bioreactor; orbital shaking; mass transfer; computation fluid dynamics; mathematical modelling; mixing; mammalian cells; recombinant protein; shear stress; fluid velocity
Monteil Dominique (2013), Disposable 600-mL orbitally shaken bioreactor for mammalian cell cultivation in suspension, in Biochemical Engineering Journal
, 76, 6-12.
Discacciati Marco (2013), Numerical simulation of orbitally shaken viscous fluids with free surface, in INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS
, 71, 294-315.
Tissot Stéphanie (2012), kLa as a predictor for successful probe-independent mammalian cell bioprocesses in orbitally shaken bioreactors, in New Biotechnology
, 29(3), 387-394.
Tissot Stéphanie (2011), Efficient and reproducible mammalian cell bioprocesses without probes and controllers?, in New Biotechnology
, 28, 382-390.
Tissot Stéphanie (2010), Determination of a scale-up factor from mixing time studies in orbitally shaken bioreactors, in Biochemical Engineering Journal
, 52, 181-186.
Discacciati Marco, Numerical approximation of internal discontinuity interface problems, in SIAM Journal on Scientific Computing
The main objective of this collaborative project is to understand transport phenomena (oxygen transfer and mixing) in orbitally shaken bioreactors in order to improve their design and operation and to ultimately achieve predictable cell growth profiles over a range of volumetric scales. Numerical approaches based on Computational Fluid Dynamics (CFD) will be combined with experiments in fluid dynamics and cell cultivation to simulate and optimize mixing and mass transfer in shaken bioreactors for the suspension cultivation of mammalian cells. The project will be initiated by characterization of mass transfer and mixing in a shaken 30 L cylindrical vessel, a medium-scale bioreactor suitable for the experimental and computational methods described here. Mixing and mass transfer in this vessel will be simulated by CFD, and the model will be compared to experimental measurements of fluid velocity, gas transfer, and mixing. At the same time, a cell culture model based on cultivation of Chinese hamster ovary (CHO) cells in orbitally shaken containers will be generated and incorporated into the CFD model. Simulations of the validated CFD-derived model (with and without cell growth) will be used to improve the geometric design of the 30 L cylindrical vessel to facilitate mixing, gas transfer, and cell growth. The most effective designs, as judged by simulations, will be validated experimentally. Finally, the scalability of shaken cylindrical vessels and vessels with other geometries will be determined through a combination of numerical and experimental methods.