Department of Chemistry, Wichita State University, 1845 Fairmount, Wichita, Kansas 67260, United States.
Anal Chem. 2020 Oct 20;92(20):13855-13863. doi: 10.1021/acs.analchem.0c02551. Epub 2020 Sep 28.
Ion mobility spectrometry (IMS) with mass spectrometry has grown into a powerful approach to simplify complex mixtures, disentangle isomers, and elucidate their geometries. Two established branches are linear IMS based on the absolute mobility at moderate normalized electric field / and field asymmetric waveform IMS (FAIMS) relying on the evolution of at high / causing strong ion heating. Here, we introduce low-field differential IMS (LODIMS), where the field is too weak for significant heating but suffices to lock the permanent macromolecular ion dipoles, producing novel separations based solely on their alignment. The method is demonstrated for a prototypical large protein-albumin. Its oligomers start separating at fields of just 1 kV/cm (4 Td), or ∼5% of those typical for FAIMS. Negligible ion heating at such fields allows preserving fragile species, in particular the noncovalent complexes up to pentamers (332 kDa) destroyed in FAIMS and not detected without it. The separation parameter (compensation field, ) in this regime scales with the field linearly versus cubically in FAIMS. The dipole moments obtained from threshold fields for alignment and directional cross sections estimated from the slope of said linear dependence appear reasonable.
离子淌度谱（IMS）与质谱联用已经发展成为一种强大的方法，可以简化复杂混合物、解析异构体并阐明其几何结构。两种成熟的分支是基于中等归一化电场下的绝对淌度的线性 IMS/ 和依赖于高电场下的演变导致强烈离子加热的场不对称波形 IMS（FAIMS）。在这里，我们引入了低场差分 IMS（LODIMS），其中电场太弱，不足以引起明显的加热，但足以锁定永久的大分子离子偶极子，从而仅基于它们的取向产生新的分离。该方法已应用于典型的大蛋白-白蛋白进行了演示。其低聚物仅在 1 kV/cm（4 Td）的场中开始分离，这大约是 FAIMS 典型场的 5%。在如此弱的场中，几乎没有离子加热，可以保留脆弱的物质，特别是非共价复合物，直到五聚体（332 kDa）在 FAIMS 中被破坏，没有它就无法检测到。在该区域，分离参数（补偿场，）与 FAIMS 中线性与立方的场呈线性缩放。从用于对准的阈值场获得的偶极矩和从所述线性 依赖关系的斜率估计的定向横截面看起来是合理的。
