NUTRIENT AND METABOLITE GRADIENTS IN MAMMALIAN-CELL HOLLOW FIBER BIOREACTORS

This work has investigated high density CRL-1606 hybridoma cell culture in the shell-side of ultrafiltration hollow fiber bioreactors. Oxygen depletion was measured in the recycle stream, and has been identified as the critical, axial scale-limiting factor in these reactors. The composition of the extracapillary space has been studied by rapidly freezing these reactors in liquid nitrogen to recover samples of the shell-side environment. The accumulation of inhibitory metabolites should have only a marginal impact on growth and product formation of this hybridoma cell line. Oxygen depletion is expected to be the major limiting factor for both the axial and radial scale-up of hollow fiber bioreactors.