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.