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

Abstract

Differential ion mobility spectrometry (FAIMS) separates ions in gases based on the difference between their mobilities in strong and weak electric fields, captured directly employing a periodic waveform with dissimilar profiles in opposite polarities. As that difference is not tightly correlated with the ion size or mass, FAIMS separations are generally quite orthogonal to both conventional IMS (based on the absolute ion mobility that reflects the physical ion size) and mass spectrometry (based on mass). Until a few years ago, that advantage was largely offset by poor FAIMS resolving power (∼10-20), an order of magnitude below that achieved with conventional (drift-tube) IMS. This article summarizes the major recent technical developments that have raised FAIMS resolving power up to ∼500. These include use of higher and more stable voltages provided by new waveform generators, novel buffer gas compositions comprising high helium or hydrogen fractions, and extended filtering times up to ∼1 s. These advances have enabled previously unthinkable analyses such as broad baseline separations of peptide sequence inversions, localization variants (post-translationally modified peptides with differing PTM attachment sites) even for the larger "middle-down" peptides and smallest PTMs, and lipid regioisomers.Keywords: ion mobility spectrometry, differential IMS, FAIMS, proteomics, post-translational modifications, lipidomics (Received November 19, 2012; Accepted January 21, 2013) Fast gas-phase separations using ion mobility spectrometry (IMS) prior to mass spectrometry (MS) are becoming ubiquitous, moving beyond research laboratories to practical everyday analyses thanks to the recent introduction of IMS/MS systems by major vendors including Waters (Synapt), 1) AB Sciex (Selexion), 2) and Thermo Scientific.3) While the IMS peak capacity in present commercial platforms is short of the need for most complex samples, it allows drastically reducing the separation power required of upfront condensed-phase stages such as liquid chromatography (LC) and thus raising the throughput and/or dynamic range of analyses. 4)As the single-step drift-tube (DT) IMS technology developed since 1960s becomes routine, 5) research and instrumentation development are moving to novel approaches beyond simple separations by low-field ion mobility. Sciences studying perturbations in media (such as optics, acoustics, and fluid dynamics) have at some point shifted from the linear to nonlinear paradigm, where a perturbation propagates depending on its magnitude and driving force. 6) While the technology within linear description remains industrially important (for example, eyewear and architectural glass for optics), frontline research has moved to nonlinear phenomena. IMS is undergoing that transition now with the rise of differential or field asymmetric waveform IMS (FAIMS) based on the evolution of mobility (K) as a function of electric field intensity E, rather than the absolute K in conventional IMS. 7) We expect that process to continue as the...

Mass spectrometric methods to analyze the structural organization of macromolecular complexes

“…Absolute collision cross-sections can be obtained directly by measuring ion drift time. In TWIG [84] and FAIMS [85][86][87] MS, the voltage and time relationship is nonlinear, thus ion drift time does not directly correlate to the collision cross-sections. Calibrants, with their collision cross-sections obtained by LDT IMS-MS, are required to relate the drift time values to collision cross-sections.…”

Advances in Mass Spectrometric Tools for Probing Neuropeptides

“…Other ion mobility separation modes exist. For example, differential, or field-asymmetrical, ion mobility spectrometry separates ions by measuring their mobilityintime-varyingelectricfields(51,54). The creation of dimers or molecular complexes also causes mobility differences.…”

Advances in ion mobility-mass spectrometry instrumentation and techniques for characterizing structural heterogeneity

“…[or differential mobility spectrometry (DMS)], 14 this technique is not discussed here as the purpose of this review is to describe techniques for which collision cross sections can be determined to provide a description of structural heterogeneity.…”