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Abstract：
The widely used 0.2/0.22 µm 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 μm 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 µm MSN membranes results in a dramatically different structure than the traditional 0.2/0.22 µm 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 µm 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.
摘要：
广泛使用的0.2/0.22μm聚合物无菌过滤器是为小分子和蛋白质无菌过滤而开发的，但不太适合生产大型非蛋白质生物治疗剂。导致显著的产量损失和生产成本增加。这里,我们报告了使用硅微加工生产微狭缝氮化硅（MSN）膜的具有等孔亚0.2μm矩形棱柱孔的膜的开发。0.2µmMSN膜的非常高的孔隙率（〜33％）和超薄（200nm）性质导致与传统的0.2/0.22µm聚合物无菌过滤器的结构截然不同，产生可比的性能特性(包括气体和水力渗透率，最大压差公差,纳米颗粒筛分/结垢行为)。细菌滞留试验的结果,根据监管机构的指导，证明了0.2µmMSN膜可以有效地用作无菌过滤器。预计本研究中提出的结果和技术将在非蛋白质生物治疗剂的生产以及其他生物和生物医学应用中找到未来的效用。
