Large scale animal cells culture is still a challenge regarding engineering considerations. A global process optimization must take into account the.
Computational Fluid Dynamics Applied to Laboratory Scale Cell Culture Reactors for the Prediction of Hydrodynamic Stress Eric Olmos1, Nicolas Fischbach1, Annie Marc1 1
Laboratoire des Sciences du Génie Chimique UPR CNRS 6811-INPL; 2, avenue de la forêt de Haye BP172, 54505 Vandoeuvre les Nancy CEDEX France
Abstract:
Using Computational Fluid Dynamics, a method for the design of animal cell culture reactors is proposed. This approach is based on the concept of Fluid Stress Distribution and on the calculation of animal cell paths.
Key words:
Computational Fluid Dynamics, hydrodynamics, culture reactor, Fluid Stress Distribution
1. INTRODUCTION 1.1 Context of the study Large scale animal cells culture is still a challenge regarding engineering considerations. A global process optimization must take into account the reactor design and the operating parameters. To do this, local phenomena have to be well understood and, if possible, precisely controlled. Among phenomena which influence animal cell culture kinetics, hydrodynamic stress due to mechanical agitation and bubble rupture have been the subject of numerous studies. Nevertheless, in these studies, these hydrodynamic stresses are generally fairly estimated and the effective stress quantity in terms of intensity and duration is not well known. 1.2 Aim of the work Computational Fluid Dynamics (CFD) is used to simulate the velocity fields in two laboratory reactors: a roller bottle and a Taylor-Couette reactor (TCR, dedicated to long term cultures with low-level hydrodynamic stress). 587 R. Smith (ed.), Cell Technology for Cell Products, 587–590. © 2007 Springer.
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Then, Fluid Stress Distributions (FSD) of these reactors and their variability within the operating conditions and within the reactor are predicted. These distributions provide global but relevant information on the local constraints. Animal cell trajectories in the reactor (and consequently local cell concentration) are calculated in order to detect a possible poor mixing and/or local cell accumulation.
2. COMPUTATIONAL APPROACH Computational Fluid Dynamics consists in solving the Navier-Stokes equations. In this study, the finite-volume method is used. Steady-state flow and incompressibility are supposed. When turbulence occurs, the Reynolds Stress turbulence model is used. The transport of animal cells in the calculated flow is performed by integrating the force balance on the cell in a Lagrangian frame. The force balance equates the particle inertia with the forces acting on the particle. Both buoyancy and drag force are taken into account (Morsi and Alexander 1972). The equations are solved with the commercial software Fluent 6.2. The Fluid Stress Distributions are obtained by post-processing numerical simulation results with the Scilab freeware.
3. RESULTS Concerning the roller bottle, the calculation of animal cell trajectories puts into evidence possible cell accumulations which may lead to reactor malfunction due to a high concentration of toxics or a lack of nutriments (Figure 1). The numerical simulations of the TCR allow the prediction of the transition from the laminar to the Taylor-Couette regime with a unique model, which is an original contribution. Moreover, the velocities calculated obtained are well validated by those measured experimentally (Haut et al., 2003). Another original result concerns Fluid Stress Distributions (FSD). Starting from sophisticated numerical simulations, an easy tool is proposed to test a priori the operation of the reactor (Figure 2).
Computational Fluid Dynamics Applied to Laboratory Scale Cell
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Figure 1. Animal cell hydrodynamic paths in the roller bottle.
Figure 2. Fluid Stress Distributions in the Taylor-Couette reactor.
4. CONCLUSION AND PERSPECTIVES Using CFD, we put into evidence possible culture reactor malfunction (poor mixing, cell accumulation) and we proposed an innovating method to numerically test the efficiency of a given reactor, in terms of hydrodynamic stress distributions. This work has now to be completed by: a house made experimental validation by Particle Image Velocimetry (PIV) and Laser Doppler Anemometry (LDA), the calculation of the amount of stress received by a cell during a classic culture, the coupling of hydrodynamics
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with culture kinetics and the generalization of the method to industrial stirred reactors for an optimized design.
REFERENCES Haut , B., Ben Amor, H., Coulon, A., Jacquet, A., Halloin, V. 2003. Hydrodynamics and mass transfer in a Couette-Taylor bioreactor for the culture of animal cells, Chem. Eng. Sci. 58 777-784. Morsi, S.A. and Alexander, A.J. 1972, An investigation of particle trajectories in two-phase flow systems, J. Fluid Mech. 55 193-208.
