Imaging protein crystal growth behaviour in batch cooling crystallisation

doi:10.1016/j.cjche.2015.08.020

Chinese Journal of Chemical Engineering ›› 2016, Vol. 24 ›› Issue (1): 101-108.DOI: 10.1016/j.cjche.2015.08.020

• 第25届中国过程控制会议专栏 • 上一篇下一篇

Imaging protein crystal growth behaviour in batch cooling crystallisation

Jing J. Liu^1,2, Cai Y.Ma², Xue Z. Wang^1,2

1 School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China;
2 Institute of Particle Science and Engineering, School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK

收稿日期:2014-11-22 修回日期:2015-05-03 出版日期:2016-01-28 发布日期:2016-02-23
通讯作者: Xue Z. Wang
基金资助:
Supported by the China One Thousand Talent Scheme, the National Natural Science Foundation of China under its Major Research Scheme of Meso-scale Mechanism and Control in Multi-phase Reaction Processes (91434126), the Natural Science Foundation of Guangdong Province (2014A030313228), and also benefited from early work funded byUKEngineering and Physical Science Research Council (EP/H008012/1, EP/H008853/1).

Imaging protein crystal growth behaviour in batch cooling crystallisation

Jing J. Liu^1,2, Cai Y.Ma², Xue Z. Wang^1,2

1 School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China;
2 Institute of Particle Science and Engineering, School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK

Received:2014-11-22 Revised:2015-05-03 Online:2016-01-28 Published:2016-02-23
Contact: Xue Z. Wang
Supported by:
Supported by the China One Thousand Talent Scheme, the National Natural Science Foundation of China under its Major Research Scheme of Meso-scale Mechanism and Control in Multi-phase Reaction Processes (91434126), the Natural Science Foundation of Guangdong Province (2014A030313228), and also benefited from early work funded byUKEngineering and Physical Science Research Council (EP/H008012/1, EP/H008853/1).

摘要/Abstract

摘要： The temporal and spatial growth behaviour of protein crystals, subject to different cooling strategies in protein crystallisation was investigated. Although the impact of temperature and cooling rate on crystal growth of small moleculeswaswell documented, much less has been reported on their impact on the crystallisation of proteins. In this paper, an experimental set-up is configured to carry out such a study which involves an automatic temperature controlled hot-stage crystalliser fittedwith a real-time imaging system. Linbro parallel crystallisation experiments (24-well plate)were also conducted to find the suitable initial conditions to be used in the hot-stage crystallisation experiments, including the initial concentration of HEWlysozyme solutions, precipitate concentration and pH value. It was observed that fast cooling rates at the early stage led to precipitates while slow cooling rates produced crystal nuclei, and very slowcooling rates,much smaller than for smallmolecules are critical to the growth of the nuclei and the crystals to a desired shape. The interesting results provide valuable insight aswell as experimental proof of the feasibility and effectiveness of cooling as a means for achieving controlled protein crystallisation, compared with the evaporation approach which was widely used to grow single large crystals for X-ray diffraction study. Since cooling rate control can be easily achieved and has good repeatability, it suggests that large-scale production of protein crystals can be effectively achieved by manipulating cooling rates.

关键词: Hot-stage reactor, On-line imaging of crystal growth, Hen-Egg-White lysozyme cooling, crystallisation, Protein crystallisation, Real-time in-process imaging

Abstract: The temporal and spatial growth behaviour of protein crystals, subject to different cooling strategies in protein crystallisation was investigated. Although the impact of temperature and cooling rate on crystal growth of small moleculeswaswell documented, much less has been reported on their impact on the crystallisation of proteins. In this paper, an experimental set-up is configured to carry out such a study which involves an automatic temperature controlled hot-stage crystalliser fittedwith a real-time imaging system. Linbro parallel crystallisation experiments (24-well plate)were also conducted to find the suitable initial conditions to be used in the hot-stage crystallisation experiments, including the initial concentration of HEWlysozyme solutions, precipitate concentration and pH value. It was observed that fast cooling rates at the early stage led to precipitates while slow cooling rates produced crystal nuclei, and very slowcooling rates,much smaller than for smallmolecules are critical to the growth of the nuclei and the crystals to a desired shape. The interesting results provide valuable insight aswell as experimental proof of the feasibility and effectiveness of cooling as a means for achieving controlled protein crystallisation, compared with the evaporation approach which was widely used to grow single large crystals for X-ray diffraction study. Since cooling rate control can be easily achieved and has good repeatability, it suggests that large-scale production of protein crystals can be effectively achieved by manipulating cooling rates.

Key words: Hot-stage reactor, On-line imaging of crystal growth, Hen-Egg-White lysozyme cooling, crystallisation, Protein crystallisation, Real-time in-process imaging

Jing J. Liu, Cai Y.Ma, Xue Z. Wang. Imaging protein crystal growth behaviour in batch cooling crystallisation[J]. Chinese Journal of Chemical Engineering, 2016, 24(1): 101-108.

Jing J. Liu, Cai Y.Ma, Xue Z. Wang. Imaging protein crystal growth behaviour in batch cooling crystallisation[J]. Chin.J.Chem.Eng., 2016, 24(1): 101-108.

参考文献

[1] J.K. Baird, S.C. Hill, J.C. Clunie, Kinetics of protein crystal nucleation and growth in the batch method, J. Cryst. Growth 196 (2-4) (1999) 220-225.

[2] E. Cacioppo, S. Munson, M.L. Pusey, Protein solubilities determined by a rapid technique and modification of that technique to a micro-method, J. Cryst. Growth 110 (1-2) (1991) 66-71.

