We examine the use of a z² flow distribution and collection feature for enhancing the separation efficiency of a laterally-fed membrane chromatography (or LFMC) device. The new device is designated z²LFMC. 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 z²LFMC 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 z²LFMC 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 z²LFMC device was significantly higher than that obtained with the equivalent resin-packed column. Therefore, the z²LFMC device combines high-speed with high-resolution. We demonstrate the suitability of the z²LFMC 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az ²流量分配和收集功能来提高侧向进样膜色谱仪（或LFMC）设备的分离效率。新设备命名为z ² LFMC。使用两种不同的离子交换膜制造了两种设备：孔径为0.8微米的强阴离子交换（Q）和孔径为3-5 µm的强阳离子交换（S）。这些z ^2中每单位膜床高度的理论塔板数LFMC设备比其他装有类似膜的膜色谱设备（包括较旧版本的LFMC设备）报告的设备更高。基于计算流体动力学（CFD）模拟解释了分离效率的提高。模型蛋白质分离实验表明，z ² LFMC装置的分离度与等效的树脂填充柱类似，但流速比色谱柱高40倍。在可比的流速下，使用z ² LFMC装置获得的分离度明显高于使用相同的树脂填充柱获得的分离度。因此，z ² LFMC设备将高速与高分辨率结合在一起。我们证明了z ²的适用性LFMC设备通过两个案例研究来进行快速有效的生物药物分离，即分离单克隆抗体电荷变体和分离单克隆抗体聚集体。