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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- 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
References
Croughan MS, Wang DI (1991) Hydrodynamic effects on animal cells in microcarrier bioreactors. Biotechnology 17:213–249
Eibl R, Eibl D (2006) Design and use of the wave bioreactor for plant cell culture. In: Dutta Gupta S, Ibaraki Y (eds.) Plant Tissue Culture Engineering. Springer, Dordrecht, pp. 64–72
Fluent Inc. (2006) Fluent 6.3 User’s Guide, Lebanon, USA
Freshney RI (1994) Culture of Animal Cells: A Manual of Basic Technique, 3rd edn. Wiley-Liss Inc., New York, NY
Gao D, Morley NB, Dhir V (2003) Numerical simulation of wavy falling film flow using VOF method. J Comput Phys 192:624–642
Genzel Y, Olmer RM, Schäfer B, Reichl U (2006) Wave microcarrier cultivation of MDCK cells for influenza virus production in serum containing and serum-free media. Vaccine 24:6074–6087
Genzel Y, Reichl U (2007) Vaccine production – state of the art and future needs in upstream processing. In: Pörtner R (ed) Animal Cell Biotechnology – Methods and Protocols. Humana Press Inc., Totowa, NJ, pp. 73–85
Gunjal PR, Ranade VV, Chaudhari RV (2005) Dynamics of drop impact on solid surface: Experiments and VOF simulations. AIChE J 51:59–78
Hirt CW, Nichols BD (1981) Volume of fluid (VOF) method for the dynamics of free boundaries. J Comput Phys 39:201–225
Hundt B, Best C, Schlawin N, Kaßner H, Genzel Y, Reichl U (2007) Establishment of a mink enteritis vaccine production process in stirred-tank reactor and Wave® Bioreactor microcarrier culture in 1–10 L scale. Vaccine 25:3987–3995
Joshi JB, Elias CB, Patole MS (1996) Role of hydrodynamic shear in the cultivation of animal, plant and microbial cells. Chem Eng J Biochem Eng J 62:121–141
Loudon C, Tordesillas A (1998) The use of the dimensionless Womersley number to characterize the unsteady nature of internal flow. J Theor Biol 191:63–78
Marchisio DL, Fox RO (2005) Solution of population balance equations using the direct quadrature method of moments. J Aerosol Sci 36:43–73
Öncül AA, Kalmbach A, Genzel Y, Reichl U, Thévenin D (2009) Characterization of flow conditions in 2 L and 20 L Wave Bioreactors® using computational fluid dynamics. Biotechnol Prog. doi:10.1021/bp.312
Palazón J, Mallol A, Eibl R, Lettenbauer C, Cusidó RM, Piñol MT (2003) Growth and ginsenoside production in hairy root cultures of Panax ginseng using a novel bioreactor. Planta Med 69:344–349
Richardson EG, Tyler E (1929) The transverse velocity gradient near the mouths of pipes in which an alternating or continuous flow of air is established. Proc Phys Soc 42:1–15
Schmalzriedt S, Jenne M, Mauch K, Reuss M (2003) Integration of physiology and fluid dynamics. In: von Stockar U, van der Wielen LAM (eds.) Advances in Biochemical Engineering/Biotechnology. Springer, Berlin, pp. 19–68
Singh V (1999) Disposable bioreactor for cell culture using wave-induced agitation. Cytotechnology 30:149–158
Singh V (2001) Method for culturing cells using wave-induced agitation. United States Patent, Patent No. US 6,190,913 B1
Spier RE (ed) (2000) Encyclopedia of Cell Technology. Wiley, New York, NY
Tomiyama A, Zun I, Sou A, Sakaguchi T (1993) Numerical analysis of bubble motion with the VOF method. Nucl Eng Des 141:69–82
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”.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this paper
Cite this paper
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
Download citation
DOI: https://doi.org/10.1007/978-94-007-0884-6_78
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-0883-9
Online ISBN: 978-94-007-0884-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)