Simulated moving bed

In chromatography, the simulated moving bed (SMB) technique is a a variant of high performance liquid chromatography; it is used to separate particles and/or chemical compounds 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.

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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;

and

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 a 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, where the separation process is driven by entropy, 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 must be done on a very large scale.

For the production of Fructose e.g. in High fructose corn syrup or amino-acids, biological-acids, etc. industrial scale chromatography is used.