We have developed novel, single-use membrane chromatography media in an effort to improve sustainability of downstream processing of biologics. These devices can offer many advantages over traditional, resin-based chromatography processes including decreased need for cleaning-in-place and water for injection, resulting in lower risk of contamination, lower operating costs, and overall increased operational flexibility. Historically, membrane devices used in downstream processing have utilized a porous, cast membrane substrates which have limited surface area and suffer from significant pressure drop across the membrane when used at high flow rates. This has limited the use of membrane-based separation processes to off-line applications such as microfiltration, ultrafiltration and diafiltration. To address these issues, our group has developed chromatography devices that utilize meltblown nonwoven substrates. These nonwoven substrates are coated with a UV-initiated polymer hydrogel which can be functionalized with various ligands to effect ion exchange or multimodal protein binding mechanisms. Meltblown membranes with extremely high porosity (0.8-0.9) have been shown to effectively operate well below residence times of 1 minute. The polymer coating employed in these membranes enhances binding capacity without the need for nanoscale fiber diameters to increase surface area for binding.
In this presentation we will discuss recent studies to characterize important facets of the manufacturing process and their impact on chromatography performance. The meltblown nonwoven was produced using a polyamide extruded on a 1.2-meter wide Reifenhäuser Reicofil pilot line by the Nonwovens Institute at NC State University. During optimization of the meltblowing process, the hot air injector pressure was varied from 100 to 245 bar, driving changes in the web properties including thickness, air permeability, and fiber size. At the same time, critical parameters for the successful polymer grafting process were considered and tested for impact on sample uniformity and protein binding performance. It was determined that membrane grafting uniformity was significantly improved through precise control of initiator concentrations, membrane surface area and lamp surface temperature. Through these improvements the standard deviation of grafting uniformity was reduced from 3.6% to 0.9%.