Increasing demand for tissue, proteins, and antibodies derived from mammalian cell cultures is limited by low protein yields and growth rates. Host productivity may be increased through genomic modification while volumetric productivity is maximized through novel bioreactor research to increase maximum cell culture density. The centrifugal bioreactor (CCBR) is a novel bioreactor which can be used to increases volumetric productivity by maintaining densities above 10⁸ cells/mL using counter-flow centrifugation to immobilize cells.

System rotation necessary for cell immobilization in the CCBR results in Coriolis forces that affect momentum transport. At operating conditions typical of cell culture, 300-1200 RPM and inlet velocities of 4-16 cm/s, Coriolis forces dominate system fluid dynamics and streamlines indicate preferential flow along the leading wall of the reactor to the chamber’s widest point, after which fluid transverses the reactor to the trailing wall. This unique flow profile is completely disrupted during cell culture leading to uniform flow through the cell bed creating a well mixed fluidized bed of cells. These phenomena are observed experimentally and in numerical simulation results of the CCBR reactor chamber during operation.

The uniform high cell density fluidized bed in the CCBR is maintained through convective transport of nutrients and metabolites allowing for the development of a hybridoma growth rate kinetic model from low density batch experiments. A model has been developed to predict glucose, lactate, ammonium ion, and monoclonal antibody concentrations during reactor operation within 13%. This model provides a tool to determine necessary dilution rates to ensure the maximum cellular growth rate is maintained at any operational cell density.

Finally, CCBR applicability has been expanded to include adherent cells which can be mechanically stimulated with multiple mechanical forces resulting from the unique method of cell immobilization. Isolated chondrocytes were stimulated with hydrostatic pressure and low shear during 3 weeks cultures, after which a solid tissue construct resulted. When compared with pellet cultures, the CCBR constructs contained similar levels of both glycosaminoglycan and collagen, per weight of DNA. Optimization of mechanical force magnitudes and stimulation regimens will provide a unique model system for the future study of cartilage development and degeneration.