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Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes
Authors:Li‐kuan Zhu  Bo‐yan Song  Zhen‐long Wang  Dominique T Monteil  Xiao Shen  David L Hacker  Maria De Jesus  Florian M Wurm
Affiliation:1. School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People's Republic of China;2. Laboratory of Cellular Biotechnology (LBTC), Faculty of Life Sciences, école Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;3. Protein Expression Core Facility (PECF), Faculty of Life Sciences, école Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;4. ExcellGene SA, Monthey, Switzerland
Abstract:Orbitally shaken cylindrical bioreactors OrbShake bioreactors (OSRs)] without an impeller or sparger are increasingly being used for the suspension cultivation of mammalian cells. Among small volume OSRs, 50‐mL tubes with a ventilated cap (OSR50), originally derived from standard laboratory centrifuge tubes with a conical bottom, have found many applications including high‐throughput screening for the optimization of cell cultivation conditions. To better understand the fluid dynamics and gas transfer rates at the liquid surface in OSR50, we established a three‐dimensional simulation model of the unsteady liquid forms (waves) in this vessel. The studies verified that the operating conditions have a large effect on the interfacial surface. The volumetric mass transfer coefficient (kLa) was determined experimentally and from simulations under various working conditions. We also determined the liquid‐phase mass transfer coefficient (kL) and the specific interfacial area (a) under different conditions to demonstrate that the value of a affected the gas transfer rate more than did the value of kL. High oxygen transfer rates, sufficient for supporting the high‐density culture of mammalian cells, were found. Finally, the average axial velocity of the liquid was identified to be an important parameter for maintaining cells in suspension. Overall these studies provide valuable insights into the preferable operating conditions for the OSR50, such as those needed for cell cultures requiring high oxygen levels. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:192–200, 2017
Keywords:CHO cells  orbitally shaken bioreactors  computational fluid dynamics  cell suspension  oxygen transfer rate
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