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

项目摘要 除了浓度外，蛋白质、碳水化合物、代谢物和 核酸是区分健康和疾病状态的基本特征。事实上， 质谱技术的进步，以其无与伦比的选择性、速度和灵敏度， 研究人员对生物学有了新的认识，并提出了关于分子和生物物理学的其他问题。 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， 生物系统中的分子形状和动力学。然而，样品利用率相对较低， 和分离效率阻碍了其在生物分析和临床领域的广泛采用。与 最近，在印刷电路板（PCB）制造领域中广泛可用的技术进步， 这类离子迁移率分离能够在很大程度上克服其前代的缺点。的 无损离子操纵结构（SLIM）框架通过建立动态电 能够将电离分子限制在扩展的时间段沿着内的场， 当代SLIM实验取得了令人印象深刻的结果， 水平的气相离子分离，但只集中在一个维度的分离，由于限制很大程度上 由下面的PCB电极布置和控制电子器件施加。将SLIM平台铸造成 多个分离维度，实现生物相关诊断的新水平，目前的努力 旨在开发和推广一个经济的串联IMS平台， 简化战略。其中包括集成低成本电极开关， SLIM平台内的多功能性和一系列旨在产生高密度离子的离子压缩策略 人口。最重要的是，在质谱分析之前，我们将利用离子的高度压缩特性 通过使这些物质经受高强度紫外光子以诱导分子 破坏并产生关于目标生物系统的更多信息。同时使用激光 辐射和一类新的UV-C发光二极管将与后者提供相当大的 节约成本。第三，本项目的综合目标是解决现有SLIM的工作周期问题 通过完全多路复用串联SLIM-紫外光解离（UVPD）平台，与添加的 IMSn和扩展的多通道SLIM路径的功能，系统的分离能力是 预计代表国家的最先进的。在拟议的研究结论，我们希望实现一个 功能齐全、高效的SLIM-UVPD框架，能够与所有质量分析仪类接口， 准备解决从代谢组学到结构生物学的一系列生物学问题。

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.