Diffusion and Inhibition Processes in a Hollow-fiber Membrane Bioreactor for Hybridoma Culture. Development of a Mathematical Model

L. Legazpi, A. Laca, S. Collado, A. Laca and M. Díaz

Abstract
The performance of a hollow-fiber membrane bioreactor (HFBR) (molecular weight cut-off 30 kD, fiber surface area 2050 cm2) containing a culture of hybridoma cells has been investigated. Experimental data were used as basis to develop a model of general application. Concentrations of fundamental nutrients (glucose and glutamine), inhibitory products (ammonium and lactate), and monoclonal antibodies (MAb) against bovine lactoferrin (IgG1) were monitored over time. Exchange of nutrients and products occurred across the capillary surface, whereas cells and MAb remained in the extra-capillary space (ECS). A protein-free culture medium (Hybrimax) with and without antibiotics was used. In both cases, the final MAb concentration was the same; however, antibiotic presence slowed down the time to achieve this concentration. Diffusion assays have been carried out in order to support the development of a mathematical model that describes the performance of the HFBR, including mass transfer and reaction terms. Inhibition by ammonium and lactate has been considered in the kinetics, providing model results consistent with experimental data. Further research with other cell lines and/or culture media will allow to broaden the field of application of this model for general use in HFBR systems.

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Keywords
hollow-fiber membrane bioreactor, diffusion, inhibition, hybridoma, modelling