PROTEIN-TRANSPORT IN PACKED-BED ULTRAFILTRATION HOLLOW-FIBER BIOREACTORS

A mathematical model was developed to describe the coupled hydrodynami cs and high molecular weight protein transport in cell-filled ultrafil tration hollow-fibre bioreactors (HFBRs). The multi-fibre reactor was represented by a single, straight fibre surrounded by a symmetry envel ope containing a homogeneous packed bed of cells. The low Reynolds num ber flow in this cell-packed extracapillary space (ECS) was described by Darcy's law. Since the protein transport and HFBR hydrodynamics wer e coupled, numerical methods were required to solve the governing equa tions of both the two-dimensional (axial and radial) and one-dimension al (axial) models developed to predict the redistribution of proteins retained in the ECS. Because of the large length/radius ratio of the r epresentative fibre unit, the two-dimensional model predictions were c losely duplicated by the simpler one-dimensional model over a wide ran ge of operating conditions. An HFBR filed with mammalian cells was sim ulated experimentally by filling the ECS of a hollow-fibre module with an agarose/protein solution to form a porous medium with uniform init ial protein concentration. All of the ECS protein distributions, measu red after 5-16 days of lumen flow, were adequately described by the mo del if an effective ECS conductivity of 5 x 10(-15) m(2) was assumed. The model was then used to predict transient and steady-state protein distributions in HFBRs under various packed-bed conditions. It was sho wn that, for low ECS conductivities typical of values measured for mam malian tissues, diffusion begins to compete effectively with convectio n as an important mechanism of axial protein transport. Also, the rate and extent of protein polarization in these cases was greatly reduced compared to the predictions obtained for a cell-free HFBR. The implic ations of these findings, particularly for product protein harvesting from a cell-packed ECS, were discussed. (C) 1997 Elsevier Science Ltd. All rights reserved.