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Sample records for mobility spectrometry faims

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

    PubMed Central

    A. Shvartsburg, Alexandre; A. Anderson, Gordon; D. Smith, Richard

    2013-01-01

    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. PMID:24349930

  2. Peak deconvolution in high-field asymmetric waveform ion mobility spectrometry (FAIMS) to characterize macromolecular conformations

    NASA Astrophysics Data System (ADS)

    Robinson, Errol W.; Sellon, Rachel E.; Williams, Evan R.

    2007-01-01

    Protonated poly(ethylene glycol), produced by electrospray ionization (ESI), with molecular weights ranging from 0.3 to 5 kDa and charge states from 1+ to 7+ were characterized using high-field asymmetric waveform ion mobility spectrometry (FAIMS). Results for all but some of the 3+ and 4+ charge states are consistent with a single gas-phase conformer or family of unresolved conformers for each of these charge states. The FAIMS compensation voltage scans resulted in peaks that could be accurately fit with a single Gaussian for each peak. The peak widths increase linearly with compensation voltage for maximum ion transmission but do not depend on m/z or molecular weight. Fitting parameters obtained from the poly(ethylene glycol) data were used to analyze conformations of oxidized and reduced lysozyme formed from different solutions. For oxidized lysozyme formed from a buffered aqueous solution, a single conformer (or group of unresolved conformers) was observed for the 7+ and 8+ charge states. Two conformers were observed for the 9+ and 10+ charge states formed from more denaturing solutions. Data for the fully reduced form indicate the existence of up to three different conformers for each charge state produced directly by ESI and a general progression from a more extended to a more folded structure with decreasing charge state. These results are consistent with those obtained previously by proton-transfer reactivity and drift tube ion mobility experiments, although more conformers were identified for the fully reduced form of lysozyme using FAIMS.

  3. Enhancing Biological Analyses with Three Dimensional Field Asymmetric Ion Mobility, Low Field Drift Time Ion Mobility and Mass SpectrometryFAIMS/IMS-MS) Separations

    SciTech Connect

    Zhang, Xing; Ibrahim, Yehia M.; Chen, Tsung-Chi; Kyle, Jennifer E.; Norheim, Randolph V.; Monroe, Matthew E.; Smith, Richard D.; Baker, Erin Shammel

    2015-06-30

    We report the first evaluation of a platform coupling a high speed field asymmetric ion mobility spectrometry microchip (µFAIMS) with drift tube ion mobility and mass spectrometry (IMS-MS). The µFAIMS/IMS-MS platform was used to analyze biological samples and simultaneously acquire multidimensional information of detected features from the measured FAIMS compensation fields and IMS drift times, while also obtaining accurate ion masses. These separations thereby increase the overall separation power, resulting increased information content, and provide more complete characterization of more complex samples. The separation conditions were optimized for sensitivity and resolving power by the selection of gas compositions and pressures in the FAIMS and IMS separation stages. The resulting performance provided three dimensional separations, benefitting both broad complex mixture studies and targeted analyses by e.g. improving isomeric separations and allowing detection of species obscured by “chemical noise” and other interfering peaks.

  4. Enhancement of mass spectrometry performance for proteomic analyses using high-field asymmetric waveform ion mobility spectrometry (FAIMS).

    PubMed

    Bonneil, Eric; Pfammatter, Sibylle; Thibault, Pierre

    2015-11-01

    Remarkable advances in mass spectrometry sensitivity and resolution have been accomplished over the past two decades to enhance the depth and coverage of proteome analyses. As these technological developments expanded the detection capability of mass spectrometers, they also revealed an increasing complexity of low abundance peptides, solvent clusters and sample contaminants that can confound protein identification. Separation techniques that are complementary and can be used in combination with liquid chromatography are often sought to improve mass spectrometry sensitivity for proteomics applications. In this context, high-field asymmetric waveform ion mobility spectrometry (FAIMS), a form of ion mobility that exploits ion separation at low and high electric fields, has shown significant advantages by focusing and separating multiply charged peptide ions from singly charged interferences. This paper examines the analytical benefits of FAIMS in proteomics to separate co-eluting peptide isomers and to enhance peptide detection and quantitative measurements of protein digests via native peptides (label-free) or isotopically labeled peptides from metabolic labeling or chemical tagging experiments. PMID:26505763

  5. LESA FAIMS Mass Spectrometry for the Spatial Profiling of Proteins from Tissue.

    PubMed

    Griffiths, Rian L; Creese, Andrew J; Race, Alan M; Bunch, Josephine; Cooper, Helen J

    2016-07-01

    We have shown previously that coupling of high field asymmetric waveform ion mobility spectrometry (FAIMS), also known as differential ion mobility, with liquid extraction surface analysis (LESA) mass spectrometry of tissue results in significant improvements in the resulting protein mass spectra. Here, we demonstrate LESA FAIMS mass spectrometry imaging of proteins in sections of mouse brain and liver tissue. The results are compared with LESA mass spectrometry images obtained in the absence of FAIMS. The results show that the number of different protein species detected can be significantly increased by incorporating FAIMS into the workflow. A total of 34 proteins were detected by LESA FAIMS mass spectrometry imaging of mouse brain, of which 26 were unique to FAIMS, compared with 15 proteins (7 unique) detected by LESA mass spectrometry imaging. A number of proteins were identified including α-globin, 6.8 kDa mitochondrial proteolipid, macrophage migration inhibitory factor, ubiquitin, β-thymosin 4, and calmodulin. A total of 40 species were detected by LESA FAIMS mass spectrometry imaging of mouse liver, of which 29 were unique to FAIMS, compared with 24 proteins (13 unique) detected by LESA mass spectrometry imaging. The spatial distributions of proteins identified in both LESA mass spectrometry imaging and LESA FAIMS mass spectrometry imaging were in good agreement indicating that FAIMS is a suitable tool for inclusion in mass spectrometry imaging workflows. PMID:27228471

  6. Using the FAIMS Mobile App for field data recording

    NASA Astrophysics Data System (ADS)

    Ballsun-Stanton, Brian; Klump, Jens; Ross, Shawn

    2016-04-01

    Multiple people creating data in the field poses a hard technical problem: our ``web 2.0'' environment presumes constant connectivity, data ``authority'' held by centralised servers, and sees mobile devices as tools for presentation rather than origination. A particular design challenge is the remoteness of the sampling locations, hundreds of kilometres away from network access. The alternative, however, is hand collection with a lengthy, error prone, and expensive digitisation process. This poster will present a field-tested open-source solution to field data recording. This solution, originally created by a community of archaeologists, needed to accommodate diverse recording methodologies. The community could not agree on standard vocabularies, workflows, attributes, or methodologies, but most agreed that at app to ``record data in the field'' was desirable. As a result, the app is generalised for field data collection; not only can it record a range of data types, but it is deeply customisable. The NeCTAR / ARC funded FAIMS Project, therefore, created an app which allows for arbitrary data collection in the field. In order to accomplish this ambitious goal, FAIMS relied heavily on OSS projects including: spatialite and gdal (for GIS support), sqlite (for a lightweight key-attribute-value datastore), Javarosa and Beanshell (for UI and scripting), Ruby, and Linux. Only by standing on the shoulders of giants, FAIMS was able to make a flexible and highly generalisable field data collection system that CSIRO geoscientists were able to customise to suit most of their completely unanticipated needs. While single-task apps (i.e. those commissioned by structural geologists to take strikes and dips) will excel in their domains, other geoscientists (palaeoecologists, palaeontologists, anyone taking samples) likely cannot afford to commission domain- and methodology-specific recording tools for their custom recording needs. FAIMS shows the utility of OSS software

  7. Improving FAIMS Sensitivity Using a Planar Geometry with Slit Interfaces

    PubMed Central

    Mabrouki, Ridha; Kelly, Ryan T.; Prior, David C.; Shvartsburg, Alexandre A.; Tang, Keqi; Smith, Richard D.

    2010-01-01

    Differential mobility spectrometry or field asymmetric waveform ion mobility spectrometry (FAIMS) is gaining broad acceptance for analyses of gas-phase ions, especially in conjunction with largely orthogonal separation methods such as mass spectrometry (MS) and/or conventional (drift tube) ion mobility spectrometry. In FAIMS, ions are filtered while passing through a gap between two electrodes that may have planar or curved (in particular, cylindrical) geometry. Despite substantial inherent advantages of the planar configuration and its near-universal adoption in current stand-alone FAIMS devices, commercial FAIMS/MS systems have employed curved FAIMS geometries that could be interfaced to MS more effectively. Here we report a new planar (p-) FAIMS design with slit-shaped entrance and exit apertures that substantially increase ion transmission in and out of the analyzer. The front slit interface effectively couples p-FAIMS to multi-emitter electrospray ionization (ESI) sources, improving greatly the ion current introduced to the device and allowing liquid flow rates up to ~50 μL/min. The back slit interface increases the transmission of ribbon-shaped ion beams output by the p-FAIMS to downstream stages such as a MS. Overall, the ion signal in ESI/FAIMS/MS analyses increases by over an order of magnitude without affecting FAIMS resolution. PMID:19616967

  8. To What Extent is FAIMS Beneficial in the Analysis of Proteins?

    NASA Astrophysics Data System (ADS)

    Cooper, Helen J.

    2016-04-01

    High field asymmetric waveform ion mobility spectrometry (FAIMS), also known as differential ion mobility spectrometry, is emerging as a tool for biomolecular analysis. In this article, the benefits and limitations of FAIMS for protein analysis are discussed. The principles and mechanisms of FAIMS separation of ions are described, and the differences between FAIMS and conventional ion mobility spectrometry are detailed. Protein analysis is considered from both the top-down (intact proteins) and the bottom-up (proteolytic peptides) perspective. The roles of FAIMS in the analysis of complex mixtures of multiple intact proteins and in the analysis of multiple conformers of a single protein are assessed. Similarly, the application of FAIMS in proteomics and targeted analysis of peptides are considered.

  9. To What Extent is FAIMS Beneficial in the Analysis of Proteins?

    PubMed

    Cooper, Helen J

    2016-04-01

    High field asymmetric waveform ion mobility spectrometry (FAIMS), also known as differential ion mobility spectrometry, is emerging as a tool for biomolecular analysis. In this article, the benefits and limitations of FAIMS for protein analysis are discussed. The principles and mechanisms of FAIMS separation of ions are described, and the differences between FAIMS and conventional ion mobility spectrometry are detailed. Protein analysis is considered from both the top-down (intact proteins) and the bottom-up (proteolytic peptides) perspective. The roles of FAIMS in the analysis of complex mixtures of multiple intact proteins and in the analysis of multiple conformers of a single protein are assessed. Similarly, the application of FAIMS in proteomics and targeted analysis of peptides are considered. Graphical Abstract ᅟ. PMID:26843211

  10. Ion mobility-mass spectrometry.

    PubMed

    Kanu, Abu B; Dwivedi, Prabha; Tam, Maggie; Matz, Laura; Hill, Herbert H

    2008-01-01

    This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided. PMID:18200615

  11. On an Aerodynamic Mechanism to Enhance Ion Transmission and Sensitivity of FAIMS for Nano-Electrospray Ionization-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Prasad, Satendra; Belford, Michael W.; Dunyach, Jean-Jacques; Purves, Randy W.

    2014-12-01

    Simulations show that significant ion losses occur within the commercial electrospray ionization-field asymmetric waveform ion mobility spectrometer (ESI-FAIMS) interface owing to an angular desolvation gas flow and because of the impact of the FAIMS carrier gas onto the inner rf (radio frequency) electrode. The angular desolvation gas flow diverts ions away from the entrance plate orifice while the carrier gas annihilates ions onto the inner rf electrode. A novel ESI-FAIMS interface is described that optimizes FAIMS gas flows resulting in large improvements in transmission. Simulations with the bromochloroacetate anion showed an improvement of ~9-fold to give ~70% overall transmission). Comparable transmission improvements were attained experimentally for six peptides (2+) in the range of m/z 404.2 to 653.4 at a chromatographic flow rate of 300 nL/min. Selected ion chromatograms (SIC) from nano-LC-FAIMS-MS analyses showed 71% (HLVDEPQNLIK, m/z 653.4, 2+) to 95% (LVNELTEFAK, m/z 582.3, 2+) of ion signal compared with ion signal in the SIC from LC-MS analysis. IGSEVYHNLK (580.3, 2+) showed 24% more ion signal compared with LC-MS and is explained by enhanced desolvation in FAIMS. A 3-10 times lower limits of quantitation (LOQ) (<15% RSD) was achieved for chemical noise limited peaks with FAIMS. Peaks limited by ion statistics showed subtle improvement in RSD and yielded comparable LOQ to that attained with nano-LC-MS (without FAIMS). These improvements were obtained using a reduced FAIMS separation gap (from 2.5 to 1.5 mm) that results in a shorter residence time (13.2 ms ± 3.9 ms) and enables the use of a helium free transport gas (100% nitrogen).

  12. Decreased Gap Width in a Cylindrical High-Field Asymmetric Waveform Ion Mobility Spectrometry Device Improves Protein Discovery.

    PubMed

    Swearingen, Kristian E; Winget, Jason M; Hoopmann, Michael R; Kusebauch, Ulrike; Moritz, Robert L

    2015-12-15

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas phase ions according to their characteristic dependence of ion mobility on electric field strength. FAIMS can be implemented as a means of automated gas-phase fractionation in liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments. We modified a commercially available cylindrical FAIMS device by enlarging the inner electrode, thereby narrowing the gap and increasing the effective field strength. This modification provided a nearly 4-fold increase in FAIMS peak capacity over the optimally configured unmodified device. We employed the modified FAIMS device for on-line fractionation in a proteomic analysis of a complex sample and observed major increases in protein discovery. NanoLC-FAIMS-MS/MS of an unfractionated yeast tryptic digest using the modified FAIMS device identified 53% more proteins than were identified using an unmodified FAIMS device and 98% more proteins than were identified with unaided nanoLC-MS/MS. We describe here the development of a nanoLC-FAIMS-MS/MS protocol that provides automated gas-phase fractionation for proteomic analysis of complex protein digests. We compare this protocol against prefractionation of peptides with isoelectric focusing and demonstrate that FAIMS fractionation yields comparable protein recovery while significantly reducing the amount of sample required and eliminating the need for additional sample handling. PMID:26560994

  13. Ion Mobility Spectrometry (IMS) and Mass Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.

    2010-04-20

    In a media of finite viscosity, the Coulomb force of external electric field moves ions with some terminal speed. This dynamics is controlled by “mobility” - a property of the interaction potential between ions and media molecules. This fact has been used to separate and characterize gas-phase ions in various modes of ion mobility spectrometry (IMS) developed since 1970. Commercial IMS devices were introduced in 1980-s for field detection of volatile traces such as explosives and chemical warfare agents. Coupling to soft-ionization sources, mass spectrometry (MS), and chromatographic methods in 1990-s had allowed IMS to handle complex samples, enabling new applications in biological and environmental analyses, nanoscience, and other areas. Since 2003, the introduction of commercial systems by major instrument vendors started bringing the IMS/MS capability to broad user community. The other major development of last decade has been the differential IMS or “field asymmetric waveform IMS” (FAIMS) that employs asymmetric time-dependent electric field to sort ions not by mobility itself, but by the difference between its values in strong and weak electric fields. Coupling of FAIMS to conventional IMS and stacking of conventional IMS stages have enabled two-dimensional separations that dramatically expand the power of ion mobility methods.

  14. Analysis of paralytic shellfish toxins using high-field asymmetric waveform ion mobility spectrometry with liquid chromatography-mass spectrometry.

