Zhang Da, Patel Parag, Strauss Daniel, Qian Xianghong, Wickramasinghe S Ranil
Ralph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, Arkansas, USA.
Asahi Kasei Bioprocess America, USA.
Biotechnol Prog. 2021 May;37(3):e3115. doi: 10.1002/btpr.3115. Epub 2021 Jan 2.
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.
切向流过滤对于生物反应器的澄清是有利的，因为透过液流可以直接引入后续的产物捕获步骤。然而，膜污染以及高产物截留率限制了它的应用。在此，研究了一种反向不对称中空纤维膜的性能，该膜更开放的孔结构面向进料流，而阻挡层面向透过液流。开放表面包含直径达40μm的孔，而较致密的阻挡层平均孔径为0.4μm。在补料分批操作中预期的条件下，研究了中国仓鼠卵巢细胞进料流的过滤情况。将反向不对称膜的性能与标称孔径为0.2和0.65μm的对称中空纤维膜的性能进行了比较。使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。该膜稳定了一个内部高渗透性滤饼，其作用类似于深层过滤器。这种稳定的滤饼可以去除如果阻挡层面向进料流就会使其污染的颗粒物。已经建立了一个经验模型来描述使用反向不对称膜过滤期间通量和跨膜压降的变化。我们的结果表明，使用反向不对称膜可以避免生物反应器澄清过程中与阻挡层污染相关的严重通量下降。
