High resolution mass spectrometry for the post-genomic age: challenges and opportunities.
Evolution of mankind is inextricably linked to the development of an ever expanding multitude of tools in all areas of human activity. Though overwhelmingly diverse, these tools tend to evolve towards increasing fidelity, intensity and hierarchic complexity. Following a brief overview of the major trends of tool evolution, the inaugural lecture of Alexander Makarov gradually focuses onto its main theme, mass spectrometry (MS), a fast-growing analytical technique for very sensitive identification of molecules on the basis of their masses and charges. Makarov is Professor by Special Appointment of High Resolution Mass Spectrometry at the Department of Chemistry and the Bijvoet Center.
The major drivers for expansion of this technique appear to be a need for increasing accuracy of mass measurement, improvement of fragment processing, and refinement of ionisation techniques. Makarov’s lecture is devoted not just to the history of this process, but also to exciting future opportunities yet to be realised. Makarov will start by recounting first-hand the short but eventful history of Orbitrap instrumentation that has driven a revolution in high mass accuracy, high resolution MS over the last decade.
Present-day Orbitrap MS is used not only for high-end proteomic and metabolomic research, but also for screening or targeted analysis in a broad range of applications, from anti-doping to environmental and clinical analysis. In effect, the technique turns out to increasingly complement capabilities of genetic analysis in life science research.
All these achievements pave the road to future development of high resolution MS, which is expected to proceed along two major paths. The first path is democratisation of the current capabilities, making them accessible to hospitals and routine labs.
The second path is further enhancement of analytical capabilities, which requires a significant improvement of technology on multiple levels. At the level of the high-resolution analyser, analytical throughput could be increased using new signal processing methods and new ion-optical schemes. At the level of instrument operation, the next frontier in sensitivity is expected to be elimination of vast losses taking place nowadays in MS/MS experiments when only one ion species is selected for fragmentation and all remaining ones are discarded.
Outside the usual realm
A third very promising direction of research in high resolution MS deals with venturing outside of the usual realm of the method altogether, by interfacing it to emerging techniques resulting in yet to be discovered analytical potential. Examples of such hyphenations include not only known combinations with ion mobility, imaging or different ion sources, but also with such novel methods such as nanoelectromechanical single-molecule measurement systems and ultraviolet photofragmentation spectroscopy of cold ions.
Each of those advances promises to further improve the quality of information beyond the reach of existing methods for all molecules of interest, be it protein complexes, highly modified proteins, metabolites, or environmental factors.