Continuous Spherical Crystallization of Lysozyme in an Oscillatory Baffled Crystallizer Using Emulsion Solvent Diffusion in Droplets,Crystal Growth & Design

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Continuous Spherical Crystallization of Lysozyme in an Oscillatory Baffled Crystallizer Using Emulsion Solvent Diffusion in Droplets
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2020-01-22 , DOI: 10.1021/acs.cgd.9b01313
Joseph A. Oliva ₁ , Wei-Lee Wu ₁ , Michael R. Greene ₁ , Kanjakha Pal ₁ , Zoltan K. Nagy ₁

Affiliation

Continuous protein crystallization is a cost-effective alternative to traditional chromatographic purification techniques. However, proteins characteristically have slow growth rates, requiring long crystallization times to generate particles large enough for efficient isolation. In this work, spherical crystallization using an emulsion solvent diffusion (ESD) based methodology is proposed to produce large lysozyme agglomerates in an oscillatory baffled crystallizer (OBC). Process sensitivity analysis was performed to investigate the effect of the process parameters on the product’s crystal size distribution at two different scales. The concentration of ethanol in the bulk phase was found to have a significant effect on the crystallization kinetics, as its diffusivity drives supersaturation at the droplet interface. Although controlling supersaturation is important in determining product quality, maintaining droplet suspension near the injection site is critical for process longevity, as fouling is most likely to occur in this high supersaturation region. Similarly, in scaling this process, the ratio of droplet diameter to tube diameter plays a significant role in the formation of encrust. Increasing the size of the droplets, relative to the diameter of the system, increases the role of wall effects in distorting the final product quality. Overall, these tunable process parameters make the OBC an ideal platform for spherical protein crystallization.

中文翻译：

使用液滴中的乳液溶剂扩散在振荡挡板结晶器中溶菌酶的连续球形结晶

连续蛋白质结晶是传统色谱纯化技术的一种经济高效的替代方法。但是，蛋白质通常具有较慢的生长速度，需要较长的结晶时间才能生成足够大的颗粒以进行有效分离。在这项工作中，提出了使用基于乳液溶剂扩散（ESD）的方法进行球形结晶，以在振荡折流结晶器（OBC）中产生较大的溶菌酶附聚物。进行了工艺敏感性分析，以研究工艺参数对两种不同规模的产品晶体尺寸分布的影响。发现本体相中的乙醇浓度对结晶动力学具有显着影响，因为其扩散性驱动液滴界面处的过饱和。尽管控制过饱和度对确定产品质量很重要，但保持液滴在注射位置附近的悬浮对于延长工艺寿命至关重要，因为结垢最有可能在此高过饱和度区域发生。类似地，在缩放该过程时，液滴直径与管子直径的比率在结壳的形成中起着重要作用。相对于系统直径，液滴尺寸的增加会增加壁效应在扭曲最终产品质量中的作用。总体而言，这些可调的工艺参数使OBC成为球形蛋白质结晶的理想平台。类似地，在缩放该过程时，液滴直径与管直径的比率在结壳的形成中起着重要作用。相对于系统直径，液滴尺寸的增加会增加壁效应在扭曲最终产品质量中的作用。总体而言，这些可调的工艺参数使OBC成为球形蛋白质结晶的理想平台。类似地，在缩放该过程时，液滴直径与管直径的比率在结壳的形成中起着重要作用。相对于系统直径，液滴尺寸的增加会增加壁效应在扭曲最终产品质量中的作用。总体而言，这些可调的工艺参数使OBC成为球形蛋白质结晶的理想平台。

更新日期：2020-01-23

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