Operation and pressure distribution of immobilized cell hollow fiber bioreactors

Abstract

It has been cited in the literature on hollow fiber systems that pressure gradients persist, and the transmembrane flux of the hollow fiber system is dependent on the pattern of the pressure gradients. The pattern can be used to its advantage in immobilized enzyme systems. However, with immobilized living cell systems, the pressure gradients lead to a nonuniform environment within the hollow fiber cartridge and not necessarily favorable results. This article provides pertinent pressure-drop data on hollow fiber cartridges which are in flow configurations typical of immobilized cell culture work. The results illuminate operational problems that may arise in the culture of either anchorage dependent or independent cells. Possible solutions with crossflow systems are suggested.

Effect of harvesting protocol on performance of a hollow fiber bioreactor

“…The elevated level of IC medium recirculation can drive a secondary flow in the EC space termed a Starling flow (Heath et al, 1990;Tharakan and Chau, 1986). Starling flow results from a portion of the IC medium entering the EC space near the entrance of the bioreactor due to the natural hydraulic permeability of the fibers and the pressure distribution within the bioreactor.…”

A novel multi‐coaxial hollow fiber bioreactor for adherent cell types. Part 1: Hydrodynamic studies

“…5) clearly shows that there is no axial¯ow at the walls of the middle ®ber and that the axial¯uid¯ow in the ECC and ICC is laminar. Also,¯ow experiments determined that there was a negligible pressure drop axially across the ICC and ECC and, therefore, the radial¯ow was considered to be constant across the axis of the bioreactor as found by others for similar radial-¯ow con®gurations (Tharakan and Chau, 1986b;Tharakan et al, 1988). Therefore, the data obtained from the¯ow experiments correlated well with the predictions of the radial¯ow (Fig.…”

“…The ®ber permeability will decrease with cell culture because of membrane fouling, and this is especially true for a radial-¯ow con®guration whereby macromolecules in the media or derived from cells will clog the membrane pores Chau, 1986a and1986b). Fouling will decrease continually the hydraulic permeability values with time (Belfort et al, 1994).…”

“…4, A and B), and the MRI studies corroborated the assumed axial ow pro®les in the ICC and ECC compartment. The combination of standard¯ow experiments of bioreactors as described by others (Tharakan and Chau, 1986b) and velocity encoded MRI are a powerful combination of empirical methods to establish mathematical models for bioreactors.…”

Hollow fiber bioreactor: New development for the study of contrast agent transport into hepatocytes by magnetic resonance imaging

“…Increasing the flow rate over 100 mL/min would not have changed the diffusion rate (which was stable between 75 and 100 mL) but could have improved O 2 and nutrient delivery to the hepatocytes. However, a high flow rate can increase cell shear stress when hepatocytes are present in the HFB, which might be prejudicial to cell viability (Tharakan, 1986). Thus, a compromise between optimal diffusion, adequate oxygenation, and minimal cell shear stress was made and the flow rate was fixed at 100 mL/min.…”