Differential Ion Mobility Separations in the Low-Pressure Regime

Ion mobility spectrometry (IMS) in conjunction with mass spectrometry (MS) has emerged as a powerful platform for biological and environmental analyses. An inherent advantage of differential or field asymmetric waveform IMS (FAIMS) based on the derivative of mobility vs electric field over linear IMS based on absolute mobility is much greater orthogonality to MS. Effective coupling of linear IMS to MS and diverse IMS/MS arrangements and modalities impossible at ambient buffer gas pressure were enabled at much reduced pressures. In contrast, FAIMS devices operate at or near atmospheric pressure, which complicated integration with MS. Here, we show FAIMS at ∼15-30 Torr using a planar-gap stage within the MS instrument envelope. Fields up to ∼300 Td permitted by the Paschen law at these pressures greatly raise the separation speed, providing fair resolution in ∼10 ms and FAIMS scans in under 5 s. Rapid separation and efficient ion collection at low pressure minimize losses in the FAIMS step. Separations for key analyte classes and their dependences on electric field mirror those at ambient pressure. The potential for proteomics is demonstrated by separations of isomeric peptides with variant localization of post-translational modifications.