“…Modular drift-tube systems have recently been developed and coupled to various ion trap and Orbitrap instruments. − One of the first IMS-enabled Orbitrap systems utilized ambient-pressure drift tubes to separate small isomers (<2 kDa), as demonstrated for a series of peptides, saccharides, lipids, and metabolites. , However, the incompatibility of the timescales of the IMS separation (milliseconds) and the Orbitrap mass analysis (tens of milliseconds to seconds) results in a poor duty cycle of <1%, thus wasting more than 99% of ions that are generated using an ESI source. The design of Fourier transform (FT)-based multiplexing strategies, originally implemented on quadrupole ion trap and linear ion trap systems, involves controlled frequency modulation of a dual-gate pulsing scheme of a drift tube, increasing the duty cycle to 25%. ,,− This type of FT multiplexing offers an innovative approach to overcome the duty-cycle mismatch and establishes the framework for the development of FT-IMS-Orbitrap platforms. Advancements have also been made in data collection and processing to improve the throughput, resolution, and sensitivity of FT methods, including the adoption of basis pursuit denoising and absorption-mode FT .…”