High Efficiency Linked Scan Mass Spectrometer

描述（由申请人提供）：翻译后修饰与细胞中蛋白质功能的调节密切相关。检测蛋白质修饰的存在和量化它们的丰度是理解它们在生物过程中的作用的先决条件。尽管在使用放射照相、Edman测序和免疫化学等几种技术来揭示修饰方面取得了一定的成功，但这项研究仍然面临着巨大的分析挑战。基于质谱的方法开始在这项任务中发挥越来越重要的作用。几种类型质谱仪的链接扫描操作模式显示出检测和分析几种类型修改的特殊前景。该技术具有高度选择性，并且基于在化合物的碎片谱中观察特定特征碎片的巧合。目前，由于前体离子选择步骤，该模式的效率仅达到百分之几，在此过程中，所有其他离子都被拒绝链接扫描分析。本项目的目的是：(1)建立一种新型的质谱仪，用于收集效率接近100%的链接扫描光谱；(2)实现该质谱仪对蛋白质修饰位点的检测和分析。质谱仪的结构是基于一种新型的高离子容量线性离子阱与四极杆碰撞池和四极杆质量分析仪相结合的串联结构。这种新型的线性离子阱可以存储大量的离子而不会因空间电荷效应而导致性能下降。在弹射过程中，存储在离子阱中的所有离子都可以在碰撞单元中依次破碎，但只有特定的离子碎片可以通过四极杆质量分析仪传输到探测器，该分析仪的扫描与离子阱弹射扫描相连。因此，在仪器的单次扫描期间，可以从存储在离子阱中的所有离子获得链接的扫描光谱，从而使设备的效率提高100-1000倍。这种质谱仪可以以前所未有的速度和灵敏度检测蛋白质上的修饰位点。它对于监测复杂混合物中的特定产物，并最终收集所有观察物种的破碎光谱具有巨大的价值。一旦建成，它将迅速成为推进生物医学研究前沿不可缺少的研究工具。

DESCRIPTION (provided by applicant): Post-translational modifications are intimately involved in regulation of the protein function in the cell. Detecting the presence of modifications on proteins and quantifying their abundance is a prerequisite for understanding their role in biological processes. Despite a certain success in using several techniques such as radiography, Edman sequencing and immunochemistry to reveal modifications, this study continues to present formidable analytical challenge. Mass spectrometry based methods are beginning to play an increasingly important role in this task. A linked scan mode of operation of several types of mass spectrometers exhibits an exceptional promise for detecting and profiling several types of modifications. The technique is highly selective and based on the coincidence of observing a particular characteristic fragment in the fragmentation spectrum of a compound. Presently, the efficiency of this mode reaches only a fraction of percent because of the precursor ion selection step during which all other ions are rejected linked scan analysis. The aim of this project is (1) to build a new type of mass spectrometer for collecting linked scan spectra with efficiency close to 100 percent and (2) to implement this mass spectrometer for detecting and profiling modification sites on proteins. The construction of the mass spectrometer is based on a novel high ion capacity linear ion trap combined in a tandem configuration with a quadrupole collision cell and a quadrupole mass analyzer. The novel linear ion trap can store a large number of ions without degradation in performance because of space charge effects. All ions stored in the ion trap can be sequentially fragmented in the collision cell during the ejection process, but only particular ion fragments can be transmitted to the detector through the quadrupole mass analyzer whose scan is linked to the ion trap ejection scan. Thus, a linked scan spectrum can be obtained from all ions stored in the ion trap during a single scan of the instrument resulting in 100-1000 fold increase in efficiency of the device. This mass spectrometer can be used to detect modification sites on proteins with an unprecedented speed and sensitivity. It will have an immense value for monitoring particular products in the complex mixtures and, ultimately, for collecting fragmentation spectra from all observed species. When built, it will quickly become an indispensable research tool for advancement the frontiers of the biomedical research.