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Comparison of control strategies for fed‐batch culture of hybridoma cells based on on‐line monitoring of oxygen uptake rate, optical cell density and glucose concentration
Author(s) -
Casablancas Antoni,
Gámez Xavier,
Lecina Martí,
Solà Carles,
Cairó Jordi J.,
Gòdia Francesc
Publication year - 2013
Publication title -
journal of chemical technology and biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.64
H-Index - 117
eISSN - 1097-4660
pISSN - 0268-2575
DOI - 10.1002/jctb.4019
Subject(s) - fed batch culture , cell culture , batch processing , cell growth , exponential growth , biology , biological system , microbiology and biotechnology , biochemical engineering , computer science , biochemistry , fermentation , mathematics , engineering , mathematical analysis , genetics , programming language
BACKGROUND Improvement of the mammalian cell culture process is based on the implementation of culture strategies with higher productivities, such as fed‐batch or perfusion processes. The efficient development of these culture strategies depends strongly on the availability of suitable monitoring tools to determine the activity of cell culture and adjust nutrient feeding correspondingly . RESULTS In this study oxygen uptake rate ( OUR ), cell density and glucose concentration on‐line monitoring systems are applied to control fed‐batch processes. Different combinations of these monitoring systems were used to determine cell growth and metabolic activity of cell culture in order to adjust substrate feeding in a balanced manner. Application of these monitoring tools in fed‐batch processes allowed extension of the exponential growth of hybridoma cells up to 2–3‐fold and increased antibody productivity from 84 to 168% with respect to conventional batch culture . CONCLUSIONS The three control strategies tested have been successful in providing improvement of the fed‐batch culture of the hybridoma cell line used. Among the different alternatives studied, the use of OUR on‐line monitoring to simultaneously determine cell growth and metabolic activity appears to be the best method to adjust substrate feeding owing to its simplicity and robustness. © 2012 Society of Chemical Industry