title: Minimizing hydrodynamic stress in mammalian cell culture through the lobed Taylor-Couette bioreactor.
abstract: The objective of the present study was to investigate the effect of hydrodynamic stress heterogeneity on metabolism and productivity of an industrial mammalian cell line. For this purpose, a novel Lobed Taylor-Couette (LTC) mixing unit combining a narrow distribution of hydrodynamic stresses and a membrane aeration system to prevent cell damage by bubble bursting was developed. A hydrodynamic analysis of the LTC was developed to reproduce, in a uniform hydrodynamic environment, the same hydrodynamic stress encountered locally by cells in a stirred tank, particularly at the large scale, e.g., close and far from the impeller. The developed LTC was used to simulate the stress values near the impeller of a laboratory stirred tank bioreactor, equal to about 0.4 Pa, which is however below the threshold value leading to cell death. It was found that the cells actively change their metabolism by increasing lactate production and decreasing titer while the consumption of the main nutrients remains substantially unchanged. When considering average stress values ranging from 1 to 10 Pa found by other researchers to cause physiological response of cells to the hydrodynamic stress in heterogeneous stirred vessels, our results are close to the lower boundary of this interval.
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland.
authors.forename: Robin
authors.initials: R
authors.lastname: Sorg
authors.forename: Timm
authors.initials: T
authors.lastname: Tanzeglock
authors.forename: Miroslav
authors.initials: M
authors.lastname: Soos
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
authors.forename: Arnaud
authors.initials: A
authors.lastname: Périlleux
authors.forename: Thomas
authors.initials: T
authors.lastname: Solacroup
authors.forename: Hervé
authors.initials: H
authors.lastname: Broly
mesh_terms: D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D060846:Cell Engineering / Q000295:instrumentation / Q000379:methods*; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004867:Equipment Design; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D013314:Stress, Mechanical
chemical_list: D008567:Membranes, Artificial