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