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

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.