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Performance of virus filtration membranes: Effects of membrane morphology and operating mode.

机译:病毒过滤膜的性能:膜形态和操作模式的影响。

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The removal of viruses from biotechnological and blood-related products is critical to assuring product safety and meeting regulatory guidelines. Virus filtration offers an attractive option to clear viruses from bioprocess streams on the basis of size. Virus removal membranes typically feature a multi-layer structure that is uniquely designed to provide the needed virus clearance while allowing high recovery of the desired protein product. The objective of this thesis is to develop a better fundamental understanding of how the underlying membrane structure and operating mode affect the membrane performance, including the role of membrane compaction, protein fouling, and osmotic pressure.; Experimental studies were performed using Millipore's Viresolve 180 membrane, which has an asymmetric structure with a permselective "skin" on top of a more open substructure. Significant compaction of the membrane was observed only when the membrane was used with the skin-side down. However, the membrane permeability in the skin-side up orientation is sensitive to fouling caused by even trace amounts of submicron-sized particles. This type of fouling was not seen with the skin-side down since the substructure acted as a pre-filter.; The filtrate flux and sieving characteristics of the Viresolve 180 membrane are strong functions of operating conditions and membrane orientation. The performance in the skin-side up orientation was determined primarily by protein osmotic pressure effects arising from protein retention due to a tightly packed fouling deposit on the membrane surface. In contrast, the performance in the skin-side down orientation was governed by the resistance of the protein cake that forms within the membrane substructure. These different fouling mechanisms led to large differences in capacity; the capacity in the skin-side down orientation was as much as a factor of 30 greater than that in the skin-side down orientation. A combined cake filtration/osmotic pressure model was developed to describe the performance of the Viresolve 180 membrane, capturing many of the key features observed experimentally.
机译:从生物技术和血液相关产品中清除病毒对于确保产品安全并满足法规要求至关重要。病毒过滤提供了一个有吸引力的选项,可以根据大小从生物过程流中清除病毒。病毒去除膜通常具有多层结构,该结构经过独特设计,可提供所需的病毒清除率,同时可高度回收所需的蛋白质产物。本文的目的是对潜在的膜结构和操作模式如何影响膜性能,包括膜压实,蛋白质结垢和渗透压的作用,有一个更好的基本了解。使用Millipore的Viresolve 180膜进行了实验研究,该膜具有不对称结构,在更开放的子结构上具有选择性渗透的“皮肤”。仅当以皮肤朝下的方式使用膜时,才观察到膜的显着压实。但是,在皮肤朝上的方向上的膜渗透性对甚至痕量的亚微米级颗粒引起的结垢敏感。由于下部结构充当了预过滤器,因此在皮肤朝下时看不到这种污垢。 Viresolve 180膜的滤液通量和筛分特性与操作条件和膜取向密切相关。皮肤朝上定向的性能主要取决于由于膜表面紧密堆积的结垢沉积物而引起的蛋白质滞留引起的蛋白质渗透压效应。相反,皮肤朝下的方向的性能由在膜子结构内形成的蛋白饼的阻力控制。这些不同的结垢机制导致容量差异很大。皮肤朝下方向的容量比皮肤朝下方向的容量大30倍。建立了滤饼/渗透压组合模型来描述Viresolve 180膜的性能,并捕获了实验观察到的许多关键特征。

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