Michael Smith Laboratories and the Department of Chemical and Biological Engineering, University of British Columbia, Vancouver V6T 1Z4, Canada.
J Chromatogr A. 2011 Aug 5;1218(31):5071-8. doi: 10.1016/j.chroma.2011.05.017. Epub 2011 May 14.
Conventional models of both packed-bed and stacked-membrane chromatography typically attribute elution band broadening to non-idealities within the column. However, when the column length to diameter ratio is greatly reduced, as in stacked-membrane chromatography, variations in solute residence times within the feed-distribution (inlet) and eluent-collection (outlet) manifolds can also contribute to band broadening. We report on a new zonal rate model (ZRM) for stacked-membrane chromatography that improves on existing hold-up volume models that rely on one plug-flow reactor and one stirred-tank reactor in series to describe dispersion of solute during transport into and out of the column. The ZRM radially partitions the membrane stack and the hold-up volumes within the inlet and outlet manifolds into zones to better capture non-uniform flow distribution effects associated with the large column diameter to height ratio. Breakthrough curves from a scaled-down anion-exchange membrane chromatography module using ovalbumin as a model protein were collected at flow rates ranging from 1.5 to 20 mL min(-1) under non-binding conditions and used to evaluate the ZRM as well as previous models. The ZRM was shown to be significantly more accurate in describing protein dispersion and breakthrough. The model was then used to decompose breakthrough data, where it was found that variations in solute residence time distributions within the inlet and outlet manifolds make the dominant contribution to solute dispersion over the recommended range of feed flow rates. The ZRM therefore identifies manifold design as a critical contributor to separation quality within stacked-membrane chromatography units.
传统的填充床和堆积膜色谱模型通常将洗脱带展宽归因于柱内的非理想性。然而，当柱长径比大大降低时，如在堆积膜色谱中，溶质在进料分布（入口）和洗脱液收集（出口）歧管内的停留时间变化也会导致带展宽。我们报告了一种新的堆积膜色谱的区域速率模型（ZRM），该模型改进了现有的保留体积模型，这些模型依赖于一个推流反应器和一个搅拌釜反应器串联来描述溶质在进入和离开柱时的传输过程中的分散。ZRM 将膜堆和入口和出口歧管内的保留体积径向分区成多个区域，以更好地捕捉与大柱径高比相关的非均匀流动分布效应。在非结合条件下，使用卵清蛋白作为模型蛋白，在 1.5 至 20 mL min(-1) 的流速范围内，从小规模的阴离子交换膜色谱模块中收集到突破曲线，并用于评估 ZRM 以及以前的模型。结果表明，ZRM 能更准确地描述蛋白质的分散和突破。然后，该模型被用于分解突破数据，发现入口和出口歧管内溶质停留时间分布的变化对溶质分散的贡献在推荐的进料流速范围内占主导地位。因此，ZRM 确定了歧管设计是堆积膜色谱单元分离质量的关键因素。
