Waters Corporation, Stamford Avenue, Altrincham Road, Wilmslow SK9 4AX, United Kingdom.
Department of Chemistry, University of Michigan, University Ave., Ann Arbor, Michigan 48109, United States.
Anal Chem. 2021 Feb 23;93(7):3542-3550. doi: 10.1021/acs.analchem.0c04948. Epub 2021 Feb 8.
The combination of ion-mobility (IM) separation with mass spectrometry (MS) has impacted global measurement efforts in areas ranging from food analysis to drug discovery. Reasons for the broad adoption of IM-MS include its significantly increased peak capacity, duty-cycle, and ability to reconstruct fragmentation data in parallel, all of which greatly enable the analyses of complex mixtures. More fundamentally, however, measurements of ion-gas molecule collision cross sections (CCSs) are used to support compound identification and quantitation efforts as well as study the structures of large biomolecules. As the first commercialized form of IM-MS, Traveling Wave Ion Mobility (TWIM) devices are operated at low pressures (∼3 mbar) and voltages, are relatively short (∼25 cm), and separate ions on a timescale of tens of milliseconds. These qualities make TWIM ideally suited for hybridization with MS. Owing to the complicated motion of ions in TWIM devices, however, IM transit times must be calibrated to enable CCS measurements. Applicability of these calibrations has hitherto been restricted to primarily singly charged small molecules and some classes of large, multiply charged ions under a significantly narrower range of instrument conditions. Here, we introduce and extensively characterize a dramatically improved TWIM calibration methodology. Using over 2500 experimental TWIM data sets, covering ions that span over 3.5 orders of magnitude of molecular mass, we demonstrate robust calibrations for a significantly expanded range of instrument conditions, thereby opening up new analytical application areas and enabling the expansion of high-precision CCS measurements for both existing and next-generation TWIM instrumentation.
离子淌度（IM）分离与质谱（MS）的结合已经影响了从食品分析到药物发现等各个领域的全球测量工作。IM-MS 被广泛采用的原因包括其显著增加的峰容量、工作周期以及并行重构碎片化数据的能力，所有这些都极大地促进了复杂混合物的分析。然而，更根本的是，离子-气体分子碰撞截面（CCS）的测量用于支持化合物的鉴定和定量工作，以及研究大分子的结构。作为商业化的第一形式的 IM-MS，行波离子淌度（TWIM）设备在低压力（约 3 mbar）和电压下运行，相对较短（约 25 厘米），并在数十毫秒的时间尺度上分离离子。这些特性使 TWIM 非常适合与 MS 杂交。然而，由于 TWIM 设备中离子的复杂运动，IM 传输时间必须进行校准以实现 CCS 测量。这些校准的适用性迄今为止仅限于主要带一个电荷的小分子和一些带多个电荷的大、多电荷离子，并且在仪器条件的明显更窄的范围内。在这里，我们介绍并广泛描述了一种显著改进的 TWIM 校准方法。使用超过 2500 个实验 TWIM 数据集，涵盖跨越超过 3.5 个数量级分子量的离子，我们展示了对显著扩展的仪器条件范围的稳健校准，从而开辟了新的分析应用领域，并为现有和下一代 TWIM 仪器扩展高精度 CCS 测量。
