Analysis of Protein Purification Using Ion-Exchange Membranes

Abstract

The performance of ion-exchange membranes for protein purification is analyzed using numerical solutions of different mathematical models. The models incorporate nonlinear sorption isotherms and mass-transfer coefficients based on either the overall or local solid-phase and liquid-phase driving forces. The numerical solutions are compared to analytical solutions which use overall mass-transfer coefficients only and, in general, are theoretically incorrect for nonlinear isotherms. The numerical solutions are fit to experimental breakthrough curves from the literature. The models allow the determination of the rate-controlling mass-transfer phenomena and solid-phase concentration, and prediction of the operating and membrane-design parameters needed to obtain sharp breakthrough curves.

Breakthrough performance of stacks of dye-cellulosic fabric in affinity chromatography of lysozyme

“…To overcome these plugging problems, a new generation of large-pore-size (ten to several hundred micrometers) woven membranes have been investigated. In these chromatographic supports not without limitations, pore and film mass transfer seems to dominate the overall mass transfer resistance, in contrast to previous work, where these effects where not observed because the membrane pore size was too small [12,14]. One of the consequences of mass transfer limitations in these large-pore-size membrane systems is that, in order to meet a 70% of BTC sharpness criterion [15,16], the required residence time of the liquid in the membrane system has been estimated as 13 h, which is too high to be practical [12].…”

“…Using the above column model, a residence time of the liquid of 1.65 h (0.1 ml/min flow rate) was estimated to meet this criterion. This time is considerable lower than the residence time of 13 h reported for BSA adsorption in large-pore-size membranes [12]. The shorter diffusional path produced by the perfusion of the liquid in the disks fibers seems to be the leading cause of this effect, since the ratio of diffusivity values for lysozyme and BSA is less than 2.…”

“…A simplified but sufficiently accurate method to describe this behavior is commonly used [1,12,14,19]. In order to use this method to describe the effect of the inlet flow rate on the system dispersion behavior, the BTC under no adsorption condition, also called the system dispersion curve (SDC), was obtained at flow rates of 0.2, 1, 2, 5, and 10 ml/min.…”

“…Recovery processes typically involve several consecutive separation steps, such as homogenization, clarification, concentration, and purification. Integration of these different separation steps into one step can increase the process yield, compactness, and economics and reduce the time to market, labor cost, and product variability, all while attaining targets for product purity [12].…”

Breakthrough performance of linear-DNA on ion-exchange membrane columns

“…A simplified but sufficiently accurate method to describe this behavior is based on obtaining the system BTC under no adsorption condition also called system dispersion curve (SDC) [21,25,31,32].…”