    PubMed

    Beach, Daniel G; Melanson, Jeremy E; Purves, Randy W

    2015-03-01

    The analysis of paralytic shellfish toxins (PSTs) by liquid chromatography-mass spectrometry remains a challenge because of their high polarity, large number of analogues and the complex matrix in which they occur. Here we investigate the potential utility of high-field asymmetric waveform ion mobility spectrometry (FAIMS) as a gas-phase ion separation tool for analysis of PSTs by mass spectrometry. We investigate the separation of PSTs using FAIMS with two divergent goals: using FAIMS as a primary separation tool for rapid screening by electrospray ionization (ESI)-FAIMS-MS or combined with LC in a multidimensional LC-ESI-FAIMS-MS separation. First, a survey of the parameters that affect the sensitivity and selectivity of PST analysis by FAIMS was carried out using ESI-FAIMS-MS. In particular, the use of acetonitrile as a gas additive in the carrier gas flow offered good separation of all PST epimeric pairs. A second set of FAIMS conditions was also identified, which focussed PSTs to a relatively narrow CV range allowing development of an LC-ESI-FAIMS-MS method for analysis of PST toxins in complex mussel tissue extracts. The quantitative capabilities of this method were evaluated by analysing a PST containing mussel tissue matrix material. Results compared favourably with analysis by an established LC-post-column oxidation-fluorescence method with recoveries ranging from 70 to 106%, although sensitivity was somewhat reduced. The current work represents the first successful separation of PST isomers using ion mobility and shows the promise of FAIMS as a tool for analysis of algal biotoxins in complex samples and outlines some critical requirements for its future improvement. PMID:25619987

  15. Nontarget analysis of urine by electrospray ionization-high field asymmetric waveform ion mobility-tandem mass spectrometry.

    PubMed

    Beach, Daniel G; Gabryelski, Wojciech

    2011-12-01

    Nearly a decade after first commercialization, high field asymmetric waveform ion mobility spectrometry (FAIMS) has yet to find its place in routine chemical analysis. Prototypes have been used to demonstrate the utility of this separation technique combined with mass spectrometry (MS). Unfortunately, first generation commercial FAIMS instruments have gone practically unused by early adopters. Here, we show this to be due to poor ion transmission in the FAIMS-MS source interface. We present simple instrumental modifications and optimization of experimental conditions to achieve good performance from the first generation commercial FAIMS device (the Ionalytics Selectra) coupled to a high resolution Q-TOF-MS. In combination with nanospray ionization, we demonstrate for the first time the nontarget analysis of urine by FAIMS with minimal sample preparation. We show the unique suitability of electrospray ionization (ESI)-FAIMS-MS for identification of low abundance species such as urinary biomarkers of damage of nucleic acids in a complex biological matrix. The elimination of electrospray noise and matrix components by FAIMS and the continuous flow of analytes through FAIMS for accurate and tandem mass analysis produce high quality spectral data suitable for structural identification of unknowns. These characteristics make ESI-FAIMS-MS ideal for nontarget identification, even when compared to high efficiency LC-ESI-MS. PMID:21978137

  16. Online LC-FAIMS-MS/MS for the Analysis of Phosphorylation in Proteins.

    PubMed

    Zhao, Hongyan; Creese, Andrew J; Cooper, Helen J

    2016-01-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a gas-phase separation technique which, when coupled with liquid chromatography tandem mass spectrometry, offers benefits for analysis of complex proteomics samples such as those encountered in phosphoproteomics experiments. Results from LC-FAIMS-MS/MS are typically complementary, in terms of proteome coverage and isomer identification, to those obtained by use of solution-phase separation methods, such as prefractionation with strong cation-exchange chromatography. Here, we describe the protocol for large-scale phosphorylation analysis by LC-FAIMS-MS/MS. PMID:26584930

  17. Optimization of the design and operation of FAIMS analyzers.

    PubMed

    Shvartsburg, Alexandre A; Tang, Keqi; Smith, Richard D

    2005-01-01

    Field asymmetric waveform ion mobility spectrometry (FAIMS) holds significant promise for post-ionization separations in conjunction with mass-spectrometric analyses. However, a limited understanding of fundamentals of FAIMS analyzers has made their design and operation largely an empirical exercise. Recently, we developed an a priori simulation of FAIMS that accounts for both ion diffusion (including anisotropic components) and Coulomb repulsion, and validated it by extensive comparisons with FAIMS/MS data. Here it is corroborated further by FAIMS-only measurements, and applied to explore how key instrumental parameters (analytical gap width and length, waveform frequency and profile, the identity and flow speed of buffer gas) affect FAIMS response. We find that the trade-off between resolution and sensitivity can be managed by varying gap width, RF frequency, and (in certain cases) buffer gas, with equivalent outcome. In particular, the resolving power can be approximately doubled compared to "typical" conditions. Throughput may be increased by either accelerating the gas flow (preferable) or shortening the device, but below certain minimum residence times performance deteriorates. Bisinusoidal and clipped-sinusoidal waveforms have comparable merit, but switching to rectangular waveforms would improve resolution and/or sensitivity. For any waveform profile, the ratio of two between voltages in high and low portions of the cycle produces the best performance. PMID:15653358

  18. Liquid extraction surface analysis field asymmetric waveform ion mobility spectrometry mass spectrometry for the analysis of dried blood spots.

    PubMed

    Griffiths, Rian L; Dexter, Alex; Creese, Andrew J; Cooper, Helen J

    2015-10-21

    Liquid extraction surface analysis (LESA) is a surface sampling technique that allows electrospray mass spectrometry analysis of a wide range of analytes directly from biological substrates. Here, we present LESA mass spectrometry coupled with high field asymmetric waveform ion mobility spectrometry (FAIMS) for the analysis of dried blood spots on filter paper. Incorporation of FAIMS in the workflow enables gas-phase separation of lipid and protein molecular classes, enabling analysis of both haemoglobin and a range of lipids (phosphatidylcholine or phosphatidylethanolamine, and sphingomyelin species) from a single extraction sample. The work has implications for multiplexed clinical assays of multiple analytes. PMID:26198596

  19. Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Arthur, Kayleigh L.; Eiceman, Gary A.; Reynolds, James C.; Creaser, Colin S.

    2016-05-01

    Miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS), combined with mass spectrometry (MS), has been applied to the study of self-assembling, noncovalent supramolecular complexes of 3-methylxanthine (3-MX) in the gas phase. 3-MX forms stable tetrameric complexes around an alkali metal (Na+, K+) or ammonium cation, to generate a diverse array of complexes with single and multiple charge states. Complexes of (3-MX)n observed include: singly charged complexes where n = 1-8 and 12 and doubly charged complexes where n = 12-24. The most intense ions are those associated with multiples of tetrameric units, where n = 4, 8, 12, 16, 20, 24. The effect of dispersion field on the ion intensities of the self-assembled complexes indicates some fragmentation of higher order complexes within the FAIMS electrodes (in-FAIMS dissociation), as well as in-source collision induced dissociation within the mass spectrometer. FAIMS-MS enables charge state separation of supramolecular complexes of 3-MX and is shown to be capable of separating species with overlapping mass-to-charge ratios. FAIMS selected transmission also results in an improvement in signal-to-noise ratio for low intensity complexes and enables the visualization of species undetectable without FAIMS.

  20. Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Arthur, Kayleigh L.; Eiceman, Gary A.; Reynolds, James C.; Creaser, Colin S.

    2016-02-01

    Miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS), combined with mass spectrometry (MS), has been applied to the study of self-assembling, noncovalent supramolecular complexes of 3-methylxanthine (3-MX) in the gas phase. 3-MX forms stable tetrameric complexes around an alkali metal (Na+, K+) or ammonium cation, to generate a diverse array of complexes with single and multiple charge states. Complexes of (3-MX)n observed include: singly charged complexes where n = 1-8 and 12 and doubly charged complexes where n = 12-24. The most intense ions are those associated with multiples of tetrameric units, where n = 4, 8, 12, 16, 20, 24. The effect of dispersion field on the ion intensities of the self-assembled complexes indicates some fragmentation of higher order complexes within the FAIMS electrodes (in-FAIMS dissociation), as well as in-source collision induced dissociation within the mass spectrometer. FAIMS-MS enables charge state separation of supramolecular complexes of 3-MX and is shown to be capable of separating species with overlapping mass-to-charge ratios. FAIMS selected transmission also results in an improvement in signal-to-noise ratio for low intensity complexes and enables the visualization of species undetectable without FAIMS.

  1. Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry.

    PubMed

    Arthur, Kayleigh L; Eiceman, Gary A; Reynolds, James C; Creaser, Colin S

    2016-05-01

    Miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS), combined with mass spectrometry (MS), has been applied to the study of self-assembling, noncovalent supramolecular complexes of 3-methylxanthine (3-MX) in the gas phase. 3-MX forms stable tetrameric complexes around an alkali metal (Na(+), K(+)) or ammonium cation, to generate a diverse array of complexes with single and multiple charge states. Complexes of (3-MX)n observed include: singly charged complexes where n = 1-8 and 12 and doubly charged complexes where n = 12-24. The most intense ions are those associated with multiples of tetrameric units, where n = 4, 8, 12, 16, 20, 24. The effect of dispersion field on the ion intensities of the self-assembled complexes indicates some fragmentation of higher order complexes within the FAIMS electrodes (in-FAIMS dissociation), as well as in-source collision induced dissociation within the mass spectrometer. FAIMS-MS enables charge state separation of supramolecular complexes of 3-MX and is shown to be capable of separating species with overlapping mass-to-charge ratios. FAIMS selected transmission also results in an improvement in signal-to-noise ratio for low intensity complexes and enables the visualization of species undetectable without FAIMS. Graphical Abstract ᅟ. PMID:26914231

  2. Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Shvartsburg, Alexandre A.; Isaac, Giorgis; Leveque, Nathalie; Smith, Richard D.; Metz, Thomas O.

    2011-07-01

    Correlations between the dimensions of a 2-D separation create trend lines that depend on structural or chemical characteristics of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is generally less correlated to MS and thus could separate those domains better. We report the first observation of chemical class separation by trend lines using FAIMS, here for lipids. For lipids, FAIMS is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation are often separated. As expected, resolution improves in He-rich gases: at 70% He, glycerolipid isomers with different fatty acid positions can be resolved. These results open the door for application of FAIMS to lipids, particularly in shotgun lipidomics and targeted analyses of bioactive lipids.

  3. Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry

    PubMed Central

    Shvartsburg, Alexandre A.; Isaac, Giorgis; Leveque, Nathalie; Smith, Richard D.; Metz, Thomas O.

    2011-01-01

    Correlations between the dimensions of a 2-D separation create trend lines that depend on structural or chemical characteristics of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is generally less correlated to MS and thus could separate those domains better. We report the first observation of chemical class separation by trend lines using FAIMS, here for lipids. For lipids, FAIMS is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation are often separated. As expected, resolution improves in He-rich gases: at 70% He, glycerolipid isomers with different fatty acid positions can be resolved. These results open the door for application of FAIMS to lipids, particularly in shotgun lipidomics and targeted analyses of bioactive lipids. PMID:21953096

  4. Simultaneous FRAP, FLIM and FAIM for measurements of protein mobility and interaction in living cells

    PubMed Central

    Levitt, James A.; Morton, Penny E.; Fruhwirth, Gilbert O.; Santis, George; Chung, Pei-Hua; Parsons, Maddy; Suhling, Klaus

    2015-01-01

    We present a novel integrated multimodal fluorescence microscopy technique for simultaneous fluorescence recovery after photobleaching (FRAP), fluorescence lifetime imaging (FLIM) and fluorescence anisotropy imaging (FAIM). This approach captures a series of polarization-resolved fluorescence lifetime images during a FRAP recovery, maximizing the information available from a limited photon budget. We have applied this method to analyse the behaviour of GFP-labelled coxsackievirus and adenovirus receptor (CAR) in living human epithelial cells. Our data reveal that CAR exists in oligomeric states throughout the cell, and that these complexes occur in conjunction with high immobile fractions of the receptor at cell-cell junctions. These findings shed light on previously unknown molecular associations between CAR receptors in intact cells and demonstrate the power of combined FRAP, FLIM and FAIM microscopy as a robust method to analyse complex multi-component dynamics in living cells. PMID:26504635

  5. Probing the Complementarity of FAIMS and Strong Cation Exchange Chromatography in Shotgun Proteomics

    NASA Astrophysics Data System (ADS)

    Creese, Andrew J.; Shimwell, Neil J.; Larkins, Katherine P. B.; Heath, John K.; Cooper, Helen J.

    2013-03-01

    High field asymmetric waveform ion mobility spectrometry (FAIMS), also known as differential ion mobility spectrometry, coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) offers benefits for the analysis of complex proteomics samples. Advantages include increased dynamic range, increased signal-to-noise, and reduced interference from ions of similar m/ z. FAIMS also separates isomers and positional variants. An alternative, and more established, method of reducing sample complexity is prefractionation by use of strong cation exchange chromatography. Here, we have compared SCX-LC-MS/MS with LC-FAIMS-MS/MS for the identification of peptides and proteins from whole cell lysates from the breast carcinoma SUM52 cell line. Two FAIMS approaches are considered: (1) multiple compensation voltages within a single LC-MS/MS analysis (internal stepping) and (2) repeat LC-MS/MS analyses at different and fixed compensation voltages (external stepping). We also consider the consequence of the fragmentation method (electron transfer dissociation or collision-induced dissociation) on the workflow performance. The external stepping approach resulted in a greater number of protein and peptide identifications than the internal stepping approach for both ETD and CID MS/MS, suggesting that this should be the method of choice for FAIMS proteomics experiments. The overlap in protein identifications from the SCX method and the external FAIMS method was ~25 % for both ETD and CID, and for peptides was less than 20 %. The lack of overlap between FAIMS and SCX highlights the complementarity of the two techniques. Charge state analysis of the peptide assignments showed that the FAIMS approach identified a much greater proportion of triply-charged ions.

  6. Control of Ion Distortion in Field Asymmetric Waveform Ion Mobility Spectrometry via Variation of Dispersion Field and Gas Temperature

    PubMed Central

    Robinson, Errol W.; Shvartsburg, Alexandre A.; Tang, Keqi; Smith, Richard D.

    2009-01-01

    Field asymmetric waveform ion mobility spectrometry (FAIMS) has emerged as an analytical tool of broad utility, especially in conjunction with mass spectrometry. Of particular promise is the use of FAIMS and 2-D ion mobility methods that combine FAIMS with conventional IMS to resolve and characterize protein and other macromolecular conformers. However, FAIMS operation requires a strong electric field and ions are inevitably heated by energetic collisions with buffer gas molecules. This may induce ion isomerization or dissociation that distort the separation properties of FAIMS (and subsequent stages) and/or reduce instrumental sensitivity. As FAIMS employs a periodic waveform, whether those processes are controlled by ion temperature at maximum or average field intensity has been debated. Here we address this issue by measuring the unfolding of compact ubiquitin ion geometries as a function of waveform amplitude (dispersion field, ED) and gas temperature, T. The field heating is quantified by matching the dependences of structural transitions on ED and T: increasing ED from 12 to 16 or from 16 to 20 kV/cm is equivalent to heating the (N2) gas by ∼15 – 25 °C. The magnitude of field heating for any ED can be estimated using the two-temperature theory, and raising ED by 4 kV/cm augments heating by ∼15 – 30 °C for maximum and ∼4 – 8 °C for average field in the FAIMS cycle. Hence, isomerization of ions in FAIMS appears to be determined by the excitation at waveform peaks. PMID:18729473

  7. Large-scale analysis of peptide sequence variants: the case for high-field asymmetric waveform ion mobility spectrometry.

