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

职业：用于分析分离和结构表征的高分辨率多维非线性离子淌度谱

• 批准号: 1552640
• 负责人: Alexandre Shvartsburg
• 金额: $ 61万
• 依托单位: Wichita State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1552640&HistoricalAwards=false
• 关键词: CAREER; Resolution; Multidimensional; Nonlinear; Ion

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.

化学测量成像计划（与生物研究计划的仪器开发共同资助）的职业生涯奖支持威奇托州立大学的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样品，MS通常在分离步骤之前，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）的更快分离所取代或补充，这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的功能。 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发现中心的IMS展览为中心，并作为K-12推广计划的一部分被带到学校。 该展览模拟IMS分离演示分辨率和灵敏度的关键方面在一个互动的格式。 这项工作是由一个夏季计划的教师从本科院校和社区学院在堪萨斯补充，为他们提供更多的机会，了解MS，IMS，及其应用程序。 将这些知识融入到他们所在机构教授的课程中，可以帮助学生为技术经济做出贡献。最初的IMS方法被设计为使测量的离子速度与施加的电场成线性比例。 场强和速度之间的关系在强场中变得更加复杂，其中离子迁移率随场强而变化，从而实现了称为场不对称波形IMS（FAIMS）的更新技术，该技术通过高场和低场的迁移率之间的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（同位素异构体）的分离。 Shvartsburg博士正在寻求多种方法，通过以全新的方式扩展非线性IMS范式来提高FAIMS的分辨率。 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IMS与偶极子方向的对齐，其中大分子偶极子的摆动锁定允许捕获定向（而不是取向）平均横截面，用于更详细的结构表征。 在降低的温度下实施FAIMS可以将摆动机制扩展到更小的离子（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变形。 组装多维分离，包括线性和非线性IMS阶段是这项工作的核心。 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发展所需的技能和理解。