Mass spectrometry (MS) coupled with methods to fragment ions is fundamental for elucidating molecular structures in biology. Combining mass measurements with fragmentation patterns is necessary as the bare ion mass (to arbitrary precision) often fails to identify the ion's molecular structure. The development of ion trapping mass spectrometers (based on Paul or Penning traps) allows multiple sequences of ion isolation and fragmentation (MSn). These instruments allow the disassembly of complex ions into components, generating a nested hierarchy of fragmentation patterns. The ensemble of fragmentation patterns substantially extends what can be determined by mass spectrometry. Ideally, combining ion disassembly with knowledge of fragment dissociation patterns could allow structural understanding for almost all complex biomolecules, e.g., peptides, oligosaccharides, lipids, and glycoconjugates. As important as these advances have been, it is also clear that present MS instruments fall short of the developing needs in biology. The explosion of genome data has accelerated a shift in biology from focusing on individual molecules and interactions into a focus where complex networks of interactions at the cell and organism level are studied. Addressing these demands will require MSn analyses of mixtures of complex molecules and a major limitation of present instruments is the loss of sensitivity in such MSn analyses. Ions are lost by deliberate ejection during the isolation of a specific component and by incidental and unwanted losses through dynamical instability during the instrumental execution of MSn steps. The objective of the research is to develop a new technology for MSn analyses that will eliminate or substantially reduce these losses.
Computer simulations of ion motion in radio frequency ion traps of a novel geometry have suggested that it is possible to couple these devices and use the array of coupled traps as a new type of MSn instrument. A prototype mass spectrometer consisting of a coupled series of ion traps mated to an orthogonal time-of-flight mass spectrometer will be built. The mass selective transfer of ions between trapping regions and characterizing ion dissociation within the traps are the immediate experimental objectives.
Experimental analysis of the prototype combined with computational simulations will be used to direct future development of this class of mass spectrometers as analytical instruments. Correlating the observations with numerical models of the device will also aid the general technology of simulating (hence designing) gas phase ion manipulation instruments. Substantially higher performance MSn mass spectrometry will be an important component in the technologies that address the analytical challenge of genome-era biology.
