A Cyclic Ion Mobility-Mass Spectrometry System

Giles, Kevin; Ujma, Jakub; Wildgoose, Jason; Pringle, Steven D.; Richardson, Keith; Langridge, David; Green, Martin R.

doi:10.1021/acs.analchem.9b01838

Cited by 388 publications

(589 citation statements)

References 62 publications

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“…The relationship between resolving power and path length was further explored to determine the conditions necessary to separate the partially resolved Cm and m 3 C components. After submitting the methyl‐cytidine mixture to 10 passes in the cIM separator (Figure j), the fully resolved m 5 C and m 4 C species were ejected from the device to prevent possible “wrap‐around” effects produced by faster ion populations overtaking slower ones that completed fewer passes . In contrast, the remaining Cm and m 3 C were submitted to additional passes under exactly the same experimental conditions (Figure ).…”

Section: Resultssupporting

confidence: 39%

“…This treatment revealed that single‐pass cIM analysis could already improve resolving power by an average ~20% over linear TW device. The corresponding R values obtained after two and three passes are close to the expected square root relationship between R and path length . Interestingly, plots of rCCS versus arrival time reveal systematic deviations from the expected power law model.…”

Section: Resultsmentioning

confidence: 70%

“…In fact, the number of ions reaching the detector can be potentially affected by putative factors, such as overall ion transmission and fragmentation, which are expected to exacerbate as a function of path length. Prior work has demonstrated that these types of experiments tend to afford a modest 2% loss of ion current per pass . In our experiments, no signs of fragmentation events were detected during methyl‐cytidine analysis.…”

Section: Resultsmentioning

confidence: 81%

“…At the same time, the mutual spacing between t D s was also considerably wider, which attested to the greater resolving power afforded by the cIM experiment even after a single pass. This observation was ascribed to the fact that this device possessed a significantly longer separation path than that of the linear TW (ie, 98 cm vs 25.4 cm) …”

Section: Resultsmentioning

confidence: 99%

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High‐resolution ion mobility spectrometry‐mass spectrometry of isomeric/isobaric ribonucleotide variants

et al. 2020

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In this report, we explored the benefits of cyclic ion mobility (cIM) mass spectrometry in the analysis of isomeric post‐transcriptional modifications of RNA. Standard methyl‐cytidine samples were initially utilized to test the ability to correctly distinguish different structures sharing the same elemental composition and thus molecular mass. Analyzed individually, the analytes displayed characteristic arrival times (tD) determined by the different positions of the modifying methyl groups onto the common cytidine scaffold. Analyzed in mixture, the widths of the respective signals resulted in significant overlap that initially prevented their resolution on the tD scale. The separation of the four isomers was achieved by increasing the number of passes through the cIM device, which enabled to fully differentiate the characteristic ion mobility behaviors associated with very subtle structural variations. The placement of the cIM device between the mass‐selective quadrupole and the time‐of‐flight analyzer allowed us to perform gas‐phase activation of each of these ion populations, which had been first isolated according to a common mass‐to‐charge ratio and then separated on the basis of different ion mobility behaviors. The observed fragmentation patterns confirmed the structures of the various isomers thus substantiating the benefits of complementing unique tD information with specific fragmentation data to reach more stringent analyte identification. These capabilities were further tested by analyzing natural mono‐nucleotide mixtures obtained by exonuclease digestion of total RNA extracts. In particular, the combination of cIM separation and post‐mobility dissociation allowed us to establish the composition of methyl‐cytidine and methyl‐adenine components present in the entire transcriptome of HeLa cells. For this reason, we expect that this technique will benefit not only epitranscriptomic studies requiring the determination of identity and expression levels of RNA modifications, but also metabolomics investigations involving the analysis of natural extracts that may possibly contain subsets of isomeric/isobaric species.

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Section: Resultssupporting

confidence: 39%

Section: Resultsmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

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High‐resolution ion mobility spectrometry‐mass spectrometry of isomeric/isobaric ribonucleotide variants

et al. 2020

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“…These larger R p values better-reflect the analytical selectivity of TWIMS, with a corresponding low percent error predicted by eqn 5. Conversion to CCS-based R p is also necessary for the recently developed cyclic TWIMS 4,47 (Point L) which indicates that this device operates with a resolving power of ca. 480 for 50 cycles (c.f., Table S1).…”

Section: Resultsmentioning

confidence: 99%

Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry

2017

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Here we examine the relationship between resolving power (Rp), resolution (Rpp), and collision cross section (CCS) for compounds analyzed in previous ion mobility (IM) experiments representing a wide variety of instrument platforms and IM techniques. Our previous work indicated these three variables effectively describe and predict separation efficiency for drift tube ion mobility spectrometry (DTIMS) experiments. In this work we seek to determine if our previous findings are a general reflection of IM behavior applicable to various instrument platforms and mobility techniques. Results suggest IM distributions are well characterized by a Gaussian model and separation efficiency can be predicted based on empirical difference in the gas-phase CCS and a CCS-based resolving power definition (CCS/ΔCCS). Notably traveling wave (TWIMS) was found to operate at substantially higher resolutions than a single-peak resolving power suggested. When a CCS-based Rp definition was utilized, TWIMS was found to operate at a resolving power of between 40 and 50, confirming the previous observations by Giles and coworkers. After converting the separation axis (and corresponding resolving power) to cross section space it is possible to effectively predict separation behavior for all mobility techniques evaluated (i.e. uniform field, trapped ion mobility, traveling wave, cyclic and overtone instruments) using the equations described in this work. Finally, we are able to establish for the first time that the current state-of-the-art ion mobility separations benchmark at a CCS-based resolving powers above 300 which is sufficient to differentiate analyte ions with CCS differences as small as 0.5%.

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Forty‐Year Evolution of High‐Throughput Mass Spectrometry

Covey

2023

High‐Throughput Mass Spectrometry in Drug Discovery

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A Cyclic Ion Mobility-Mass Spectrometry System

Cited by 388 publications

References 62 publications

High‐resolution ion mobility spectrometry‐mass spectrometry of isomeric/isobaric ribonucleotide variants

High‐resolution ion mobility spectrometry‐mass spectrometry of isomeric/isobaric ribonucleotide variants

Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry

Forty‐Year Evolution of High‐Throughput Mass Spectrometry

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