicability for cultivations of mammalian cell cultures for the first time.

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CFD for Characterizing Standard and Single-use Stirred Cell Culture Bioreactors

Cited by 13 publications

References 63 publications

Improvement of HEK293 Cell Growth by Adapting Hydrodynamic Stress and Predicting Cell Aggregate Size Distribution

Improvement of HEK293 Cell Growth by Adapting Hydrodynamic Stress and Predicting Cell Aggregate Size Distribution

Quantifying the hydrodynamic stress for bioprocesses

Development of the Travelling Wave Bioreactor. Part II: Engineering Characteristics and Cultivation Results

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