Comprehensive multidimensional separations

Abstract

Multidimensionality in the instrumental separation sciences represents improved capabilities for discovery of molecular species. The literature is replete with reports where new separation tools have allowed new compounds—or previously unreported compounds—to be detected and identified in all manner of samples. Thus multidimensional separation (MDS) methods normally involve sampling narrow zones of eluate from a first-dimension column, to be re-separated on a second dimension normally of somewhat different mechanism, to resolve compounds that are poorly resolved or completely unresolved in the first stage. This is the aim of all chromatographic methods—to resolve compounds. Therefore the MDS method succeeds by providing greater capacity for the total analysis. However, the case where multidimensionality involves just one separation stage as one of the dimensions of the analytical system also provides improved analytical capability. This is most readily recognised in the form of gas chromatography– mass spectrometry (GC–MS) and liquid chromatography (LC)–MS methodologies. In this case the two dimensions are fully orthogonal—both dimensions provide independent mechanisms of analysis. The extent to which multi-(two-)dimensio nal separations are orthogonal is a matter of some discussion, and this is especially the case for MDGC. Here the only possible mechanism is based on phase selectivity and temperature, and the independence of the mechanisms is still a useful research subject. The advent of ‘powerful’MS solutions might be apparently sufficient for many sample analyses, and we have been served well by these methods. But the overriding question should be whether an improved quality of analysis can be achieved by an MDS approach. Can MS provide an unambiguous molecular assignment where an insufficient separation is obtained? Clearly, a single MS dimension was found to be lacking in certain cases, otherwise there would have been little motivation to develop MS/MS approaches which have found many unique applications, both for specificity of molecular structural information, but especially where component overlap compromises a single MS stage. We can ask the same question for the separation stage. Given the acknowledged success of MDGC (but still the lack of widespread adoption in most GC laboratories), where does the technology of comprehensive 2D gas chromatography (GC×GC) and its liquid chromatography counterpart sit? Given that GC×GC has now about a 20-year history since it was first proposed by Professor John Phillips, have comprehensive multidimensional separations (CMS) captured the hearts and minds of the chromatographer? If not, can we rationalize the reason why? Whilst MDGC provides a relatively simple interpretation of a chromatographic result, CMS completely overturns the chromatography experiment—the way it is conducted, the conditions and technology of modulation, the need to select appropriate columns and dimensions—and optimisation, the need for appropriate detection technologies, and then there is the matter of data handling and interpretation. Literally, every aspect of both GC and LC are challenged by CMS technology. This requires development of methods and, more importantly, systems that are dedicated to CMS. But if chromatographers were not up to challenges, then perhaps we would still be using packed columns (or TLC)! The way forward to considering MDS was illuminated by Giddings, and his insights in a series of landmark papers. However, these were not supported by parallel experimental developments—they were simply impossible given the technology of the time. So his were very much ‘thought experiments’. Phillips made the first experimental developments that Published in the special issue Comprehensive Multidimensional Separations with Guest Editors James Harynuk and Philip Marriott.