Supercritical Fluid Chromatography

Supercritical fluid chromatography (SFC) is experiencing a boom in demand that it never came close to reaching when it was first released. Thanks to technological advancements and general development of the technique, the potential of SFC is now being unlocked. While its initial popularity is associated with chiral separations, considerable potential remains for its use in a wide range of applications.

SFC debuted as a commercial analytical technique in the 1980s. Academic and corporate developers based their first-generation systems on the capillary chromatography columns available at the time. However, the lack of pressure management and fraction collection technologies made early SFC products impractical. In addition, the petroleum industry, which developers targeted as a primary market, did not grow strongly. These two factors caused the SFC market to nearly collapse in the early 1990s. To the rescue came Terry Berger, who created Berger Instruments, now a part of Mettler-Toledo. He began developing packed-column SFC for the pharmaceutical market. By developing the needed fraction collection and pressure management technology, and targeting this rapidly growing market with great potential, Berger almost single-handedly caused a rebirth of the SFC market.

Supercritical fluids have the solvating strength of many organic solvents, but have higher diffusivity, lower viscosity and lower surface tension, which are major benefits in chromatography. SFC combines liquid solubility with the ability to use gas phase detectors, such as flame ionization detection. The standard SFC solvent is carbon dioxide, which is nontoxic, eliminating the health and environmental issues associated with cleanup and disposal of organic solvents, as well as providing an advantage when working with products for human consumption. Yet another benefit is the ease of reclaiming the compound of interest following separation. The net result of these factors is a high-speed technique with high productivity, high resolution and low operating costs. SFC provides performance comparable to some of the newest ultrahigh-pressure analytical liquid chromatography systems.

Although the first widespread applications of SFC were in the analytical arena, its use has expanded into preparative and, more recently, process scale applications. Chiral separations are a leading area of use due to SFC’s much-improved efficiency, which magnifies the cost advantages when dealing with chiral stationary phases. Some vendors are even developing simulated moving bed versions of SFC systems, which have the potential to provide greater cost savings for larger scale chiral separations.

The combined market for analytical, preparative and process SFC is $25–$30 million worldwide. Both preparative and analytical SFC are likely to grow in double digits, while rocess SFC, now accounting for as much as a third of this market, could grow more than 30% in the near term.

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