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High cell density and high monoclonal antibody production through medium design and rational control in a bioreactor
Author(s) -
Xie Liangzhi,
Wang Daniel I. C.
Publication year - 2000
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/(sici)1097-0290(19960920)51:6<725::aid-bit12>3.0.co;2-c
Subject(s) - bioreactor , monoclonal antibody , chemistry , production (economics) , biochemical engineering , antibody , biology , immunology , engineering , organic chemistry , macroeconomics , economics
A simple feeding strategy was developed and successfully employed for nutritional control in a 2‐L fed‐batch culture of hybridoma cells. A previously developed stoichiometric model for animal cell growth was used to design a supplemental medium for feeding. Undialyzed fetal bovine serum and trace metals (Fe 2+ , SeO 3 2− , Li + , Zn 2+ , and Cu 2+ ) were fed to the cells periodically in addition to the automatic feeding of other nutrients in the supplemental medium. In this study, the maximum viable cell density was increased from 6.3 × 10 6 to 1.7 × 10 7 cells/mL, and the culture span was extended from 340 to 550 hours. The final monoclonal antibody titer achieved was 2400 mg/L. The specific production rates for ammonia and lactate were further reduced from 0.0045 and 0.0048 in our previous fed‐batch experiments to 0.0028 and 0.0036 mmol/10 9 cell h, respectively. Only 3.4% of the total glucose consumption was converted into lactate, compared to 67% in a conventional batch culture.