A comparison of oxygenation methods fro high-density perfusion culture of animal cells
Article first published online: 19 FEB 2004
Copyright © 1993 John Wiley & Sons, Inc.
Biotechnology and Bioengineering
Volume 41, Issue 7, pages 685–692, 25 March 1993
How to Cite
Zhang, S., Handa-Corrigan, A. and Spier, R. E. (1993), A comparison of oxygenation methods fro high-density perfusion culture of animal cells. Biotechnol. Bioeng., 41: 685–692. doi: 10.1002/bit.260410702
- Issue published online: 19 FEB 2004
- Article first published online: 19 FEB 2004
- Manuscript Accepted: 13 OCT 1992
- Manuscript Received: 22 APR 1992
- hybridoma cells;
- bubble oxygenation;
- silicone tubing oxygenation;
- perfusion culture
A perfusion culture system was developed to investigate the oxygenation of high-density hybridoma cell cultures. The culture system was composed of a stirred-tank bioreactor and an external microfiltration hollow fiber cartridge for medium perfusion. Cell growth and antibody production were examined with large bubble (≈5 mm in diameter), micron-sized bubble (≈ 80 μm in diameter), and silicone tubing oxygenation techniques. Comparable cell growth and monoclonal antibody (MAb) production were found for both the micron-sized and large oxygenation methods, provided that large bubbles were enriched with pure oxygen. Relatively low cell growth and MAb production were attained with the bubble-free silicone tubing oxygenation. It is concluded that direct bubble oxygenation can be applied successfully in high-density animal cell cultures, provided that the culture medium is supplemented with Pluronic F-68. The accumulation of ammonia in the culture medium rather than oxygen limitation was found to be one of the possible problems that eventually inhibited cell growth. This and the fouling of the filtration cartridge during long-term cultivation were found to be more problematic than simple bubble oxygenation of high-density cell culture. The micron-sized bubble oxygenation method is highly recommended for high-density animal cell cultures, provided that Pluronic F-68 is supplemented into the culture medium. © 1993 John Wiley & Sons, Inc.