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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 poorly compatible with online liquid-phase separations. Here, we report FAIMS employing hydrogen, specifically in mixtures with N(2) containing up to 90% H(2). 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 H(2) fractions above ~50%. Higher resolution can be exchanged for acceleration of the analyses by up to ~4 times. 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 H(2) should consistently improve resolution for all analytes.

Accelerated High-Resolution Differential Ion Mobility Separations Using Hydrogen