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Native IM-Orbitrap MS: Resolving what was hidden

Poltash, Michael L., McCabe, Jacob W., Shirzadeh, Mehdi, Laganowsky, Arthur, Russell, David H.
Trends in analytical chemistry 2019
equipment design, protein structure, spectroscopy
Native ion mobility-mass spectrometry (IM-MS) is an emerging biophysical approach to probe the intricate details of protein structure and function. The instrument design enables measurements of accurate first-principle determinations of rotationally-averaged ion-neutral collision cross sections coupled with high-mass, high-resolution mass measurement capabilities of Orbitrap MS. The inherent duty-cycle mismatch between drift tube IM and Orbitrap MS is alleviated by operating the drift tube in a frequency modulated mode while continuously acquiring mass spectra with the Orbitrap MS. Fourier transform of the resulting time-domain signal, i.e., ion abundances as a function of the modulation frequency, yields a frequency domain spectrum that is then converted (s−1 to s) to IM drift time. This multiplexed approach allows for a duty-cycle of 25% compared to <1% for traditional “pulse-and-wait” IM-ToF-MS. Improvements in mobility and mass resolution of the IM-Orbitrap allows for accurate analysis of intact protein complexes and the possibility of capturing protein dynamics.