Multiple RF Ion Trap Coupled to Orthogonal TOF Mass Spectrometer

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Abstract Reinhold Mass spectrometry (MS) coupled with methods to fragment ions is fundamentalfor elucidating molecular structures in biology. Combining mass measurementswith fragmentation patterns is necessary as the bare ion mass (to arbitraryprecision) often fails to identify the ion's molecular structure. Thedevelopment of ion trapping mass spectrometers (based on Paul or Penningtraps) 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 offragmentation patterns substantially extends what can be determined by massspectrometry. Ideally, combining ion disassembly with knowledge of fragmentdissociation patterns could allow structural understanding for almost allcomplex biomolecules, e.g., peptides, oligosaccharides, lipids, andglycoconjugates. As important as these advances have been, it is also clearthat present MS instruments fall short of the developing needs in biology.The explosion of genome data has accelerated a shift in biology fromfocusing on individual molecules and interactions into a focus where complexnetworks of interactions at the cell and organism level are studied.Addressing these demands will require MSn analyses of mixtures of complexmolecules and a major limitation of present instruments is the loss ofsensitivity in such MSn analyses. Ions are lost by deliberate ejectionduring the isolation of a specific component and by incidental and unwantedlosses through dynamical instability during the instrumental execution ofMSn steps. The objective of the research is to develop a new technology forMSn analyses that will eliminate or substantially reduce these losses.Computer simulations of ion motion in radio frequency ion traps of a novelgeometry have suggested that it is possible to couple these devices and usethe array of coupled traps as a new type of MSn instrument. A prototype massspectrometer consisting of a coupled series of ion traps mated to anorthogonal time-of-flight mass spectrometer will be built. The massselective transfer of ions between trapping regions and characterizing iondissociation within the traps are the immediate experimental objectives.Experimental analysis of the prototype combined with computationalsimulations will be used to direct future development of this class of massspectrometers as analytical instruments. Correlating the observations withnumerical models of the device will also aid the general technology ofsimulating (hence designing) gas phase ion manipulation instruments.Substantially higher performance MSn mass spectrometry will be an importantcomponent in the technologies that address the analytical challenge ofgenome-era biology.