    PubMed

    Creese, Andrew J; Smart, Jade; Cooper, Helen J

    2013-05-21

    Large scale analysis of proteins by mass spectrometry is becoming increasingly routine; however, the presence of peptide isomers remains a significant challenge for both identification and quantitation in proteomics. Classes of isomers include sequence inversions, structural isomers, and localization variants. In many cases, liquid chromatography is inadequate for separation of peptide isomers. The resulting tandem mass spectra are composite, containing fragments from multiple precursor ions. The benefits of high-field asymmetric waveform ion mobility spectrometry (FAIMS) for proteomics have been demonstrated by a number of groups, but previously work has focused on extending proteome coverage generally. Here, we present a systematic study of the benefits of FAIMS for a key challenge in proteomics, that of peptide isomers. We have applied FAIMS to the analysis of a phosphopeptide library comprising the sequences GPSGXVpSXAQLX(K/R) and SXPFKXpSPLXFG(K/R), where X = ADEFGLSTVY. The library has defined limits enabling us to make valid conclusions regarding FAIMS performance. The library contains numerous sequence inversions and structural isomers. In addition, there are large numbers of theoretical localization variants, allowing false localization rates to be determined. The FAIMS approach is compared with reversed-phase liquid chromatography and strong cation exchange chromatography. The FAIMS approach identified 35% of the peptide library, whereas LC-MS/MS alone identified 8% and LC-MS/MS with strong cation exchange chromatography prefractionation identified 17.3% of the library. PMID:23646896

  8. Separation of Opiate Isomers Using Electrospray Ionization and Paper Spray Coupled to High-Field Asymmetric Waveform Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Manicke, Nicholas E.; Belford, Michael

    2015-05-01

    One limitation in the growing field of ambient or direct analysis methods is reduced selectivity caused by the elimination of chromatographic separations prior to mass spectrometric analysis. We explored the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS), an ambient pressure ion mobility technique, to separate the closely related opiate isomers of morphine, hydromorphone, and norcodeine. These isomers cannot be distinguished by tandem mass spectrometry. Separation prior to MS analysis is, therefore, required to distinguish these compounds, which are important in clinical chemistry and toxicology. FAIMS was coupled to a triple quadrupole mass spectrometer, and ionization was performed using either a pneumatically assisted heated electrospray ionization source (H-ESI) or paper spray, a direct analysis method that has been applied to the direct analysis of dried blood spots and other complex samples. We found that FAIMS was capable of separating the three opiate structural isomers using both H-ESI and paper spray as the ionization source.

  9. Control of Ion Distortion in Field Asymmetric Waveform Ion Mobility Spectrometry via Variation of Dispersion Field and Gas Temperature

    SciTech Connect

    Robinson, Errol W.; Shvartsburg, Alexandre A.; Tang, Keqi; Smith, Richard D.

    2008-10-01

    Field asymmetric waveform ion mobility spectrometry (FAIMS) has emerged as an analytical tool of broad utility, especially in conjunction with mass spectrometry. Of particular promise is the use of FAIMS and 2-D ion mobility methods that combine it with conventional IMS to resolve and characterize protein and other macromolecular conformers. However, FAIMS operation requires high electric fields and ions are inevitably heated by above-thermal collisions with buffer gas molecules. This may induce ion isomerization and dissociation that distort separation properties determined by FAIMS and subsequent stages and/or reduce instrumental sensitivity. As FAIMS employs a periodic waveform, the ion temperature can be characterized at the maximum or average field intensity (E). Which method is most applicable to temperature sensitive ions, such as protein ions, has been debated. Here we address this issue by measuring the unfolding of compact ubiquitin ion geometries as a function of waveform amplitude (dispersion field, ED) and gas temperature, T. The field heating is quantified by matching the dependences of structural transitions on ED and T. Increasing ED from 12 to 16 or from 16 to 20 kV/cm is equivalent to heating the (N2) gas by ~15 - 25 oC. The magnitude of field heating for any E can be calculated using the two-temperature theory, and raising ED by 4 kV/cm augments heating by ~15 - 30 oC for maximum and ~4 - 8 oC for average E in the FAIMS cycle. Hence, isomerization of ions in FAIMS appears to be governed by the maximum internal temperature at waveform peaks.

  10. A laser-based FAIMS detector for detection of ultra-low concentrations of explosives

    NASA Astrophysics Data System (ADS)

    Akmalov, Artem E.; Chistyakov, Alexander A.; Kotkovskii, Gennadii E.; Sychev, Alexey V.; Tugaenko, Anton V.; Bogdanov, Artem S.; Perederiy, Anatoly N.; Spitsyn, Eugene M.

    2014-06-01

    A non-contact method for analyzing of explosives traces from surfaces was developed. The method is based on the laser desorption of analyzed molecules from the surveyed surfaces followed by the laser ionization of air sample combined with the field asymmetric ion mobility spectrometry (FAIMS). The pulsed radiation of the fourth harmonic of a portable GSGG: Cr3+ :Nd3+ laser (λ = 266 nm) is used. The laser desorption FAIMS analyzer have been developed. The detection limit of the analyzer equals 40 pg for TNT. The results of detection of trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX) and cyclotetramethylenetetranitramine (HMX) are presented. It is shown that laser desorption of nitro-compounds from metals is accompanied by their surface decomposition. A method for detecting and analyzing of small concentrations of explosives in air based on the laser ionization and the FAIMS was developed. The method includes a highly efficient multipass optical scheme of the intracavity fourthharmonic generation of pulsed laser radiation (λ = 266 nm) and the field asymmetric ion mobility (FAIM) spectrometer disposed within a resonator. The ions formation and detection proceed inside a resonant cavity. The laser ion source based on the multi-passage of radiation at λ = 266 nm through the ionization region was elaborated. On the basis of the method the laser FAIMS analyzer has been created. The analyzer provides efficient detection of low concentrations of nitro-compounds in air and shows a detection limit of 10-14 - 10-15 g/cm3 both for RDX and TNT.

  11. Mass spectrometric characterization of a high-field asymmetric waveform ion mobility spectrometer

    NASA Astrophysics Data System (ADS)

    Purves, Randy W.; Guevremont, Roger; Day, Stephen; Pipich, Charles W.; Matyjaszczyk, Matthew S.

    1998-12-01

    Ion mobility spectrometry (IMS) has become an important method for the detection of many compounds because of its high sensitivity and amenability to miniaturization for field-portable monitoring; applications include detection of narcotics, explosives, and chemical warfare agents. High-field asymmetric waveform ion mobility spectrometry (FAIMS) differs from IMS in that the electric fields are applied using a high-frequency periodic asymmetric waveform, rather than a dc voltage. Furthermore, in FAIMS the compounds are separated by the difference in the mobility of ions at high electric field relative to low field, rather than by compound to compound differences in mobility at low electric field (IMS). We report here the first cylindrical-geometry-FAIMS interface with mass spectrometry (FAIMS-MS) and the MS identification of the peaks observed in a FAIMS compensation voltage (CV) spectrum. Using both an electrometer-based-FAIMS (FAIMS-E) and FAIMS-MS, several variables that affect the sensitivity of ion detection were examined for two (polarity reversed) asymmetric waveforms (modes 1 and 2) each of which yields a unique spectrum. An increase in the dispersion voltage (DV) was found to improve the sensitivity and separation observed in the FAIMS CV spectrum. This increase in sensitivity and the unexpected dissimilarity in modes 1 and 2 suggest that atmospheric pressure ion focusing is occurring in the FAIMS analyzer. The sensitivity and peak locations in the CV spectra were affected by temperature, gas flow rates, operating pressure, and analyte concentration.

  12. Separation of a Set of Peptide Sequence Isomers Using Differential Ion Mobility Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.; Creese, Andrew J.; Smith, Richard D.; Cooper, Helen J.

    2011-08-15

    Protein identification in bottom-up proteomics requires disentangling isomers of proteolytic peptides, a major class of which are sequence inversions. Separation of sequence isomers using ion mobility spectrometry (IMS) has been reported, but limited to pairs of species. Here we demonstrate baseline separation of all seven sequences for a tryptic peptide with eight residues using differential IMS or FAIMS. Evaluations of peak capacity of the method indicate that even larger libraries should generally be separated for heavier peptides with higher charge states.

  13. Improvement of phosphoproteome analyses using FAIMS and decision tree fragmentation. application to the insulin signaling pathway in Drosophila melanogaster S2 cells.

    PubMed

    Bridon, Gaëlle; Bonneil, Eric; Muratore-Schroeder, Tara; Caron-Lizotte, Olivier; Thibault, Pierre

    2012-02-01

    This report examines the analytical benefits of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to liquid chromatography mass spectrometry (LC-MS) for phosphoproteomics analyses. The ability of FAIMS to separate multiply charged peptide ions from chemical interferences confers a unique advantage in phosphoproteomics by enhancing the detection of low abundance phosphopeptides. LC-FAIMS-MS experiments performed on TiO(2)-enriched tryptic digests from Drosophila melanogaster provided a 50% increase in phosphopeptide identification compared to conventional LC-MS analysis. Also, FAIMS can be used to select different population of multiply charged phosphopeptide ions prior to their activation with either collision activated dissociation (CAD) or electron transfer dissociation (ETD). Importantly, FAIMS enabled the resolution of coeluting phosphoisomers of different abundances to facilitate their unambiguous identification using conventional database search engines. The benefits of FAIMS in large-scale phosphoproteomics of D. melanogaster are further investigated using label-free quantitation to identify differentially regulated phosphoproteins in response to insulin stimulation. PMID:22059388

  14. Simulation of Ion Motion in FAIMS through Combined Use of SIMION and Modified SDS

    SciTech Connect

    Prasad, Satendra; Tang, Keqi; Manura, David; Papanastasiou, Dimitris; Smith, Richard D.

    2009-11-01

    Over the years, the use of Field Asymmetric Ion Mobility Spectrometry (FAIMS) has grown with applications spanning from explosives detection to separation of complex biological mixtures. Although, the principles of ion separation in FAIMS is understood and comprehensively characterized, little effort has been made in developing commercially available computational tools that can simulate ion motion in FAIMS. Such a tool could be of great value for refining theory, optimizing the performance of the instrument for specific applications, and in modeling the fringe-fields caused by rf decay at the entrance and exit of FAIMS which can significantly affect ion transmission. An algorithm using SIMIONTM as its core structure was developed in this study to realistically compute ion trajectory at different ratios of electric field to buffer gas number density (E/N). The E/N can vary from a few Td to ~80 Td in FAIMS as created by an asymmetric square waveform. The Statistical Diffusion Simulation (SDS) model was further incorporated in the algorithm to simulate the ion diffusion in the FAIMS gap. The algorithm was validated using a FAIMS analyzer model similar to the Sionex Corporation model SVAC in terms of its dimensions and geometry. Hydroxyproline and Leucine ions with similar reduced mobility Ko (2.17 and 2.18 cm2.V-1.s-1, respectively) were used as model ions to test the new algorithm and demonstrate the effects of gas flow and waveform (voltage pulse amplitude and frequency) on peak shape and ion current transmission. Simulation results from three ion types: O2-(H2O)3, (A type), (C3H6O)2H+ (B type), and (C12H24O)2H+ (C type) were then compared with the experimental data (available in the literature). The SIMION-SDS-Field Dependent Mobility Calculation (FDMC) algorithm provided good agreement with experimental measurements of the ion peak position in FAIMS compensation voltage (CV) spectrum, peak width, and the ion transmission over a broad range of E/N.

  15. Pendular proteins in gases and new avenues for characterization of macromolecules by ion mobility spectrometry

    PubMed Central

    Shvartsburg, Alexandre A.; Noskov, Sergei Y.; Purves, Randy W.; Smith, Richard D.

    2009-01-01

    Polar molecules align in electric fields when the dipole energy (proportional to field intensity E × dipole moment p) exceeds the thermal rotational energy. Small molecules have low p and align only at inordinately high E or upon extreme cooling. Many biomacromolecules and ions are strong permanent dipoles that align at E achievable in gases and room temperature. The collision cross-sections of aligned ions with gas molecules generally differ from orientationally averaged quantities, affecting ion mobilities measured in ion mobility spectrometry (IMS). Field asymmetric waveform IMS (FAIMS) separates ions by the difference between mobilities at high and low E and hence can resolve and identify macroion conformers based on the mobility difference between pendular and free rotor states. The exceptional sensitivity of that difference to ion geometry and charge distribution holds the potential for a powerful method for separation and characterization of macromolecular species. Theory predicts that the pendular alignment of ions in gases at any E requires a minimum p that depends on the ion mobility, gas pressure, and temperature. At ambient conditions used in current FAIMS systems, p for realistic ions must exceed ≈300–400 Debye. The dipole moments of proteins statistically increase with increasing mass, and such values are typical above ≈30 kDa. As expected for the dipole-aligned regime, FAIMS analyses of protein ions and complexes of ≈30–130 kDa show an order-of-magnitude expansion of separation space compared with smaller proteins and other ions. PMID:19351899

  16. Pendular Proteins in Gases and New Avenues for Characterization of Macromolecules by Ion Mobility Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.; Noskov, Sergei; Purves, Randy; Smith, Richard D.

    2009-04-21

    Polar molecules align in electric fields when the dipole energy (proportional to field intensity E × dipole moment p) exceeds the thermal rotational energy. Small molecules have low p and align only at inordinately high E or upon extreme cooling. Many biomacromolecules and ions are strong permanent dipoles and may align at E achievable in gases and room temperature. The collision cross sections of aligned ions with gas molecules generally differ from orientationally averaged quantities, affecting ion mobilities measured in ion mobility spectrometry (IMS). Field asymmetric waveform IMS (FAIMS) separates ions by the difference between mobilities at high and low E and hence can resolve and identify macroion conformers based on the mobility difference between pendular and free rotor states. An exceptional sensitivity of that difference to the ion geometry and charge distribution holds the potential for a powerful new method for separation and characterization of macromolecular species. Theory predicts that the pendular alignment of ions in gases at any E requires a minimum p depending on the ion mobility, gas pressure, and temperature. At ambient conditions used in current FAIMS systems, the p for realistic ions must exceed ~300 - 400 Debye. The dipole moments of proteins statistically increase with increasing mass, and such values are typical above ~30 kDa. FAIMS analyses of protein ions and complexes of ~30 - 130 kDa show an order-of-magnitude expansion of separation space compared to smaller proteins and other ions, consistent with expectations for the dipole-aligned regime.

  17. Differential Ion Mobility Separations of Peptides with Resolving Power Exceeding 50

    PubMed Central

    Shvartsburg, Alexandre A.; Tang, Keqi; Smith, Richard D.

    2010-01-01

    Differential ion mobility spectrometry (IMS) or field asymmetric waveform IMS (FAIMS) sorts gas-phase ions by mobility differences with respect to the electric field intensity. A major emerging FAIMS application is the fractionation of proteolytic digests. Using a planar FAIMS unit with helium/nitrogen mixtures, we have increased FAIMS resolving powers for peptide analyses from the prior maximum of ~20 – 30 to ~50 – 70. The resolution improved nearly 3-fold, allowing, in particular, separation of previously unresolved conformers. PMID:19938817

  18. Developing Fieldable Systems for Chemical Sensing Using Field Asymmetric Ion Mobility Spectrometry and Mass Spectrometry

    SciTech Connect

    Kevin Kyle, Stephan Weeks, R. Trainham

    2008-03-01

    Currently, there is an urgent need for field-rugged and field-programmable sensor systems that provide highly selective, universal monitoring of vapors and aerosols at detectable levels from persons or areas involved with illicit chemical/biological/explosives (CBE) production. These devices must be portable, low cost, robust, and provide accurate measurements to avoid both false positive and negative results. Furthermore, the information provided by the devices must be received in a timely manner so that informed decisions can be immediately made and the appropriate actions taken. Two technologies that are unparalleled in their sensitivity, selectivity, and trace-level detection capabilities are field asymmetric ion mobility spectrometry (FAIMS) and mass spectrometry. Here, we will show progress that has been made toward developing fieldable FAIMS systems and mass spectrometers. Working in collaboration with Sionex Corporation, the microDMx detector was equipped with a continuous air sampling system to develop selective methods for the analysis of compounds of interest. A microdiaphragm pump (KNF Neuberger, Inc.) is used to pull in gas-phase analytes directly from the air for separation and detection with the FAIMS system. The FAIMS evaluation platform (SVAC) unit currently measures 9.8-inch x 4.6-inch x 3.2-inch, weighs 3.1 lb, and utilizes a {sup 63}Ni source to ionize incoming compounds. Analytes entering the unit are separated and identified by their characteristic response to the compensation voltage (V{sub c}) at a given rf field strength (V{sub rf}). This response has been observed to be unique for a wide range of substances studied. If additional verification were required or a targeted analyte present in a complex chemical matrix, a FAIMS unit equipped with a fast gas chromatography column has been evaluated. The unit combines the separation capabilities of gas chromatography with the selectivity of FAIMS. It measures 9.5-inch x 5.25-inch x 3.5-inch

  19. High-Field Asymmetric-Waveform Ion Mobility Spectrometry and Electron Detachment Dissociation of Isobaric Mixtures of Glycosaminoglycans

    NASA Astrophysics Data System (ADS)

    Kailemia, Muchena J.; Park, Melvin; Kaplan, Desmond A.; Venot, Andre; Boons, Geert-Jan; Li, Lingyun; Linhardt, Robert J.; Amster, I. Jonathan

    2013-11-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is shown to be capable of resolving isomeric and isobaric glycosaminoglycan negative ions and to have great utility for the analysis of this class of molecules when combined with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tandem mass spectrometry. Electron detachment dissociation (EDD) and other ion activation methods for tandem mass spectrometry can be used to determine the sites of labile sulfate modifications and for assigning the stereochemistry of hexuronic acid residues of glycosaminoglycans (GAGs). However, mixtures with overlapping mass-to-charge values present a challenge, as their precursor species cannot be resolved by a mass analyzer prior to ion activation. FAIMS is shown to resolve two types of mass-to-charge overlaps. A mixture of chondroitin sulfate A (CSA) oligomers with 4-10 saccharides units produces ions of a single mass-to-charge by electrospray ionization, as the charge state increases in direct proportion to the degree of polymerization for these sulfated carbohydrates. FAIMS is shown to resolve the overlapping charge. A more challenging type of mass-to-charge overlap occurs for mixtures of diastereomers. FAIMS is shown to separate two sets of epimeric GAG tetramers. For the epimer pairs, the complexity of the separation is reduced when the reducing end is alkylated, suggesting that anomers are also resolved by FAIMS. The resolved components were activated by EDD and the fragment ions were analyzed by FTICR-MS. The resulting tandem mass spectra were able to distinguish the two epimers from each other.

