High‐field asymmetric waveform ion mobility spectrometry (FAIMS) coupled with high‐resolution electron transfer dissociation mass spectrometry for the analysis of isobaric phosphopeptides

Xuan, Yue; Creese, Andrew J.; Horner, Julie A.; Cooper, Helen J.

doi:10.1002/rcm.4101

Cited by 76 publications

(136 citation statements)

References 39 publications

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“…In particular, MS/MS can tell apart only two of three or more localization isomers because all fragments of others (with either collision-induced or electron capture/transfer dissociation) are isobaric to those from a mixture of the first two. 24,27) Consequently, PTMs are often assigned to a protein region rather than a residue, 28) although variants with PTMs at nearby sites may have different and even opposite activities in vivo.…”

Section: Vol 2 (2013) S0011mentioning

confidence: 99%

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

2013

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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...

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Section: Vol 2 (2013) S0011mentioning

confidence: 99%

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

2013

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“…We must note that orthogonal modes of ion selection (e.g., as realized in ion-mobility MS) separate interferent ions from the analyte ion only before their detection. This process acts after ion formation, and hence it does not prevent the occurrence of ionization-related matrix effects (34 ).…”

Section: Role Of Calibrator Materialsmentioning

confidence: 99%

Pitfalls Associated with the Use of Liquid Chromatography–Tandem Mass Spectrometry in the Clinical Laboratory

2010

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BACKGROUND Novel mass spectrometric techniques such as atmospheric pressure ionization and tandem mass spectrometry have substantially extended the spectrum of clinical chemistry methods during the past decade. In particular, liquid chromatography tandem–mass spectrometry (LC-MS/MS) has become a standard tool in research laboratories as well as in many clinical laboratories. Although LC-MS/MS has features that suggest it has a very high analytical accuracy, potential sources of inaccuracy have recently been identified. CONTENT The sources of inaccuracy in LC-MS/MS methods used in the routine quantification of small molecules are described and discussed. Inaccuracy of LC-MS/MS methods can be related to the process of ionization through the insource transformation of conjugate metabolites or target analytes and may also be attributable to ionization matrix effects that have a differential impact on target analytes and internal-standard compounds. Inaccuracy can also be associated with the process of ion selection, which mainly occurs when compounds from the sample matrix share mass transitions with a target analyte. In individual assays, most potential sources of inaccuracy can be controlled by sufficient LC separation–based sample workup before MS analysis. SUMMARY LC-MS/MS methods should undergo rigorous and systematic validation before introduction into patient care.

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“…However, the analytical resolving powers (defined as the peak arrival time/full width at half height (FWHH)) of the current conventional IM-MS systems are limited to under~70 [9,10]. Often, the IM profiles of various ionic species with similar (or very close) collision cross sections (CCSs) are not completely resolved [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, incorrect AT values obtained from the unresolved IM profiles can result in erroneous CCS calculations. The second challenge with the unresolved IM profiles is associated with the incorrect structural character-ization of the overlapped species using post IM separation fragmentation techniques (e.g., collision-induced dissociation (CID) [17] and electron transfer dissociation (ETD) [12,13]). The gas-phase fragmentation patterns of the mobilityseparated species are often used to identify the unknown species [6, 11-13, 16, 18].…”

Section: Introductionmentioning

confidence: 99%

“…Employing a similar approach to conventional GC/MS peak deconvolution (viz., comparing single ion chromatograms (SIC) across a GC peak), Clemmer et al [11] and Cooper et al [12,13] utilized post-IM fragmentation techniques for deconvolution of mobility-overlapped profiles. Clemmer et al acquired post-IM/CID MS data for mass isolated mobility-overlapped isobaric precursor ions [11] and by inspecting the CID mass spectra across the mobility profiles of the mass isolated precursor ions, fragment ions specific to each species were identified.…”

Section: Introductionmentioning

confidence: 99%

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Chemometric Data Analysis for Deconvolution of Overlapped Ion Mobility Profiles

Zekavat

Solouki

2012

J. Am. Soc. Mass Spectrom.

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We present the details of a data analysis approach for deconvolution of the ion mobility (IM) overlapped or unresolved species. This approach takes advantage of the ion fragmentation variations as a function of the IM arrival time. The data analysis involves the use of an in-house developed data preprocessing platform for the conversion of the original post-IM/collisioninduced dissociation mass spectrometry (post-IM/CID MS) data to a Matlab compatible format for chemometric analysis. We show that principle component analysis (PCA) can be used to examine the post-IM/CID MS profiles for the presence of mobility-overlapped species. Subsequently, using an interactive self-modeling mixture analysis technique, we show how to calculate the total IM spectrum (TIMS) and CID mass spectrum for each component of the IM overlapped mixtures. Moreover, we show that PCA and IM deconvolution techniques provide complementary results to evaluate the validity of the calculated TIMS profiles. We use two binary mixtures with overlapping IM profiles, including (1) a mixture of two non-isobaric peptides (neurotensin (RRPYIL) and a hexapeptide (WHWLQL)), and (2) an isobaric sugar isomer mixture of raffinose and maltotriose, to demonstrate the applicability of the IM deconvolution.

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High‐field asymmetric waveform ion mobility spectrometry (FAIMS) coupled with high‐resolution electron transfer dissociation mass spectrometry for the analysis of isobaric phosphopeptides

Cited by 76 publications

References 39 publications

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

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

Pitfalls Associated with the Use of Liquid Chromatography–Tandem Mass Spectrometry in the Clinical Laboratory

Chemometric Data Analysis for Deconvolution of Overlapped Ion Mobility Profiles

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