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Multiplexed Charge Detection Mass Spectrometer for Extended Mass and Collisional Cross Section Measurements

用于扩展质量和碰撞截面测量的多重电荷检测质谱仪

基本信息

批准号：
10473780
负责人：
Evan R Williams
金额：
$ 30.18万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-22 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10473780
关键词：
Area Bypass Cell physiology Charge Complex Complex Mixtures Consumption Data Detection Development Dissociation Drug Targeting Electrospray Ionization Electrostatics Event Frequencies Gases Generations Goals Health Heterogeneity Hour Human Individual Injections Ions Lipoproteins Macromolecular Complexes Mass Spectrum Analysis Measurement Measures Methods Modeling Molecular Optics Parents Pathway interactions Phase Polymers Process Proteins Publishing Research Resolution Sampling Scheme Signal Transduction Solvents Speed System Techniques Testing Therapeutic Therapeutic Agents Time Viral Vector Virus-like particle Work base design detector evaporation experience experimental study improved innovation insight instrument instrumentation ion mobility macromolecular assembly macromolecule mass spectrometer molecular assembly/self assembly molecular shape next generation novel prevent protein aggregation stem targeted delivery tool transmission process viral DNA

项目摘要

Project Summary Large biomolecular assemblies constitute much of the molecular machinery necessary for cellular function. These assemblies are often the target of a host of therapeutic molecules. Other large biomolecular assemblies, including virus-like particles, proteinaceous cellular compartments, and some large synthetic polymers, are potential delivery agents for these therapeutics. The large molecules and molecular assemblies involved in cellular function can be challenging to analyze using conventional mass spectrometry methods owing to their high mass (>MDa) and heterogeneity. Electrospray ionization can transfer intact large molecules/complexes into the gas phase, but overlapping and unresolved charge states that stem from the heterogeneity inherent to high mass analytes often prevent mass measurements using conventional mass spectrometers. Charge detection mass spectrometry weighs individual ions, avoiding these interferences between ions and can be used to analyze molecules with masses well above 100 MDa. However, this method can be slow because only one ion is analyzed at a time. Here, a new generation of charge detection mass spectrometry is proposed which provides information about the mass, the collisional cross section and the dissociation pathways of individual ions of large macromolecular complexes, information that cannot be obtained using conventional instruments. A key innovation is the development of multiplexing methods that make it possible to simultaneously weigh many individual ions. These methods have the potential to increase the speed of these measurements by up to 150x and reduce sample analysis times to less than one minute. This ion multiplexing is aided by a novel decoupling scheme whereby ions with a controlled range of energies are introduced into the electrostatic ion detector trap so that two or more ions with the same m/z can have different frequencies. The mass of each ion can be obtained from simultaneous measurements of the individual ion frequency, energy, and charge. This scheme significantly reduces the potential for overlapping ion signal by distributing the signal over a broad frequency bandwidth. The rate of ion energy change can also be determined from these measurements, providing information about collisional cross sections and giving insight into molecular shape. Similarly, individual ion fragmentation events can be tracked and used to obtain additional structural information.

项目摘要大型生物分子组件构成了许多必要的分子机械细胞功能。这些组件通常是一系列治疗分子的靶标。其他大的生物分子组件，包括病毒样颗粒、蛋白质细胞隔室和一些大型合成聚合物是这些药物的潜在递送剂治疗学。参与细胞功能的大分子和分子组件可以是由于其高质量，使用传统的质谱学方法分析具有挑战性 (&gt；丙二醛)和异质性。电喷雾电离可以原封不动地转移大量分子/络合物进入气相，但重叠和未分解的电荷状态源于高质量分析物固有的异质性通常阻碍了质量测量使用传统的质谱仪。电荷检测质谱仪称量个体离子，避免了离子之间的干扰，可以用来分析分子质量远高于100 mda。然而，这种方法可能会很慢，因为只有一个离子一次分析。在这里，我们提出了新一代电荷检测质谱学。它提供了关于质量、碰撞截面和离解的信息大分子络合物的单个离子的路径，不能被使用常规仪器获得的。一项关键的创新是多路传输的发展使同时称重许多单个离子成为可能的方法。这些方法有可能将这些测量的速度提高高达150倍并降低样品分析时间不到一分钟。这种离子多路传输得到了一种新的一种去耦合方案，将具有受控能量范围的离子引入静电离子探测器陷阱，使两个或更多具有相同m/z的离子可以具有不同的频率。每个离子的质量可以通过同时测量单个离子的频率、能量和电荷。这一计划显著降低了通过在宽频带上分布信号来重叠离子信号。这一速度离子能量的变化也可以从这些测量中确定，提供信息关于碰撞截面和对分子形状的洞察。类似地，单个离子可以跟踪碎片事件并使用它来获取其他结构信息。