  20. High-Definition Differential Ion Mobility Spectrometry with Resolving Power up to 500

    SciTech Connect

    Shvartsburg, Alexandre A.; Seim, Thomas A.; Danielson, William F.; Norheim, Randolph V.; Moore, Ronald J.; Anderson, Gordon A.; Smith, Richard D.

    2013-01-20

    As the resolution of analytical methods improve, further progress tends to be increasingly limited by instrumental parameter instabilities that could be ignored before. This is now the case with differential ion mobility spectrometry (FAIMS), where fluctuations of the voltages and gas pressure have become critical. A new high-definition generator for FAIMS compensation voltage reported here provides a stable and accurate output than can be scanned with negligible steps. This reduces the spectral drift and peak width, thus improving the resolving power (R) and resolution. The gain for multiply-charged peptides that have narrowest peaks is up to ~40%, and R ~ 400 - 500 is achievable using He/N2 or H2/N2 gas mixtures.

  1. Ultrahigh-Resolution Differential Ion Mobility Spectrometry Using Extended Separation Times

    PubMed Central

    Smith, Richard D.

    2010-01-01

    Ion mobility spectrometry (IMS), and particularly differential IMS or FAIMS, is emerging as a versatile tool for separation and identification of gas-phase ions, especially in conjunction with mass spectrometry. For over two decades since its inception, the utility of FAIMS was constrained by resolving power (R) of less than ~20. Stronger electric fields and optimized gas mixtures have recently raised achievable R to ~200, but further progress with such approaches is impeded by electrical breakdown. However, the resolving power of planar FAIMS devices using any gas and field intensity scales as the square root of separation time (t). Here, we extended t from the previous maximum of 0.2 s up to fourfold by reducing the carrier gas flow and increased the resolving power by up to twofold as predicted, to >300 for multiply-charged peptides. The resulting resolution gain has enabled separation of previously “co-eluting” peptide isomers, including folding conformers and localization variants of modified peptides. More broadly, a peak capacity of ~200 has been reached in tryptic digest separations. PMID:21117630

  2. Gridless overtone mobility spectrometry.

    PubMed

    Zucker, Steven M; Ewing, Michael A; Clemmer, David E

    2013-11-01

    A novel overtone mobility spectrometry (OMS) instrument utilizing a gridless elimination mechanism and cooperative radio frequency confinement is described. The gridless elimination region uses a set of mobility-discriminating radial electric fields that are designed so that the frequency of field application results in selective transmission and elimination of ions. To neutralize ions with mobilities that do not match the field application frequency, active elimination regions radially defocus ions toward the lens walls. Concomitantly, a lens-dependent radio frequency waveform is applied to the transmission regions of the drift tube resulting in radial confinement for mobility-matched ions. Compared with prior techniques, which use many grids for ion elimination, the new gridless configuration substantially reduces indiscriminate ion losses. A description of the apparatus and elimination process, including detailed simulations showing how ions are transmitted and eliminated is presented. A prototype 28 cm long OMS instrument is shown to have a resolving power of 20 and is capable of attomole detection limits of a model peptide (angiotensin I) spiked into a complex mixture (in this case peptides generated from digestion of β-casein with trypsin). PMID:24125033

  3. Gridless Overtone Mobility Spectrometry

    PubMed Central

    Zucker, Steven M.; Ewing, Michael A.; Clemmer, David E.

    2013-01-01

    A novel overtone mobility spectrometry (OMS) instrument utilizing a gridless elimination mechanism and cooperative radio frequency confinement is described. The gridless elimination region uses a set of mobility-discriminating radial electric fields that are designed so that the frequency of field application results in selective transmission and elimination of ions. To neutralize ions with mobilities that do not match the field application frequency, active elimination regions radially defocus ions towards the lens walls. Concomitantly, a lens-dependent radio frequency waveform is applied to the transmission regions of the drift tube resulting in radial confinement for mobility-matched ions. Compared with prior techniques, which use many grids for ion elimination, the new gridless configuration substantially reduces indiscriminate ion losses. A description of the apparatus and elimination process, including detailed simulations showing how ions are transmitted and eliminated is presented. A prototype 28 cm long OMS instrument is shown to have a resolving power of 20 and is capable of attomole detection limits of a model peptide (angiotensin I) spiked into a complex mixture (in this case peptides generated from digestion of β-casein with trypsin). PMID:24125033

  4. Separation of Peptide Isomers with Variant Modified Sites by High-Resolution Differential Ion Mobility Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.; Creese, Andrew; Smith, Richard D.; Cooper, Helen J.

    2010-10-01

    Many proteins and proteolytic peptides incorporate the same post-translational modification (PTM) at different sites, creating multiple localization variants with different functions or activities that may coexist in cells. Current analytical methods based on liquid chromatography (LC) followed by tandem mass spectrometry (MS/MS) are challenged by such isomers that often co-elute in LC and/or produce non-unique fragments. Application of ion mobility spectrometry (IMS) has previously been explored, but success was limited by insufficient resolution. We show that the recently developed high-resolution differential ion mobility spectrometry (FAIMS) using helium-rich gases can readily separate phosphopeptides with variant modified sites. Specifically, use of He/N2 mixtures containing up to 74% He has allowed separating to >95% three monophosphorylated peptides of identical sequence. Similar separation was achieved at 50% He, using an elevated electric field. Bisphosphorylated isomers that differ in only one modification site were separated to the same extent. We anticipate the FAIMS capabilities for such separations to extend to other PTMs.

  5. Separation of Peptide Isomers with Variant Modified Sites by High-Resolution Differential Ion Mobility Spectrometry

    PubMed Central

    Shvartsburg, Alexandre A.; Creese, Andrew J.; Smith, Richard D.; Cooper, Helen J.

    2010-01-01

    Many proteins and proteolytic peptides incorporate the same post-translational modification (PTM) at different sites, creating multiple localization variants with different functions or activities that may coexist in cells. Current analytical methods based on liquid chromatography (LC) followed by tandem mass spectrometry (MS/MS) are challenged by such isomers that often co-elute in LC and/or produce non-unique fragment ions. The application of ion mobility spectrometry (IMS) was explored, but success has been limited by insufficient resolution. We show that high-resolution differential ion mobility spectrometry (FAIMS) employing helium-rich gases can readily separate phosphopeptides with variant modification sites. Use of He/N2 mixtures containing up to 74% He has allowed separating to >95% three monophosphorylated peptides of identical sequence. Similar separation was achieved at 50% He, using an elevated electric field. Bisphosphorylated isomers that differ in only one modification site were separated to the same extent. We anticipate FAIMS capabilities for such separations to extend to other PTMs. PMID:20843012

  6. Trying to detect gas-phase ions? Understanding Ion Mobility Spectrometry

    PubMed Central

    Cumeras, R.; Figueras, E.; Davis, C.E.; Baumbach, J.I.; Gràcia, I.

    2014-01-01

    Ion Mobility Spectrometry (IMS) is a widely used and ‘well-known’ technique of ion separation in gaseous phase based on the differences of ion mobilities under an electric field. This technique has received increased interest over the last several decades as evidenced by the pace and advances of new IMS devices available. In this review we explore the hyphenated techniques that are used with IMS, especially mass spectrometry as identification approach and multi-capillary column as pre-separation approach. Also, we will pay special attention to the key figures of merit of the ion mobility spectrum and how data is treated, and the influences of the experimental parameters in both a conventional drift time IMS (DTIMS) and a miniaturized IMS also known as high Field Asymmetric IMS (FAIMS) in the planar configuration. The current review article is preceded by a companion review article which details the current instrumentation and to the sections that configures both a conventional DTIMS and FAIMS devices. Those reviews will give the reader an insightful view of the main characteristics and aspects of the IMS technique. PMID:25465248

  7. Review on ion mobility spectrometry. Part 2: hyphenated methods and effects of experimental parameters.

    PubMed

    Cumeras, R; Figueras, E; Davis, C E; Baumbach, J I; Gràcia, I

    2015-03-01

    Ion Mobility Spectrometry (IMS) is a widely used and 'well-known' technique of ion separation in the gaseous phase based on the differences of ion mobilities under an electric field. This technique has received increased interest over the last several decades as evidenced by the pace and advances of new IMS devices available. In this review we explore the hyphenated techniques that are used with IMS, specifically mass spectrometry as an identification approach and a multi-capillary column as a pre-separation approach. Also, we will pay special attention to the key figures of merit of the ion mobility spectrum and how data sets are treated, and the influences of the experimental parameters on both conventional drift time IMS (DTIMS) and miniaturized IMS also known as high Field Asymmetric IMS (FAIMS) in the planar configuration. The present review article is preceded by a companion review article which details the current instrumentation and contains the sections that configure both conventional DTIMS and FAIMS devices. These reviews will give the reader an insightful view of the main characteristics and aspects of the IMS technique. PMID:25465248

  8. Hooked differential mobility spectrometry apparatus and method therefore

    DOEpatents

    Shvartsburg, Alexandre A [Richland, WA; Tang, Keqi [Richland, WA; Ibrahim, Yehia M [Richland, WA; Smith, Richard D [Richland, WA

    2009-02-17

    Disclosed are a device and method for improved interfacing of differential mobility spectrometry (DMS) or field asymmetric waveform ion mobility spectrometry (FAIMS) analyzers of substantially planar geometry to subsequent or preceding instrument stages. Interfacing is achieved using curved DMS elements, where a thick ion beam emitted by planar DMS analyzers or injected into them for ion filtering is compressed to the gap median by DMS ion focusing effect in a spatially inhomogeneous electric field. Resulting thinner beams are more effectively transmitted through necessarily constrained conductance limit apertures to subsequent instrument stages operated at a pressure lower than DMS, and/or more effectively injected into planar DMS analyzers. The technology is synergetic with slit apertures, slit aperture/ion funnels, and high-pressure ion funnel interfaces known in the art which allow for increasing cross-sectional area of MS inlets. The invention may be used in integrated analytical platforms, including, e.g., DMS/MS, LC/DMS/MS, and DMS/IMS/MS that could replace and/or enhance current LC/MS methods, e.g., for proteomics research.

  9. Separation of Variant Methylated Histone Tails by Differential Ion Mobility

    SciTech Connect

    Shvartsburg, Alexandre A.; Zheng, Yupeng; Smith, Richard D.; Kelleher, Neil

    2012-07-18

    Differential ion mobility spectrometry (FAIMS) is emerging as a broadly useful tool for separation of isomeric modified peptides with post-translational modifications (PTMs) attached to alternative residues. Such separations were anticipated to become more challenging for smaller PTMs and longer peptides. Here we show that FAIMS can fully resolve localization variants involving a PTM as minuscule as methylation, even for larger peptides in the middle-down range.

  10. Comprehensive mapping of O‐glycosylation in flagellin from Campylobacter jejuni 11168: A multienzyme differential ion mobility mass spectrometry approach

    PubMed Central

    Ulasi, Gloria N.; Creese, Andrew J.; Hui, Sam Xin; Penn, Charles W.

    2015-01-01

    Glycosylation of flagellin is essential for the virulence of Campylobacter jejuni, a leading cause of bacterial gastroenteritis. Here, we demonstrate comprehensive mapping of the O‐glycosylation of flagellin from Campylobacter jejuni 11168 by use of a bottom‐up proteomics approach that incorporates differential ion mobility spectrometry (also known as high field asymmetric waveform ion mobility spectrometry or FAIMS) together with proteolysis with proteinase K. Proteinase K provides complementary sequence coverage to that achieved following trypsin proteolysis. The use of FAIMS increased the number of glycopeptides identified. Novel glycans for this strain were identified (pseudaminic acid and either acetamidino pseudaminic acid or legionaminic acid), as were novel glycosylation sites: Thr208, Ser343, Ser348, Ser349, Ser395, Ser398, Ser423, Ser433, Ser436, Ser445, Ser448, Ser451, Ser452, Ser454, Ser457 and Thr465. Multiply glycosylated peptides were observed, as well as variation at individual residues in the nature of the glycan and its presence or absence. Such extreme heterogeneity in the pattern of glycosylation has not been reported previously, and suggests a novel dimension in molecular variation within a bacterial population that may be significant in persistence of the organism in its natural environment. These results demonstrate the usefulness of differential ion mobility in proteomics investigations of PTMs. PMID:25884275

  11. Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution.

    PubMed

    Zhu, Shaolong; Campbell, J Larry; Chernushevich, Igor; Le Blanc, J C Yves; Wilson, Derek J

    2016-06-01

    Differential mobility spectrometry (DMS) is an ion mobility technique that has been adopted chiefly as a pre-filter for small- to medium-sized analytes (<1 000 Da). With the exception of a handful of studies that employ an analogue of DMS-field asymmetric waveform ion mobility spectroscopy (FAIMS)-the application of DMS to intact biomacromolecules remains largely unexplored. In this work, we employ DMS combined with gas-phase hydrogen deuterium exchange (DMS-HDX) to probe the gas-phase conformations generated from proteins that were initially folded, partially-folded, and unfolded in solution. Our findings indicate that proteins with distinct structural features in solution exhibit unique deuterium uptake profiles as function of their optimal transmission through the DMS. Ultimately we propose that DMS-HDX can, if properly implemented, provide rapid measurements of liquid-phase protein structural stability that could be of use in biopharmaceuticals development. Graphical Abstract ᅟ. PMID:26965162

  12. Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

    NASA Astrophysics Data System (ADS)

    Zhu, Shaolong; Campbell, J. Larry; Chernushevich, Igor; Le Blanc, J. C. Yves; Wilson, Derek J.

    2016-06-01

    Differential mobility spectrometry (DMS) is an ion mobility technique that has been adopted chiefly as a pre-filter for small- to medium-sized analytes (<1 000 Da). With the exception of a handful of studies that employ an analogue of DMS—field asymmetric waveform ion mobility spectroscopy (FAIMS)—the application of DMS to intact biomacromolecules remains largely unexplored. In this work, we employ DMS combined with gas-phase hydrogen deuterium exchange (DMS-HDX) to probe the gas-phase conformations generated from proteins that were initially folded, partially-folded, and unfolded in solution. Our findings indicate that proteins with distinct structural features in solution exhibit unique deuterium uptake profiles as function of their optimal transmission through the DMS. Ultimately we propose that DMS-HDX can, if properly implemented, provide rapid measurements of liquid-phase protein structural stability that could be of use in biopharmaceuticals development.

