High-resolution Qq-TOF MS instrument

描述(申请人提供)：现代蛋白质组学任务需要将快速高效的色谱分离与能够每秒记录数十个高质量质谱图的高分辨率质谱仪相结合。在保持记录光谱的高质量精度的同时，现代飞行时间质谱仪(QTOF-MS)可以实现高通量。重要的任务是对于质量电荷比超过800的离子，将QTOF质量分辨率提高到50-60,000到与Orbitrap相当的水平。这项提议的主要目标是设计和建造快速(至少每秒20个平均质谱图)Q-TOF质谱仪的关键部件，以在800-10,000 Da质量范围内定期达到50,000以上的质量分辨率，并展示超过5个数量级的动态范围。这些措施包括用于在离子注入飞行时间质谱仪之前对离子进行有效碰撞冷却的低温冷却离子导轨接口；带有两个离子反射镜的倾斜衬套以提供更长的飞行时间；计时精度低于ppm的数据采集系统；以及(模拟和数字)联合多通道信号采集系统。这种新的高分辨率TOF仪器将用于对含有潜在生物标志物和药物靶标的复杂蛋白质消化混合物进行定量分析。公共卫生相关性：高通量质谱分析仪器的开发在现代蛋白质组学及其临床应用以及药物开发中发挥着重要作用。我们建议建立一种新型的非常高分辨率的飞行时间质谱仪，它将利用低温冷却的子系统、离子光学部件的精细设计和多通道数据采集来提高复杂蛋白质消化混合物的质量分析的可靠性和吞吐量。

DESCRIPTION (provided by applicant): Modern proteomics tasks necessitate combining fast high-performance chromatographic separations with high-resolution mass spectrometers capable of recording tens of high- quality mass spectra per second. While retaining high mass accuracy of recorded spectra, high throughput can be achieved in modern time-of-flight mass spectrometer (QTOF-MS). Important task is to increase QTOF mass resolution to 50-60,000 to a level comparable to that in Orbitrap for ions with mass-to-charge ratios exceeding 800. The main goal of this proposal is designing and building key components of a fast (at least 20 averaged mass spectra per second) Q-TOF mass spectrometer to regularly achieve mass resolution over 50,000 over 800-10,000 Da mass range and demonstrate dynamic range exceeding 5 orders of magnitude. These include cryogenically cooled ion guide interface for efficient collisional cooling of ions before their injection into the of TOF-MS; tilted liner with two ion mirrors to provide longer flight times; data acquisition system with sub-ppm timing accuracy; and combined (analog and digital) multi-channel signal acquisition system. This new high-resolution TOF instrument will be used to provide quantitative analysis of complex protein digest mixtures containing potential biomarkers and pharmaceutical targets. PUBLIC HEALTH RELEVANCE: The development of instruments for high-throughput mass spectrometric analysis plays an important role in modern proteomics and its clinical applications, as well as in drug discovery. We propose to build a novel very high-resolution time-of-flight mass spectrometer, which will utilized cryogenically cooled subsystems, refined design of the ion optical parts, and multi-channel data acquisition to increase reliability and throughput of mass analysis of complex mixtures of protein digests.