High-resolution Qq-TOF MS instrument

描述（由申请人提供）：现代蛋白质组学任务需要将快速高效色谱分离与能够每秒记录数十个高质量质谱的高分辨率质谱仪相结合。现代飞行时间质谱仪（QTOF-MS）在保持记录光谱的高质量准确度的同时，可以实现高通量。重要的任务是将QTOF质量分辨率提高到50- 60，000，达到与Orbitrap中质荷比超过800的离子相当的水平。该提案的主要目标是设计和构建快速（每秒至少20个平均质谱）Q-TOF质谱仪的关键组件，以在800- 10，000 Da质量范围内定期实现超过50，000的质量分辨率，并展示超过5个数量级的动态范围。这些包括低温冷却离子导向接口，用于在离子注入TOF-MS之前对离子进行有效的碰撞冷却;带有两个离子镜的倾斜衬垫，以提供更长的飞行时间;具有亚ppm定时精度的数据采集系统;以及组合（模拟和数字）多通道信号采集系统。这种新的高分辨率TOF仪器将用于定量分析含有潜在生物标志物和药物靶点的复杂蛋白质消化混合物。公共卫生相关性：高通量质谱分析仪器的发展在现代蛋白质组学及其临床应用以及药物发现中起着重要作用。我们建议建立一个新的非常高分辨率的飞行时间质谱仪，这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，以提高可靠性和吞吐量的复杂混合物的蛋白质质谱分析。

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.