  13. Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

    NASA Astrophysics Data System (ADS)

    Zhu, Shaolong; Campbell, J. Larry; Chernushevich, Igor; Le Blanc, J. C. Yves; Wilson, Derek J.

    2016-03-01

    Differential mobility spectrometry (DMS) is an ion mobility technique that has been adopted chiefly as a pre-filter for small- to medium-sized analytes (<1 000 Da). With the exception of a handful of studies that employ an analogue of DMS—field asymmetric waveform ion mobility spectroscopy (FAIMS)—the application of DMS to intact biomacromolecules remains largely unexplored. In this work, we employ DMS combined with gas-phase hydrogen deuterium exchange (DMS-HDX) to probe the gas-phase conformations generated from proteins that were initially folded, partially-folded, and unfolded in solution. Our findings indicate that proteins with distinct structural features in solution exhibit unique deuterium uptake profiles as function of their optimal transmission through the DMS. Ultimately we propose that DMS-HDX can, if properly implemented, provide rapid measurements of liquid-phase protein structural stability that could be of use in biopharmaceuticals development.

  14. Detection, identification, and occurrence of thiotetronic acids in drinking water from underground sources by electrospray ionization-high field asymmetric waveform ion mobility spectrometry-quadrupole time-of-flight-mass spectrometry.

    PubMed

    Lyczko, Jadwiga; Beach, Daniel; Gabryelski, Wojciech

    2015-10-01

    This paper demonstrates that electrospray ionization (ESI) with differential ion mobility spectroscopy (FAIMS) and "soft" mass spectrometry (MS) provide unique analytical capabilities that led to the discovery of sulfur-containing polar congeners of thiotetronic acid (TA) in drinking water from underground sources in Canada and the United States. Polar TAs accumulate in underground aquifers and appear to be the most abundant class of organic compounds in bottled water but cannot be detected by conventional mass spectrometry methods. We show that normally stable TAs are converted into very reactive ions in ESI which have to be analyzed using special conditions in ESI-FAIMS-MS to avoid extensive dissociation and ion/molecule reactions. De novo identification of 10 TAs was accomplished by the comparative tandem mass spectrometry analysis of authentic TA derivatives from groundwater samples and synthetic TA analogues prepared for this study. We present highlights of gas phase ion chemistry of polar TAs to explain their unique properties and reactivity. TA derivatives were originally isolated from soil bacteria and are of interest in the pharmaceutical industry due to their potent activity against a broad spectrum of pathogenic bacteria and negligible toxicity to mammals. We suspect that TAs are natural disinfection agents protecting groundwater from bacterial contamination, but these compound undergo modifications or decompose during an ozonation water treatment. PMID:26340067

  15. Feasibility of Higher-Order Differential Ion Mobility Separations Using New Asymmetric Waveforms

    PubMed Central

    Shvartsburg, Alexandre A.; Mashkevich, Stefan V.; Smith, Richard D.

    2011-01-01

    Technologies for separating and characterizing ions based on their transport properties in gases have been around for three decades. The early method of ion mobility spectrometry (IMS) distinguished ions by absolute mobility that depends on the collision cross section with buffer gas atoms. The more recent technique of field asymmetric waveform IMS (FAIMS) measures the difference between mobilities at high and low electric fields. Coupling IMS and FAIMS to soft ionization sources and mass spectrometry (MS) has greatly expanded their utility, enabling new applications in biomedical and nanomaterials research. Here, we show that time-dependent electric fields comprising more than two intensity levels could, in principle, effect an infinite number of distinct differential separations based on the higher-order terms of expression for ion mobility. These analyses could employ the hardware and operational procedures similar to those utilized in FAIMS. Methods up to the 4th or 5th order (where conventional IMS is 1st order and FAIMS is 2nd order) should be practical at field intensities accessible in ambient air, with still higher orders potentially achievable in insulating gases. Available experimental data suggest that higher-order separations should be largely orthogonal to each other and to FAIMS, IMS, and MS. PMID:16494377

  16. Developments in ion mobility spectrometry-mass spectrometry.

    PubMed

    Collins, D C; Lee, M L

    2002-01-01

    Ion mobility spectrometry (IMS) has been used for over 30 years as a sensitive detector of organic compounds. The following is a brief review of IMS and its principles with an emphasis on its usage when coupled to mass spectrometry. Since its inception, IMS has been interfaced with quadrupole, time-of-flight, and Fourier-transform ion cyclotron resonance mass spectrometry. These hybrid instruments have been employed for the analysis of a variety of target analytes, including biomolecules, explosives, chemical warfare degradation products, and illicit drugs. PMID:11939214

  17. Third International Workshop on Ion Mobility Spectrometry

    NASA Technical Reports Server (NTRS)

    Cross, John H. (Editor)

    1995-01-01

    Basic research in ion mobility spectrometry has given rise to rapid advancement in hardware development and applications. The Third International Workshop on Ion Mobility Spectrometry (IMS) was held October 16-19, 1994, at Johnson Space Center to provide a forum for investigators to present the most recent results of both basic and applied IMS research. Presenters included manufacturers and various users, including military research organizations and drug enforcement agencies. Thirty papers were given in the following five sessions: Fundamental IMS Studies, Instrument Development, Hyphenated IMS Techniques, Applications, and Data Reduction and Signal Processing. Advances in hardware development, software development, and user applications are described.

  18. The Detection of Patients at Risk of Gastrointestinal Toxicity during Pelvic Radiotherapy by Electronic Nose and FAIMS: A Pilot Study

    PubMed Central

    Covington, James A.; Wedlake, Linda; Andreyev, Jervoise; Ouaret, Nathalie; Thomas, Matthew G.; Nwokolo, Chuka U.; Bardhan, Karna D.; Arasaradnam, Ramesh P.

    2012-01-01

    It is well known that the electronic nose can be used to identify differences between human health and disease for a range of disorders. We present a pilot study to investigate if the electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry), can be used to identify and help inform the treatment pathway for patients receiving pelvic radiotherapy, which frequently causes gastrointestinal side-effects, severe in some. From a larger group, 23 radiotherapy patients were selected where half had the highest levels of toxicity and the others the lowest. Stool samples were obtained before and four weeks after radiotherapy and the volatiles and gases emitted analysed by both methods; these chemicals are products of fermentation caused by gut microflora. Principal component analysis of the electronic nose data and wavelet transform followed by Fisher discriminant analysis of FAIMS data indicated that it was possible to separate patients after treatment by their toxicity levels. More interestingly, differences were also identified in their pre-treatment samples. We believe these patterns arise from differences in gut microflora where some combinations of bacteria result to give this olfactory signature. In the future our approach may result in a technique that will help identify patients at “high risk” even before radiation treatment is started. PMID:23201982

  19. Chemical Standards in Ion Mobility Spectrometry

    PubMed Central

    Fernández-Maestre, Roberto; Harden, Charles Steve; Ewing, Robert Gordon; Crawford, Christina Lynn; Hill, Herbert Henderson

    2010-01-01

    In ion mobility spectrometry (IMS), reduced mobility values (K0) are used as a qualitative measure of gas phase ions, and are reported in the literature as absolute values. Unfortunately, these values do not always match those collected in the field. One reason for this discrepancy is that the buffer gas may be contaminated with moisture or other volatile compounds. In this study, the effect of moisture and organic contaminants in the buffer gas on the mobility of IMS standards and analytes was investigated for the first time using IMS directly coupled to mass spectrometry. 2,4-dimethylpyridine, 2,6-di-tert-butyl pyridine (DTBP), and tetrabutylammonium, tetrapropylammonium, tetraethylammonium, and tetramethylammonium chlorides were used as chemical standards. In general, the mobility of IMS standard product ions was not affected by small amounts of contamination while the mobilities of many analytes were affected. In the presence of contaminants in the buffer gas, the mobility of analyte ions is often decreased by forming ion-molecule clusters with the contaminant. To ensure the measurement of accurate reduced mobility values, two IMS standards are required: an instrument and a mobility standard. An instrument standard is not affected by contaminants in the buffer gas, and provides an accurate measurement of the instrumental parameters, such as voltage, drift length, pressure, and temperature. The mobility standard behaves like an analyte ion in that the compound’s mobility is affected by low levels of contamination in the buffer gas. Prudent use of both of these standards can lead to improved measurement of accurate reduced mobility values. PMID:20369157

  20. Chemical standards in ion mobility spectrometry

    SciTech Connect

    Fernandez-Maestre, Robert; Harden, Charles S.; Ewing, Robert G.; Crawford, Christina L.; Hill, Jr, Herbert H.

    2010-08-01

    In ion mobility spectrometry (IMS), reduced mobility values (K0) are used as a qualitative measure of gas phase ions, and are reported in the literature as absolute values. Unfortunately, these values do not always match with those collected in the field. One reason for this discrepancy is that the buffer gas may be contaminated with moisture or other volatile compounds. In this study, the effect of moisture and organic contaminants in the buffer gas on the mobility of IMS standards and analytes was investigated for the first time using IMS directly coupled to mass spectrometry. 2,4-Dimethylpyridine, 2,6-di- tertbutylpyridine (DTBP), and tetrabutylammonium, tetrapropylammonium, tetraethylammonium, and tetramethylammonium chlorides were used as chemical standards. In general, the mobility of IMS standard product ions was not affected by small amounts of contamination while the mobilities of many analytes were affected. In the presence of contaminants in the buffer gas, the mobility of analyte ions is often decreased by forming ion–molecule clusters with the contaminant. To ensure the measurement of accurate reduced mobility values, two IMS standards are required: an instrument and a mobility standard. An instrument standard is not affected by contaminants in the buffer as, and provides an accurate measurement of the instrumental parameters, such as voltage, drift length, pressure, and temperature. The mobility standard behaves like an analyte ion in that the compound’s mobility is affected by low levels of contamination in the buffer gas. Prudent use of both of these standards can lead to improved measurement of accurate reduced mobility values.

  1. Fundamentals of Trapped Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Michelmann, Karsten; Silveira, Joshua A.; Ridgeway, Mark E.; Park, Melvin A.

    2015-01-01

    Trapped ion mobility spectrometry (TIMS) is a relatively new gas-phase separation method that has been coupled to quadrupole orthogonal acceleration time-of-flight mass spectrometry. The TIMS analyzer is a segmented rf ion guide wherein ions are mobility-analyzed using an electric field that holds ions stationary against a moving gas, unlike conventional drift tube ion mobility spectrometry where the gas is stationary. Ions are initially trapped, and subsequently eluted from the TIMS analyzer over time according to their mobility ( K). Though TIMS has achieved a high level of performance ( R > 250) in a small device (<5 cm) using modest operating potentials (<300 V), a proper theory has yet to be produced. Here, we develop a quantitative theory for TIMS via mathematical derivation and simulations. A one-dimensional analytical model, used to predict the transit time and theoretical resolving power, is described. Theoretical trends are in agreement with experimental measurements performed as a function of K, pressure, and the axial electric field scan rate. The linear dependence of the transit time with 1/ K provides a fundamental basis for determination of reduced mobility or collision cross section values by calibration. The quantitative description of TIMS provides an operational understanding of the analyzer, outlines the current performance capabilities, and provides insight into future avenues for improvement.

  2. An excimer-based FAIMS detector for detection of ultra-low concentration of explosives

    NASA Astrophysics Data System (ADS)

    Chistyakov, Alexander A.; Kotkovskii, Gennadii E.; Sychev, Alexey V.; Perederiy, Anatoly N.; Budovich, V. L.; Budovich, D. V.

    2014-05-01

    A new method of explosives detection based on the field asymmetric ion mobility spectrometry (FAIMS) and ionization by an excimer emitter has been developed jointly with a portable detector. The excimer emitter differs from usual UVionizing lamps by mechanism of emitting, energy and spectral characteristics. The developed and applied Ar2-excimer emitter has the working volume of 1 cm3, consuming power 0.6 W, the energy of photons of about 10 eV (λ=126 nm), the FWHM radiation spectrum of 10 nm and emits more than 1016 photon per second that is two orders of magnitude higher than UV-lamp of the same working volume emits. This also exceeds by an order of magnitude the quantity of photons per second for 10-Hz solid state YAG:Nd3+ - laser of 1mJ pulse energy at λ=266 nm that is also used to ionize the analyte. The Ar2-excimer ionizes explosives by direct ionization mechanism and through ionization of organic impurities. The developed Ar2-excimer-based ion source does not require cooling due to low level discharge current of emitter and is able to work with no repair more than 10000 hrs. The developed excimer-based explosives detector can analyze both vapors and traces of explosives. The FAIMS spectra of the basic types of explosives like trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX), dinitrotoluene (DNT), cyclotetramethylenetetranitramine (HMX), nitroglycerine (NG), pentaerythritol tetranitrate (PETN) under Ar2-excimer ionization are presented. The detection limit determined for TNT vapors equals 1x10-14 g/cm3, for TNT traces- 100 pg.

  3. Process analysis using ion mobility spectrometry.

    PubMed

    Baumbach, J I

    2006-03-01

    Ion mobility spectrometry, originally used to detect chemical warfare agents, explosives and illegal drugs, is now frequently applied in the field of process analytics. The method combines both high sensitivity (detection limits down to the ng to pg per liter and ppb(v)/ppt(v) ranges) and relatively low technical expenditure with a high-speed data acquisition. In this paper, the working principles of IMS are summarized with respect to the advantages and disadvantages of the technique. Different ionization techniques, sample introduction methods and preseparation methods are considered. Proven applications of different types of ion mobility spectrometer (IMS) used at ISAS will be discussed in detail: monitoring of gas insulated substations, contamination in water, odoration of natural gas, human breath composition and metabolites of bacteria. The example applications discussed relate to purity (gas insulated substations), ecology (contamination of water resources), plants and person safety (odoration of natural gas), food quality control (molds and bacteria) and human health (breath analysis). PMID:16132133

  4. Environment applications for ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Ritchie, Robert K.; Rudolph, Andreas

    1995-01-01

    The detection of environmentally important polychlorinated aromatics by ion mobility spectrometry (IMS) was investigated. Single polychlorinated biphenyl (PCB) isomers (congeners) having five or more chlorine atoms were reliably detected in isooctane solution at levels of 35 ng with a Barringer IONSCAN ion mobility spectrometer operating in negative mode; limits of detection (LOD) were extrapolated to be in the low ng region. Mixtures of up to four PCB congeners, showing characteristic multiple peaks, and complex commercial mixtures of PCBs (Aroclors) were also detected. Detection of Aroclors in transformer oil was suppressed by the presence of the antioxidant BHT (2,6-di-t-butyl4-methylphenol) in the oil. The wood preservative pentachlorophenol (PCP) was easily detected in recycled wood shavings at levels of 52 ppm with the IONSCAN; the LOD was extrapolated to be in the low ppm region.

  5. Ion Mobility Separation of Peptide Isotopomers

    NASA Astrophysics Data System (ADS)

    Kaszycki, Julia L.; Bowman, Andrew P.; Shvartsburg, Alexandre A.

    2016-03-01

    Differential or field asymmetric waveform ion mobility spectrometry (FAIMS) operating at high electric fields fully resolves isotopic isomers for a peptide with labeled residues. The naturally present isotopes, alone and together with targeted labels, also cause spectral shifts that approximately add for multiple heavy atoms. Separation qualitatively depends on the gas composition. These findings may enable novel strategies in proteomic and metabolomic analyses using stable isotope labeling.

