Multiple RF Ion Trap Coupled to Orthogonal TOF Mass Spectrometer

莱因霍尔德质谱（Reinhold Mass spectrometry，MS）结合离子碎片化技术是生物分子结构解析的基础。结合质量测量与碎裂模式是必要的，因为裸离子质量（任意精度）通常无法识别离子的分子结构。离子捕获质谱仪（基于Paul或Penningtrap）的发展允许离子分离和碎裂（MSn）的多个序列。这些仪器允许将复杂离子分解成组分，产生碎裂模式的嵌套层次结构。整体碎裂模式基本上扩展了质谱法可以确定的范围。理想情况下，将离子分解与碎片分解模式的知识相结合，可以理解几乎所有复杂生物分子的结构，肽、寡糖、脂质和糖缀合物。尽管这些进步很重要，同样清楚的是，目前的MS仪器不能满足生物学发展的需要。基因组数据的爆炸加速了生物学的转变，从关注单个分子和相互作用转向关注在细胞和生物体水平上研究复杂的相互作用网络。满足这些要求将需要对复杂分子的混合物进行MS分析，而目前的MS仪器的主要局限性是：仪器是损失的灵敏度在这样的MSn分析。离子在分离特定组分时会因故意喷射而丢失，在MSn步骤的仪器执行过程中，离子会因动力学不稳定性而意外和不希望的损失而丢失。本研究的目的是开发一种新的MSn分析技术，以消除或大大减少这些损失。计算机模拟的离子运动的射频离子阱的novelgeometry建议，它是可能的耦合这些设备和usethe阵列的耦合阱作为一种新型的MSn仪器。一个原型质谱仪组成的一系列耦合离子阱交配anorthogonal飞行时间质谱仪将建成。离子在阱区之间的质量选择性转移和阱内离子解离的表征是当前的实验目标，对原型的实验分析与计算机模拟相结合将指导这类质谱仪作为分析仪器的未来发展。将观察结果与设备的数值模型相关联也将有助于模拟（从而设计）气相离子操纵仪器的一般技术。更高性能的MSn质谱仪将成为解决基因组时代生物学分析挑战的技术的重要组成部分。

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.