Recent Developments in Hyphenated Supercritical Fluid Systems Including Extraction and Chromatography

Supercritical fluid extraction (SFE) and chromatography (SFC) are well established as independent techniques. Recently, commercial instruments hyphenating these two separation steps as SFE-SFC have been made available. In addition, hyphenation of SFC to mass spectrometry (MS) is routinely used, although the best way to hyphenate SFC to MS takes different forms and is still a matter of debate.
On another hand, two-dimensional chromatographic systems including supercritical fluids in the first, second or both dimensions are attracting interest, but are not yet ready for routine use. In particular, 2D-SFC systems would be of great interest as there would be no problems with fluid compatibility between the first and second dimensions, contrary to 2D systems combining LC and SFC. As SFC can be carried out in numerous modes (e.g. chiral or achiral, normal-phase, reversed-phase, ion-exchange etc.), complementary separations can be obtained simply by using different stationary phases in the two dimensions. Therefore, there would be a great advantage in developing 2D-SFC hyphenated systems.
However, in 2D systems, the compressible supercritical fluid is causing specific behaviour in hyphenating the different parts of the instruments, which can be the source of difficulties but also a source of opportunities. Typically, large volumes of samples can be transferred from the first to the second dimension without causing significant damage to the chromatographic quality as the fluid is compressed at the column entrance.
In this presentation, the difficulties that should be overcome when hyphenating SFE, SFC and MS steps will be discussed, while the interest in developing such instruments will be exemplified with sample applications related to therapeutic devices(a) and natural products(b).

a. B. Caux et al., J. Chromatogr. A 1735 (2024) 465323. DOI: 10.1016/j.chroma.2024.465323
b. L. Réset et al., Anal. Chem. 96, 29 (2024) 11969-11976. DOI: 10.1021/acs.analchem.4c01795