Selectivity improvements in highly charged UF membranes

Abstract

We have previously developed a family of charge-modified ultrafiltration membranes with greatly enhanced properties. Both yield and selectivity can be improved when using these membranes by appropriately varying solution ionic strength and pH. The technology is based on Ultracel™ PLC (composite regenerated cellulose) membranes and maintains their desirable properties of ultra-low protein binding and robust process performance. We have now developed an improved chemistry that allows us to significantly increase the ligand density and the resulting level of charge on the membrane. Higher charge is desirable to maximize the benefits of the technology. These benefits had already been shown using membranes with lower charge densities. Significantly, it has been shown that critical process steps in monoclonal antibody purification processes can be replaced or even eliminated by using an ultrafiltration step with charged membranes. For this work, we have measured the performance of membranes with both low and high charge density. In order to quantify the expected higher filtration selectivity, a high-sensitivity sieving test was developed. We have used this test with both neutral and charged solutes as well as buffers of varying ionic strengths. Our results confirm the benefits of high membrane charge and low solution ionic strength. Most notably, higher selectivity can be achieved at a significantly higher ionic strength. This property enables a broader application window including higher conductivity process streams. Charged UF membranes can now offer even better performance for biotech purification processes, such as protein-impurity separations.