  6. Ion Mobility Separation of Peptide Isotopomers.

    PubMed

    Kaszycki, Julia L; Bowman, Andrew P; Shvartsburg, Alexandre A

    2016-05-01

    Differential or field asymmetric waveform ion mobility spectrometry (FAIMS) operating at high electric fields fully resolves isotopic isomers for a peptide with labeled residues. The naturally present isotopes, alone and together with targeted labels, also cause spectral shifts that approximately add for multiple heavy atoms. Separation qualitatively depends on the gas composition. These findings may enable novel strategies in proteomic and metabolomic analyses using stable isotope labeling. Graphical Abstract ᅟ. PMID:26944281

  7. Ion Mobility Separation of Peptide Isotopomers

    NASA Astrophysics Data System (ADS)

    Kaszycki, Julia L.; Bowman, Andrew P.; Shvartsburg, Alexandre A.

    2016-05-01

    Differential or field asymmetric waveform ion mobility spectrometry (FAIMS) operating at high electric fields fully resolves isotopic isomers for a peptide with labeled residues. The naturally present isotopes, alone and together with targeted labels, also cause spectral shifts that approximately add for multiple heavy atoms. Separation qualitatively depends on the gas composition. These findings may enable novel strategies in proteomic and metabolomic analyses using stable isotope labeling.

  8. Accelerated High-Resolution Differential Ion Mobility Separations Using Hydrogen

    PubMed Central

    Shvartsburg, Alexandre A.; Smith, Richard D.

    2011-01-01

    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 incompatible with online liquid-phase separations. Here, we report FAIMS employing hydrogen, specifically in mixtures with N2 containing up to 90% H2. 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 H2 fractions above ~50%. Higher resolution can be exchanged for acceleration of the analyses by up to ~4 times, at least. 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 H2 should consistently improve resolution for all analytes. PMID:22074292

  9. High-Resolution Differential Ion Mobility Separations Using Planar Analyzers at Elevated Dispersion Field

    PubMed Central

    Prior, David C.; Tang, Keqi; Smith, Richard D.

    2010-01-01

    The ion mobility spectrometry (IMS) methods are grouped into conventional IMS, based on the absolute ion mobility, and differential or field asymmetric waveform IMS (FAIMS), based on the mobility difference in strong and weak electric fields. A key attraction of FAIMS is substantial orthogonality to mass spectrometry (MS). Although several FAIMS/MS platforms were commercialized, their utility was limited by FAIMS resolving power, typically ∼10 - 20. Recently, gas mixtures comprising up to 75% He has enabled resolving power >100 that permits separation of numerous heretofore “co-eluting” isomers. This performance opens major new proteomic and other biological applications. Here, we show that raising the separation field by ∼35% over the previous 21 kV/cm provides similar or better resolution (with resolving powers of >200 for multiply-charged peptides) using only 50% He, which avoids problems due to elevated pressure and He content in the mass spectrometer. The heating of ions by the separation field in this regime exceeds that at higher He content but weaker field, inducing greater izomerization of labile species. PMID:20666414

  10. A Method of Highly Sensitive Detecting of Explosives on the Basis of FAIMS Analyzer with Laser Ion Source

    NASA Astrophysics Data System (ADS)

    Chistyakov, A. A.; Kotkovskii, G. E.; Odulo, I. P.; Spitsyn, E. M.; Shestakov, A. V.

    In this work comparison of the desorption effectiveness of picosecond and nanosecond laser sources (λ=266, 532 nm) were carried out to investigate the possibility of creating a non-contact sampling device for detectors of explosives on the principles of ion mobility spectrometry (IMS) and field asymmetric ion mobility spectrometry (FAIMS). The results of mass spectrometric studies of TNT (2,4,6-Trinitrotoluene), HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), RDX (1,3,5-Trinitro-1,3,5-triazacyclohexane) laser desorption from a quartz substrate are presented. It is shown that the most effective laser source is a Nd:YAG3+ laser (λ = 266 nm; E = 1 mJ; τ = 5-10 ns; q = 108 W/cm2). The typical desorbed mass is 2 ng for RDX, 4-6 ng for TNT and 0.02 ng HMX per single laser pulse. The results obtained make it possible to create a non-contact portable laser sampling device operating in frequency mode with high efficiency.

  11. Coulombic Effects in Ion Mobility Spectrometry

    PubMed Central

    Tolmachev, Aleksey V.; Clowers, Brian H.; Belov, Mikhail E.; Smith, Richard D.

    2009-01-01

    Ion mobility spectrometry (IMS) has been increasingly employed in a number of applications. When coupled to mass spectrometry (MS), IMS becomes a powerful analytical tool for separating complex samples and investigating molecular structure. Therefore, improvements in IMS-MS instrumentation, e.g. IMS resolving power and sensitivity, are highly desirable. Implementation of an ion trap for accumulation and pulsed ion injection to IMS based on the ion funnel has provided considerably increased ion currents, and thus a basis for improved sensitivity and measurement throughput. However, large ion populations may manifest Coulombic effects contributing to the spatial dispersion of ions traveling in the IMS drift tube, and reduction in the IMS resolving power. In this study, we present an analysis of Coulombic effects on IMS resolution. Basic relationships have been obtained for the spatial evolution of ion packets due to Coulombic repulsion. The analytical relationships were compared with results of a computer model that simulates IMS operation based on a first principles approach. Initial experimental results reported here are consistent with the computer modeling. A noticeable decrease in the IMS resolving power was observed for ion populations of >10,000 elementary charges. The optimum IMS operation conditions which would minimize the Coulombic effects are discussed. PMID:19438247

  12. Field applications of ion-mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Brown, Patricia A.

    1997-02-01

    Ion mobility spectrometry (IMS) is an excellent tool for detection of controlled substances under field conditions. Plasmagrams and tables showing the results of field applications will be discussed. Residues of drugs, such as cocaine and heroin, can be left anywhere including vehicles, boats, and houses. In houses, the carpets, walls, and floors are good locations for residues to adhere. Individual clothing can also be contaminated with drug residue. Vehicles that are suspected of having previously smuggled illegal substances can be vacuumed and screened. Tablets that look similar and respond the same when screened with the Marquis reagent can be differentiated by IMS. With Southern California being the 'methamphetamine capital of the world' and the resurgence of phencyclidine, IMS has proven extremely valuable in the screening of abandoned clandestine laboratory sites and vehicles in which the clandestine laboratories; chemicals and glassware were transported. IMS is very responsive to ephedrine/pseudophedrine, a precursor of methamphetamine and 1-piperidinocyclohexanecarbonitrile, an intermediate of phencyclidine. Once residues are detected, vacuum samples, and/or methanol wipes are collected and analyzed at the DEA Laboratory for confirmation of the suspected substance using GC-IRD or Mass Spectrometry.

  13. Analysis of a series of chlorogenic acid isomers using differential ion mobility and tandem mass spectrometry.

    PubMed

    Willems, Jamie L; Khamis, Mona M; Mohammed Saeid, Waleed; Purves, Randy W; Katselis, George; Low, Nicholas H; El-Aneed, Anas

    2016-08-24

    Chlorogenic acids are among the most abundant phenolics found in the human diet. Of these, the mono-caffeoylquinic acids are the predominant phenolics found in fruits, such as apples and pears, and products derived from them. In this research, a comprehensive study of the electrospray ionization (ESI) tandem mass spectrometric (MS/MS) dissociation behavior of the three most common mono-caffeoylquinic acids, namely 5-O-caffeoylquinic acid (5-CQA), 3-O-caffeoylquinic acid (3-CQA) and 4-O-caffeoylquinic acid (4-CQA), were determined using both positive and negative ionization. All proposed structures of the observed product ions were confirmed with second-generation MS(3) experiments. Similarities and differences between the dissociation pathways in the positive and negative ion modes are discussed, confirming the proposed structures and the established MS/MS fingerprints. MS/MS dissociation was primarily driven via the cleavage of the ester bond linking the quinic acid moiety to the caffeic acid moiety within tested molecules. Despite being structural isomers with the same m/z values and dissociation behaviors, the MS/MS data in the negative ion mode was able to differentiate the three isomers based on ion intensity for the major product ions, observed at m/z 191, 179 and 173. This differentiation was consistent among various MS instruments. In addition, ESI coupled with high-field asymmetric waveform ion mobility spectrometry-mass spectrometry (ESI-FAIMS-MS) was employed for the separation of these compounds for the first time. By combining MS/MS data and differential ion mobility, a method for the separation and identification of mono-caffeoylquinic in apple/pear juice samples was developed with a run time of less than 1 min. It is envisaged that this methodology could be used to identify pure juices based on their chlorogenic acid profile (i.e., metabolomics), and could also be used to detect juice-to-juice adulteration (e.g., apple juice addition to pear juice

  14. Detection of Potato Storage Disease via Gas Analysis: A Pilot Study Using Field Asymmetric Ion Mobility Spectrometry

    PubMed Central

    Rutolo, Massimo; Covington, James A.; Clarkson, John; Iliescu, Daciana

    2014-01-01

    Soft rot is a commonly occurring potato tuber disease that each year causes substantial losses to the food industry. Here, we explore the possibility of early detection of the disease via gas/vapor analysis, in a laboratory environment, using a recent technology known as FAIMS (Field Asymmetric Ion Mobility Spectrometry). In this work, tubers were inoculated with a bacterium causing the infection, Pectobacterium carotovorum, and stored within set environmental conditions in order to manage disease progression. They were compared with controls stored in the same conditions. Three different inoculation time courses were employed in order to obtain diseased potatoes showing clear signs of advanced infection (for standard detection) and diseased potatoes with no apparent evidence of infection (for early detection). A total of 156 samples were processed by PCA (Principal Component Analysis) and k-means clustering. Results show a clear discrimination between controls and diseased potatoes for all experiments with no difference among observations from standard and early detection. Further analysis was carried out by means of a statistical model based on LDA (Linear Discriminant Analysis) that showed a high classification accuracy of 92.1% on the test set, obtained via a LOOCV (leave-one out cross-validation). PMID:25171118

  15. Detection of potato storage disease via gas analysis: a pilot study using field asymmetric ion mobility spectrometry.

    PubMed

    Rutolo, Massimo; Covington, James A; Clarkson, John; Iliescu, Daciana

    2014-01-01

    Soft rot is a commonly occurring potato tuber disease that each year causes substantial losses to the food industry. Here, we explore the possibility of early detection of the disease via gas/vapor analysis, in a laboratory environment, using a recent technology known as FAIMS (Field Asymmetric Ion Mobility Spectrometry). In this work, tubers were inoculated with a bacterium causing the infection, Pectobacterium carotovorum, and stored within set environmental conditions in order to manage disease progression. They were compared with controls stored in the same conditions. Three different inoculation time courses were employed in order to obtain diseased potatoes showing clear signs of advanced infection (for standard detection) and diseased potatoes with no apparent evidence of infection (for early detection). A total of 156 samples were processed by PCA (Principal Component Analysis) and k-means clustering. Results show a clear discrimination between controls and diseased potatoes for all experiments with no difference among observations from standard and early detection. Further analysis was carried out by means of a statistical model based on LDA (Linear Discriminant Analysis) that showed a high classification accuracy of 92.1% on the test set, obtained via a LOOCV (leave-one out cross-validation). PMID:25171118

  16. Ion Mobility Spectrometry of Heavy Metals.

    PubMed

    Ilbeigi, Vahideh; Valadbeigi, Younes; Tabrizchi, Mahmoud

    2016-07-19

    A simple, fast, and inexpensive method was developed for detecting heavy metals via the ion mobility spectrometry (IMS) in the negative mode. In this method, Cl(-) ion produced by the thermal ionization of NaCl is employed as the dopant or the ionizing reagent to ionize heavy metals. In practice, a solution of mixed heavy metals and NaCl salts was directly deposited on a Nichrome filament and electrically heated to vaporize the salts. This produced the IMS spectra of several heavy-metal salts, including CdCl2, ZnSO4, NiCl2, HgSO4, HgCl2, PbI2, and Pb(Ac)2. For each heavy metal (M), one or two major peaks were observed, which were attributed to M·Cl(-) or [M·NaCl]Cl(-)complexes. The method proved to be useful for the analysis of mixed heavy metals. The absolute detection limits measured for ZnSO4 and HgSO4 were 0.1 and 0.05 μg, respectively. PMID:27321408

  17. Total hydrocarbon analysis by ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Cross, John H.; Limero, Thomas F.; James, John T.

    1994-01-01

    Astronauts must be alerted quickly to chemical leaks that compromise their health and the success of their missions. An ideal leak detector would be equally sensitive to all compounds that might constitute a hazard and insensitive to nontoxic compounds. No ideal sensor exists; thus, selection of a methodology is a series of compromises. The commonly used methods are either insensitive at the low exposure levels set by OSHA, NASA, and other organizations or are selectively insensitive to important classes of chemicals such as Freons. After extensive study and experience, the Toxicology Group at JSC has selected ion mobility spectrometry (IMS) for development into a broad range, sensitive detector. In addition to the sensing method, signal processing is important leak detection because a background signal can be expected at all times. The leak-detecting instrument must be programmed to discriminate between authentic leaks and background fluctuations caused by routine operations. The results of an evaluation of the prototype THA is presented in terms related to spacecraft operations. The evaluation included determination of instrumental parameters such as stability and response times. We also included responses to some common components of spacecraft atmospheres in pure form and in binary and ternary mixtures. The output of the four algorithms to the mixtures was found to be noticeably different. These responses are compared on the basis of their utility for signaling a chemical leak. As a means of evaluating its resistance to a falsely positive response, the THA was challenged with carbon dioxide and methane, compounds whose concentrations normally increase in spacecraft air during human habitation. The instrument showed virtually no response to these interferences. Although the prototype THA is designed for space flight, this detector is expected to be useful for field screening at chemical waste dumps and other environmentally sensitive locations.

  18. Ion Mobility Separation of Variant Histone Tails Extending to the “Middle-down” Range

    SciTech Connect

    Shvartsburg, Alexandre A.; Zheng, Yupeng; Smith, Richard D.; Kelleher, Neil

    2012-05-15

    Differential ion mobility spectrometry (FAIMS) can baseline-resolve multiple variants of post-translationally modified peptides extending to the 3 - 4 kDa range, which differ in the localization of a PTM as small as acetylation. Essentially orthogonal separations for different charge states expand the total achievable peak capacity in proportion to the number of observed states that increases for longer polypeptides. This might enable resolving localization variants for even larger peptides and intact proteins.

  19. Modeling vapor uptake induced mobility shifts in peptide ions observed with transversal modulation ion mobility spectrometry-mass spectrometry.

    PubMed

    Rawat, Vivek K; Vidal-de-Miguel, Guillermo; Hogan, Christopher J

    2015-10-21

    Low field ion mobility spectrometry-mass spectrometry (IMS-MS) techniques exhibit low orthogonality, as inverse mobility often scales with mass to charge ratio. This inadequacy can be mitigated by adding vapor dopants, which may cluster with analyte ions and shift their mobilities by amounts independent of both mass and mobility of the ion. It is therefore important to understand the interactions of vapor dopants with ions, to better quantify the extent of dopant facilitated mobility shifts. Here, we develop predictive models of vapor dopant facilitated mobility shifts, and compare model calculations to measurements of mobility shifts for peptide ions exposed to variable gas phase concentrations of isopropanol. Mobility measurements were made at atmospheric pressure and room temperature using a recently developed transversal modulation ion mobility spectrometer (TMIMS). Results are compared to three separate models, wherein mobility shifts due to vapor dopants are attributed to changes in gas composition and (I) no vapor dopant uptake is assumed, (II) site-specific dopant uptake by the ion is assumed (approximated via a Langmuir adsorption model), and (III) site-unspecific dopant uptake by the ion is assumed (approximated via a classical nucleation model). We find that mobility shifts in peptide ions are in excellent agreement with model II, site-specific binding predictions. Conversely, mobility shifts of tetraalkylammonium ions from previous measurements were compared with these models and best agreement was found with model III predictions, i.e. site-unspecific dopant uptake. PMID:26051323

  20. A method for detecting ultra-low quantities of explosives with use a picosecond laser FAIMS analyzer

    NASA Astrophysics Data System (ADS)

    Chistyakov, Alexander A.; Kotkovskii, Gennadii E.; Odulo, Ivan P.; Sychev, Alexey V.; Bogdanov, Artem S.; Perederiy, Anatoly N.; Spitsyn, Evgeny M.; Shestakov, Alexander V.

