The influence of dissolved oxygen tension on the metabolic activity of an immobilized hybridoma population.

In the study presented here a laboratory scale (150 ml) fluidized bed bioreactor was used as a tool for making kinetic measurements on the production of monoclonal antibodies (MAb) with a hybridoma cell line. We determined the influence of dissolved oxygen tension (DOT) on the metabolic activity of a hybridoma population immobilized in macroporous collagen microspheres. The data obtained showed a reduction of the metabolic activity of the immobilized population at reduced DOT, the total number of immobilized cells, however, remained constant. At decreasing DOT an increasing lactate yield from glucose at reduced glutamine consumption was noticed, indicating a shift in the pattern of substrate usage. A mathematical description of maintenance metabolism was formulated and the parameters of growth and maintenance requirements were calculated. A growth associated MAb production was determined under the conditions applied leading to space time yields of 225 mg MAb per liter of total reactor volume and day.