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Flow Characterization in Wave Bioreactors Using Computational Fluid Dynamics

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Part of the book series: ESACT Proceedings ((ESACT,volume 5))

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.

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Abbreviations

H l :

local liquid surface height, mm

t :

time, s

u x :

component of the liquid velocity along the direction of rotation, m/s

Greek letters :

τ l :

liquid shear stress, Pa

τ max :

maximum shear stress, Pa

τ w :

wall shear stress, Pa

Abbreviations :

CFD:

Computational Fluid Dynamics

DQMOM:

Direct Quadrature Method of Moments

MDCK:

Madine Darby Canine Kidney

PBM:

Population Balance Model

PET:

Polyethylene Terephthalate

VOF:

Volume of Fluid

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Acknowledgements

The support of Andreas Kalmbach for the experimental work presented here is gratefully acknowledged. The authors thank Dr. Gábor Janiga for his assistance and helpful discussions. The capacitive probes have been produced by Dirk Meinecke at the Institut für Strömungstechnik und Thermodynamik. The financial support of the Excellence Programme of the state Saxony-Anhalt (Germany) concerning “Dynamic Systems in Biology, Medicine, and Process Engineering” is gratefully acknowledged (Project number: XD3639HP/0306). Special thanks go to Christine Lettenbauer from Wave Biotech AG for her cooperation during the special preparation of the cellbags. The authors would finally like to acknowledge the effective support of the Fraunhofer-Institut für Fabrikbetrieb und -automatisierung (IFF Magdeburg, Germany) concerning the measurement of the exact bag geometry using the laser measuring technique “OptoInspect 3D-Flex”.

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Correspondence to Alper A. Öncül .

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Öncül, A.A., Genzel, Y., Reichl, U., Thévenin, D. (2012). Flow Characterization in Wave Bioreactors Using Computational Fluid Dynamics. In: Jenkins, N., Barron, N., Alves, P. (eds) Proceedings of the 21st Annual Meeting of the European Society for Animal Cell Technology (ESACT), Dublin, Ireland, June 7-10, 2009. ESACT Proceedings, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0884-6_78

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