High-Resolution Ion Mobility Mass Spectrometer

描述（由申请人提供）：要求使用配备电喷雾电离（ESI）和基质辅助激光解吸/电离（MALDI）源以及表面诱导解离（SID）的独特最先进的混合离子迁移质谱仪（IM-MS），用于表征各种分子。该工具将成为支持超过9个NIH支持项目的研究目标的重要组成部分。这些研究涉及多种蛋白质结构相关的研究，包括蛋白质-蛋白质的表征 和蛋白质-配体相互作用，用于疾病检测和预后的生物标志物的鉴定，以及组织中药物生物分布的测定。该研究将影响一系列人类健康问题，包括神经退行性疾病，如阿尔茨海默病和肌萎缩侧索硬化症（ALS），细菌感染性疾病，辐射敏感性和癌症。离子迁移率测量提供了基于分子大小和形状的分离和结构信息的额外维度，这在质谱中不可用。IM与MALDI-MS的耦合对于大分子和小分子分布实验的基于MALDI的组织成像可以是特别强大的。直接组织分析和成像质谱法提供了对复杂分子模式及其在组织样本内的空间分布的详细评估。基于MALDI的药物化合物的组织成像可能是用于确定动物模型中的生物分布的快速方法，并且可以产生关于新代谢物的额外信息。表面诱导解离将特别适用于探测大蛋白质复合物的结构和拓扑结构，而SID与IM的耦合将是结构生物学项目的有力工具。拟议的离子迁移率质谱仪系统将由加州大学洛杉矶分校分子仪器中心（MIC）支持和管理，该中心是一个校园范围内的综合设施，旨在提高现有共享的先进仪器设施对该机构更广泛的研究社区的可访问性。

DESCRIPTION (provided by applicant): A unique state-of-the-art hybrid ion mobility mass spectrometer (IM-MS) equipped with electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) sources, and surface induced dissociation (SID) for characterization of a broad range of molecules is requested. This instrument will be a vital component to support the research aims of over 9 NIH-supported projects. The studies involve a variety of protein structure- related research, including the characterization of protein-protein and protein-ligand interactions, the identification of biomarkers for disease detection and prognosis, and also the determination of drug biodistribution in tissue. The research will impact a range of human health issues, including neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS), bacterial infectious diseases, radiation sensitivity, and cancer. Ion mobility measurements provide an additional dimension of separation and structural information, based on molecular size and shape, not available in a mass spectrum. Coupling IM with MALDI-MS can be especially powerful for MALDI-based tissue imaging for both large and small molecule distribution experiments. Direct tissue profiling and imaging mass spectrometry provide a detailed assessment of the complex molecular pattern and its spatial distribution within a tissue sample. MALDI-based tissue imaging of drug compounds is potentially a rapid method for determining the biodistribution in animal models, and can yield additional information on novel metabolites. Surface induced dissociation will be especially useful for probing the architecture and topology of large protein complexes, and coupling SID with IM will be a powerful tool for structural biology projects. The proposed ion mobility mass spectrometer system will be supported and administered by the UCLA Molecular Instrumentation Center (MIC), a campus-wide, integrated facility formed to enhance the accessibility of existing shared, sophisticated instrumentation facilities to the broader research community at the institution.