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.
A variation of the simulated-moving-bed (SMB) operation, called Enriched Extract SMB (EE-SMB), is investigated, in which a portion of the extract product is concentrated and the resulting enriched stream is re-injected into the SMB at that same point, i.e., at the inlet of section 2. This operation has been recently patented. [Bailly et al., U.S. Patent Application No. WO2004039468, 2004.] Equilibrium Theory is used (i) to obtain the constraints on the operating parameters and (ii) to identify the operating regimes for the EE-SMB operation. This analysis is performed for a binary mixture whose adsorption behavior is described by a Langmuir isotherm. The operating regimes are translated into regions on the (m 2 , m 3 ) plane representation, which can be easily compared with the corresponding operating regimes of the standard SMB given by the Triangle Theory. In particular, for the EE-SMB operation, the region of complete separation turns out to be a line segment, i.e., a one-dimensional locus. The theoretical findings are confirmed through detailed simulations of the process, and the value of the new EE-SMB operation mode is assessed.
The Simulated Moving Bed technology is extended to incorporate a cleaning in place step, and it is then applied by exploiting size exclusion chromatography to purify plasmid DNA. Experimental performances are discussed in the light of our theoretical understanding of the SMB behavior.
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