CAREER: High-Resolution Multidimensional Nonlinear Ion Mobility Spectrometry for Analytical Separations and Structural Characterization

该职业奖来自化学测量与成像项目（与生物研究仪器开发项目共同资助），支持威奇托州立大学Alexandre Shvartsburg教授开发生物材料表征新技术的努力。质谱（MS）是一种用于鉴定和表征生物和环境样品的技术。为了能够应用于复杂的样品，质谱之前通常有一个分离步骤，通常采用基于溶液的液相色谱或电泳方法。这些方法越来越多地被基于气相离子迁移谱法（IMS）的更快的分离所取代或补充，IMS可以提供对离子结构元素的额外见解。Shvartsburg博士和他的团队正在基于全新的测量概念推进IMS的能力。这项研究与一项教育计划相结合，该计划以威奇托探索中心和全国其他科学博物馆和探索中心的IMS展览为中心，并作为K-12外展计划的一部分带到学校。该展览模拟了IMS分离，以交互式格式演示了分辨率和灵敏度的关键方面。这项工作还得到了堪萨斯州本科院校和社区学院教师暑期项目的补充，为他们提供了更多了解MS、IMS及其应用的机会。将这些知识纳入本国院校的课程中，可能有助于学生为以技术为基础的经济做出贡献。最初的IMS方法被设计为测量离子速度与外加电场成线性比例。在强场中，场强和速度之间的关系变得更加复杂，离子的迁移率随场强而变化，从而实现了一种名为场不对称波形IMS （FAIMS）的新技术，该技术根据高场和低场的迁移率差异对离子进行分类。FAIMS能够提供非常精细的分离，在有利的情况下，扩展到同位素异构体的分离。Shvartsburg博士正在寻求多种方法，通过从根本上新颖的方式扩展非线性IMS范式来提高FAIMS的分辨力。一种方法是采用更复杂的非对称波形来实现独特的分离的高阶差分IMS。另一种是偶极子方向对准的IMS，其中大分子偶极子的钟摆锁定允许捕获方向（而不是方向）平均横截面，以获得更详细的结构表征。在较低温度下实施FAIMS可以将摆动状态扩展到更小的离子（包括基本上所有的肽），并避免将离子加热到室温以上，这可能导致高场IMS系统中的解离或结构扭曲。由线性和非线性IMS阶段组成的多维分离的组装是这项工作的核心。通过设计和分享与这些复杂概念相关的教学工具，Shvartsburg博士不仅提高了我们的表征能力，而且还帮助学生掌握了推进技术状态所需的技能和理解。

This CAREER award from the Chemical Measurement & Imaging Program (with co-funding from the Instrument Development for Biological Research Program) supports the efforts of Professor Alexandre Shvartsburg at Wichita State University to develop new technologies for the characterization of biomaterials. Mass spectrometry (MS) is a technique used to identification and characterization biological and environmental samples. To enable application to complex samples, MS is usually preceded by a separation step, typically employing solution-based methods of liquid chromatography or electrophoresis. These methods are increasingly being replaced or complemented by much faster separations based on gas-phase ion mobility spectrometry (IMS), which can provide additional insight into elements of ion structure. Dr. Shvartsburg and his group are advancing the capabilities of IMS based on fundamentally new measurement concepts. The research is integrated with an educational program centered on an IMS exhibit in the Wichita Exploration Place and other science museums and discovery centers nationwide, and taken to schools as part of a K-12 outreach program. The exhibit emulates IMS separations demonstrating the key aspects of resolution and sensitivity in an interactive format. This effort is complemented by a summer program for faculty from undergraduate institutions and community colleges in Kansas, providing them with opportunities to learn more about MS, IMS, and their applications. Incorporation of this knowledge into courses taught at their home institutions may help prepare students to contribute to a technology-based economy.Initial IMS methods were designed such that measured ion velocities are linearly proportional to the applied electric field. The relationship between field strength and velocity becomes more complex in strong fields, where ion mobility varies with field strength, enabling a newer technique called field asymmetric waveform IMS (FAIMS) that sorts ions by the difference between mobilities at high and low fields. FAIMS is capable of providing exceptionally fine separations, extending, in favorable cases, to separations of isotopic isomers (isotopomers). Dr. Shvartsburg is pursuing multiple approaches to advancing the resolving power of FAIMS by expanding the nonlinear IMS paradigm in fundamentally novel ways. One approach is higher-order differential IMS employing more complex asymmetric waveforms to achieve unique separations. Another is IMS with alignment of dipole direction, where the pendular locking of macromolecular dipoles permits capturing the directionally (rather than orientationally) averaged cross sections for more detailed structural characterization. Implementation of FAIMS at reduced temperatures may extend the pendular regime to smaller ions (including essentially all peptides) and avoid heating ions above room temperature, which can cause dissociation or structural distortion in high-field IMS systems. Assembly of multidimensional separations comprising linear and nonlinear IMS stages is central to this work. By devising and sharing teaching tools related to these sophisticated concepts, Dr. Shvartsburg is not only advancing our characterization capabilities, but also helping prepare students with the skills and understanding needed to advance the state of technology.