Abstract
A BHK 21 cell line expressing a recombinant antibody was grown in a fixed bed reactor (FBR) system using a porous support made of Siran glass beads. The contribution of five process variables (bead and inoculum sizes; circulation and dilution rates; glutamine concentration of the feed) to the productivity of the process (defined as production rate, effluent product concentration or yield of product on medium supplied) was investigated using a partial factorial experimental design. Individually, none of the variables tested had a significant affect upon productivity. The combination of smaller bead and inoculum sizes, higher circulation and dilution rates, plus higher feed glutamine concentration gave a markedly higher productivity than any other combination of variable levels tested. This combination of variable levels suggested that better results shold be obtained using a fluidised bed reactor system. However, comparison of the productivities of the two systems showed that the FBR gave the better results. This result can be explained in terms of the relationship of QsrAb to μ.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- C:
-
concentration
- D:
-
dilution rate
- FBR:
-
fixed bed bioreactor
- FIBR:
-
fluidised bed bioreactor
- Gln:
-
glutamine
- Qs:
-
cell specific rate
- Qv:
-
volumetric rate
- rAb:
-
recombinant antibody
- Xv :
-
viable cell density
- μ:
-
specific growth rate
References
Al-Rubeai MA, Rookes S and Emery AN (1990) Studies of cell proliferation and monoclonal antibody synthesis and secretion in algina teentrapped hybridoma cells. In: de Bont JAM, Visser J, Mattiasson B, Tramper J (eds) Physiology of Immobilised Cells pp. 181–188. Elsevier Science Publishers BV, Amsterdam.
Kumar PKR and Schügerl K (1990) Immobilisation of genetically engineered cells: a new strategy for higher stability. J. Biotechnol. 14: 255–372.
Lee GM and Palsson BO (1990) Immobilisation can improve the stability of hybridoma antibody productivity in serum-free media. Biotechnol. Bioeng. 36: 1049–1055.
Lee GM, Chuck AS and Palsson BO (1993) Cell culture conditions determine the enhancement of specific monoclonal antibody productivity of calcium alginate-entrapped S3H5//γbA2 hybridoma cells. Biotechnol. Bioeng. 41: 330–340.
Looby D and Griffiths JB (1987) Optimisation of glass-sphere immobilised bed cultures. In: Spier RE and Griffiths JB (eds) Modern Approaches to Animal Cell Technology (pp. 342–352). Butterworth-Heinemann, Oxford.
Looby D, Racher AJ, Griffiths JB and Dowsett AB (1990) The immobilisation of animal cells in fixed and fluidised porous sphere reactors. In: de Bont JAM, Visser J, Mattiasson E, Tramper J (eds) Physiology of Immobilised Cells (pp. 255–264). Elsevier Science Publishers BV, Amsterdam.
Park S and Stephanopoulos G (1993) Packed bed bioreactor with porous ceramic beads for animal cell culture. Biotechnol. Bioeng. 41: 25–34.
Plackett RL and Burman JP (1946) The design of optimum multifactorial experiments. Biometrica 33: 305–325.
Racher AJ, Looby D and Griffiths JB (1990) Studies on monoclonal antibody production by a hybridoma cell line (C1E3) immobilised in a fixed bed, porosphere culture system. J. Biotechnol. 15: 129–146.
Sinclair CG and Kristiansen B (1987) Fermentation Kinetics and Modelling. Open University Press, Milton Keynes.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Racher, A.J., Griffiths, J.B. Investigation of parameters affecting a fixed bed bioreactor process for recombinant cell lines. Cytotechnology 13, 125–131 (1993). https://doi.org/10.1007/BF00749939
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00749939