Journal of Zhejiang University-SCIENCE A

, Volume 5, Issue 12, pp 1613–1620 | Cite as

Mathematical modeling of salt-gradient ion-exchange simulated moving bed chromatography for protein separations



The salt-gradient operation mode used in ion-exchange simulated moving bed chromatography (SMBC) can improve the efficiency of protein separations. A detailed model that takes into account any kind of adsorption/ion-exchange equilibrium, salt gradient, size exclusion, mass transfer resistance, and port periodic switching mechanism, was developed to simulate the complex dynamics. The model predictions were verified by the experimental data on upward and downward gradients for protein separations reported in the literature. All design and operating parameters (number, configuration, length and diameter of columns, particle size, switching period, flow rates of feed, raffinate, desorbent and extract, protein concentrations in feed, different salt concentrations in desorbent and feed) can be chosen correctly by numerical simulation. This model can facilitate the design, operation, optimization, control and scale-up of salt-gradient ion-exchange SMBC for protein separations.

Key words

Simulated moving bed chromatography Salt gradients Size exclusion Proteins Mathematical model 

CLC number

O657.7 TQ460.35 


  1. Abel, S., Mazzotti, M., Morbidelli, M., 2004. Solvent gradient operation of simulated moving beds 2. Langmuir isotherms. J. Chromatography A, 1026:47–55.CrossRefGoogle Scholar
  2. Finlayson, B.A., 1980. Non-linear Analysis in Chemical Engineering. McGraw-Hill, New York.Google Scholar
  3. Gao, Y.G., Guan, Y.X., Yao, S.J., Cho, M.G., 2003. Lysozyme refolding at high concentration by dilution and size-exclusion chromatography. J. Zhejiang University SCIENCE, 4(2):136–141.CrossRefGoogle Scholar
  4. Gu, T., 1995. Mathematical Modeling and Scale-up of Liquid Chromatography. Springer, Berlin.CrossRefGoogle Scholar
  5. Gu, T., Tsai, G.J., Tsao, G.T., 1990. New approach to a general nonlinear multicomponent chromatography model. AIChE J., 36:784–788.CrossRefGoogle Scholar
  6. Helfferich, F.G., 1983. Ion-exchange Kinetics-Evolution of A Theory. In: Liberti, L., Helfferich, F.G. (Eds.), Mass Transfer and Kinetics of Ion-exchange (NATO ASI Series E: Applied Science, No. 71). Martinus Nijhoff, The Hague, p. 162.Google Scholar
  7. Houwing, J., Billiet, H.A.H., van der Wielen, L.A.M., 2002a. Optimization of azeotropic protein separations in gradient and isocratic ion-exchange simulated moving bed chromatography. J. Chromatography A, 944:189–201.CrossRefGoogle Scholar
  8. Houwing, J., van Hateren, S.H., Billiet, H.A.H., van der Wielen, L.A.M., 2002b. Effect of salt gradients on the separation of dilute mixtures of proteins by ion-exchange in simulated moving beds. J. Chromatography A, 952:85–98.CrossRefGoogle Scholar
  9. Houwing, J., Jensen, T.B., van Hateren, S.H., Billiet, H.A.H., van der Wielen, L.A.M., 2003a. Positioning of salt gradients in ion-exchange SMB. AIChE J., 49:665–674.CrossRefGoogle Scholar
  10. Houwing, J., Billiet, H.A.H., van der Wielen, L.A.M., 2003b. Mass-transfer effects during separation of proteins in SMB by size exclusion. AIChE J., 49:1158–1167.CrossRefGoogle Scholar
  11. Hritzko, B.J., Xie, Y., Wooley, R.J., Wang, N.H.L., 2002. Standing-wave design of tandem SMB for linear multicomponent systems. AIChE J., 48:2769–2787.CrossRefGoogle Scholar
  12. Kaczmarski, K., Mazzotti, M., Storti, G., Morbidelli, M., 1997. Modeling fixed-bed adsorption columns through orthogonal collocations on moving finite elements. Comput. Chem. Eng., 21:641–660.CrossRefGoogle Scholar
  13. Lu, J.G., 1995. Preparative Ion-Exchange Chromatography of Amino Acids. Ph. D. Thesis, Chem. Eng. Dept., Zhejiang Univ., Hangzhou (in Chinese).Google Scholar
  14. Lu, J.G., 2003. A non-linear non-ideal model of simulated moving bed chromatography for chiral separations. Chinese J. Chem. Eng., 11:234–239.Google Scholar
  15. Lu, J.G., Wu, P.D., 1997. Dynamics of preparative ion-exchange chromatography of amino acids. J. Chem. Eng. Chinese Univ., 11:163–165 (in Chinese).Google Scholar
  16. Migliorini, C., Mazzotti, M., Zenoni, G., Morbidelli, M., 2002. Shortcut experimental method for designing chiral SMB separations. AIChE J., 48:69–77.CrossRefGoogle Scholar
  17. Minceva, M., Pais, L.S., Rodrigues, A.E., 2003. Cyclic steady state of simulated moving bed processes for enantiomers separation. Chem. Eng. Proc., 42:93–104.CrossRefGoogle Scholar
  18. Pais, L.S., Rodrigues, A.E., 2003. Design of simulated moving bed and Varicol processes for preparative separations with a low number of columns. J. Chromatography A, 1006:33–44.CrossRefGoogle Scholar
  19. Silva, E.A.B., Souza, A.A.U., Souza, S.M.A.G.U., 2002. The use of simulated moving bed in chromatographic separations: Study of the SMB configuration. Sep. Sci. Technol., 37:1489–1504.CrossRefGoogle Scholar
  20. Yamamoto, S., Nakanishi, K., Matsuno, R., 1988. Ion-Exchange Chromatography of Proteins. Marcel-Dekker, New York and Basel.Google Scholar
  21. Yu, H.W., Ching, C.B., 2002. Optimization of a simulated moving bed based on an approximated Langmuir model. AIChE J., 48:2240–2246.CrossRefGoogle Scholar
  22. Yu, Q., Wang, N.H.L., 1989. Computer simulations of multicomponent ion exchange and adsorption in fixed beds-Gradient-directed moving finite element method. Comput. Chem. Eng., 13:915–926.CrossRefGoogle Scholar
  23. Zhang, Z.Y., Hidajat, K., Ray, A.K., Morbidelli, M., 2002. Multiobjective optimization of SMB and varicol process for chiral separation. AIChE J., 48:2800–2816.CrossRefGoogle Scholar

Copyright information

© Zhejiang University Press 2004

Authors and Affiliations

  1. 1.National Laboratory of Industrial Control Technology, Institute of Industrial Process ControlZhejiang UniversityHangzhouChina

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