k(L)a as a predictor for successful probe-independent mammalian cell bioprocesses in orbitally shaken bioreactors

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 coeffic...

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Bibliographic Details
Published inNew biotechnology Vol. 29; no. 3; pp. 387 - 394
Main Authors Tissot, Stéphanie, Michel, Patrik O, Hacker, David L, Baldi, Lucia, De Jesus, Maria, Wurm, Florian M
Format Journal Article
LanguageEnglish
Published Netherlands 15.02.2012
Subjects
Animals
Bioreactors
Cell Culture Techniques - methods
CHO Cells
Cricetinae
Cricetulus
Humans
Hydrogen-Ion Concentration
Oxygen - analysis
Oxygen Consumption - physiology
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Summary: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.
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ISSN:1876-4347
DOI:10.1016/j.nbt.2011.10.010