    2015-05-01

    A method for detecting ultralow quantities of explosives in air with use a state-of-the-art picosecond chip Nd3+:YAG laser has been developed. The method combines field asymmetric ion mobility spectrometry (FAIMS) with laser ionization of examined air samples. Radiation of λ = 266nm, τpulse = 300ps, Epulse = 30-150μJ, ν = 20-300Hz was used. Processes in the ion source for the use both picosecond and nanosecond ionization modes were analyzed. Parameters of the laser ion source have been specially optimized. The dependences on frequency, pulse energy, peak intensity, and average power for trinitrotoluene (TNT) and cyclotrimethylenetrinitramine (RDX) were obtained. It was shown that the optimal peak intensity should be no less 3·106 W/cm2. The detected ion signals for all explosives were shown to be threefold higher for picosecond excitation in comparison with use a nanosecond laser of the same average power. The estimated detection threshold of the prototype equals 1. 10-15 g/cm3. The results are promising for the development of a highly sensitive, portable laser explosive detector.

  1. On the structural denaturation of biological analytes in trapped ion mobility spectrometry - mass spectrometry.

    PubMed

    Liu, Fanny C; Kirk, Samuel R; Bleiholder, Christian

    2016-06-01

    Key to native ion mobility/mass spectrometry is to prevent the structural denaturation of biological molecules in the gas phase. Here, we systematically assess structural changes induced in the protein ubiquitin during a trapped ion mobility spectrometry (TIMS) experiment. Our analysis shows that the extent of structural denaturation induced in ubiquitin ions is largely proportional to the amount of translational kinetic energy an ion gains from the applied electric field between two collisions with buffer gas particles. We then minimize the efficiency of the structural denaturation of ubiquitin ions in the gas phase during a TIMS experiment. The resulting "soft" TIMS spectra of ubiquitin are found largely identical to those observed on "soft" elevated-pressure ion mobility drift tubes and the corresponding calibrated cross sections are consistent with structures reported from NMR experiments for the native and A-state of ubiquitin. Thus, our analysis reveals that TIMS is useful for native ion mobility/mass spectrometry analysis. PMID:26998732

  2. Coulomb Repulsion in Miniature Ion Mobility Spectrometry

    SciTech Connect

    Xu, J.; Whitten, W.B.; Ramsey, J.M.

    1999-08-08

    We have undertaken a study of ion mobility resolution in a miniature ion mobility spectrometer with a drift channel 1.7 mm in diameter and 35 mm in length. The device attained a maximum resolution of 14 in separating ions of NO, O{sub 2}, and methyl iodine. The ions were generated by pulses from a frequency-quadrupled Nd:YAG laser. Broadening due to Coulomb repulsion was modeled theoretically and shown experimentally to have a major effect on the resolution of the miniature device.

  3. LABORATORY DETECTION OF PLASTICS IN SEEDCOTTON WITH ION MOBILITY SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The US cotton industry wants to increase market share and value by supplying pure cotton. Removing contamination requires developing a means to detect plastics in seedcotton. This study was conducted to determine if Ion Mobility Spectrometry (IMS) could be used to find small amounts of plastic in ...

  4. Ion mobility spectrometers and methods for ion mobility spectrometry

    SciTech Connect

    Dahl, David A; Scott, Jill R; Appelhans, Anthony D; McJunkin, Timothy R; Olson, John E

    2009-04-14

    An ion mobility spectrometer may include an inner electrode and an outer electrode arranged so that at least a portion of the outer electrode surrounds at least a portion of the inner electrode and defines a drift space therebetween. The inner and outer electrodes are electrically insulated from one another so that a non-linear electric field is created in the drift space when an electric potential is placed on the inner and outer electrodes. An ion source operatively associated with the ion mobility spectrometer releases ions to the drift space defined between the inner and outer electrodes. A detector operatively associated with at least a portion of the outer electrode detects ions from the drift space.

  5. Ion mobility spectrometry after supercritical fluid chromatography

    SciTech Connect

    Morrissey, M.A.

    1988-01-01

    In this work, a Fourier transform ion mobility spectrometer (FT-IMS) was constructed and evaluated as a detector for supercritical fluid chromatography (SFC). The FT-IMS provides both quantitative and qualitative data of a wide range of compounds, selective and nonselective modes of chromatographic detection, and it is compatible with a wide range of SFC mobile phases. Drift spectra are presented for a number of samples, including polymers, lipids, herbicides, antibiotics, and pharmaceuticals. The unique properties of supercritical fluids made it possible to introduce these compounds into the spectrometer. While the drift spectra presented are generally simple, showing only a quasi-molecular ion, a few are surprising complex. Examples of selective and non-selective detection demonstrate the usefulness of the detector. Examples are presented for fish oil concentrate, bacon grease extract, soil extract, and polymer mixtures. In the case of Triton X-100, a non-ionic surfactant, the FT-IMS was able to selectively detect individual oligomers in the polymer mixture. In the case of a polydimethylsilicone mixture the detector isolated a contaminant in the mixture.

  6. Direct Liquid Sampling for Corona Discharge Ion Mobility Spectrometry.

    PubMed

    Sabo, Martin; Malásková, Michaela; Harmathová, Olga; Hradski, Jasna; Masár, Marián; Radjenovic, Branislav; Matejčík, Štefan

    2015-07-21

    We present a new technique suitable for direct liquid sampling and analysis by ion mobility spectrometry (IMS). The technique is based on introduction of a droplet stream to the IMS reaction region. The technique was successfully used to detect explosives dissolved in methanol and oil as well as to analyze amino acids and dipeptides. One of the main advantages of this technique is its ability to analyze liquid samples without the requirement of any special solution. PMID:26154532

  7. Detection of gunpowder stabilizers with ion mobility spectrometry.

    PubMed

    West, C; Baron, G; Minet, J-J

    2007-03-01

    This study is the first reported ion mobility detection of ethyl centralite and diphenylamine (DPA) smokeless gunpowder stabilizers, together with the nitroso and nitro derivatives of diphenylamine. First, the applicability of the ion mobility spectrometry (IMS) for the substances of interest was determined. The existence of numerous peaks, both in positive and negative modes, clearly demonstrates the success of these experiments. All mono and di-nitro derivatives of DPA tested were detected with this method. Unfortunately, many of the ions generated were not accurately identified. However, reduced mobility constants representative of each ion generated under defined operating conditions could be used for purpose of compound identification. The method was then successfully tested on real gunpowder samples. By the use of IMS, we managed to establish a rapid, simple and sensitive screening method for the detection and identification of smokeless gunpowder organic components. PMID:16828537

  8. Separation of Protein Conformers by Differential Ion Mobility in Hydrogen-Rich Gases

    PubMed Central

    Shvartsburg, Alexandre A.; Smith, Richard D.

    2013-01-01

    Proteins in solution or the gas phase tend to exhibit multiple conformational families, each comprising distinct structures. Separation methods have generally failed to resolve these, with their convolution producing wide peaks. Here we report full separation of >10 conformers for most ubiquitin charge states by the new approach of differential ion mobility spectrometry (FAIMS) employing H2/N2 gas mixtures with up to 85% H2. The resolving power (up to 400) is five times the highest previously achieved (using He/N2 buffers), greatly increasing the separation specificity. The peak widths match the narrowest obtained by FAIMS for any species under same conditions and scale with the protein charge state (z) and ion residence time (t) as z−1/2 and t−1/2, as prescribed for instrumental (diffusional) broadening. This suggests resolution of specific geometries rather than broader ensembles. PMID:23855890

  9. Separation of Protein Conformers by Differential Ion Mobility in Hydrogen-Rich Gases

    SciTech Connect

    Shvartsburg, Alexandre A.; Smith, Richard D.

    2013-06-25

    Proteins in solution or the gas phase tend to exhibit multiple conformational families, each comprising distinct structures. Separation methods have generally failed to resolve these, with their convolution producing wide peaks. Here we report full separation of >10 conformers for most ubiquitin charge states by the new approach of differential ion mobility spectrometry (FAIMS) employing H2/N2 gas mixtures with up to 85% H2. The resolving power (up to 400) is five times the highest previously achieved (using He/N2 buffers), greatly increasing the separation specificity. The peak widths match the narrowest obtained by FAIMS for any species under same conditions and scale with the protein charge state (z) and ion residence time (t) as z-1/2 and t-1/2, as prescribed for instrumental (diffusional) broadening. This suggests resolution of specific geometries rather than broader ensembles.

  10. Review on ion mobility spectrometry. Part 1: current instrumentation.

    PubMed

    Cumeras, R; Figueras, E; Davis, C E; Baumbach, J I; Gràcia, I

    2015-03-01

    Ion Mobility Spectrometry (IMS) is a widely used and 'well-known' technique of ion separation in the gaseous phase based on the differences in ion mobilities under an electric field. All IMS instruments operate with an electric field that provides space separation, but some IMS instruments also operate with a drift gas flow that provides also a temporal separation. In this review we will summarize the current IMS instrumentation. IMS techniques have received an increased interest as new instrumentation and have become available to be coupled with mass spectrometry (MS). For each of the eight types of IMS instruments reviewed it is mentioned whether they can be hyphenated with MS and whether they are commercially available. Finally, out of the described devices, the six most-consolidated ones are compared. The current review article is followed by a companion review article which details the IMS hyphenated techniques (mainly gas chromatography and mass spectrometry) and the factors that make the data from an IMS device change as a function of device parameters and sampling conditions. These reviews will provide the reader with an insightful view of the main characteristics and aspects of the IMS technique. PMID:25465076

  11. Review on Ion Mobility Spectrometry. Part 1: Current Instrumentation

    PubMed Central

    Cumeras, R.; Figueras, E.; Davis, C.E.; Baumbach, J.I.; Gràcia, I.

    2014-01-01

    Ion Mobility Spectrometry (IMS) is a widely used and ‘well-known’ technique of ion separation in gaseous phase based on the differences of ion mobilities under an electric field. All IMS instruments operate with an electric field that provides space separation, but some IMS instruments also operate with a drift gas flow which provides also a temporal separation. In this review we will summarize the current IMS instrumentation. IMS techniques have received an increased interest as new instrumentation has become available to be coupled with mass spectrometry (MS). For each of the eight types of IMS instruments reviewed it is mentioned whether they can be hyphenated with MS and whether they are commercially available. Finally, out of the described devices, the six most-consolidated ones are compared. The current review article is followed by a companion review article which details the IMS hyphenated techniques (mainly gas chromatography and mass spectrometry) and the factors that make the data from an IMS device change as function of device parameters and sampling conditions. These reviews will provide the reader with an insightful view of the main characteristics and aspects of the IMS technique. PMID:25465076

  12. Identification of carbohydrate anomers using ion mobility-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Hofmann, J.; Hahm, H. S.; Seeberger, P. H.; Pagel, K.

    2015-10-01

    Carbohydrates are ubiquitous biological polymers that are important in a broad range of biological processes. However, owing to their branched structures and the presence of stereogenic centres at each glycosidic linkage between monomers, carbohydrates are harder to characterize than are peptides and oligonucleotides. Methods such as nuclear magnetic resonance spectroscopy can be used to characterize glycosidic linkages, but this technique requires milligram amounts of material and cannot detect small amounts of coexisting isomers. Mass spectrometry, on the other hand, can provide information on carbohydrate composition and connectivity for even small amounts of sample, but it cannot be used to distinguish between stereoisomers. Here, we demonstrate that ion mobility-mass spectrometry--a method that separates molecules according to their mass, charge, size, and shape--can unambiguously identify carbohydrate linkage-isomers and stereoisomers. We analysed six synthetic carbohydrate isomers that differ in composition, connectivity, or configuration. Our data show that coexisting carbohydrate isomers can be identified, and relative concentrations of the minor isomer as low as 0.1 per cent can be detected. In addition, the analysis is rapid, and requires no derivatization and only small amounts of sample. These results indicate that ion mobility-mass spectrometry is an effective tool for the analysis of complex carbohydrates. This method could have an impact on the field of carbohydrate synthesis similar to that of the advent of high-performance liquid chromatography on the field of peptide assembly in the late 1970s.

  13. Ion mobility spectrometry for pharmacokinetic studies – exemplary application

    PubMed Central

    Ruzsanyi, V.

    2013-01-01

    Breath analysis is an attractive non-invasive method for diagnosis and therapeutic monitoring. It uses endogenously produced compounds and metabolites of isotopically labelled precursors. In order to make such tests clinically useful, it is important to have relatively small portable instruments detecting volatile compounds within short time. A particularly promising analytical technique is ion mobility spectrometry (IMS) coupled to a multicapillary column (MCC). The present paper focuses on demonstrating the suitability of breath analysis for pharmacokinetic applications using MCC-IMS with respect to practicability and reproducibility testing the model substrate eucalyptol. Validation of the MCC-IMS measurements were performed using proton transfer reaction mass spectrometry (PTR-MS) and resulted in an excellent correspondence of the time-dependent concentrations presented by the two different analytical techniques. Moreover, the good accordance in variance of kinetic parameters with repeated measures, and the determined inter-subject differences indicate the eligibility of the analysis method. PMID:24287589

  14. Separation of steroid isomers by ion mobility mass spectrometry.

    PubMed

    Ahonen, Linda; Fasciotti, Maíra; Gennäs, Gustav Boije Af; Kotiaho, Tapio; Daroda, Romeu J; Eberlin, Marcos; Kostiainen, Risto

    2013-10-01

    Ion mobility mass spectrometry performed in a compact traveling wave cell (TWIM-MS) is shown to provide a reliable, fast and repeatable method to separate derivatized steroid isomers. Three steroid isomer pairs were analyzed in their native form and as their p-toluenesulfonyl isocyanate derivatives. The native steroids were separated from each other, but no separation could be attained for the isomers. The derivatized steroid isomers were, however, properly separated by TWIM-MS with peak-to-peak resolutions close to or as high as baseline resolution (Rp-p=0.77-1.08). PMID:23992881

  15. Ion mobility spectrometry for detection of skin volatiles

    PubMed Central

    Ruzsanyi, Veronika; Mochalski, Pawel; Schmid, Alex; Wiesenhofer, Helmut; Klieber, Martin; Hinterhuber, Hartmann; Amann, Anton

    2012-01-01

    Volatile organic compounds (VOCs) released by humans through their skin were investigated in near real time using ion mobility spectrometry after gas chromatographic separation with a short multi-capillary column. VOCs typically found in a small nitrogen flow covering the skin are 3-methyl-2-butenal, 6-methylhept-5-en-2-one, sec-butyl acetate, benzaldehyde, octanal, 2-ethylhexanol, nonanal and decanal at volume fractions in the low part per billion-(ppb) range. The technique presented here may contribute to elucidating some physiological processes occurring in the human skin. PMID:23217311

  16. Differential Mobility Spectrometry: Preliminary Findings on Determination of Fundamental Constants

    NASA Technical Reports Server (NTRS)

    Limero, Thomas; Cheng, Patti; Boyd, John

    2007-01-01

    The electron capture detector (ECD) has been used for 40+ years (1) to derive fundamental constants such as a compound's electron affinity. Given this historical perspective, it is not surprising that differential mobility spectrometry (DMS) might be used in a like manner. This paper will present data from a gas chromatography (GC)-DMS instrument that illustrates the potential capability of this device to derive fundamental constants for electron-capturing compounds. Potential energy curves will be used to provide possible explanation of the data.

