Ultrahigh-Resolution Differential Ion Mobility Spectrometry Using Extended Separation Times

摘要

Ion mobility spectrometry (IMS), and particularly differentialnIMS or field asymmetric waveform IMS (FAIMS), is emerg-ning as a versatile tool for separation and identification of gas-nphase ions, especially in conjunction with mass spectrom-netry. For over two decades since its inception, the utility ofnFAIMS was constrained by resolving power (R) of less thann∼20. Stronger electric fields and optimized gas mixturesnhave recently raised achievable R to ∼200, but furthernprogress with such approaches is impeded by electricalnbreakdown. However, the resolving power of planar FAIMSndevices using any gas and field intensity scales as the squarenroot of separation time (t). Here, we extended t from thenprevious maximum of 0.2 s up to 4-fold by reducing thencarrier gas flow and increased the resolving power by up ton2-fold as predicted, to 300 for multiply charged peptides.nThe resulting resolution gain has enabled separation ofnpreviously “co-eluting” peptide isomers, including foldingnconformers and localization variants of modified peptides.nMore broadly, a peak capacity of ∼200 has been reachednin tryptic digest separations.