Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, 24 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
Anal Chem. 2021 May 4;93(17):6638-6645. doi: 10.1021/acs.analchem.0c04889. Epub 2021 Apr 23.
Modifiers provide fast and reliable tuning of separation in differential mobility spectrometry (DMS). DMS selectivity for separating isomeric molecules depends on the clustering modifier concentration, which is typically 1.5-3 mol % ratio of isopropanol or ethanol in nitrogen. Low concentrations (0.1%) of isopropanol were found to improve resolution and sensitivity but at the cost of practicality and robustness. Replacing the single-channel DMS pump with a binary high-performance liquid chromatography (HPLC) pump enabled the generation of modifier mixtures at a constant flow rate using an isocratic or gradient mode, and the analytical benefits of the system were investigated considering cyclohexane, -hexane, or -octane as nonclustering modifiers and isopropanol or ethanol as clustering modifiers. It was found that clustering and nonclustering modifier mixtures enable optimization of selectivity, resolution, and sensitivity for different positional isomers and diastereoisomers. Data further suggested different ion separation mechanisms depending on the modifier ratios. For 85 analytes, the absolute difference in compensation voltages (CoVs) between pure nitrogen and cyclohexane at 1.5 mol % ratio was below 4 V, demonstrating its potential as a nonclustering modifier. Cyclohexane's nonclustering behavior was further supported by molecular modeling using density functional theory (DFT) and calculated cluster binding energies, showing positive Δ values. The ability to control analyte CoVs by adjusting modifier concentrations in isocratic and gradient modes is beneficial for optimizing multidimensional LCxDMS-MS. It is fast and effective for manipulating the DMS scanning window size to realize shorter mass spectrometry (MS) acquisition cycle times while maintaining a sufficient number of CoV steps and without compromising DMS separation performance.
调节剂可快速可靠地调节差分迁移率谱（DMS）中的分离度。DMS 对分离异构体分子的选择性取决于聚类调节剂的浓度，通常为氮气中异丙醇或乙醇的 1.5-3 摩尔%比例。研究发现，低浓度（0.1%）的异丙醇可以提高分辨率和灵敏度，但代价是实用性和稳健性降低。用二元高效液相色谱（HPLC）泵代替单通道 DMS 泵，可以在恒流速下使用等度或梯度模式生成调节剂混合物，并考虑环己烷、正己烷或正辛烷作为非聚类调节剂，异丙醇或乙醇作为聚类调节剂，研究了该系统的分析优势。结果表明，聚类和非聚类调节剂混合物可以优化不同位置异构体和非对映异构体的选择性、分辨率和灵敏度。数据进一步表明，根据调节剂比例，存在不同的离子分离机制。对于 85 种分析物，在 1.5 摩尔%比例下，纯氮气和环己烷之间的补偿电压（CoV）绝对差值低于 4V，表明其作为非聚类调节剂的潜力。环己烷的非聚类行为进一步得到了密度泛函理论（DFT）和计算的团簇结合能的分子建模的支持，显示出正值Δ。通过在等度和梯度模式下调整调节剂浓度来控制分析物 CoV 的能力有利于优化多维 LCxDMS-MS。它可快速有效地操作 DMS 扫描窗口大小，在保持足够数量的 CoV 步骤且不影响 DMS 分离性能的情况下，实现更短的质谱（MS）采集循环时间。
