Abstract
A new approach using microtiter plate cultivation with on-line measurement of dissolved oxygen (DO) was applied for medium optimization of mammalian cell culture. Applying dynamic liquid phase balance, oxygen uptake rates were calculated from the DO level and used as an indicator for culture viability. The developed method was successfully applied to optimization of the concentration of glucose, glutamine and inorganic salts for cultivation of a Chinese Hamster Ovary (CHO) cell line. Using 23 full factorial central composite design, the optimum medium composition could be identified in one single run. The concentration of inorganic salts had a significant influence on cultivation. The developed method exhibits high potential to improve procedures of medium optimization for animal cell cultivation by allowing the investigation of large sets of potentially important variables in short time and with reduced effort.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
K. Adinarayana P. Ellaiah (2002) ArticleTitleResponse surface optimization of the critical medium components for the production of alkaline protease by a newly isolated Bacillus sp J. Pharm. Pharm. Sci. 5 272–278 Occurrence Handle12553896
P.M. Castro P.M. Hayter A.P. Ison A.T. Bull (1992) ArticleTitleApplication of a statistical design to the optimization of culture medium for recombinant interferon-gamma production by Chinese hamster ovary cells Appl. Microbiol. Biotechnol. 38 84–90 Occurrence Handle10.1007/BF00169424 Occurrence Handle1369013
C. Chun K. Heineken D. Szeto T. Ryll S. Chamow J.D. Chung (2003) ArticleTitleApplication of factorial design to accelerate identification of CHO growth factor requirements Biotechnol. Prog. 19 52–57 Occurrence Handle12573006
R.R. Deshpande E. Heinzle (2004) ArticleTitleOn-line oxygen uptake rate and culture viability measurement of animal cell culture using microplates with integrated oxygen sensors Biotechnol. Lett. 26 763–767 Occurrence Handle10.1023/B:BILE.0000024101.57683.6d Occurrence Handle15195979
R.J. Ertola A.M. Giulietti F.J. Castillo (1995) ArticleTitleDesign, formulation, and optimization of media Bioprocess Technol. 21 89–137 Occurrence Handle7765644
K. Eyer A. Oeggerli E. Heinzle (1995) ArticleTitleOn-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake rate estimation and its application to controlled feeding of glutamine Biotechnol. Bioeng. 45 54–62 Occurrence Handle10.1002/bit.260450108
F. Hesse R. Wagner (2000) ArticleTitleDevelopments and improvements in the manufacturing of human therapeutics with mammalian cell cultures Trend. Biotechnol. 18 173–180 Occurrence Handle10.1016/S0167-7799(99)01420-1
G.T. John I. Klimant C. Wittmann E. Heinzle (2003) ArticleTitleIntegrated optical sensing of dissolved in microtiter plates: a novel tool for microbial cultivation Biotechnol. Bioeng. 81 829–836 Occurrence Handle10.1002/bit.10534 Occurrence Handle12557316
R. Kimura W.M. Miller (1996) ArticleTitleEffects of elevated pCO2 and/or osmolality on the growth and recombinant tPA production of CHO cells Biotechnol. Bioeng. 52 152–160 Occurrence Handle10.1002/(SICI)1097-0290(19961005)52:1<152::AID-BIT15>3.0.CO;2-Q
G.M. Lee E.J. Kim N.S. Kim S.K. Yoon Y.H. Ahn J.Y. Song (1999) ArticleTitleDevelopment of a serum-free medium for the production of erythropoietin by suspension culture of recombinant Chinese hamster ovary cells using a statistical design J. Biotechnol. 69 85–93 Occurrence Handle10.1016/S0168-1656(99)00004-8 Occurrence Handle10361720
D.L. Massart B.G.M. Vandeginste L.M.C. Buydens S. Jong ParticleDe P.J. Lewi J. Smeyers-Verbeke (1997) Handbook of Chemometrics and Qualimetrics: Part A Elsevier Science The Netherlands
C. Morris J.B. Griffiths S. Warburton C.M.L. West M. Al-Rubeai J.B. Clarke F. Simione A. Doyle (1997) Core techniques A. Doyle J.B. Griffiths (Eds) Mammalian Cell Culture: Essential Techniques. J. Wiley Cambridge 47–102
E. Palmqvist H. Grage N.Q. Meinander B. Hahn-Hagerdal (1999) ArticleTitleMain and interaction effects of acetic acidfurfural, and p-hydroxybenzoic acid on growth and ethanol productivity of yeasts Biotechnol. Bioeng. 63 46–55 Occurrence Handle10.1002/(SICI)1097-0290(19990405)63:1<46::AID-BIT5>3.0.CO;2-J Occurrence Handle10099580
O.T. Ramirez R. Mutharasan (1990) ArticleTitleCell cycle- and growth phase dependent variations in size distribution, antibody productivity, and oxygen demand in hybridoma cultures Biotechnol. Bioeng. 36 839–848 Occurrence Handle10.1002/bit.260360814
I. Schoenherr T. Stapp T. Ryll (2000) ArticleTitleA comparison of different methods to determine the end of exponential growth in CHO cells cultures for optimization of scale up Biotechnol. Prog. 16 815–821 Occurrence Handle10.1021/bp000074e Occurrence Handle11027176
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deshpande, R.R., Wittmann, C. & Heinzle, E. Microplates with integrated oxygen sensing for medium optimization in animal cell culture. Cytotechnology 46, 1–8 (2004). https://doi.org/10.1007/s10616-004-6401-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-004-6401-9