(199e) Membrane Chromatography: How Important Is the Device?

Membrane chromatography lies at the interface of membrane science and chromatography. The aim of this technique is to combine the good elements of membrane science with chromatography, to develop efficient and scalable devices and processes, for fast, and high-resolution purification of biopharmaceuticals. Microporous membranes are particularly well suited for chromatographic separations on account of the presence of low-micron- to sub-micron- sized flow pores. The transport of solute molecules within these pores is largely convective in nature. The van Deemter equation, which is widely used to model dispersion in chromatography columns predicts that if stack of microporous membranes were used as separation media, very high-resolution chromatographic separation of macromolecules such as proteins would be obtained, even at very high superficial velocities. This is primarily due to the low resistance to mass transfer in the membrane pores. However, resolution with commercially available membrane chromatography devices is found to be very low. Consequently, these devices as used primarily for low resolution applications such as removal of trace impurities such as viruses and endotoxins from biopharmaceutical products. The primary reason for this that a membrane stack has a large frontal area. Commercially available membrane chromatography devices are poorly designed in terms of their ability to distribute and collect fluid uniformly from a membrane stack. Therefore, significant macroscale convective dispersion is observed with these devices. This drastically reduces resolution. Macroscale convective dispersion within a membrane chromatography device could be significantly reduced through proper design of the device. In recent studies, it has been shown that a new class of membrane chromatography devices, called the laterally-fed membrane chromatography (or LFMC) devices, that were designed specifically to minimize macroscale convective dispersion, are suitable for fast, high-resolution purification of biopharmaceuticals such as monoclonal antibodies. More recently, improved variants of the LFMC devices called the z²LFMC devices have been designed and developed. These devices allow the membrane housed in them to be used optimally, such that both high-speed and high-resolution is obtained in a given separation process. Recent studies have shown that such devices not only outperform resin-based columns in terms of speed, but also in terms of resolution. The workings of such efficient membrane chromatography devices and some application case studies will be presented. This presentation also highlights the key role played by the device in membrane chromatography.