Cytotechnology

, Volume 9, Issue 1–3, pp 3–9

Maximisation of perfusion systems and process comparison with batch-type cultures

Maximisation of perfusion cultures
  • J. B. Griffiths
  • D. Looby
  • A. J. Racher
Article
  • 58 Downloads

Abstract

A comparison of cell yields and monoclonal antibody productivity from the same hybridoma has been made in a wide range of cell bioreactors including both batch and continuous perfusion cultures. The most productive systems were based on porous microcarriers in fixed and fluidised beds which can be operated with a high degree of efficiency and reliability from the physico-chemical engineering point of view. Further improvements should be possible by improving the physiological environment in dense cell cultures, as indicated by the preliminary studies that are described. These include experimental data showing the relationship between monoclonal antibody production rates with glucose, glutamine, ammonia, and oxygen levels in microporous beads.

The results strongly indicate that perfusion processes that are scaleable in both volume and cell density can significantly reduce production costs. Manufacturers of biologicals from animal cells now have a choice between the proven batch-type processes and reliable perfusion systems based on microporous beads.

Key words

perfusion batch culture immobilised culture fixed bed reactor fluidised beds verax microspheres mAb productivity cell physiology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Griffiths JB (1988). Overview of cell culture systems and their scale-up. In: Animal Cell Biotechnology. Spier RE and Griffiths JB (eds) vol 3, Academic Press Ltd., London, pp. 179–220.Google Scholar
  2. Griffiths JB (1990). Animal cells—the breakthrough to a dominant technology. Cytotechnology 3: 109–116.CrossRefGoogle Scholar
  3. Griffiths JB (1991). Relative advantages of continuous versus batch processes. In: Animal Cell Culture and Production of Biologicals. Sasaki R and Ikura K (eds), Kluwer Academic Publishers, Dordrecht, pp. 401–410.Google Scholar
  4. Griffiths JB (1992a). Closing the culture gap. Bio/Technology 10: 30–32.CrossRefGoogle Scholar
  5. Griffiths, J.B. (1992b). Animal cell culture processes—batch or continuous. J. Biotechnol. 22: 21–30.CrossRefGoogle Scholar
  6. Griffiths JB (1992c). Alternative strategies to the scale-up of animal cells. Annual New York Academy of Science, (in press).Google Scholar
  7. Lee GM, Varma A and Palsson BO (1991). Production of monoclonal antibody using free-suspended and immobilised hybridoma cells: effect of serum. Biotechnol. Bioeng. 38: 821–830.CrossRefGoogle Scholar
  8. Looby D and Griffiths JB (1988). Fixed bed porous glass sphere (porosphere) bioreactors for animal cells. Cytotechnology 1: 339–346.CrossRefGoogle Scholar
  9. Looby D, Racher A and Griffiths JB (1992). Productivity of a hybridoma cell line in a range of suspension and immobilised culture systems. In: Animal Cell Technology: Developments, Processes and Products. Spier RE, Griffiths JB and MacDonald C (eds), Butterworths, Oxford, (in press).Google Scholar
  10. Lullau E, Dreisbach C, Grogg A, Biselli M and Wandrey C (1992). Immobilisation of animal cells on chemically modified Siran carrier.ibid..Google Scholar
  11. Miller WM and Blanch HW (1991). Regulation of animal cell metabolism in bioreactors. In: Animal Cell Bioreactors. Ho CS and Wang DIC (eds), Butterworth-Heinemann, Stoneham, pp. 119–161.Google Scholar
  12. Racher AJ, Looby D and Griffiths JB (1990a). Studies on monoclonal antibody production by a hybridoma cell line (C1E3) immobilised in a fixed bed, porosphere culture system. J. Biotechnol. 15: 129–146.CrossRefGoogle Scholar
  13. Racher AJ, Looby D and Griffiths JB (1990b). Use of lactate dehydrogenase release to assess changes in culture viability. Cytotechnology 3: 301–307.CrossRefGoogle Scholar
  14. Racher AJ, Looby D. and Griffiths JB (1992). Influence of ammonium ion and glucose on mAb production in suspension and fixed bed hybridoma cultures. J. Biotechnol. (in press).Google Scholar
  15. Suzuki E and Ollis DF (1990). Enhanced antibody production at slowed growth rate: experimental demonstration and a simple structured model. Biotechnol. Prog. 6: 231–236.CrossRefGoogle Scholar
  16. Vournakis JN and Runstadler PW (1989). Microenvironment: the key to improved cell products. Bio/Technology 7: 143–145.CrossRefGoogle Scholar
  17. Wright JP and Balfor AH (1983). Monoclonal antibodies to Toxoplasma gondii. Parasitology 87: LXVI.Google Scholar
  18. Young MW and Dean RC (1987). Optimization of mammalian cell bioreactors. Bio/Technology 5: 835–837.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • J. B. Griffiths
    • 1
  • D. Looby
    • 1
  • A. J. Racher
    • 1
  1. 1.Division of BiologicsPHLS CAMRUK

Personalised recommendations