Department of Chemistry and Biochemistry and ‡Biomolecular Sciences Institute, Florida International University , Miami, Florida 33199, United States.
Anal Chem. 2016 Jul 19;88(14):7404-12. doi: 10.1021/acs.analchem.6b01946. Epub 2016 Jul 6.
In the present paper, we describe the fundamentals and analytical advantages of Oversampling Selective Accumulation Trapped Ion Mobility Spectrometry (OSA-TIMS) when coupled to ultrahigh resolution mass analyzers (e.g., FT-ICR MS). During TIMS analysis, ion packages are spatially resolved based on their mobilities along the TIMS analyzer axis and multiple strategies can be utilized during the trapping and elution of the ion population of interest. In the case of OSA-TIMS-FT-ICR MS, the TIMS operation sequence, trapping conditions, and operations are optimized to increase the signal-to-noise and the number of points across the mobility domain, which leads to more accurate mobility and mass measurements. Experimental results show that accurate ion-neutral collision cross sections (<1%) can be measured using OSA-TIMS-FT-ICR MS with high mobility resolving powers (RIMS up to 250), high mass accuracy (<1 ppm), and ultrahigh mass resolution (RMS up to 600-1200k at m/z 400) in a single analysis. The analytical advantages of OSA-TIMS over SA-TIMS were illustrated for the analysis of structural peptide isomers (SDGRG and GRGDS M + H), conformational isomers (AT-hook peptide 3 KRGRGRPRK M + 2H), and a complex mixture of polyaromatic hydrocarbons (PAH) from coal tar. Baseline separation of the structural peptide isomers SDGRG and GRGDS, M + H, was observed, and three conformations were identified for the AT-hook peptide 3 KRGRGRPRK M + 2H during OSA-TIMS-FT-ICR MS. A 2-fold increase in the number of molecular features and a 2-6-fold signal-to-noise increase was observed for OSA-TIMS when compared with SA-TIMS during the PAH analysis. This work provides the proof-of-principle for further application of OSA-TIMS-FT-ICR MS for the unsupervised analysis of complex mixtures based on the characterization of the conformational space and the assignment of chemical formulas in a single analysis.
在本文中，我们描述了过采样选择累积俘获离子迁移谱（OSA-TIMS）与超高分辨率质量分析器（如傅里叶变换离子回旋共振质谱仪（FT-ICR MS））联用的基本原理和分析优势。在 TIMS 分析过程中，离子包根据它们在 TIMS 分析器轴上的迁移率沿轴向进行空间分辨，并且可以在感兴趣的离子群体的俘获和洗脱过程中利用多种策略。在 OSA-TIMS-FT-ICR MS 的情况下，TIMS 操作序列、俘获条件和操作被优化，以增加信号噪声比和迁移率域内的点数，从而获得更准确的迁移率和质量测量。实验结果表明，使用 OSA-TIMS-FT-ICR MS 可以以高迁移率分辨率（RIMS 高达 250）、高质量精度（<1 ppm）和超高质量分辨率（RMS 高达 600-1200k 在 m/z 400 处）在单次分析中测量准确的离子-中性碰撞截面（<1%）。通过对结构肽异构体（SDGRG 和 GRGDS [M+H](+））、构象异构体（AT 钩肽 3 KRGRGRPRK [M+2H](+2））和煤焦油中复杂的多环芳烃（PAH）混合物的分析，说明了 OSA-TIMS 相对于 SA-TIMS 的分析优势。观察到结构肽异构体 SDGRG 和 GRGDS，[M+H](+）的基线分离，并在 OSA-TIMS-FT-ICR MS 期间鉴定了 AT 钩肽 3 KRGRGRPRK [M+2H](+2）的三种构象。与 SA-TIMS 相比，在 PAH 分析中，OSA-TIMS 的分子特征数量增加了 2 倍，信号噪声增加了 2-6 倍。这项工作为进一步应用 OSA-TIMS-FT-ICR MS 提供了原理证明，用于基于单次分析中构象空间的表征和化学式的分配对复杂混合物进行无监督分析。
