Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L7 Canada.
Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L7 Canada.
J Chromatogr A. 2020 Oct 11;1629:461453. doi: 10.1016/j.chroma.2020.461453. Epub 2020 Aug 8.
We examine the use of a z flow distribution and collection feature for enhancing the separation efficiency of a laterally-fed membrane chromatography (or LFMC) device. The new device is designated zLFMC. Two devices were fabricated using two different ion-exchange membranes: strong anion exchange (Q) with 0.8-micron pore size, and strong cation exchange (S) with pore size in the 3-5 µm range. The number of theoretical plates per unit membrane bed height in these zLFMC devices were higher than those reported for other membrane chromatography devices housing similar membranes, including the older versions of LFMC devices. The enhancement in separation efficiency is explained based on computational fluid dynamic (CFD) simulations. Model protein separation experiments showed that the zLFMC device gave similar resolution as an equivalent resin-packed column, at 40-time greater flow rate than that used with the column. At a comparable flow rate, the resolution obtained with the zLFMC device was significantly higher than that obtained with the equivalent resin-packed column. Therefore, the zLFMC device combines high-speed with high-resolution. We demonstrate the suitability of the zLFMC devices for carrying out fast and efficient biopharmaceutical separations through two case studies, i.e. the fractionation of monoclonal antibody charge variants, and monoclonal antibody aggregates separation.
我们研究了使用 z 流分布和收集功能来提高横向进样膜色谱（LFMC）装置的分离效率。新装置被命名为 zLFMC。使用两种不同的离子交换膜制造了两个装置：具有 0.8 微米孔径的强阴离子交换（Q）和孔径在 3-5 微米范围内的强阳离子交换（S）。这些 zLFMC 装置中单位膜床高度的理论塔板数高于其他容纳类似膜的膜色谱装置报告的值，包括 LFMC 装置的早期版本。基于计算流体动力学（CFD）模拟，解释了分离效率的提高。模型蛋白分离实验表明，zLFMC 装置在 40 倍于柱流动速率的情况下，可获得与等效树脂填充柱相同的分辨率。在可比的流速下，zLFMC 装置获得的分辨率明显高于等效的树脂填充柱。因此，zLFMC 装置将高速与高分辨率结合在一起。我们通过两个案例研究证明了 zLFMC 装置在进行快速有效的生物制药分离方面的适用性，即单克隆抗体电荷变体的分级分离和单克隆抗体聚集物的分离。
