蛋白质核和结晶过程与处理分析技术在批量结晶器中的过程
Wenqing Tian1, Wei Li1, Huaiyu Yang1
1Department of Chemical Engineering, Loughborough University, Loughborough LE113TU, U.K.
Crystal growth & design
|July 10, 2023
概括
使用聚焦束反射率测量 (FBRM) 实时监测蛋白质结晶,为过程阶段和动力学提供了关键的见解. 这种方法准确地估计了诱导时间,并揭示了超和盐度如何影响界面能量和产量.
科学领域:
- 生物技术是生物技术.
- 化学工程是化学工程的重要组成部分.
- 结晶科学 结晶科学
背景情况:
- 蛋白质结晶在制药中比传统的下游加工具有优势.
- 目前对蛋白质结晶动态的理解有限,需要实时监测.
- 在现场跟踪对于优化蛋白质结晶过程至关重要.
研究的目的:
- 开发和实施蛋白质批量结晶的实时监测系统.
- 为了识别蛋白质结晶过程中的不同阶段.
- 分析超和,盐度和蛋白质度对结晶动力学和产量的影响.
主要方法:
- 使用了一台100毫升批量结晶器,配备了一个聚焦束反射度测量 (FBRM) 探头和热电偶.
- 在现场监测与离线度测量和晶体成像相结合.
- 基于FBRM数据和溶液条件的诱导时间,界面能量和最终产量的分析.
主要成果:
- 确定了三个结晶阶段:核形成,快速结晶和生长/断裂.
- FBRM有效估计了诱导时间,这与超和水平相关.
- 核形成的界面能量随着盐度的增加而减少.
- 通过优化蛋白质和盐度,可以获得高产量 (高达99%) 和受控的晶体大小 (中位数为26.5微米).
结论:
- 聚焦束反射度测量 (FBRM) 是实时监测和理解蛋白质结晶的宝贵工具.
- 过和盐度等过程参数显著影响结晶动力学和热力学.
- 优化的条件允许高产量的蛋白质结晶,具有受控的晶体特性.
相关概念视频
Crystal Growth: Principles of Crystallization
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Crystallization is a phase transformation process in which crystals are precipitated from a supersaturated solution or formed from other sources. During crystallization, atoms or molecules arrange themselves into a well-defined, rigid crystal lattice to minimize energy.
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent...
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