Membrane Chromatography and Filtration

A number of recent reviews on the use of membrane chromatography have suggested that theoretically this approach could have a number of advantages over traditional packed bed chromatography. Membrane chromatography can exhibit dynamic binding capacities of up to 10 times higher and flow rates of up to a 100 times faster than packed bed chromatography, especially for selected applications such as the purification of large particles. Membrane chromatography is also significantly cheaper per cycle if hidden costs, including validation, cleaning and the manpower involved in packed bed chromatography, are taken into account. Despite these perceived advantages, membrane chromatography has not been widely adopted by the bioprocessing industry, mainly because it is limited by the throughput as a result of the available surface area per unit compared with packed bed chromatography.
Membrane filtration is also used as an alternative method of clarifying cell culture media and cell extracts and techniques such as ultrafiltration and high-performance tangential flow filtration (HPTFF) have been investigated as integral steps in downstream processing schemes. Indeed, there have been reports where HPTFF has been successfully used as a polishing step. Perhaps one of the more significant advances in this area has been the use of pH and charged membranes to manipulate the product. These approaches have been shown to be useful for the
removal of viruses from mammalian cell systems and endotoxins from bacterial systems. Despite such advances, these approaches have not been fully adopted and membrane fouling remains a problem during such processing, and these approaches are usually used prior to chromatographic steps.