title: k(L)a as a predictor for successful probe-independent mammalian cell bioprocesses in orbitally shaken bioreactors.
abstract: The aim of this study was to gain a better understanding of orbitally shaken bioreactors (OSRs) operated without controllers for pH and dissolved oxygen (DO) concentration. We used cylindrical OSRs with working volumes ranging from 250mL to 200L to determine that the volumetric mass transfer coefficient of oxygen (k(L)a) is a good predictor of the performance of OSRs at different scales. We showed that k(L)a values of 7-10hour(-1) were required to avoid DO limitations and to prevent conditions of low pH during the cultivation of CHO cells. Overall, cell cultures in probe-independent OSRs of different nominal volumes ranging from 250mL to 200L achieved similar cell densities, recombinant protein concentrations, and pH and DO profiles when having the same k(L)a. We conclude that k(L)a is a key parameter for probe-independent bioprocesses in OSRs and can be used as a scale-up factor for their operation.
authors.affiliation: Laboratory of Cellular Biotechnology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Tissot
authors.forename: Patrik O
authors.initials: PO
authors.lastname: Michel
authors.forename: David L
authors.initials: DL
authors.lastname: Hacker
authors.forename: Lucia
authors.initials: L
authors.lastname: Baldi
authors.forename: Maria
authors.initials: M
authors.lastname: De Jesus
authors.forename: Florian M
authors.initials: FM
authors.lastname: Wurm
mesh_terms: D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000032:analysis*; D010101:Oxygen Consumption / Q000502:physiology
chemical_list: D010100:Oxygen