Simulated Moving Bed Chromatography: from chiral molecules to biocompounds

The Simulated moving bed (SMB) technology was developed in the '60s and used for large-scale separations of hydrocarbons in the oil industry. The SMB concept has been extended towards new fields of application since then, first in the large-scale food industry, e.g. separation of sugars, and lately in the separation of fine chemicals, particularly chiral molecules where it is now an established technique (Juza et al., 2000). This is partly due to changes in the technological scenario, particularly the development of stable and efficient stationary phases.

Nowadays SMB is stepping into the field of biotechnology (Abel et al., 2004a; Paredes et al., 2004b) where batch chromatography is the established technique. Many things change when moving to bioseparations and a joint effort between the SMB practitioners and the biotechnologists has to be made in order to understand the characteristics and requirements of these new applications (sanitation, stability of the substances, validation issues, etc. Contrary to standard SMB applications where organic solvents are mostly used, in bioprocesses chromatography is carried out in aqueous solutions using buffers and modifiers. Since the solute retention is very sensitive to the solution composition this is a good example of the new SMB challenges mentioned above.

In general, SMB shows significant benefits with respect to batch chromatography in terms of solvent consumption and productivity. Furthermore it is possible to achieve high purities even when the resolution on a single column is poor. A preliminary design of the operation can easily be carried out using relatively simple criteria (Mazzotti et al., 1997), and there are tools to carry out a detailed SMB optimization. Recently new operation modes have been introduced leading to more flexible and powerful applications; these include solvent gradient, and the three fraction SMB (3F-SMB) and the CIP-SMB operations (Abel et al, 2004a; Paredes et al., 2004a). This is of special importance for applications in bioseparations, since it addresses the important problem of media regeneration or cleaning-in-place (CIP). Generally the feed mixtures are rather complex and may develop particulate matter, denaturated proteins, etc, that would reduce the performance of the columns during operation if a cleaning was not carried out periodically. The scheme of such a unit is shown in Figure 1; the CIP is carried out in section 0 and the column is regenerated in the Equilibration section before being inserted back into the loop.

Lately it could be shown that the flexible bench chromatographic unit ÄKTAexplorer^TM (GE Healthcare) can be adopted to use it as a SMB unit for small scale production by adding standard hardware elements, and doing the corresponding changes to the software. An example of this modified ÄKTAexplorer is shown in the Figure.

The future of SMB in biotechnology is promising and it will hopefully contribute to some of the next fascinating advances in this field.

Bibliography

S. Abel, M. Bäbler, C. Arpagaus, M. Mazzotti, and J. Stadler. J. Chromatogr. A, 1043:201-210, 2004a.
M. Juza, M. Mazzotti, and M. Morbidelli. Tibtech, 18:108-118, 2000.
M. Mazzotti, G. Storti, and M. Morbidelli. J. Chromatogr. A, 769:3-24, 1997.
G. Paredes, S. Abel, M. Mazzotti, M. Morbidelli, and J. Stadler. Ind. Chem. Eng. Res., 43:6157-6167, 2004a.
G. Paredes, M. Mazzotti, J. Stadler, S. Makart, and M. Morbidelli.Adsorption, accepted for publication, 2000b

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