SFC may be a faster and more-efficient alternative to liquid chromatography (LC) in a number of cases. It can be faster, mainly because diffusion coefficients in supercritical fluids are higher than those in liquids.
It is incorrect (but all to common) to say that supercritical fluids combine the advantages of liquid (high solvation power) with those of gases (high diffusivity and low viscosity. More realistically, supercritical fluids provide compromise conditions between gases and liquids.
In almost all current implementations of SFC carbon dioxide (CO2) is the main component of the mobile phase. CO2 has attractive critical properties (critical temperature just above 30oC; critical pressure just above 7 MPa), which are well within the operation range of (modified) LC equipment. Moreover, it is readily available in high purity at low cost (in comparison with typical LC solvents), non-toxic and UV transparent.
In most cases modifiers, such as methanol and other additives are needed to achieve separations. These raise the critical temperature of the mobile phase and it implies that SFC is more commonly performed below the critical temperature (subcritical-fluid chromatography) than above (supercritical-fluid chromatography). Fortunately, the abbreviation SFC covers both.
Modified LC equipment is used almost exclusively for SFC. To pump SFC as a liquid cooling of the pump is required. When using a UV detector a high-pressure cell is needed. Most importantly, a back-pressure regulator (BPR) is required to maintain and control a high outlet pressure. Mass spectrometers can be used in SFC, usually from a branched exit before the BPR.
SFC has proven an attractive alternative to normal-phase liquid chromatography (NPLC), especially for chiral separations. By adding small amounts of water to the (organic component of the) mobile phase HILIC-like SFC separations can be obtained of highly polar analytes, such as peptides. SFC is a less-likely alternative for reversed-phase liquid chromatography (RPLC), with the possible (fairly rare) exception of non-aqueous RPLC of lipids.
