Multiple RF Ion Trap Coupled to Orthogonal TOF Mass Spectrometer

摘要雷诺质谱(MS)与离子裂解方法相结合是阐明生物学中分子结构的基础。将质量测量与碎裂模式相结合是必要的，因为裸离子质量(达到任意精度)往往无法确定离子的分子结构。离子捕获质谱仪(基于Paul或Penningtraps)的发展允许多种离子隔离和碎裂(MSN)序列。这些仪器允许将复杂的离子分解成组分，产生嵌套的碎裂模式层次结构。整体裂解模式大大扩展了可以通过质谱学确定的范围。理想情况下，将离子拆解与碎片解离模式的知识相结合，可以使人们了解几乎所有复杂生物分子的结构，例如肽、寡糖、脂类和糖共轭化合物。与这些进展一样重要的是，目前的MS仪器显然不能满足生物学发展的需要。基因组数据的爆炸性增长加速了生物学从关注单个分子和相互作用转向研究细胞和生物水平上复杂的相互作用网络。满足这些需求将需要对复杂分子的混合物进行MSN分析，而现有仪器的一个主要限制是在这种MSN分析中失去灵敏度。离子在分离特定成分的过程中由于故意的喷射而丢失，在MSn步骤的仪器执行过程中由于动力不稳定而附带的和意外的损失而丢失。这项研究的目的是开发一种新的MSN分析技术，以消除或大幅减少这些损失。对一种新颖几何结构的射频离子陷阱中离子运动的计算机模拟表明，将这些设备耦合起来并将耦合陷阱阵列用作新型MSN仪器是可能的。将建立一个由一系列耦合的离子陷阱与一个正交的飞行时间质谱计组成的质谱计原型。离子在囚禁区域之间的质量选择性转移和表征囚禁区域内的离子离解是直接的实验目标。对样机的实验分析和计算模拟将被用来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(从而设计)气相离子操纵仪器的一般技术。实质上更高性能的MSN质谱学将是解决基因组时代生物学分析挑战的技术中的一个重要组成部分。

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.