Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation

使用无损离子操作和光解离结构的易处理串联离子淌度技术

• 批准号: 10322113
• 负责人: Brian Clowers
• 金额: $ 29.5万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10322113
• 关键词: Address; Adoption; Biological; Carbohydrates; Characteristics; Charge; Chemicals; Clinical; Communities; Complement; Cost Savings; Coupling; Data; Development; Diagnostic; Diffusion; Dimensions; Discipline; Disease; Dissociation; Electrodes; Electronics; Evaluation; Foundations; Gases; Goals; Health; Intelligence; Ion Channel; Ions; Lasers; Light; Mass Spectrum Analysis; Measurement; Measures; Minor; Modality; Modernization; Molecular; Molecular Conformation; Multidimensional NMR Techniques; Nature; Noise; Nucleic Acids; Outcome; Peptides; Performance; Phase; Photons; Population; Protein Conformation; Proteins; Proteomics; Radial; Research; Research Personnel; Resolution; Role; Sampling; Series; Signal Transduction; Spectrometry; Speed; Structure; System; Techniques; Technology; Time; Transcend; Travel; Variant; biological systems; biophysical properties; comparative; cost; cost effective; data acquisition; density; electric field; experience; experimental study; innovation; insight; instrumentation; ion mobility; irradiation; mass analyzer; metabolomics; molecular dynamics; molecular shape; pressure; printed circuit board; programs; promoter; protein folding; prototype; stereochemistry; structural biology; success; tandem mass spectrometry; tool; transmission process; ultra high resolution; ultraviolet

Project Summary In addition to concentration, the orientation and conformation of proteins, carbohydrates, metabolites, and nucleic acids are essential characteristics differentiating healthy and diseased states. In fact, broadly available advances in mass spectrometry (MS), with unparalleled levels of selectivity, speed, and sensitivity, have armed researchers with new biological insights and prompt additional questions regarding molecular and biophysical parameters that differentiate disease states but transcend MS measurements. Ion mobility spectrometry (IMS) is a gas-phase separation technique that directly complements MS measurements and expands understanding regarding molecular shape and dynamics in biological systems. However, comparatively low sample utilization and separation efficiencies have hindered its broad adoption in the bioanalytical and clinical communities. With recent, broadly available technological advances in the field of printed circuit board (PCB) manufacturing a new class of ion mobility separation is enabled that largely alleviates the drawbacks of its predecessors. The Structures for Lossless Ion Manipulations (SLIM) framework achieves this goal by establishing a dynamic electric field capable of confining ionized molecules for expanded periods of time along with a means to efficiently fractionate the different classes prior to analysis using MS. Contemporary SLIM experiments achieve impressive levels of gas-phase ion separation, but focus only on one dimension of separation due to restrictions largely imposed by the underlying PCB electrode arrangements and control electronics. To cast the SLIM platform into multiple separation dimensions and achieve new levels of biologically relevant diagnostics, the present effort aims to develop and disseminate an economical tandem IMS platform that integrates a series of innovative, simplifying strategies. These include the integration of a low-cost electrode switch that expands the experimental versatility within the SLIM platform and a series of ion compression strategies aimed at creating high-density ion populations. Most importantly, and prior to MS analysis, we will exploit the highly compressed nature of the ion beams within the SLIM by subjecting these species to high intensity ultraviolet photons to induce molecular disruption and yield more information regarding the target biological system. Concurrent efforts using laser irradiation and a new class of UV-C light emitting diodes will be compared with the latter offering considerable cost-savings. The third, composite goal of this project is to address the duty cycle issues of existing SLIM concepts by fully multiplexing the tandem SLIM-ultraviolet photodissociation (UVPD) platform. With the added functionality of IMSn and the extended, multi-channel SLIM paths, the separation power of the system is anticipated to represent the state-of-the-art. At the conclusion of the proposed research we expect to realize a fully functioning, high-efficiency SLIM-UVPD framework capable of interfacing to all mass analyzers classes and ready to address a suite of biological problems ranging from metabolomics to structural biology.

项目概要 除了浓度之外，蛋白质、碳水化合物、代谢物和蛋白质的方向和构象 核酸是区分健康状态和疾病状态的基本特征。事实上，广泛可用 质谱 (MS) 技术的进步，具有无与伦比的选择性、速度和灵敏度， 研究人员获得了新的生物学见解，并提出了有关分子和生物物理的其他问题 区分疾病状态但超越 MS 测量的参数。离子迁移谱 (IMS) 是一种气相分离技术，可直接补充 MS 测量并扩展理解 关于生物系统中的分子形状和动力学。但样本利用率相对较低 分离效率阻碍了其在生物分析和临床领域的广泛采用。和 印刷电路板 (PCB) 制造领域最近广泛应用的技术进步 实现了离子淌度分离的一类，大大减轻了其前身的缺点。这 无损离子操纵结构（SLIM）框架通过建立动态电来实现这一目标 能够在较长时间内限制电离分子的场以及有效地限制电离分子的方法 在使用 MS 进行分析之前对不同类别进行分级。当代 SLIM 实验取得了令人印象深刻的成果 气相离子分离的水平，但由于很大程度上限制，仅关注分离的一个维度 由底层 PCB 电极排列和控制电子设备施加。将SLIM平台铸成 多个分离维度并实现生物学相关诊断的新水平，目前的努力 旨在开发和传播一个经济的串联 IMS 平台，该平台集成了一系列创新、 简化策略。其中包括集成低成本电极开关，扩展了实验范围 SLIM 平台的多功能性和一系列旨在创建高密度离子的离子压缩策略 人口。最重要的是，在 MS 分析之前，我们将利用离子的高度压缩特性 通过将这些物质置于高强度紫外光子下以诱导分子在 SLIM 内产生光束 破坏并产生有关目标生物系统的更多信息。使用激光同时进行 辐照和新型 UV-C 发光二极管将与后者进行比较，提供相当大的 节省成本。该项目的第三个综合目标是解决现有 SLIM 的占空比问题 通过完全复用串联 SLIM-紫外线光解 (UVPD) 平台的概念。随着添加的 IMSn 的功能和扩展的多通道 SLIM 路径，系统的分离能力为 预计代表最先进的技术。在拟议的研究结束时，我们期望实现 功能齐全、高效的 SLIM-UVPD 框架能够连接到所有质量分析仪类别和 准备好解决从代谢组学到结构生物学的一系列生物学问题。