Cellulose-graft-polyethyleneamidoamine Anion-Exchange Nanofiber Membranes for Simultaneous Protein Adsorption and Virus Filtration

Development of bioseparation media that can perform separations based on both ion exchange and size exclusion provide a transformative technology to purify therapeutic proteins with fewer operations in downstream processing. Thus, in this study, we have developed cellulose-graftpolyethyleneamidoamine (CL-g-PEAA) anion-exchange nano fiber membrane adsorbers with a narrow effective pore size distribution using redox polymerization. Structural characterization illustrated the functionalization of each nanofiber of the CL-g-PEAA membrane adsorbers with three-dimensional nanolayers of amidoamine functionality. The ion-exchange separation efficiency of the CL-g-PEAA anion-exchange membranes, evaluated using bovine serum albumin (BSA), exhibited an excellent static adsorption of 239 mg/g of nanofibers. The BSA dynamic binding capacity in flow through mode at 10% breakthrough of these membranes was 69 mg/g (corresponding to a volume capacity of 31 g/L) with an approximate residence time of 8 s. Meanwhile, CL-g-PEAA membranes have shown 80-100% rejection for model bead particles of various sizes (200, 100, and 40 nm), which illustrated the potential in removing viruses, microbial agents, and cellular debris from the harvested cell culture fluid (HCCF) during downstream processing. Overall performance of the CL-g-PEAA membranes illustrated that undesired impurities (viruses, host cell proteins, and DNA) in HCCF could be removed in a single step by an anion-exchange membranes with ion-exchange and size-exclusion-based separation mechanisms.

可以基于离子交换和尺寸排阻进行分离的生物分离介质的开发提供了一种转化技术，可在下游处理中以较少的操作纯化治疗性蛋白质。因此，在这项研究中，我们使用氧化还原聚合反应开发了具有窄有效孔径分布的纤维素接枝聚乙烯基氨基酰胺（CL-g-PEAA）阴离子交换纳米纤维膜吸附器。结构表征说明了具有酰胺基胺官能团的三维纳米层的CL-g-PEAA膜吸附器的每个纳米纤维的功能化。使用牛血清白蛋白（BSA）评估的CL-g-PEAA阴离子交换膜的离子交换分离效率显示出239 mg / g纳米纤维的出色静态吸附。在这些膜的10％穿透率下，流过模式下的BSA动态结合能力为69 mg / g（对应于31 g / L的体积容量），停留时间约为8 s。同时，CL-g-PEAA膜对各种尺寸（200、100和40 nm）的模型珠粒表现出80-100％的排斥率，这说明了从收获的细胞中去除病毒，微生物剂和细胞碎片的潜力下游加工过程中的培养液（HCCF）。 CL-g-PEAA膜的整体性能表明，HCCF中不需要的杂质（病毒，宿主细胞蛋白质和DNA）可以通过具有离子交换和尺寸排阻分离的阴离子交换膜在单个步骤中除去机制。

Published: 2018

Journal ：ACS APPLIED NANO MATERIALS

Impact Factor：There is no data at this time

Paper link: https://pubs.acs.org/doi/abs/10.1021/acsanm.8b00519