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Oxygen supply for CHO cells immobilized on a packed‐bed of Fibra‐Cel® disks
Author(s) -
Meuwly F.,
Loviat F.,
Ruffieux P.A.,
Bernard A.R.,
Kadouri A.,
von Stockar U.
Publication year - 2006
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.20766
Subject(s) - bioreactor , packed bed , chinese hamster ovary cell , chromatography , productivity , chemistry , perfusion , oxygenation , volume (thermodynamics) , cell culture , chemical engineering , biology , biochemistry , thermodynamics , engineering , medicine , ecology , physics , receptor , cardiology , genetics , organic chemistry , economics , macroeconomics
Packed‐bed bioreactors (PBR) have proven to be efficient systems to culture mammalian cells at very high cell density in perfusion mode, thus leading to very high volumetric productivity. However, the immobilized cells must be continuously supplied with all nutrients in sufficient quantities to remain viable and productive over the full duration of the perfusion culture. Among all nutrients, oxygen is the most critical since it is present at very low concentration due to its low solubility in cell culture medium. This work presents the development of a model for oxygenation in a packed‐bed bioreactor system. The experimental system used to develop the model was a packed‐bed of Fibra‐Cel® disk carriers used to cultivate Chinese Hamster Ovary cells at high density (∼6.1 × 10 7 cell/mL) in perfusion mode. With the help of this model, it was possible to identify if a PBR system is operated in optimal or sub‐optimal conditions. Using the model, two options were proposed, which could improve the performance of the basal system by about twofold, that is, by increasing the density of immobilized cells per carrier volume from 6.1 × 10 7 to 1.2 × 10 8 cell/mL, or by increasing the packed‐bed height from 0.2 to 0.4 m. Both strategies would be rather simple to test and implement in the packed‐bed bioreactor system used for this study. As a result, it would be possible to achieve a substantial improvement of about twofold higher productivity as compared with the basal conditions. © 2005 Wiley Periodicals, Inc.