Simulated Moving Bed
Encyclopedia
In chromatography
Chromatography
Chromatography is the collective term for a set of laboratory techniques for the separation of mixtures....

, the simulated moving bed (SMB) technique is a variant of high performance liquid chromatography
High performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...

; it is used to separate particles and/or chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...

s that would be difficult or impossible to resolve otherwise. This increased separation is brought about by a valve-and-column arrangement that is used to lengthen the stationary phase indefinitely.

In the moving bed technique of preparative chromatography the feed entry and the analyte recovery are simultaneous and continuous, but because of practical difficulties with a continuously moving bed in the simulated moving bed technique instead of moving the bed, the sample inlet and the analyte exit positions are moved continuously, giving the impression of a moving bed. in

True moving bed chromatography (MBC) is only a theoretical concept. Its simulation, SMBC is achieved by the use of a multiplicity of columns in series and a complex valve arrangement, which provides for sample and solvent feed, and also analyte and waste takeoff at appropriate locations of any column, whereby it allows switching at regular intervals the sample entry in one direction, the solvent entry in the opposite direction, whilst changing the analyte and waste takeoff positions appropriately as well.

Ref 3 explains that the advantage of the SMBC is high speed, because a system could be near continuous, whilst its disadvantage is that it only separates binary mixtures. It does not say, but perhaps it can be assumed that this is equivalent with the separation of a single component from a group of compounds. With regard to efficiency it compares with simple chromatography technique like continuous distillation does with batch distillation.

Construction

Specifically, an SMB system has two or more identical columns, which are connected to the mobile phase pump, and each other, by a multi-port valve. The plumbing is configured in such a way that:
a) all columns will be connected in series, regardless of the valve's position;

b) each different position of the valve will reconnect the columns to one another in one possible sequential arrangement of the columns;


c) all possible positions of the valve will arrange the columns in every possible sequential order.


For example, consider a case where two HPLC columns, A and B, are connected to one another, and the mobile-phase pump, via a six-port, two-position valve (e.g. a Rheodyne 7000). One valve position will distribute the flow in the manner
Pump-->Column A-->Column B-->Waste,


while the other position will distribute the flow in the manner
Pump-->Column B-->Column A-->Waste.


Consequently, switching of the valve will "leapfrog" the columns over one another. If elution across two columns in series is not adequate to resolve two compounds in a given run, the eluent can then be made to go through 3, 4, 5... columns in additional runs by carefully timed switching. This increases the number of theoretical plates until separation can be attained.

Advantages

When affinity differences between molecules are very small, it is sometimes not possible to improve resolution via mobile- or stationary-phase changes. In these cases, the multi-pass approach of SMB can separate mixtures of those compounds by allowing their small retention time differences to accumulate.

At industrial scale an SMB chromatographic separator is operated continuously, requiring less resin and less solvent than batch chromatography. The continuous operation facilitates operation control and integration into production plants.

Drawbacks

The drawbacks of the SMB are higher investment cost compared to single column operations, a higher complexity, as well as higher maintenance costs. But these drawbacks are effectively compensated by the better yield and a much lower solvent consumption as well as a much higher productivity compared to simple batch separations.

For purifications, in particular the isolation of an intermediate single component or a fraction out of a multicomponent mixture, the SMB is not suited in general. It can only separate two fractions from each other and it does not implement linear solvent gradients as required for the purification of biomolecules.

Applications

In size exclusion chromatography
Size exclusion chromatography
Size-exclusion chromatography is a chromatographic method in which molecules in solution are separated by their size, and in some cases molecular weight . It is usually applied to large molecules or macromolecular complexes such as proteins and industrial polymers...

, where the separation process is driven by entropy
Entropy
Entropy is a thermodynamic property that can be used to determine the energy available for useful work in a thermodynamic process, such as in energy conversion devices, engines, or machines. Such devices can only be driven by convertible energy, and have a theoretical maximum efficiency when...

, it is not possible to increase the resolution attained by a column via temperature or solvent gradients. Consequently, these separations often require SMB, to create usable retention time differences between the molecules or particles being resolved. SMB is also very useful in the pharmaceutical industry, where resolution of molecules having different chirality
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 must be done on a very large scale.

For the production of Fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

 e.g. in High fructose corn syrup
High fructose corn syrup
High-fructose corn syrup  — also called glucose-fructose syrup in the UK, glucose/fructose in Canada, and high-fructose maize syrup in other countries — comprises any of a group of corn syrups that has undergone enzymatic processing to convert some of its glucose into fructose to produce...

or amino-acids, biological-acids, etc. industrial scale chromatography is used.
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