Effect of zinc chloride and PEG concentrations on the critical flux during tangential flow microfiltration of BSA precipitates

微滤 聚乙二醇 PEG比率 错流过滤 化学 焊剂(冶金) 降水 过滤(数学) 膜污染 色谱法 结垢 体积流量 浓差极化 超滤(肾) 剪切速率 粘度 化学工程 材料科学 热力学 生物化学 有机化学 复合材料 数学 经济 气象学 工程类 物理 财务 统计
作者
Zhao Li,Andrew L. Zydney
出处
期刊:Biotechnology Progress [Wiley]
卷期号:33 (6): 1561-1567 被引量:14
标识
DOI:10.1002/btpr.2545
摘要

There is renewed interest in the possibility of using precipitation for initial capture of high value therapeutic proteins as part of an integrated continuous downstream process. These precipitates can be continuously washed using tangential flow filtration, with long term operation achieved by operating the membrane modules below the critical filtrate flux for fouling. Our hypothesis was that the critical flux for the precipitated protein would be a function of the properties of the precipitate as determined by the precipitation conditions. We evaluated the critical flux using a flux‐stepping procedure for model protein precipitates (bovine serum albumin) generated using a combination of a crosslinking agent (zinc chloride) and an excluded volume precipitant (polyethylene glycol [PEG]). The critical flux varied with shear rate to approximately the 1/3 power, consistent with predictions of the classical polarization model. The critical flux increased significantly with increasing zinc chloride concentration, going from 60 L/m 2 /h for a 2 mM ZnCl 2 solution to 200 L/m 2 /h for an 8 mM ZnCl 2 solution. In contrast, the critical flux achieved a maximum value at an intermediate PEG concentration. Independent measurements of the effective size and viscosity of the protein precipitates were used to obtain additional understanding of the effects of ZnCl 2 and PEG on the precipitation and the critical flux. These results provide important insights into the development of effective tangential flow filtration systems for processing large quantities of precipitated protein as would be required for large scale continuous protein purification by precipitation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog. , 33:1561–1567, 2017
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