Molecular Biotechnology

, Volume 17, Issue 3, pp 225–238

Scale-up of suspension and anchorage-dependent animal cells

Protocol

Abstract

Alternative culture processes for laboratory scale-up (to 20 L) are described for both suspension and anchorage-dependent cells. Systems range from simple multiple culture units such as the roller bottle, through stirred suspension and microcarrier unit bioreactors, to highly sophisticated perfusion culture capable of maintaining cells at densities of about 108/mL. Critical parameters in scale-up are discussed, and the advantages and disadvantages of each culture system are critically evaluated.

Index Entries

Mammalian cell culture suspension culture microcarrier culture culture scale-up anchorage-dependent cells animal cell bioreactors 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Griffiths, J. B. (1988) Overview of cell culture systems and their scale-up, in Animal Cell Biotechnology, vol. 3. (Spier, R. E. and Griffiths, J. B., eds.), Academic, London, UK, pp. 179–220.Google Scholar
  2. 2.
    Spier, R. E. and Griffiths, J. B. (1983) An examination of the data and concepts germane to the oxygenation of cultured animal cells. Develop. Biol. Stand. 55, 81–92.Google Scholar
  3. 3.
    Griffiths, J. B. (1986) Scaling-up of animal cells, in Animal Cell Culture: A Practical Approach (Freshney, I., ed.), IRL, Oxford, UK, pp. 33–70.Google Scholar
  4. 4.
    Handa-Corrigan, A. (1991) Bioreactors for mammalian cells, in Mammalian Cell Biotechnology, A Practical Approach (Butler, M., ed.), IRL, Oxford, UK, pp. 139–158.Google Scholar
  5. 5.
    Griffiths, J. B., Cameron, D. R., and Looby, D. (1987) A comparison of unit process systems for anchorage dependent cells. Develop. Biol. Stand. 66, 331–338.Google Scholar
  6. 6.
    Singh, R. P., Fassnacht, D., Perani, A., et al. (1998) Modulation of apoptosis in high cell density perfusion cultures, in New Developments and New Applications in Animal Cell Technology (Merten, O-W., Perrin, P., and Griffiths, J. B., eds.), Kluwer, Dordrecht, pp. 235–241.Google Scholar
  7. 7.
    Falkenberg, F. W., Weichart, H., Krane, M., Bartels, I., Palme, M., Nagels, H-O., and Fiebig, H. (1995) J. Immunol. Methods 179, 13.PubMedCrossRefGoogle Scholar
  8. 8.
    Hanak, J. A. J. and Davis, J. M. (1993) Hollow fibre bioreactors: the endotronics Acusyst JR and maximizer 500, in Cell and Tissue Culture: Laboratory Procedures (Doyle, A., Griffiths, J. B., and Newell, D. G., eds.), Wiley, Chichester, p. 28D:3.1-16.Google Scholar
  9. 9.
    Ronning, O. (1993) Detoxification of cell cultures, in In Cell and Tissue Culture: Laboratory Procedures (Doyle, A., Griffiths, J. B., and Newell, D. G., eds.), Wiley, Chichester, UK, p. 28D:1.1-3.Google Scholar
  10. 10.
    Griffiths, J. B. (1986) Can cell culture medium costs be reduced? Strategies and possibilities. Trends Biotechnol. 4, 268–272.CrossRefGoogle Scholar
  11. 11.
    Looby, D. and Griffiths, J. B. (1987). Optimization of glass-sphere immobilized/bed cultures, in Modern Approaches to Animal Cell Technology (Spier, R. E., and Griffiths, J. B., eds.), Butterworths, Oxford, UK, pp. 342–352.Google Scholar
  12. 12.
    Whiteside, J. P. and Spier, R. E. (1981) The scale-up from 0.1 to 100 liter of a unit process system based on 3 mm diameter glass spheres for the production of four strains of FMDV from BHK monolayer cells. Biotechnol. Bioeng. 23, 551–565.CrossRefGoogle Scholar
  13. 13.
    Looby, D., Racher, A. J., Fuller, J. P., and Griffiths, J. B. (1995) Evaluation of a porous silicone carrier (ImmobaSil), in Animal Cell Technology: Developments Towards the 21st Century (Beuvery, E. C., Griffiths, J. B., and Zeijlemaker, W. P., eds.), Kluwer, Dordrecht, pp. 783–786.Google Scholar
  14. 14.
    Mignot, G., Faure, T., Ganne, V., Arbeille, B., Pavirani, A., and Romet-Lemonne, J. L. (1990) Production of recombinant Von Willebrand factor by CHO cells cultured in macroporous microcarriers. Cytotechnology 4, 163–171.PubMedCrossRefGoogle Scholar
  15. 15.
    Looby, D. and Griffiths, J. B. (1988) Fixed bed porous glass sphere (poro-sphere bioreactors for animal cells. Cytotechnology 1, 339–346.CrossRefGoogle Scholar
  16. 16.
    Looby, D. and Griffiths, J. B. (1989) Immobilisation of animal cells in fixed and fluidised porous glass sphere reactors, in Advances in Animal Cell Biology and Technology for Bioprocessors (Spier, R. E., Griffiths, J. B., Stepbenne, J., and Crooy, P. J., eds.), Butterworths, Guildford, UK, pp. 336–344.Google Scholar
  17. 17.
    Looby, D., Racher, A. J., Griffiths, J. B., and Dowsett, A. B. (1990) The immobilisation of animal cells in fixed and fluidised porous glass sphere reactors, in Physiology of Immobilised Cells (deBont, J. A. M., Visser, J., Mattiasson, B., and Tramper, J., eds.), Elsevier, Amsterdam, pp. 225–264.Google Scholar
  18. 18.
    Ray, N., Tung, A. S., Hayman, E., Voumakis, J. N., and Runstadler, Jr., P. W. (1990) Continuous cell culture in fluidised bed reactors: cultivation of hybridomas and recombinant CHO cells immobilised in collagen microspheres. Ann. NY Acad. Sci. Biochem. Eng. VI 589, 443–457.CrossRefGoogle Scholar
  19. 19.
    Reiter, M., Hohenwarter, O., Gaida, T., et al. (1990) The use of macroporous carriers for the cultivation of mammalian cells in fluidised bed reactors. Cytotechnology 3, 271–277.PubMedCrossRefGoogle Scholar
  20. 20.
    Looby, D. and Griffiths, J. B. (1998) Porous microcarrier and fixed-bed culture, in Laboratory Procedures in Biotechnology (Doyle, A. and Griffiths, J. B., eds.), Wiley, Chichester, UK, pp. 268–292.Google Scholar
  21. 21.
    Looby, D. (1993) Fluidized bed culture, in Cell and Tissue Culture: Laboratory Procedures. (Doyle, A., Griffiths, J. B., and Newell, D. G., eds.), Wiley, Chichester, UK, pp. 28D:1.1–16.Google Scholar
  22. 22.
    Valle, M. A., Kaufman, J., Bentley, W. E., and Shiloach, J. (1998) Evaluation of porous microcarriers in fluidized bedbreactor for protein production by HEK 293 cells, in New Developments and New Applications in Animal Cell Technology (Merten, O-W., Perrin, P., and Griffiths, J. B., eds.), Kluwer, Dordrecht, The Netherlands, pp. 381–384.Google Scholar
  23. 23.
    Reiter, M., Bliiml, G., Gaida, T., et al. (1991) Modular integrated fluidised bed bioreactor technology. Biotechnology 9, 1100–1102.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  1. 1.SC&PPorton, SalisburyUK

Personalised recommendations