Development of isoporous microslit silicon nitride membranes for sterile filtration applications

The widely used 0.2/0.22 mu m polymer sterile filters were developed for small molecule and protein sterile filtration but are not well-suited for the production of large nonprotein biological therapeutics, resulting in significant yield loss and production cost increases. Here, we report on the development of membranes with isoporous sub-0.2 mu m rectangular prism pores using silicon micromachining to produce microslit silicon nitride (MSN) membranes. The very high porosity (33%) and ultrathin (200 nm) nature of the 0.2 mu m MSN membranes results in a dramatically different structure than the traditional 0.2/0.22 mu m polymer sterile filter, which yielded comparable performance properties (including gas and hydraulic permeance, maximum differential pressure tolerance, nanoparticle sieving/fouling behavior). The results from bacteria retention tests, conducted according to the guidance of regulatory agencies, demonstrated that the 0.2 mu m MSN membranes can be effectively used as sterile filters. It is anticipated that the results and technologies presented in this study will find future utility in the production of non-protein biological therapeutics and in other biological and biomedical applications.