An Improved Calibration Approach for Traveling Wave Ion Mobility Spectrometry: Robust, High-Precision Collision Cross Sections
An Improved Calibration Approach for Traveling Wave Ion Mobility Spectrometry: Robust, High-Precision Collision Cross Sections
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DOI：
10.1021/acs.analchem.0c04948
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发表时间：
2021-02-23
影响因子：
7.4
通讯作者：
Ruotolo, B. T.
中科院分区：
文献类型：
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作者：
Richardson, K.;Langridge, D.;Ruotolo, B. T.
离子迁移率（IM）分离与质谱（MS）的结合影响了从食品分析到药物发现等领域的全球测量工作。广泛采用IM-MS的原因包括其显著增加的峰值容量，占空比和并行重建碎片数据的能力，所有这些都大大有助于分析复杂混合物。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，以及研究大生物分子的结构。作为IM-MS的第一种商业化形式，行波离子迁移率（TWIM）设备在低压（类似于3毫巴）和电压下操作，相对较短（类似于25厘米），并且在几十毫秒的时间尺度上分离离子。这些品质使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渡越时间必须校准以实现CCS测量。迄今为止，这些校准的适用性主要限于单电荷的小分子和某些类别的大，多电荷的离子在一个显着较窄的范围内的仪器条件。在这里，我们介绍和广泛的特点显着改善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个数量级的分子质量的离子，我们展示了强大的校准范围显着扩大的仪器条件，从而开辟了新的分析应用领域，并使现有和下一代TWIM仪器的高精度CCS测量扩展。
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 (similar to 3 mbar) and voltages, are relatively short (similar to 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.