Analysis of a Simulated Moving Bed Operation for Three-Fraction Separations (3F-SMB)

Abstract

A three-fraction simulated moving bed (3F-SMB) unit for separating feed mixtures into three fractions is presented. Criteria for the selection of the flow rate ratios in the four sections of the unit under linear chromatographic conditions are developed. These criteria translate into a region of complete three-fraction separation in the (m 2 , m 3 ) plane. The performance of the 3F-SMB unit is investigated through detailed simulations using as a model system the separation of the four nucleosides: 2′-deoxyadenosine, 2′-deoxythymidine, 2′-deoxyguanosine, and 2′-deoxycytidine. For nonlinear chromatographic conditions, simulations on the same model system allowed qualitative conclusions on the performance of the 3F-SMB to be drawn. Further, the possibility of using the 3F-SMB unit to implement a cleaning-in-place (CIP) step within a standard SMB is shown and validated through simulations, using as a model system a mixture of two nucleosides and one highly retained impurity.

SMB Operation for Three-Fraction Separations: Purification of Plasmid DNA

“…Section r is required to re-equilibrate the column that has undergone CIP with the solvent buffer system used for the separation. This is a special case of the three fraction SMB operation that has been recently demonstrated through experiments (Abel et al, 2003) and simulations (Paredes et al, 2004). A similar scheme was proposed also in the patent literature (Voigt et al, 2001).…”

Simulated Moving Bed Chromatography: From Concept to Proof‐of‐Concept

“…Side-stream SMB [72][73][74] or multiextract/raffinate [75] are also referred in the literature. These techniques can be classified as five-or more section SMBs and the latter (side-stream) presents particular features for multicomponent separations, as indicated, e.g., by the 3F-SMB process [76] or the partial collection strategy [77].…”

“…During the second step, the feed stream is closed and the unit works as a standard SMB where the less and more retained products are collected at the extract and raffinate ports. The use of two different adsorbents [134], solvent gradient [135] (see also the MCSGP process in Section 2.8), five-section SMB [76], with partial-feed [136], and partial-collecting strategies [77] have also been reported for multicomponent separations using a same unit.…”

Simulated Moving Bed Operation for Size Exclusion Plasmid Purification

“…In the case of the SMB, the equations described above are coupled with mass balances at the nodes, and the switching mechanism has to be implemented. A detailed description of the model equations has been reported earlier [21].…”

“…In some cases, disposal of the chromatographic media is recommended, but it is clear that no conclusions can be drawn about this point without an optimized cleaning protocol that would compare cleaning in place (CIP) costs and chromatographic media expenses. The technical implementation of a CIP step into the SMB operation has been addressed recently [21,25]. The socalled CIP-SMB scheme is illustrated in Fig.…”