A z2 laterally-fed membrane chromatography device for fast high-resolution purification of biopharmaceuticals.

Abstract

We examine the use of a z2 flow distribution and collection feature for enhancing the separation efficiency of a laterally-fed membrane chromatography (or LFMC) device. The new device is designated z2LFMC. Two devices were fabricated using two different ion-exchange membranes: strong anion exchange (Q) with 0.8-micron pore size, and strong cation exchange (S) with pore size in the 3-5 µm range. The number of theoretical plates per unit membrane bed height in these z2LFMC devices were higher than those reported for other membrane chromatography devices housing similar membranes, including the older versions of LFMC devices. The enhancement in separation efficiency is explained based on computational fluid dynamic (CFD) simulations. Model protein separation experiments showed that the z2LFMC device gave similar resolution as an equivalent resin-packed column, at 40-time greater flow rate than that used with the column. At a comparable flow rate, the resolution obtained with the z2LFMC device was significantly higher than that obtained with the equivalent resin-packed column. Therefore, the z2LFMC device combines high-speed with high-resolution. We demonstrate the suitability of the z2LFMC devices for carrying out fast and efficient biopharmaceutical separations through two case studies, i.e. the fractionation of monoclonal antibody charge variants, and monoclonal antibody aggregates separation.