[3] A.C. Dumetz, A.M. Chockla, E.W. Kaler, A.M. Lenhoff, Effects of pH on protein-protein interactions and implications for protein phase behavior, Biochim. Biophys. Acta Proteins Proteomics 1784 (4) (2008) 600-610.

[4] E. Forsythe, M. Lee Pusey, The effects of temperature and NaCl concentration on tetragonal lysozyme face growth rates, J. Cryst. Growth 139 (1-2) (1994) 89-94.

[5] E.F. Forsythe, M.L. Pusey, Studies on tetragonal lysozyme crystal growth rates, Acta Crystallogr. D50 (1994) 614-619.

[6] E.L. Forsythe, R.A. Judge,M.L. Pusey, Tetragonal chicken egg white lysozyme solubility in sodium chloride solutions, J. Chem. Eng. Data 44 (3) (1999) 637-640.

[7] J. Dong, J.Z. Pan, X.T. Niu, Y.C. Zhou, R.C. Bi, The influence of microgravity on crystal structure of protein, Chin. Sci. Bull. 45 (1) (2000) 55-59.

[8] X.Y. Liu, G.L. Dai, S.J.Wang, Study of the effect of impurities on protein crystal, Chin. J. Biotechnol. 27 (12) (2007) 101-108.

[9] X.H. Dai, R.C. Bi, Effect of precipitation agent types on the molecular packing of protein crystals, J. Biol. Chem. 18 (4) (2002) 394-398.

[10] G.L. Dai, Y. Xie, Q. Kang, W.R. Hu, Study of intrinsic reason of effect of solution heat history on protein crystal growth, J. Chem. 65 (13) (2007) 1202-1206.

[11] K.M. Gernert, R. Smith, D.C. Carter, A simple apparatus for controlling nucleation and size in protein crystal-growth, Anal. Biochem. 168 (1) (1988) 141-147.

[12] L.J. Delucas, C.D. Smith, H.W. Smith, S. Vijaykumar, S.E. Senadhi, S.E. Ealick, D.C. Carter, R.S. Snyder, P.C. Weber, F.R. Salemme, D.H. Ohlendorf, H.M. Einspahr, L.L. Clancy, M.A. Navia, B.M. McKeever, T.L. Nagabhushan, G. Nelson, A. McPherson, S. Koszelak, G. Taylor, D. Stammers, K. Powell, G. Darby, C.E. Bugg, Protein crystalgrowth in microgravity, Science 246 (4930) (1989) 651-654.

[13] W. Heinrichs, M. Heinrichs, H. Schonert, Growth of protein single-crystals in a periodically changing solubility gradient—Description of the method and 1st results, J. Cryst. Growth 122 (1-4) (1992) 186-193.

[14] R.C. Demattei, R.S. Feigelson, Controlling nucleation in protein solutions, J. Cryst. Growth 122 (1-4) (1992) 21-30.

[15] F. Rosenberger, S.B. Howard, J.W. Sowers, T.A. Nyce, Temperature dependence of protein solubility—Determination and application to crystallisation in X-ray capillaries, J. Cryst. Growth 129 (1-2) (1993) 1-12.

[16] R. Murai, S. Nakata, M. Kashii, H. Adachl, A. Niino, K. Takano, H. Matsumura, S. Murakami, T. Inoue, Y. Mori, T. Sasaki, Cooling-rate screening system for determining protein crystal growth conditions, J. Cryst. Growth 292 (2) (2006) 433-436.

[17] H. Adachi, A. Niino, K. Takano, H. Matsumura, S. Murakami, T. Inoue, Y. Mori, T. Sasaki, Temperature-screening system for determining protein crystallisation conditions, Jpn. J. Appl. Phys. 44 (6) (2005) 4080-4083.

[18] S.K. Basu, C.P. Govardhan, C.W. Jung, Protein crystals for the delivery of biopharmaceuticals, Expert. Opin. Biol. Ther. 4 (3) (2004) 301-317.

[19] J.J. Liu, Y.D. Hu, X.Z.Wang, Optimization and control of crystal shape and size in protein crystallisation process, in: I.A. Karimi, R. Srinivasan (Eds.),11th international symposium on process systems engineering, Pts a and B, vol. 31 2012, pp. 1160-1164.

[20] J.J. Liu, Y.D. Hu, X.Z.Wang, Optimization and control of crystal shape and size in protein crystallisation process, Comput. Chem. Eng. 57 (2013) 133-140.

[21] J.J. Liu, C.Y.Ma, Y.D. Hu, X.Z. Wang,Morphological population balancemodels for the dynamic evolution of particle shape and size distribution in protein crystallisation, in: R.M. de Brito Alves, C.A.O. do Nascimento, E.C. Biscaia (Eds.),10th international symposium on process systems engineering, vol. 27 2009, pp. 1911-1916.

[22] J.J. Liu, C.Y. Ma, Y.D. Hu, X.Z. Wang, Effect of seed loading and cooling rate on crystal size and shape distributions in protein crystallisation—A study using morphological population balance simulation, Comput. Chem. Eng. 34 (12) (2010) 1945-1952.

[23] J.J. Liu, C.Y. Ma, Y.D. Hu, X.Z.Wang, Modelling protein crystallisation using morphological population balance models, Chem. Eng. Res. Des. 88 (4A) (2010) 437-446.

[24] Linkam, www.linkam.co.uk.

[25] J. Calderon De Anda, X.Z.Wang, X. Lai, K.J. Roberts, Classifying organic crystals via inprocess image analysis and the use of monitoring charts to follow polymorphic and morphological changes, J. Process Control 15 (7) (2005) 785-797.

Imaging protein crystal growth behaviour in batch cooling crystallisation

Imaging protein crystal growth behaviour in batch cooling crystallisation

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics

本文评价