(47b) Protein Purification Using a Laterally-Fed Membrane Chromatography Device

Membrane chromatography, which has been proposed as an alternative to packed bed or column chromatography is gradually gaining acceptance in the biotechnology industry. Over the past decade, product titres in bioreactors have gradually crept up while downstream processing capabilities have struggled to keep up. Column chromatography has been widely identified as the bottleneck in bio-manufacturing. Membrane chromatography which has several advantages over column chromatography has been proposed as a solution for this problem. The predominance of convective transport of target solutes to and from the binding sites on a membrane, compared to the slow diffusion within the porous beads makes membrane chromatography a significantly faster technique. Other advantages include lower buffer usage and lower pressure drop. Also, the relatively low cost of membrane chromatography devices makes disposable units possible, thereby eliminating the need for cleaning and validation. Currently used membrane chromatography devices are commonly available in two formats: stacked-disk and radial-flow. Hollow fiber devices are also available but they are not as commonly used. Stacked-disks are mainly used for small-scale applications. Radial flow devices, which are typically used in large-scale applications, perform quite well separations carried out in the flow-through mode. However, they are not very suitable for bind-and-elute separations, particularly where multiple components need to be separated. Therefore, there exists a niche application segment, for which appropriate membrane chromatography devices are currently not available. In this presentation, we discuss a laterally-fed membrane chromatography device which houses a stack of rectangular adsorptive membranes [1, 2]. The device has a significantly lower dead volume and distribution of flow path lengths compared to equivalent radial flow membrane chromatography devices. Single component bind-and-elute experiments were carried out with the laterally-fed device and its equivalent radial flow device, using different model proteins, and the peak shapes were compared. The laterally-fed device gave a significantly superior performance in these experiments. Multi-component protein separation experiments were then carried out in the pulse-mode using different model proteins to demonstrate the suitability of the laterally-fed device for carrying out high-resolution multi-component protein purification.

References

1. R. Ghosh, Laterally-fed membrane module, US Patent Application No. 62074858 filing date November 4, 2014.

2. P. Madadkar, Q. Wu, R. Ghosh, A laterally-fed membrane chromatography module, J. Membr. Sci., 487 (2015) 173–179.