Ultra-High-Resolution Ion Mobility Separations Over Extended Path Lengths and Mobility Ranges Achieved using a Multilevel Structures for Lossless Ion Manipulations Module

Abstract

Over the past few years, structures for lossless ion manipulations (SLIM) have used traveling waves (TWs) to move ions over long serpentine paths that can be further lengthened by routing the ions through multiple passages of the same path. Such SLIM “multipass” separations provide unprecedentedly high ion mobility resolving powers but are ultimately limited in their ion mobility range because of the range of mobilities spanned in a single pass; that is, higher mobility ions ultimately “overtake” and “lap” lower mobility ions that have experienced fewer passes, convoluting their arrival time distribution at the detector. To achieve ultrahigh resolution separations over broader mobility ranges, we have developed a new multilevel SLIM possessing multiple stacked serpentine paths. Ions are transferred between SLIM levels through apertures (or ion escalators) in the SLIM surfaces. The initial multilevel SLIM module incorporates four levels and three interlevel ion escalator passages, providing a total path length of 43.2 m. Using the full path length and helium buffer gas, high resolution separations were achieved for Agilent tuning mixture phosphazene ions over a broad mobility range (K 0 ≈ 3.0 to 1.2 cm2/(V*s)). High sensitivity was achieved using “in-SLIM” ion accumulation over an extended trapping region of the first SLIM level. High transmission efficiency of ions over a broad mobility range (e.g., K 0 ≈ 3.0 to 1.67 cm2/(V*s)) was achieved, with transmission efficiency rolling off for the lower mobility ions (e.g., K 0 ≈ 1.2 cm2/(V*s)). Resolving powers of up to ∼560 were achieved using all four ion levels to separate reverse peptides (SDGRG1+ and GRGDS1+). A complex mixture of phosphopeptides showed similar coverage could be achieved using one or all four SLIM levels, and doubly charged phosphosite isomers not significantly separated using one SLIM level were well resolved when four levels were used. The new multilevel SLIM technology thus enables wider mobility range ultrahigh-resolution ion mobility separations and expands on the ability of SLIM to obtain improved separations of complex mixtures with high sensitivity.

Developments in tandem ion mobility mass spectrometry

“…Developed later were structures for lossless ion manipulation (SLIM) [ 42 ], which formed the basis of future tandem IM devices such as the SUPER [ 43 ] and M-SLIM [ 44 ] instruments discussed later. These structures were based on TWIMS, and utilised modified RF amplitudes and DC guarding voltages in order to allow manipulation of the ion packet with almost completely negligible transmission losses.…”

“…One of the limitations of the systems which are able to perform multi-pass analysis (cIM and SUPER-SLIM) is from ‘ roll-over ’, whereby during the multiple passes of the mobility separations, high-mobility ions overtake low-mobility ions, leading to an overlap in data and artefacts. To overcome this, multi-level SLIM [ 42 , 43 ] (M-SLIM) was developed in 2020 where ions can be pushed vertically to different separation levels [ 44 ]. This cleverly circumvents collecting data over a wide mobility range without performing mobility selection (i.e.…”

“…While the instruments developed so far allow for tandem IM experiments it is worth noting that IM can be performed to the nth level, IM N , experiments are also possible with some of the instruments described [ 15 , 43 , 44 , 47 ]. Again in analogy to MS N we expect that such IM N experiments will also allow even further probing of structural ensembles.…”

Analysis of food samples made easy by microextraction technologies directly coupled to mass spectrometry

“…To compensate for the lack of a chromatographic separation step in direct‐to MS technologies, alternative MS technologies can be used. For instance, recent advances in ion mobility could have a huge impact on rapid identification and quantitation of isobars potentially coextracted by the SPME devices 41–43 . Likewise, on‐line derivatization workflows (e.g., on‐coating derivatization 44 ) and tandem MS, as well as any combinations thereof, can be a potential solution when quantifying/identifying structural isomers present in a food sample 45 .…”

“…For instance, recent advances in ion mobility could have a huge impact on rapid identification and quantitation of isobars potentially coextracted by the SPME devices. [41][42][43] Likewise, on-line derivatization workflows (e.g., on-coating derivatization 44 ) and tandem MS, as well as any combinations thereof, can be a potential solution when quantifying/identifying structural isomers present in a food sample. 45 Furthermore, high-resolution MS and, particularly, tandem-high resolution MS, have shown to be particularly useful when screening/multiple compounds with identical nominal masses and similar fragmentation features.…”