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

用于飞行时间质谱分析的机械纳米膜探测器

• 批准号: 8273631
• 负责人: LLOYD M SMITH
• 金额: $ 29.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8273631
• 关键词: Acceleration; Address; Area; Biological; Biological Markers; Caliber; Characteristics; Charge; Complex; Detection; Devices; Diagnosis; Diamond; Disease; Electrons; Electrospray Ionization; Film; Frequencies; Generations; Image; Individual; Ions; Mass Spectrum Analysis; Mechanics; Membrane; Metals; Molecular Weight; Monitor; Peptides; Performance; Polymers; Polystyrenes; Positioning Attribute; Proteins; Research; Resolution; Sampling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Technology; Time; Tissues; Tube; Variant; Work; base; detector; falls; improved; instrument; ion source; mass spectrometer; nanopattern; novel; prototype; response; vibration; voltage

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. PUBLIC HEALTH RELEVANCE: This project seeks to develop a novel detector technology to dramatically improve the mass spectrometric analysis of intact high molecular weight proteins present at low abundance and/or in complex biological samples. Research in areas such as protein variation, biomarker discovery and mass spectrometric imaging will greatly benefit from this technology, opening new possibilities in the diagnosis and treatment of disease.

描述（由申请人提供）：用于低电荷状态完整蛋白质的飞行时间（TOF）质谱分析的现有检测器，例如微通道板和电子倍增器，依赖于二次电子的发射来进行离子检测。不幸的是，随着入射离子质量的增加，二次电子产生的效率严重下降，大大降低了检测灵敏度，并限制了 TOF 质谱仪提供有关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主要针对小肽而不是完整完整蛋白质的分析的主要原因之一，这是该技术的一个关键限制。 我们开发了一种新型离子检测器 基于纳米膜的机械变形和振动来解决这个问题。传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纳米膜的振荡。我们在此建议将我们最初的原型探测器开发成一个功能强大、坚固且特性良好的设备，用于对尺寸高达兆道尔顿的完整蛋白质进行质谱分析。 这种新的检测器技术将为生物质谱领域带来许多新的机遇，例如生物标志物发现和监测、蛋白质变异的阐明以及通过 MALDI 质谱进行组织成像等领域。 公共健康相关性：该项目旨在开发一种新型检测器技术，以显着改善对低丰度和/或复杂生物样品中存在的完整高分子量蛋白质的质谱分析。蛋白质变异、生物标志物发现和质谱成像等领域的研究将极大地受益于这项技术，为疾病的诊断和治疗开辟新的可能性。