Transport modeling of convection-enhanced hollow fiber membrane bioreactors for therapeutic applications (original) (raw)
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For an efficient membrane bioreactor design, transport phenomena determining the overall mass flux of metabolites, catabolites, cell regulatory factors, and immune-related soluble factors, need to be clarified both experimentally and theoretically. In this work, experiments and calculations aimed at discerning the simultaneous influence of both diffusive and convective mechanisms to the transport of metabolites. In particular, the transmembrane mass flux of glucose, bovine serum albumin (BSA), APO-transferrin, immunoglobulin G, and ammonia was experimentally measured, under pressure and concentration gradients, through high-flux microporous hydrophilic poly-ether-sulphone (PES-HFMs) and poly-sulphone hollow fiber membranes (PS-HFMs).
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Bioprocess and Biosystems Engineering, 2019
The hollow fiber membrane bioreactor (HFMB) has been investigated for the cultivation of mammalian Chinese hamster ovary cell expansion. The experiments were carried out in Petri's dishes and in the hollow fiber membrane bioreactor having 20 fibers (S2025 from FiberCell Systems). The approach to HFMB modelling which combines the model of cell growth kinetics and hydrodynamics has been proposed. The hydrodynamic model is made using ANSYS Fluent software. The mathematical model of HFMB was developed, allowing the study of the hydrodynamics into the lumen and the extracapillary spaces, the filtration through the membrane fiber with the cell expansion on outer membrane surface. The direct nutrient medium flow variant into the extracapillary space was suggested. Based on the numerical simulations, the optimal parameters were selected for daily changes in the medium flow-rate into the lumen space. The HFMB scaling up was performed for the larger size HFMB (60 fibers). Keywords CFD modelling • Hollow fiber membrane bioreactor • Mammalian cells • CHO • Cultivation Abbreviations G Acceleration of gravity, m/s 2 I Mass flow depending on cell consumption of nutrient medium and metabolites flow per one cell, kg/m s J Mass flow passed through membrane, kg/m s 2 K Population capacity (parameter for the limitation of the number of cells in population) L Membrane thickness, m n Number of pores on membrane surface, 1/m 2 N Count of cells at timepoint t, cell P Pressure, Pa Q Medium flow-rate into the lumen space in mode 3 q c Consumption of nutrient medium for one cell, m 3 /s q met Consumption of metabolites released by one cell, m 3 /s r por Pore radius, m S Membrane surface area, m 2 t Time, s v Medium velocity along the axes, m/s Greek symbols α Membrane permeability coefficient, m 2 δ Relative calculation error, % μ Dynamic viscosity, Pa s µ cell Cell-specific growth rate, days −1 ρ Medium density, kg/m 3 φ Pore tortuosity Subscripts 1 Lumen space 2 Extracapillar space cal Data from calculation results exp Data from experiment in Input m Membrane out Output x, y, z Coordinates on axes, m w Wall
Mass transfer limitations in diffusion-limited isotropic hollow fiber bioreactors
Biotechnology techniques, 1999
Diffusional mass transfer limitations in hollow fiber bioreactors -with densely packed whole cells in its extracapillary space to perform biotransformation reactions -have been studied theoretically using a steady-state diffusion and reaction model. Simple analytical expressions have been derived to calculate the radial and axial concentration profiles for zero-and first-order kinetics, as well as to plot effectiveness factor versus Thiele modulus plots for firstorder kinetics. The influence of the magnitude of the effective diffusion coefficients, the thickness of the isotropic membrane as well as the size of the annular cell region have been assessed to optimise the reactor performance. Dimensional variables C * k substrate concentration in region k (k = 1, 2 , 3) [mol m −3 ] C 0 inlet substrate concentration [mol m −3 ] D k substrate effective diffusion coefficient in region k (k = 1, 2 , 3) [m 2 s −1 ] K m Michaelis-Menten constant [mol m −3 ] L axial reactor length [m] r * radial length coordinate [m] R membrane inner radius [m] U z average lumen fluid velocity [ms −1 ] V reaction rate [mol m −3 s −1 ] V m maximum reaction rate [mol m −3 s −1 ] z * axial length coordinate [m]
Model of oxygen transport limitations in hollow fiber bioreactors
Biotechnology and Bioengineering, 1991
Axial and radial oxygen depletion are believed to be critical scale-limiting factors in the design of cell culture hollow fiber bioreactors. A mathematical analysis of oxygen depletion has been performed in order to develop effectiveness factor plots to aid in the scaling of hollow fiber bioreactors with cells immobilized in the shell-side. Considerations of the lumen mass transport resistances and the axial gradients were added to previous analyses of this immobilization geometry. An order of magnitude analysis was used to evaluate the impact of the shell-side convective fluxes on the oxygen transport. A modified Thiele modulus and a lumen and membrane resistance factor have been derived from the model. Use of these terms in the effectiveness factor plots results in a considerable simplification of the presentation and use of the model. Design criteria such as fiber dimensions and spacing, reactor lengths, and recycle flow rates can be selected using these plots. Model predictions of the oxygen limitations were compared to experimental measurements of the axial cell distributions in a severely oxygen limited hollow fiber bioreactor. Despite considerable uncertainty in our parameters and nonidealities in hollow fiber geometry, t h e cell distribution correlated well with the modeling results.