Supercritical fluid chromatography

High-pressure gas chromatography is not a novel concept, but it is an intriguing one: the eco-friendly chimera seeks to combine the advantages of GC and HPLC, which has led to the development of supercritical fluid chromatography (SFC). But while the chromatographic age of supercritical fluids has been advertised by proponents and manufacturers for more than 50 years, SFC has largely been deprecated as science fiction due to complex method development, a perceived lack of robustness, and a tendency to fall short of expectations. For the longest time, separation scientists were justifiably skeptical—if not blissfully unaware—of the reformation process taking place within SFC, which has only recently escaped scientific anonymity/infamy by gaining industrial significance as the method of choice for chiral and semi-preparative separations. Indeed, the truly exceptional performance and a multitude of adjustable parameters make SFC arguably the most versatile of industrially employed chromatographic techniques. Here, the principal reasons for the renewed interest in SFC (what is SFC good for?) are reviewed, before addressing the underlying physical principles and instrumental requirements (what makes SFC work?). A discussion of the fundamental limitations (what is the catch?) follows. The frontiers between different types of chromatography are fading and may soon give way to unified or convergent analysis that is expected to provide a more accurate analytical vision than any singular form of chromatography.