A Mechanical Nanomembrane Detector for Time-of-Flight Mass Spectrometry

描述(由申请人提供)：现有的低电荷态完整蛋白质飞行时间(TOF)质谱学检测器，如微通道板和电子倍增器，依靠二次电子的发射进行离子检测。不幸的是，这种二次电子产生的效率随着入射离子质量的增加而严重下降，极大地降低了检测灵敏度，限制了飞行时间质谱仪提供关于大生物分子的有用质量信息的能力。离子检测中的这个问题是目前生物质谱学主要针对小肽而不是完整蛋白质进行分析的主要原因之一，这是该技术中的一个关键限制。我们已经开发了一种新型的离子探测器来 基于纳米膜的机械变形和振动来解决这个问题。进入的离子包引发纳米膜的振荡，然后通过来自膜的场发射电子电流的相应振荡来检测。我们在这里建议将我们最初的原型探测器开发成一个强大、坚固和特征良好的设备，用于大小达一兆吨的完整蛋白质的质谱分析。这一新的检测器技术将在生物标记物的发现和监测、蛋白质变异的阐明以及MALDI质谱学对组织的成像等领域为生物质谱学开辟许多新的机遇。

DESCRIPTION (provided by applicant): Existing detectors for time-of-flight (TOF) mass spectrometry of intact proteins in low charge states, such as microchannel plates and electron multipliers, rely upon the emission of secondary electrons for ion detection. Unfortunately, the efficiency of this secondary electron generation falls-off severely with increasing mass of the incident ions, dramatically reducing detection sensitivity and limiting the ability of TOF mass spectrometers to provide useful mass information on large biomolecules. This problem in ion detection is one of the major reasons that biological mass spectrometry as currently practiced is predominantly directed towards the analysis of small peptides rather than towards whole intact proteins, a critical limitation in the technology. We have developed a new type of ion detector to address this problem, based upon the mechanical deformation and vibration of a nanomembrane. An incoming ion packet initiates oscillations of the nanomembrane, which are then detected by corresponding oscillations in field emission electron current from the membrane. We propose here to develop our initial prototype detector into a powerful, robust, and well- characterized device for the mass spectrometry of intact proteins up to a megadalton in size. This new detector technology will open many new opportunities in biological mass spectrometry, in areas such as biomarker discovery and monitoring, the elucidation of protein variation, and the imaging of tissue by MALDI mass spectrometry.