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Fed‐batch cultivation of animal cells using different medium design concepts and feeding strategies
Author(s) -
Xie Liangzhi,
Wang Daniel I.C.
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.21160
Subject(s) - fed batch culture , laboratory flask , glutamine , ammonia , nutrient , food science , stoichiometry , ammonia production , cell growth , biology , cell culture , batch processing , biochemistry , chemically defined medium , chemistry , amino acid , fermentation , ecology , in vitro , genetics , organic chemistry , computer science , programming language
Abstract 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. © 2006 Wiley Periodicals, Inc.