Tangential flow filtration (TFF) has many advantages for bioreactor harvesting, as the permeate could be introduced directly to the subsequent capture step. However, membrane fouling has limited its widespread use. This is particularly problematic given the high cell densities encountered today. Here, a reverse asymmetric membrane, where the more open surface faces the feed stream and the tighter 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 yeast suspensions has been conducted under a range of conditions. The yeast cells are trapped in the open pore structure. The membrane stabilizes an internal porous cake that acts like a depth filter. This stabilized cake layer can remove particulate matter that would foul the barrier layer if it faced the feed stream. As filtration continues, a surface cake layer forms on the membrane surface. A resistance in series model has been developed to describe the permeate flux during TFF. The model contains three fitted parameters which can easily be determined from constant pressure normal flow filtration experiments and total recycle constant flux TFF experiments. The model can be used to estimate the capacity of the filter for a given feed stream. Our results suggest that using a reverse asymmetric membrane could avoid severe flux decline associated with fouling of the barrier layer during bioreactor harvesting.

中文翻译：

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使用反向不对称膜模拟切向流过滤以进行生物反应器收获

切向流过滤 (TFF) 对于生物反应器的收获具有许多优势，因为渗透物可以直接引入后续的捕获步骤。然而，膜污染限制了其广泛使用。鉴于当今遇到的高细胞密度，这尤其成问题。在这里，已经研究了一种反向不对称膜，其中更开放的表面面向进料流，更紧密的阻挡层面向渗透流。开放表面包含直径高达 40 μm 的孔，而更紧密的阻挡层具有 0.4 μm 的平均孔径。酵母悬浮液的过滤已经在一系列条件下进行。酵母细胞被困在开孔结构中。该膜稳定了内部多孔滤饼，其作用类似于深度过滤器。如果阻挡层面对进料流，这种稳定的滤饼层可以去除会污染阻挡层的颗粒物质。随着过滤的继续，在膜表面上形成表面滤饼层。已经开发了串联电阻模型来描述 TFF 期间的渗透通量。该模型包含三个拟合参数，可以很容易地从恒压正常流过滤实验和总循环恒通量​​ TFF 实验中确定。该模型可用于估计给定进料流的过滤器容量。我们的结果表明，使用反向不对称膜可以避免在生物反应器收获过程中与阻挡层结垢相关的通量严重下降。在膜表面形成表面滤饼层。已经开发了串联电阻模型来描述 TFF 期间的渗透通量。该模型包含三个拟合参数，可以很容易地从恒压正常流过滤实验和总循环恒通量​​ TFF 实验中确定。该模型可用于估计给定进料流的过滤器容量。我们的结果表明，使用反向不对称膜可以避免在生物反应器收获过程中与阻挡层结垢相关的通量严重下降。在膜表面形成表面滤饼层。已经开发了串联电阻模型来描述 TFF 期间的渗透通量。该模型包含三个拟合参数，可以很容易地从恒压正常流过滤实验和总循环恒通量​​ TFF 实验中确定。该模型可用于估计给定进料流的过滤器容量。我们的结果表明，使用反向不对称膜可以避免在生物反应器收获过程中与阻挡层结垢相关的通量严重下降。该模型可用于估计给定进料流的过滤器容量。我们的结果表明，使用反向不对称膜可以避免在生物反应器收获过程中与阻挡层结垢相关的通量严重下降。该模型可用于估计给定进料流的过滤器容量。我们的结果表明，使用反向不对称膜可以避免在生物反应器收获过程中与阻挡层结垢相关的通量严重下降。