Skip to main content
Log in

Homogenisation and oxygen transfer rates in large agitated and sparged animal cell bioreactors: Some implications for growth and production

  • Special Issue
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Because of concern for cell damage, very low agitation energy inputs have been used in industrial animal cell bioreactors, typical values being two orders of magnitude less than those found in bacterial fermentations. Aeration rates are also very small. As a result, such bioreactors might be both poorly mixed and also unable to provide the higher oxygen up-take rates demanded by more intensive operation. This paper reports experimental studies both of K L a and of mixing (via pH measurements) in bioreactors up to 8 m3 at Wellcome and of scaled down models of such reactors at Birmingham. Alongside these physical measurements, sensitivity of certain cell lines to continuously controlled dO2 has been studied and the oxygen up-take rates measured in representative growth conditions. An analysis of characteristic times and mixing theory, together with other recent work showing that more vigorous agitation and aeration can be used especially in the presence of Pluronic F-68, indicates ways of improving their performance. pH gradients offer a special challenge.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amanullah A, Nienow AW, Emery AN & McFarlane CM (1993) The use of Bacillus subtilis as an oxygen sensitive culture to simulate dissolved oxygen cycling in large scale fermenters. Trans I Chem E, Part C 71: 206–208.

    Google Scholar 

  • Amanullah A, Nienow AW, McFarlane CM & Emery AN (1994) Simuulation of pH gradients in large scale bioreactors using a scale down model. Proc 2nd Conf Adv Biochem Eng (pp 20–22) I Chem E, Rugby, U.K.

    Google Scholar 

  • Bandyopadhyay B, Humphrey AE & Taguchi H (1967) Dynamic measurement of the volmetric oxygen transfer coefficient in fermantation systems. Biotechnol Bioeng 9: 533–544.

    Google Scholar 

  • Boulton Stone JM & Blake JR (1993) Bursting bubbles at a free surface. In: Nienow AW (ed) 3rd Int. Conf. Bioreactor Bioprocess Fluid Dynamics (pp 163–174) MEP Ltd, London.

    Google Scholar 

  • Bujalski W, Nienow AW, Chatwin S & Cooke M (1987) The dependency on scale of power numbers of Rushton disc turbines. Chem Eng Sci 41: 317–326.

    Google Scholar 

  • Chalmers JJ & Bavarian F (1992) Microscopic visualisation of insect cell-bubble interactions. Biotechnol Prog 7: 151–160.

    Google Scholar 

  • Cooke M, Middleton JC & Bush J (1988) Mixing and mass transfer in filamentous fermentations. In: King R (ed) 2nd Int. Conf. on Bioreactor Fluid Dynamics (pp 37–64) Elsevier Applied Science Publishers.

  • Cronin DG, Nienow AW & Moody GW (1994) An experimental study of mixing in a protofermenter agitated by dual Rushton turbines. Trans I Chem E, Part C 72: 35–40.

    Google Scholar 

  • Edwards MF, Baker M & Godfrey JC (1992) Mixing of liquids in stirred tanks. In: Harnby N, Edwards MF & Nienow AW (eds) Mixing in the Process Industries (pp 137–158), Butterworth-Heinemann, Oxford.

    Google Scholar 

  • Kioukia N, Nienow AW, Emery AN & Al-Rubeai M (1992) The impact of fluid dynamics on the biological performance of free suspension animal cell culture: further studies. Trans I Chem E, Part C 70: 143–148.

    Google Scholar 

  • Leelavatcharama V, Emery An & Al-Rubeai M (1994) Growth and interferon-γ production in batch culture of CHO cells. Cytotechnology, 15: 65–71.

    Google Scholar 

  • Nienow AW (1996) On impeller circulation and mixing effectiveness in the turbulent flow regime. Chem Eng Sci in press.

  • Nienow AW (1990) Agitators for mycelial fermentations. Trends in Biotech 8: 224–233.

    Google Scholar 

  • Oh SKW, Nienow AW, Al-Rubeai M & Emergy AN (1989) The effects of agitation intensity with and without continuous sparging on the growth and antibody production of hybridoma cells. J Biotechnol 2: 45–62.

    Google Scholar 

  • Oh SKW, Nienow AW, Emery AN & Al-Rubeai M (1992) Further studies of the culture of mouse hybridomas in an agitated bioreactor with and without continous sparging. J Biotechnol 22: 245–270.

    Google Scholar 

  • Ruszkowski S (1994) A rational method for measuring blending performance, and comparison of different impeller types. Proc 8th Euro Conf on Mixing, I Chem E Symp Ser 136: 283–292.

    Google Scholar 

  • van't Riet K & Tramper J (1991) Basic bioreactor design. Marcel Dekker Inc. New York.

    Google Scholar 

  • van't Riet K (1979) Review of measuring methods and results in non-viscous gas-liquid mass transfer in stirred vessel. Ind Eng Chem Process Des Dev 128: 357–364.

    Google Scholar 

  • Zhang Z & Thomas CR, (1993) Modelling of animal cell damage in turbulent flows. In: Nienow AW (ed) 3rd Int. Conf. Bioreactor Bioproc. Fluid Dynamics (pp 475–482) MEP Ltd., London.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nienow, A.W., Langheinrich, C., Stevenson, N.C. et al. Homogenisation and oxygen transfer rates in large agitated and sparged animal cell bioreactors: Some implications for growth and production. Cytotechnology 22, 87–94 (1996). https://doi.org/10.1007/BF00353927

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00353927

Key words

Navigation