Performance Comparison of a Laterally-Fed Membrane Chromatography (LFMC) Device with a Commercial Resin Packed Column.

Pedram Madadkar,Raja Ghosh,Rahul Sadavarte

doi:10.3390/membranes9110138

Abstract

The use of conventional membrane adsorbers such as radial flow devices is largely restricted to flow-through applications, such as virus and endotoxin removal, as they fail to give acceptable resolution in bind-and-elute separations. Laterally-fed membrane chromatography or LFMC devices have been specifically developed to combine high-speed with high-resolution. In this study, an LFMC device containing a stack of strong cation exchange membranes was compared with an equivalent resin packed column. Preliminary characterization experiments showed that the LFMC device had a significantly greater number of theoretical plates per metre than the column. These devices were used to separate a ternary model protein mixture consisting of ovalbumin, conalbumin and lysozyme. The resolution obtained with the LFMC device was better than that obtained with the column. For instance, the LFMC device could resolve lysozyme dimer from lysozyme monomer, which was not possible using the column. In addition, the LFMC device could be operated at lower pressure and at significantly higher flow rates. The devices were then compared based on an application case study, i.e., preparative separation of monoclonal antibody charge variants. The LFMC device gave significantly better separation of these variants than the column.

Highlights

Chromatography remains the standard separation technique for high-resolution separation of biopharmaceuticals, despite some significant shortcomings [1,2,3,4]
Theoretical plate measurements could not be made at 30 mL/min flow rate using the column and so only data obtained using the LFMC device is shown for this flow rate
Our earlier studies had demonstrated the superiority of the LFMC device over stacked-disc and radial flow membrane chromatography devices

Summary

Introduction

Chromatography remains the standard separation technique for high-resolution separation of biopharmaceuticals, despite some significant shortcomings [1,2,3,4]. The main drawback associated with a resin column is the decrease in resolution with increase in flow rate. This is primarily due to diffusion being the rate-limiting solute transport mechanism. Columns have to be operated at low flow rates, which reduces productivity [5,6]. Considering that ancillary operations such as cleaning and regeneration are limited by flow rate, the overall effective productivity in resin-based chromatography is low. The other downside of resin-based chromatography is the high pressure drop across the column, even at relatively low flow rates. Columns with large diameter to bed height ratios suffer from uneven packing and flow maldistribution, which in turn reduce resolution and thereby reduce both product recovery and productivity [7,8]

Methods

Results

Conclusion