Isocratic SMBC Mode

The principles of continuous countercurrent chromatography and SMBC have been well-documented in the literature. The SMBC process was developed in the 1950’s by UOP for the large-scale separation of n-paraffins. Although many variations have been published in recent years, “classical” SMBC is carried out under isocratic conditions.

In isocratic SMBC there are typically two inlet streams (Feed and Desorbent) and two outlet streams (Raffinate and Extract). Valves between the columns are systematically switched open or closed at timed intervals (switch time) to introduce the inlet streams and withdraw the outlet streams between the separation zones. After each interval, all four streams are simultaneously switched to successive columns in the direction of fluid flow, simulating countercurrent movement of the columns. Separation occurs due to the differential migration of the Feed mixture components through the column material. Components that interact more strongly with the column material are carried into the Extract, whereas weaker-interacting components move into the Raffinate. By adjusting the stream flow rates, the switch time, and the Desorbent composition, a cycle is established in which Feed and Desorbent are continuously added and highly purified products are continuously recovered.

3-Zone isocratic SMB chromatography process animation

A 3-2-3 configuration is shown having 3 columns in Zone 1, 2 columns in Zone 2, and 3 columns in Zone 3. At defined intervals all ports are switched forward one column position to accomplish countercurrent separation.

The image to the left shows an animation of an 8-column SMBC system in a “3-2-3” configuration, initially loading and then running at equilibrium. The 3-2-3 designation refers to the number of columns in each SMBC zone. The zones are defined as follows:

  • Zone 1: Between Desorbent inlet and Extract outlet; where the more retained component is desorbed
  • Zone 2: Between Extract outlet and Feed inlet; where the less retained component is desorbed and the more retained component is enriched
  • Zone 3: Between the Feed inlet and Raffinate outlet; where the more retained component is adsorbed and the less retained component is enriched and desorbed

A fourth zone consisting of columns between the Raffinate outlet and Desorbent inlet is commonly included in large scale SMBC systems and can be configured into the Semba Octave System. This zone serves as a buffer between Zones 1 and 3 to ensure that no Raffinate enters Zone 1. It is also used in some configurations as a point to recycle the Desorbent. Because the Semba Octave System can effectively prevent flow of Raffinate into Zone 1 simply by closing off the valve between Zone 3 and Zone 1, and because volumes of Desorbent are generally low enough to eliminate the need for recycling, Zone 4 is not necessary for most applications.

The Isocratic Mode is in contrast to Step Mode operation, typically used for affinity binding purification methods.

The video illustrates Isocratic Mode operation of the Octave System. In this example, a mixture of two dyes is separated using size exclusion chromatography. A 3-2-3 column configuration is used. The red dye (Vitamin B12) is preferentially retained and is purified in the Extract, whereas the blue dye (Blue Dextran) is excluded from the resin and moves into the Raffinate.

Demonstration of isocratic SMB chromatography with the Octave™ System

The Semba Octave™ 10 bench top Chromatography System is used to demonstrate continuous size exclusion chromatography in isocratic SMB mode.