Accelerated High-Resolution Differential Ion Mobility Separations Using Hydrogen

Abstract

The resolving power of differential ion mobility spectrometry (FAIMS) was dramatically increased recently by carrier gases comprising up to 75% He or various vapors, enabling many new applications. However, the need for resolution of complex mixtures is virtually open-ended and many topical analyses demand yet finer separations. Also, the resolving power gains are often at the expense of speed, in particular making high-resolution FAIMS incompatible with online liquid-phase separations. Here, we report FAIMS employing hydrogen, specifically in mixtures with N2 containing up to 90% H2. Such compositions raise the mobilities of all ions and thus the resolving power beyond that previously feasible, while avoiding the electrical breakdown inevitable in He-rich mixtures. The increases in resolving power and ensuing peak resolution are especially significant at H2 fractions above ~50%. Higher resolution can be exchanged for acceleration of the analyses by up to ~4 times, at least. For more mobile species such as multiply-charged peptides, this exchange is presently forced by the constraints of existing FAIMS devices, but future designs optimized for H2 should consistently improve resolution for all analytes.

Pushing the Frontier of High-Definition Ion Mobility Spectrometry Using FAIMS

“…21) As anticipated from simulations, separations in He/N 2 and H 2 /N 2 with equal N 2 fractions are similar, with slightly narrower peaks and thus higher resolution for the latter. 21) The main attraction, however, is stable operation at up to 85% H 2 , with the resolving power for larger 1+ ions improving by up to threefold as absolute compensation voltages or CVs (the FAIMS separation parameter) increase while peaks narrow further (Fig. 2).…”

“…21) As analytical methods mature, the resolution usually becomes limited more by the instrument parameter instabilities than physical factors. For example, the resolving power in modern time-of-flight MS is controlled mostly by the field uniformity, pusher voltage stability, and detector jitter rather than ion-ion Coulomb repulsion or other physical effects.…”

“…A major one is sequence inversions, where two or more residues on the peptide backbone are permuted. These, as exemplified for seven isomers possible for a model nitrated tryptic octapeptide nYAAAAAAK, can be broadly resolved baseline by high-resolution FAIMS 21,25) (Fig. 3).…”

Review on Ion Mobility Spectrometry. Part 2: hyphenated methods and effects of experimental parameters

“…Shvartsburg et al . 133 have used hydrogen as dopant in a planar-FAIMS, obtaining an increase of the resolution up to 180 and exploring new applications as using them in hydrogen-rich media as in exoplanet atmospheres with dominant H 2 fractions (e.g., ∼87 and 96% for Jupiter and Saturn) 134, 135 . Puton et al .…”

Enhancing biological analyses with three dimensional field asymmetric ion mobility, low field drift tube ion mobility and mass spectrometry (μFAIMS/IMS-MS) separations

“…However, its resolving power was much lower than in conventional planar FAIMS due to the limited residence time in the short path length μFAIMS device. Several studies 25–28 have shown that the performance of the μFAIMS can be enhanced when gases comprising helium 29 , hydrogen 30 or modifiers 31 are utilized. Thus, by enhancing the μFAIMS performance, new applications can potentially be extended into complex mixture studies and targeted analyses.…”