Introduction to Continuous (SMB) Chromatography

Simulated moving bed chromatography (SMBC) was invented in the 1950’s by Broughton and colleagues at UOP for large-scale separation of n-paraffins, and is used today in many variations in the petrochemical, food, and pharmaceutical industries. The SMBC process has made liquid chromatography economically feasible on an industrial scale due to its high productivity relative to batch (single-column) methods. This enhanced productivity (up to 20-fold) is achieved through much more efficient utilization of the solid and liquid phases required for separation. In simplest terms, SMBC does more with less.

The basic concept of simulated moving bed chromatography is to use multiple smaller columns containing the solid adsorbent (beds) rather than one large column, and to “move” the beds in the opposite direction of the fluid to achieve a countercurrent flow, rather than flowing fluids through one static bed. The “simulated movement” is typically carried out through multiport valves interspersed between the columns, such that the input and output fluid streams can be periodically switched from column to column in the direction of fluid flow. Rather than applying feed and desorbent and collecting fractions sequentially with one column, all fluid streams are simultaneously applied and withdrawn at appropriate points between the columns. When running at a steady state, the various stages of separation are carried out simultaneously by different columns in a continuous cycle.

Classical SMBC as used in the petrochemical and food industries is operated in isocratic mode and utilizes true countercurrent separation. It is characterized by continuous flow of a single solvent between (usually 3 or 4) separation zones defined by Feed and Desorbent inlets and Extract and Raffinate outlets. This mode is extremely effective at separating closely-related molecules, such as p-xylene from o-and m-xylene and glucose from fructose, with high purity and yield.

A more recent variation of SMBC adapts the multicolumn approach to higher separation factor applications, such as affinity chromatography. Step mode is characterized by operation of typically four or more distinct zones having different solvent conditions in a “bind-wash-elute-clean-equilibrate”, or step gradient sequence. This mode requires more pumps, inlets and outlets than isocratic mode and enables straightforward control over the flow rates in each zone. The target molecule(s) may be recovered in any of the outlet streams depending on the separation chemistry. Step mode is especially effective in biopharmaceutical applications, such as downstream processing of monoclonal antibodies, recombinant proteins, and vaccine components.

In both Isocratic and Step operating modes, parameters for continuous chromatography are determined using data obtained from single column experiments. Semba provides software tools for each mode to convert the single column data into starting conditions for continuous separation. For more information and to visualize the principles of isocratic and step SMBC modes please see Isocratic SMBC Mode and  Step SMBC Mode.