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

Abstract

The performance of a hollow-fiber membrane bioreactor (HFBR) (molecular weight cut-off 30 kD, fiber surface area 2050 cm 2 ) 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 (IgG 1 ) 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.

Numerical Simulation of Mass Transfer in Hollow Fiber Membrane Module for Membrane-Based Artificial Organs

“…However, Macias et al by employing a semi-empirical approach, found that intermediate molecular weight toxins are primarily removed by diffusive transport [ 28 ]. Legazpi et al developed a mathematical model based on experimental data to assess the mass transfer efficiency of hollow fiber membranes, and the solute concentration distribution in the hollow fiber membrane module was in good agreement with experimental findings [ 29 ]. It should be pointed out that the mathematical model in Legazpi et al only considered diffusive solute transport [ 29 ].…”

“…Legazpi et al developed a mathematical model based on experimental data to assess the mass transfer efficiency of hollow fiber membranes, and the solute concentration distribution in the hollow fiber membrane module was in good agreement with experimental findings [ 29 ]. It should be pointed out that the mathematical model in Legazpi et al only considered diffusive solute transport [ 29 ]. Sorrell et al developed a mathematical model for the mass transfer behavior of an artificial liver hollow fiber membrane module, focusing on the transport of acetaminophen hepatotoxin and oxygen in the hollow fiber tubes, and their model assumed that the solute transport in the tube-side region is convective and diffusive, while only diffusive transport occurs in the regions of both hollow fiber membranes and shell-side [ 30 ].…”

The Application of Hollow Fiber Cartridge in Biomedicine

“…Legazpi et al used a hollow fiber bioreactor that consisted of a bundle of 2565 cellulose fibers with a molecular weight cut-off value of 30 kD and a length of 13 cm. The results showed that the concentration of monoclonal antibody produced by the hollow fiber bioreactor (HFBR) was high and the time was short, but the consumption of the medium for producing monoclonal antibody (MAb) per milligram was higher (Table 3) [68,69]. The hollow fiber bioreactor is also a promising tool to expand the production of stem cells to provide enough cells [70].…”

“…MAb production data employing different culture techniques[68]. Data were reported by Legazpi, reprinted with permission from Ref [69]…”