, Volume 9, Issue 1–3, pp 51–57 | Cite as

The membrane dialysis bioreactor with integrated radial-flow fixed bed —a new approach for continuous cultivation of animal cells

  • Armin Bohmann
  • Ralf Pörtner
  • Jörg Schmieding
  • Volker Kasche
  • Herbert Märkl


A hybridoma cell was cultivated continuously in a membrane dialysis bioreactor with an integrated radial-flow fixed bed consisting of porous Siran® carriers over a period of 6 weeks. Antibodies accumulated to an average of 100 mg l−1, approx. 10 times more than in fixed bed cultures without dialysis membrane. Serum costs could be reduced about 85% due to an appropriate feeding strategy. Siran® carriers with 3–5 mm diameter showed an advantage compared to those with 1–2 mm diameter. For the 3–5 mm carrier the specific glucose uptake rate and the MAb production rate were constant, if the velocity was between 0.09 mm s−1 and 0.75 mm s−1. At higher velocities cells are washed out of the bed. Furthermore antibody consistency and cell stability were verified in long-term cultivations over a period of 96 days. From an estimation of the antibody concentration reachable with the reactor concept under optimal conditions a concentration 45 times higher compared to axial-flow fixed bed reactors and 11 times higher compared to stirred tank reactors can be expected.

Key words

antibody consistency chromosome number continuous cultivation fixed bed reactor hybridoma membrane dialysis bioreactor 

List of symbols


cross sectional area of the axial-flow fixed bed m2


glucose concentration mmol l−1


monoclonal antibody concentration mg l−1


oxygen concentration % air saturation


dilution rate d−1


linear velocity in the axial-flow fixed bed mm s−1


specific glucose uptake rate mmol l(FB)−1 h−1


specific MAb production rate mg l(FB)−1 h−1

\(\mathop V\limits^ \cdot \)

volumetric flow rate in the axial-flow fixed bed m3 h−1


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  1. Kurosawa H, Märkl H, Niebuhr-Redder Ch and Matsumura M (1991) Dialysis bioreactor with radial-flow fixed bed for animal cell culture. J. Ferm. Bioeng. 72(1):41–45.CrossRefGoogle Scholar
  2. Linardos ThI, Kalogerakis N, Behie LA, Lamontagne, LR (1992) Monoclonal antibody production in dialyzed continuous suspension culture. Biotechnol. Bioeng. 39:504–510.CrossRefGoogle Scholar
  3. Looby D and Griffiths JB (1987) Optimization of glass-sphere immobilized bed cultures. In: Spier RE, Griffiths JB (eds) Modern Approaches to Animal Cell Technology, Buterworth.Google Scholar
  4. Looby D, Racher AJ, Griffiths JB and Dowsett AB (1989) The immobilization of animal cells in fixed and fluidized porous glass sphere reactors; Proc. of an International Symposium on “Physiology of immobilized cells”, Wageningen, Netherlands, December 10–13, 1989.Google Scholar
  5. Niebuhr-Redder Ch, Kasche V (1990) Antibodies toE. coli penicillin-G-amidase for biochemical studies and the control of fermentation processes; Proc. German-Japanese Workshop on Animal Cell Culture Technology, Hamburg, Germany, December 4–5.Google Scholar
  6. Racher AJ, Looby D, Griffiths, JB (1990) Studies on monoclonal antibody production by a hybridoma cell line (C1E3) immobilized in a fixed bed, porosphere culture system. J. Biotechnol. 15:129–146.CrossRefGoogle Scholar
  7. Pörtner R, Bohmann A and Märkl H (1991) Membrane dialysis bioreactor with integrated radial-flow fixed bed—A new concept for continuous cultivation of animal cells. Proceedings of 4th Annual meeting of Japanese Association for Animal Cell Technology (JAACT), Fukuoka, Japan, November 1991.Google Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • Armin Bohmann
    • 1
  • Ralf Pörtner
    • 1
  • Jörg Schmieding
    • 2
  • Volker Kasche
    • 2
  • Herbert Märkl
    • 1
  1. 1.Technische Universität Hamburg-Harburg, Bioprozeß- und BioverfahrenstechnikHamburg 90Germany
  2. 2.Biotransformation und BiosensorikHamburg 90Germany

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