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

使用易于管理的串联离子移动技术 无损离子操纵和光解离结构 行政副刊非-GM-21-030 R01GM140129摘要。在质谱学(MS)方面的广泛进展，具有无与伦比的水平 选择性、速度和敏感性，为研究人员提供了新的生物学见解，并促使 关于区分疾病状态但超越MS的分子和生物物理参数的问题 测量。离子迁移率光谱(IMS)是一种气相分离技术，它直接补充了 MS测量并扩展了对生物系统中分子形状和动力学的理解。 利用印刷电路板(PCB)制造领域广泛可用的技术进步，一种新的 实现了一类离子迁移率分离，这在很大程度上缓解了其前身的缺点。这个 无损离子操纵结构(SLIM)框架通过建立动态电学来实现这一目标 能够长时间限制电离分子的电场以及一种有效地 在分析之前对不同的类别进行细分，使用MS将超薄平台分成多个分离 ，并达到生物相关诊断的新水平，目前的努力旨在开发和 传播整合了一系列创新、简化策略的经济型串联IMS平台。 最重要的是，在MS分析之前，我们将利用内部离子束的高度压缩特性 通过使这些物种受到高强度紫外线(UV)光子诱导分子分裂而变得苗条 并产生关于目标生物系统的更多信息。具有Tandem IMS的附加功能 实验表明，该系统的分选能力有望代表最先进的水平。在结束时 在拟议的研究中，我们希望实现全功能、高效率的薄紫外光解离 能够与所有质量分析器类接口并准备好解决一组生物学问题的框架 从代谢组学到结构生物学。 行政补充请求。以完全适应由 超薄的平台和最高的实验精度，一台配备了 需要模拟数据转换(ADC)系统。除了加快每一次超薄实验的速度外， 这一工具性的进步有望促进超薄紫外光技术迅速融入更大的 生物分析运动。所请求的TOF-MS及其相关数据采集系统直接寻址 项目中使用的现有质量分析仪的核心局限性，并将促进实验工作 目标1、2和3。

Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation Administrative Supplement NOT-GM-21-030 R01GM140129 Summary. 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. Using widely 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 extended periods of time along with a means to efficiently fractionate the different classes prior to analysis using MS. 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. 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 (UV) photons to induce molecular disruption and yield more information regarding the target biological system. With the added functionality of tandem IMS experiment, 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-UV photodissociation framework capable of interfacing to all mass analyzer classes and ready to address a suite of biological problems ranging from metabolomics to structural biology. Administrative Supplement Request. To fully accommodate the high-density ion populations produced by the SLIM platform and maximize experimental accuracy, an ioniTOF 4000 time-of-flight (TOF) MS equipped with an analog data conversion (ADC) system is requested. In addition to enhancing the pace of each SLIM experiment, this instrumental advance promises to promote the rapid incorporation of the SLIM-UV technology into larger bioanalytical campaigns. The requested TOF-MS and its associated data acquisition system directly address the core limitations of the present mass analyzer used in the project and will facilitate experimental efforts supporting Aims 1, 2, and 3.