Multiple RF Ion Trap Coupled to Orthogonal TOF Mass Spectrometer

摘要：质谱法（MS）结合离子片段法是生物学中分子结构研究的基础。结合质量测量与碎片模式是必要的，因为裸离子质量（任意精度）往往不能识别离子的分子结构。离子捕获质谱仪的发展（基于Paul或Penningtraps）允许多个序列的离子分离和分裂（MSn）。这些仪器允许将复杂的离子分解成组件，产生嵌套的碎片模式层次结构。集合碎片模式大大扩展了质谱法可以确定的内容。理想情况下，结合离子分解和碎片解离模式的知识，可以让我们理解几乎所有复杂生物分子的结构，例如肽、低聚糖、脂质和糖缀合物。与这些进步同样重要的是，很明显，目前的质谱仪器还不能满足生物学发展中的需要。基因组数据的爆炸式增长加速了生物学的转变，从关注单个分子和相互作用转向研究细胞和生物体水平上复杂的相互作用网络。为了满足这些需求，需要对复杂分子混合物进行MSn分析，而目前仪器的一个主要限制是在这种MSn分析中失去灵敏度。离子的损失是在分离特定组分的过程中故意喷射，以及在仪器执行msn步骤期间由于动态不稳定而造成的偶然和不希望的损失。这项研究的目的是开发一种新的形式分析技术，以消除或大大减少这些损失。对一种新型几何形状的射频离子阱中离子运动的计算机模拟表明，可以将这些器件耦合起来，并将耦合阱阵列用作一种新型的微磁共振仪器。将建立一个由一系列耦合离子阱与正交飞行时间质谱仪组成的原型质谱仪。离子在捕获区域之间的质量选择性转移和表征陷阱内的离子解离是直接的实验目标。原型的实验分析与计算模拟相结合，将用于指导这类质谱仪作为分析仪器的未来发展。将观测结果与设备的数值模型相关联也将有助于模拟（因此设计）气相离子操作仪器的一般技术。更高性能的MSn质谱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.