Modeling of Axial-Flow Hollow Fiber Cell Culture Bioreactors

Abstract

A review of the mathematical modeling of axial-flow hollow fiber cell bioreactors is presented. The models cover the range of diffusion-limited to convective-flow dominant nutrient transport conditions. Mass transport limitations inherent in the axial-flow bioreactor design are illustrated with model calculations. Simulation results further demonstrate the importance of convective nutrient transport to the cell growth region. These model developments were restricted to the transport and consumption of small substrate molecules in dilute solution. Finally, convection-enhanced hollow fiber bioreactor designs and alternative schemes for operating axial-flow bioreactors are discussed.

Effect of harvesting protocol on performance of a hollow fiber bioreactor

“…Starling flow can theoretically provide more oxygen to diffusion-limited bioreactors (Schonberg and Belfort, 1987). However, for "tight" ultrafiltrative membranes, or for bioreactors at packed cell densities, this convective contribution is likely not significant compared to the diffusive oxygen flux (Piret and Cooney, 1991;Brotherton and Chau, 1996). The Starling flow may actually be detrimental to cell growth since the proteins have a tendency to be pushed to the distal end of the EC space (Piret and Cooney, 1990a).…”

“…The Starling flow may actually be detrimental to cell growth since the proteins have a tendency to be pushed to the distal end of the EC space (Piret and Cooney, 1990a). The overall conclusion is that optimization of hollow fiber bioreactors requires some method of EC convection that does not cause inhomogeneities of the cell and protein distribution in the EC space (Brotherton and Chau, 1996).…”

A theoretical method to improve and optimize the design of bioartificial livers

“…This idea was originally introduced to describe capillaries in human tissues (Krogh 1919) and now is a common approach in efforts to model HFBRs (Brotherton and Chau 1996;Hay et al, 2001;Piret and Cooney 1991;Ye et al, 2006). The model considers one fiber surrounded by an annulus of ECS and by assuming that each fiber is identical and arranged in a regular hexagonal pattern, a bundle consisting of an arbitrary number of fibers can be described ( Fig.…”

“…This is valid here as radial convection through the membrane can be assumed to be negligible (Kundu and Cohen 2001). It is also assumed that due to the low Reynolds numbers involved and small fiber radius to length ratio, entrance effects are negligible and the flow is laminar and fully developed (Brotherton and Chau 1996). Within the membrane, it is assumed that transport occurs by diffusion only (Eq.…”

Perfusion systems that minimize vascular volume fraction in engineered tissues

“…14,15 Related work in the design of hollow-fiber bioreactors has also examined similar parameters. 16 Often, the design objective in these devices is to maximize the number of cells per reactor under the constraint of a given perfusion pressure or flow profile. 17 Previous work by Baskaran and colleagues used computational methods to maximize the surface area of the vasculature in a model scaffold while holding the total vascular volume constant.…”