Sequential Simulated Moving Bed (SSMB) Chromatography

The Simulated Moving bed (SMB) or Simulated Moving bed Chromatography (SMBC) is a very advanced multi-column chromatography system generally used for the binary separation of molecules. It relies on adsorption and is a continuous separation technology.

The technology initially started way back in the 1960s as True Moving Bed (TBM) Chromatography and was used then by the Oil Product Company. The technology began to see advances right at the beginning of the 21st Century building on laboratory systems of the 1990s.

SMB is mainly exploited as a very effective method for the continuous separation of two compounds or the binary fractionation of complex mixtures. It is also the basis for combining a reactor with chromatographic separation into almost one single step. It is this feature which makes it so attractive to large-scale producers of commodity products such as glucose (Toumi & Engell, 2004).

The application is also used in the development of SMB reactors. A recent development has been the SSMB (Sequential Simulated Moving Bed).

The Theory Behind The SMB

A binary mixture in its simplest form is added to a chromatographic column. At the same time an eluent is fed in continuously. The raffinate contains poorly absorbed compounds which move with the mobile phase. These are removed down stream.

The extractant phase contains more of the absorbed compounds that move into the ‘stationary phase’. These are removed up stream.

The SMB relies on conventional fixed bed chromatographic columns. In this system, the inlet and outlet ports are switched from regularly and periodically in the direction of fluid flow. This approach simulates a countercurrent movement of the solid phase found in the original TMB process. Pure product is than taken from each exit port.

The benefits:

  • Low CAPEX compared to conventional separation systems and a low number of columns
  • Lower amounts of resin required
  • High recovery with purity up to 99%.

Issues:

  • High solvent and eluent use.

Applications:

The main application is now separation of enantiomers of chiral compounds. It is generally found that the production of a pure compound is possible at a lower cost than if a single column chromatography application is made.

  • production of fructose – crystalline
  • production of HFCS 55/95/99
  • oligosaccharides such as fructooligosaccharides (FOS) and xylo-oligosaccharides (XOS)
  • organic acid manufacture such as citric acid
  • amino acids especially aromatic variants such as tryptophan
  • monoclonal antibodies (Gottschlich and Kasche, 1997)
  • recovery of valuable products in effluents and mother liquors.

Novasep and DuPont have developed a joint system called FAST chromatography which allows for the continuous and simultaneous separation of 3 fractions. Used for reducing the sugar content of molasses such as B-molasses and C-molasses in the recovery of sucrose. The system is also being developed for bioethanol plants and will have applications in biodiesel. FAST Chromatography also used in the recovery of betaine from vinasses.

The design of these systems is still in its infancy. Optimization of any process in general is based on a dynamic process model, detailed cost functions and mathematical analysis of performance.

In 1997, Gottschlich and Kasche reported on an SMB for purifying monoclonal antibodies They used 2 purge steps to improve the purity and yield of the chromatographic process. They showed that 99% of the contaminating proteins were removed in a single step. The steady-state performance of this process was modelled by solving differential equations using a linear driving force approximation.

Dünnebier et al., (2000) explored ways and means of designing and operating a Simulated Moving Bed Chromatographic Reactor (SMBCR).

An SSMB process has been designed for the purification of xylo-oligosaccharides (Li et al., 2020). In this article, the authors find a Pareto optimal solution for a range of optimizations. That means the basic 80:20 rule is applied in layman’s terms. These optimizations are based on product purity The Pareto based approach is justified using flow rate ratios but are ‘not enough to guide tuning of the operating parameters’.

Conventional ‘Triangle Theory’ does not apply here with averaged m values.

References

Dünnebier, G., Fricke, J., & Klatt, K. U. (2000). Optimal design and operation of simulated moving bed chromatographic reactors. Industrial & engineering chemistry research39(7), pp. 2290-2304.

Gottschlich, N., & Kasche, V. (1997). Purification of monoclonal antibodies by simulated moving-bed chromatography. Journal of Chromatography A765(2), pp. 201-206.

Juza, M., Mazzotti, M., & Morbidelli, M. (2000). Simulated moving-bed chromatography and its application to chirotechnology. Trends in Biotechnology18(3), pp. 108-118.

Li, Y., Xu, J., Yu, W., & Ray, A. K. (2020). Multi-objective optimization of sequential simulated moving bed for the purification of xylo-oligosaccharides. Chemical Engineering Science211, 115279 (Article).

Paredes, G., Stadler, J., Makart, S., Morbidelli M, Mazzotti M. (2005). SMB operation for three-fraction separations: Purification of plasmid DNA. Adsorption 11 pp. 841–845

Toumi, A., & Engell, S. (2004). Optimization-based control of a reactive simulated moving bed process for glucose isomerization. Chemical Engineering Science59(18), pp. 3777-3792.

Wu, D. J., Xie, Y., Ma, Z., & Wang, N. H. (1998). Design of simulated moving bed chromatography for amino acid separations. Industrial & Engineering Chemistry Research37(10), pp. 4023-4035.

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