Modeling flux in tangential flow filtration using a reverse asymmetric membrane for Chinese hamster ovary cell clarification

Modeling flux in tangential flow filtration using a reverse asymmetric membrane for Chinese hamster ovary cell clarification
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使用反向不对称膜对切向流过滤中的通量进行建模,以进行中国仓鼠卵巢细胞澄清

DOI:
10.1002/btpr.3115
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发表时间:
2021
影响因子:
2.9
通讯作者:
Wickramasinghe, S. Ranil
Wickramasinghe, S. Ranil
中科院分区:
工程技术4区
文献类型:
--
作者:
Zhang, Da;Patel, Parag;Strauss, Daniel;Qian, Xianghong;Wickramasinghe, S. Ranil

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切向流过滤对于生物反应器澄清是有利的,因为渗透物流可以直接引入到随后的产物捕获步骤。然而,膜污染加上高的产物截留率限制了其使用。在这里,已经研究了反向不对称中空纤维膜的性能,其中更开放的孔结构面向进料流并且阻挡层面向渗透物流。开放表面包含直径达40 μm的孔,而更紧密的阻挡层的平均孔径为0.4 μm。在补料分批操作中预期的条件下,对中国仓鼠卵巢细胞进料流的过滤进行了研究。将反向非对称膜的性能与标称孔径为0.2和0.65 μm的对称中空纤维膜的性能进行比较。采用激光扫描共聚焦显微镜观察颗粒截留的位置。反向不对称膜的通量显著大于对称膜。膜稳定内部高渗透性滤饼,其作用类似于深层过滤器。这种稳定的滤饼可以去除颗粒物质,如果阻挡层面对进料流,则该颗粒物质会污染阻挡层。建立了一个描述反对称膜过滤过程中通量和跨膜压降变化的经验模型。我们的研究结果表明,使用反向不对称膜可以避免严重的通量下降与生物反应器澄清过程中的阻挡层的污垢。
Tangential flow filtration is advantageous for bioreactor clarification as the permeate stream could be introduced directly to the subsequent product capture step. However, membrane fouling coupled with high product rejection has limited its use. Here, the performance of a reverse asymmetric hollow fiber membrane where the more open pore structure faces the feed stream and the barrier layer faces the permeate stream has been investigated. The open surface contains pores up to 40 μm in diameter while the tighter barrier layer has an average pore size of 0.4 μm. Filtration of Chinese hamster ovary cell feed streams has been investigated under conditions that could be expected in fed batch operations. The performance of the reverse asymmetric membrane is compared to that of symmetric hollow fiber membranes with nominal pore sizes of 0.2 and 0.65 μm. Laser scanning confocal microscopy was used to observe the locations of particle entrapment. The throughput of the reverse asymmetric membrane is significantly greater than the symmetric membranes. The membrane stabilizes an internal high permeability cake that acts like a depth filter. This stabilized cake can remove particulate matter that would foul the barrier layer if it faced the feed stream. An empirical model has been developed to describe the variation of flux and transmembrane pressure drop during filtration using reverse asymmetric membranes. Our results suggest that using a reverse asymmetric membrane could avoid severe flux decline associated with fouling of the barrier layer during bioreactor clarification.
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