Abstract
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.
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Abbreviations
- A:
-
cross sectional area of the axial-flow fixed bed m2
- c(Glc):
-
glucose concentration mmol l−1
- c(MAb):
-
monoclonal antibody concentration mg l−1
- c(O2):
-
oxygen concentration % air saturation
- D:
-
dilution rate d−1
- U:
-
linear velocity in the axial-flow fixed bed mm s−1
- q*(Glc):
-
specific glucose uptake rate mmol l(FB)−1 h−1
- q*(MAb):
-
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
References
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Bohmann, A., Pörtner, R., Schmieding, J. et al. The membrane dialysis bioreactor with integrated radial-flow fixed bed —a new approach for continuous cultivation of animal cells. Cytotechnology 9, 51–57 (1992). https://doi.org/10.1007/BF02521731
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DOI: https://doi.org/10.1007/BF02521731