Abstract
A bioreactor system based on internal membrane aeration and perfusion was used to cultivate a variety of mammalian and insect cell lines for the production of recombinant proteins, monoclonal antibodies or biomass. The efficiency of this reactor system is evaluated with respect to maximum cell concentration, productivity and membrane lifetime in order to give some fundamental data for comparison with other stirred tank perfusion bioreactors. Due to the membrane capacities for aeration and perfusion, eight to thirty fold increases in cell concentration compared to batch cultivation in culture flasks could be obtained routinely with unchanged cell viabilities.
For further increase of the efficiency of the perfusion system several strategies have been developed. Different membrane materials and pore sizes have been investigated and the membrane lifetime has been prolonged by backflushing and membrane precoating.
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References
Blasey H.D. and Winzer U. (1989) ‘Low protein serum-free medium for antibody production in stirred bioreactors’, Biotechnol. Lett 11, 455–460
Eibl, H. and Lands, W.E.M. (1969) ‘A new sensitive determination of phosphate’ Anal. Biochem. 30, 51–57
Fane, A.G.; Fell, C.J.D. and Kim, K.J. (1985) ‘The effect of surfactant pretreatment on the ultrafiltration of proteins’, Desalination 53, 37–55
Hill, B.T. and Whatley, S. (1975) ‘A simple, rapid assay for DNA’ FEBS Lett. 56, 20–23
Himmelfarb, P.; Thayer, P.S. and Roberts, D.W. (1969) ‘Spin filter culture: The propagation of mammalian cells in suspension’, Science 164, 555–557
Kim, K.J.; Fane, A.G. and Fell C.J.D. (1988) ‘The performance of ultrafiltration membranes pretreated by polymers’, Desalination 70, 229–249
Lehmann, J.; Piehl, G.W. and Schulz, R. (1987) ‘Bubble free cell culture aeration with porous moving membranes’, Develop. biol. Standard., Vol. 66, S. Karger, Basel, pp. 227–240
Lehmann, J.; Vorlop, J. and Büntemeyer, H. (1988) ‘Bubble-free reactors and their development for continuous culture with cell recycle’, in R.E. Spier and J.B. Griffiths (eds.) ‘Animal Cell Biotechnology Vol. 3’, Acad. Press, London, pp. 221–237
Lucki-Lange, M. and Wagner, R. (1991) ‘Conditions for the production of recombinant IL-2 in stirred suspension culture using a protein-free medium’, in R.E. Spier, J.B. Griffiths, B. Meignier (eds.), ’Production of Biologicals from Animal Cells in Culture. Research, Developments and Achievements’, Butterworths Pub., Kent, in press
Mizrahi, A. (1975) ‘Pluronic polyols in human lymphocyte cell lines cultures’, J. Clin. Microbiol. 2, 11–13
Rebsamen, E; Goldinger, W.; Scheirer, W.; Merten, O.-W. and Palfi, G.E. (1987) ‘Use of a dynamic filtration method for separation of animal cells’, Develop. biol. Standard. 66, 273–277
Shintani, Y.; Iwamoto, K. and Kitano, K. (1988) ’ Polyethylene glycols for promoting the growth of mammalian cells’, Appl. Microbiol. Biotechnol. 27, 533–537
Takazawa, Y.; Tokashiki, M.; Murakami, H.; Yamada, K and Omura, H. (1988) ‘High-density culture of mouse-human hybridoma in serum-free defined medium’, Biotechnol. Bioeng. 31, 168–172
Tokashiki, M.; Hamamoto, K and Takazawa, Y. (1988) ‘Perfusion culture of hybridoma cells recycling higher-molecularweight components’, Hakkokogaku 66, 31–35
Tolbert, W.R.; Feder, J. and Kimes, R.C. (1981) ‘Large-scale rotating filter perfusion system for high-density growth of mammalian suspension cultures’ In Vitro 17, 885–890
Varecka, R. and Scheirer, W. (1987) ‘Use of a rotating wire cage for retention of animal cells in a perfusion fermentor’, Develop. biol. Standard 66, 269–272
Velez, D.; Miller, L. and Macmillan, J.D. (1988) ‘Use of tangential flow filtration in perfusion propagation of hybridoma cells for production of monoclonal antibodies’ Biotechnol Bioeng. 33, 938–940
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© 1991 Springer Science+Business Media Dordrecht
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Blasey, H.D., Jäger, V. (1991). Strategies to Increase the Efficiency of Membrane Aerated and Perfused Animal Cell Bioreactors by an Improved Medium Perfusion. In: Sasaki, R., Ikura, K. (eds) Animal Cell Culture and Production of Biologicals. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3550-4_8
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DOI: https://doi.org/10.1007/978-94-011-3550-4_8
Publisher Name: Springer, Dordrecht
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