Development of an Ion Mobility Spectrometry-Orbitrap Mass Spectrometer Platform

Complex samples benefit from multidimensional measurements where higher resolution enables more complete characterization of biological and environmental systems. To address this challenge, we developed a drift tube-based ion mobility spectrometry-Orbitrap mass spectrometer (IMS-Orbitrap MS) platform. To circumvent the time scale disparity between the fast IMS separation and the much slower Orbitrap MS acquisition, we utilized a dual gate and pseudorandom sequences to multiplex the injection of ions and allow operation in signal averaging (SA), single multiplexing (SM), and double multiplexing (DM) IMS modes to optimize the signal-to-noise ratio of the measurements. For the SM measurements, a previously developed algorithm was used to reconstruct the IMS data. A new algorithm was developed for the DM analyses involving a two-step process that first recovers the SM data and then decodes the SM data. The algorithm also performs multiple refining procedures to minimize demultiplexing artifacts. The new IMS-Orbitrap MS platform was demonstrated by the analysis of proteomic and petroleum samples, where the integration of IMS and high mass resolution proved essential for accurate assignment of molecular formulas.