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

描述（由申请人提供）：用于低电荷状态下完整蛋白质的飞行时间（TOF）质谱分析的现有检测器，如微通道板和电子倍增器，依赖于发射二次电子进行离子检测。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，显著降低了检测灵敏度并限制了TOF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实践的生物质谱法主要针对小肽而不是针对完整蛋白质的分析的主要原因之一，这是该技术的关键限制。 我们开发了一种新型的离子检测器， 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中的相应振荡来检测振荡。我们建议在这里开发我们的初始原型检测器成为一个强大的，强大的，以及表征完整的蛋白质的质谱仪高达兆道尔顿的大小的设备。 这种新的检测器技术将在生物质谱中开辟许多新的机会，例如生物标志物的发现和监测，蛋白质变异的阐明以及MALDI质谱的组织成像。

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.