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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.

项目总结