Fed-batch cultivation of animal cells using different medium design concepts and feeding strategies
Article first published online: 19 FEB 2004
Copyright © 1994 John Wiley & Sons, Inc.
Biotechnology and Bioengineering
Volume 43, Issue 11, pages 1175–1189, May 1994
How to Cite
Xie, L. and Wang, D. I. C. (1994), Fed-batch cultivation of animal cells using different medium design concepts and feeding strategies. Biotechnol. Bioeng., 43: 1175–1189. doi: 10.1002/bit.260431123
- Issue published online: 19 FEB 2004
- Article first published online: 19 FEB 2004
- Manuscript Accepted: 23 DEC 1993
- Manuscript Received: 6 AUG 1993
- medium design;
- animal cell culture;
In animal cell cultivation, cell density and product concentration are often low due to the accumulation of toxic end-products such as ammonia and lactate and/or the depletion of essential nutrients. A hybridoma cell line (CRL-1606) was cultivated in T-flasks using a newly devised medium feeding strategy. The goals were to decrease ammonia and lactate formation by the design of an initial medium which would provide a starting environment to achieve optimal cell growth. This was followed by using a stoichiometric equation governing animal cell growth and then designing a supplemental medium for feeding strategy used to control the nutritional environment. The relationship between the stoichiometric demands for glutamine and nonessential amino acids was also studied. Through stoichiometric feeding, nutrient concentrations were controlled reasonably well. Consequently, the specific production rate of lactate was decreased by fourfold compared with conventional fed-batch culture and by 26-fold compared with conventional batch culture. The specific production rate of ammonia was decreased by tenfold compared with conventional fed-batch culture and by 50-fold compared with conventional batch culture. Most importantly, total cell density and monoclonal antibody concentration were increased by five- and tenfold respectively, compared with conventional batch culture. © 1994 John Wiley & Sons, Inc.