  17. Wireless Data Acquisition of Transient Signals for Mobile Spectrometry Applications.

    PubMed

    Trzcinski, Peter; Weagant, Scott; Karanassios, Vassili

    2016-05-01

    Wireless data acquisition using smartphones or handhelds offers increased mobility, it provides reduced size and weight, it has low electrical power requirements, and (in some cases) it has an ability to access the internet. Thus, it is well suited for mobile spectrometry applications using miniaturized, field-portable spectrometers, or detectors for chemical analysis in the field (i.e., on-site). There are four main wireless communications standards that can be used for wireless data acquisition, namely ZigBee, Bluetooth, Wi-Fi, and UWB (ultra-wide band). These are briefly reviewed and are evaluated for applicability to data acquisition of transient signals (i.e., time-domain) in the field (i.e., on-site) from a miniaturized, field-portable photomultiplier tube detector and from a photodiode array detector installed in a miniaturized, field-portable fiber optic spectrometer. These are two of the most widely used detectors for optical measurements in the ultraviolet-visible range of the spectrum. A miniaturized, 3D-printed, battery-operated microplasma-on-a-chip was used for generation of transient optical emission signals. Elemental analysis from liquid microsamples, a microplasma, and a handheld or a smartphone will be used as examples. Development and potential applicability of wireless data acquisition of transient optical emission signals for taking part of the lab to the sample types of mobile, field-portable spectrometry applications will be discussed. The examples presented are drawn from past and ongoing work in the authors' laboratory. A handheld or a smartphone were used as the mobile computing devices of choice. PMID:27006023

  18. External Second Gate-Fourier Transform Ion Mobility Spectrometry.

    SciTech Connect

    Tarver, Edward E., III

    2005-01-01

    Ion mobility spectrometry (IMS) is recognized as one of the most sensitive and versatile techniques for the detection of trace levels of organic vapors. IMS is widely used for detecting contraband narcotics, explosives, toxic industrial compounds and chemical warfare agents. Increasing threat of terrorist attacks, the proliferation of narcotics, Chemical Weapons Convention treaty verification as well as humanitarian de-mining efforts has mandated that equal importance be placed on the analysis time as well as the quality of the analytical data. (1) IMS is unrivaled when both speed of response and sensitivity has to be considered. (2) With conventional (signal averaging) IMS systems the number of available ions contributing to the measured signal to less than 1%. Furthermore, the signal averaging process incorporates scan-to-scan variations decreasing resolution. With external second gate Fourier Transform ion mobility spectrometry (FT-IMS), the entrance gate frequency is variable and can be altered in conjunction with other data acquisition parameters to increase the spectral resolution. The FT-IMS entrance gate operates with a 50% duty cycle and so affords a 7 to 10-fold increase in sensitivity. Recent data on high explosives are presented to demonstrate the parametric optimization in sensitivity and resolution of our system.

  19. Combining ion mobility spectrometry, mass spectrometry, and photoelectron spectroscopy in a high-transmission instrument.

    PubMed

    Vonderach, Matthias; Ehrler, Oli T; Weis, Patrick; Kappes, Manfred M

    2011-02-01

    We have developed a novel instrument that combines ion mobility spectrometry, mass spectro-metry, and photoelectron spectroscopy. The instrument couples an electrospray ion source, a high-transmission ion mobility cell based on ion funnels, a quadrupole mass filter, and a time-of-flight (magnetic bottle) photoelectron spectrometer operated with a pulsed detachment laser. We show that the instrument can resolve highly structured anion arrival time distributions and at the same time provide corresponding photoelectron spectra-using the DNA oligonucleotide ion [dC(6) - 5H](5-) as a test case. For this multianion we find at least four different, noninterconverting isomers (conformers) simultaneously present in the gas phase at room temperature. For each of these we record well-resolved and remarkably different photoelectron spectra at each of three different detachment laser wavelengths. Two-dimensional ion mobility/electron binding energy plots can be acquired with an automated data collection procedure. We expect that this kind of instrument will significantly improve the capabilities for structure determination of (bio)molecular anions in the gas phase. PMID:21214198

  20. Online deuterium hydrogen exchange and protein digestion coupled with ion mobility spectrometry and tandem mass spectrometry.

    PubMed

    Donohoe, Gregory C; Arndt, James R; Valentine, Stephen J

    2015-05-19

    Online deuterium hydrogen exchange (DHX) and pepsin digestion (PD) is demonstrated using drift tube ion mobility spectrometry (DTIMS) coupled with linear ion trap (LTQ) mass spectrometry (MS) with electron transfer dissociation (ETD) capabilities. DHX of deuterated ubiquitin, followed by subsequent quenching and digestion, is performed within ∼60 s, yielding 100% peptide sequence coverage. The high reproducibility of the IMS separation allows spectral feature matching between two-dimensional IMS-MS datasets (undeuterated and deuterated) without the need for dataset alignment. Extracted ion drift time distributions (XIDTDs) of deuterated peptic peptides are mobility-matched to corresponding XIDTDs of undeuterated peptic peptides that were identified using collision-induced dissociation (CID). Matching XIDTDs allows a straightforward identification and deuterium retention evaluation for labeled peptides. Aside from the mobility separation, the ion trapping capabilities of the LTQ, combined with ETD, are demonstrated to provide single-residue resolution. Deuterium retention for the c- series ions across residues M(1)-L(15) and N(25)-R(42) are in good agreement with the known secondary structural elements within ubiquitin. PMID:25893550

  1. Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry.

    PubMed

    Kyle, Jennifer E; Zhang, Xing; Weitz, Karl K; Monroe, Matthew E; Ibrahim, Yehia M; Moore, Ronald J; Cha, Jeeyeon; Sun, Xiaofei; Lovelace, Erica S; Wagoner, Jessica; Polyak, Stephen J; Metz, Thomas O; Dey, Sudhansu K; Smith, Richard D; Burnum-Johnson, Kristin E; Baker, Erin S

    2016-02-15

    Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Mass spectrometry (MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids' biological roles is challenging due to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are often unresolvable using present approaches. Here we show that combining liquid chromatography (LC) and structurally-based ion mobility spectrometry (IMS) measurement with MS analyses distinguishes lipid isomers and allows insight into biological and disease processes. PMID:26734689

  2. Rapid Analysis of Isobaric Exogenous Metabolites by Differential Mobility Spectrometry Mass Spectrometry

    SciTech Connect

    Parson, Whitney B; Schneider, Bradley B; Kertesz, Vilmos; Corr, Jay; Covey, Thomas R.; Van Berkel, Gary J

    2011-01-01

    The direct separation of isobaric glucuronide metabolites from propranolol dosed tissue extracts by differential mobility spectrometry mass spectrometry (DMS-MS) with the use of a polar gas-phase chemical modifier was demonstrated. The DMS gas-phase separation was able to resolve the isobaric metabolites with separation times on the order of ms instead of mins to hrs typically required when using pre-ionization chromatographic separation methods. Direct separation of isobaric metabolites from the complex tissue extract was validated using standards as well as implementing an HPLC separation prior to the DMS-MS analysis to pre-separate the species of interest. The ability to separate isobaric exogenous metabolites directly from a complex tissue extract is expected to facilitate the drug development process by increasing analytical throughput without the requirement for pre-ionization cleanup or separation strategies.

  3. Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

    SciTech Connect

    Kyle, Jennifer E.; Zhang, Xing; Weitz, Karl K.; Monroe, Matthew E.; Ibrahim, Yehia M.; Moore, Ronald J.; Cha, Jeeyeon; Sun, Xiaofei; Lovelace, Erica S.; Wagoner, Jessica; Polyak, Stephen J.; Metz, Thomas O.; Dey, Sudhansu K.; Smith, Richard D.; Burnum-Johnson, Kristin E.; Baker, Erin S.

    2016-01-01

    Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Liquid chromatography and mass spectrometry (LC-MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging due to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are unresolvable using present LC-MS approaches. Here we show that combining structurally-based ion mobility spectrometry (IMS) with LC-MS measurements distinguishes lipid isomers and allows insight into biological and disease processes.

  4. Analysis of biogenic amines using corona discharge ion mobility spectrometry.

    PubMed

    Hashemian, Z; Mardihallaj, A; Khayamian, T

    2010-05-15

    A new method based on corona discharge ion mobility spectrometry (CD-IMS) was developed for the analysis of biogenic amines including spermidine, spermine, putrescine, and cadaverine. The ion mobility spectra of the compounds were obtained with and without n-Nonylamine used as the reagent gas. The high proton affinity of n-Nonylamine prevented ion formation from compounds with a proton affinity lower than that of n-Nonylamine and, therefore, enhanced its selectivity. It was also realized that the ion mobility spectrum of n-Nonylamine varied with its concentration. A sample injection port of a gas chromatograph was modified and used as the sample introduction system into the CD-IMS. The detection limits, dynamic ranges, and analytical parameters of the compounds with and without using the reagent gas were obtained. The detection limits and dynamic ranges of the compounds were about 2ng and 2 orders of magnitude, respectively. The wide dynamic range of CD-IMS originates from the high current of the corona discharge. The results revealed the high capability of the CD-IMS for the analysis of biogenic amines. PMID:20298897

  5. Tandem ion mobility spectrometry coupled to laser excitation

    SciTech Connect

    Simon, Anne-Laure; Choi, Chang Min; Clavier, Christian; Barbaire, Marc; Maurelli, Jacques; Dagany, Xavier; MacAleese, Luke; Dugourd, Philippe; Chirot, Fabien

    2015-09-15

    This manuscript describes a new experimental setup that allows to perform tandem ion mobility spectrometry (IMS) measurements and which is coupled to a high resolution time-of-flight mass spectrometer. It consists of two 79 cm long drift tubes connected by a dual ion funnel assembly. The setup was built to permit laser irradiation of the ions in the transfer region between the two drift tubes. This geometry allows selecting ions according to their ion mobility in the first drift tube, to irradiate selected ions, and examine the ion mobility of the product ions in the second drift tube. Activation by collision is possible in the same region (between the two tubes) and between the second tube and the time-of-flight. IMS-IMS experiments on Ubiquitin are reported. We selected a given isomer of charge state +7 and explored its structural rearrangement following collisional activation between the two drift tubes. An example of IMS-laser-IMS experiment is reported on eosin Y, where laser irradiation was used to produce radical ions by electron photodetachment starting from doubly deprotonated species. This allowed measuring the collision cross section of the radical photo-product, which cannot be directly produced with an electrospray source.

  6. On-site analysis of old deposited chemical warfare agents by combined use of ion mobility spectrometry and mass spectrometry

    SciTech Connect

    Stach, J.; Adler, J.; Brodacki, M.; Doering, H.R.; Flachowsky, J.; Loudon, A.

    1995-12-31

    The factory site of an old mustard gas plant was investigated with on-site analysis methods. Using ion mobility spectrometry and mass spectrometry a lot of degradation products of mustard gas could be detected. Sulfur mustard was found in one soil sample and in ceramic material of a bunker used for storage of the produced warfare agents. Concentrations of the mustard gas are in the sub ppb level. The results of ion mobility and mass spectrometry agreed in 95 % of the investigated samples.

  7. Development of Ion Mobility Spectrometry for Exobiology Flight Experiments

    NASA Technical Reports Server (NTRS)

    Kojiro, Daniel R.; Carle, Glenn C.; Humphry, Donald E.; Shao, Maxine; Takeuchi, Nori; Chang, Sherwood (Technical Monitor)

    1996-01-01

    Ion Mobility Spectrometry (IMS) can provide gas chromatography with sample identification independent of sample retention time, with minimal interface. Initial commercial methods of IMS however, did not possess sufficient analytical capabilities and presented operational parameters which were unsuitable for exobiology missions. Subsequent development of IMS technology, with the focus on exobiology analytical requirements and mission imposed operational limitations, has produced an IMS interfaced with a GC capable of fulfilling the analytical requirements of several exobiology missions. Future exobiology missions will require further development of the IMS, particularly in the areas of overall instrument miniaturization and complex sample identification. The evolution of the exobiology focused IMS will be presented up to the current prototype design, which is a component of several proposed exobiology instruments. Areas of future development will also be discussed.

  8. Interrogating viral capsid assembly with ion mobility-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Uetrecht, Charlotte; Barbu, Ioana M.; Shoemaker, Glen K.; van Duijn, Esther; Heck, Albert J. R.

    2011-02-01

    Most proteins fulfil their function as part of large protein complexes. Surprisingly, little is known about the pathways and regulation of protein assembly. Several viral coat proteins can spontaneously assemble into capsids in vitro with morphologies identical to the native virion and thus resemble ideal model systems for studying protein complex formation. Even for these systems, the mechanism for self-assembly is still poorly understood, although it is generally thought that smaller oligomeric structures form key intermediates. This assembly nucleus and larger viral assembly intermediates are typically low abundant and difficult to monitor. Here, we characterised small oligomers of Hepatitis B virus (HBV) and norovirus under equilibrium conditions using native ion mobility mass spectrometry. This data in conjunction with computational modelling enabled us to elucidate structural features of these oligomers. Instead of more globular shapes, the intermediates exhibit sheet-like structures suggesting that they are assembly competent. We propose pathways for the formation of both capsids.

  9. Electron Attachment Studies for CHCl3 Using Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Han, Hai-yan; Feng, Hong-tao; Li, Hu; Wang, Hong-mei; Jiang, Hai-he; Chu, Yan-nan

    2011-04-01

    The dissociative electron attachment process for CHCl3 at different electric field have been studied with nitrogen as drift and carrier gas using corona discharge ionization source ion mobility spectrometry (CD-IMS). The corresponding electron attachment rate constants varied from 1.26×10-8 cm3/(molecules s) to 8.24×10-9 cm3/(molecules s) as the electric field changed from 200 V/cm to 500 V/cm. At a fixed electric field in the drift region, the attachment rate constants are also detected at different sample concentration. The ion-molecule reaction rate constants for the further reaction between Cl- and CHCl3 are also detected, which indicates that the technique maybe becomes a new method to research the rate constants between ions and neural molecules. And the reaction rate constants between Cl- and CHCl3 are the first time detected using CD-IMS.

  10. Determination of ammonia in ethylene using ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Cross, J. H.; Limero, T. F.; Lane, J. L.; Wang, F.

    1997-01-01

    A simple procedure to analyze ammonia in ethylene by ion mobility spectrometry is described. The spectrometer is operated with a silane polymer membrane., 63Ni ion source, H+ (H2O)n reactant ion, and nitrogen drift and source gas. Ethylene containing parts per billion (ppb) (v/v) concentrations of ammonia is pulled across the membrane and diffuses into the spectrometer. Preconcentration or preseparation is unnecessary, because the ethylene in the spectrometer has no noticeable effect on the analytical results. Ethylene does not polymerize in the radioactive source. Ethylene's flammability is negated by the nitrogen inside the spectrometer. Response to ammonia concentrations between 200 ppb and 1.5 ppm is near linear, and a detection limit of 25 ppb is calculated.

  11. Anomerization of Acrylated Glucose During Traveling Wave Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Chendo, Christophe; Moreira, Guillaume; Tintaru, Aura; Posocco, Paola; Laurini, Erik; Lefay, Catherine; Gigmes, Didier; Viel, Stéphane; Pricl, Sabrina; Charles, Laurence

    2015-09-01

    Anomerization of simple sugars in the liquid phase is known as an acid- and base-catalyzed process, which highly depends on solvent polarity. This reaction is reported here to occur in the gas phase, during traveling wave ion mobility spectrometry (TWIMS) experiments aimed at separating α- and β-anomers of penta-acrylated glucose generated as ammonium adducts in electrospray ionization. This compound was available in two samples prepared from glucose dissolved in solvents of different polarity, namely tetrahydrofuran (THF) and N,N-dimethylacetamide (DMAC), and analyzed by electrospray tandem mass spectrometry (ESI-MS/MS) as well as traveling wave ion mobility (ESI-TWIMS-MS). In MS/MS, an anchimerically-assisted process was found to be unique to the electrosprayed α-anomer, and was only observed for the THF sample. In ESI-TWIMS-MS, a signal was measured at the drift time expected for the α-anomer for both the THF and DMAC samples, in apparent contradiction to the MS/MS results, which indicated that the α-anomer was not present in the DMAC sample. However, MS/MS experiments performed after TWIMS separation revealed that ammonium adducts of the α-anomer produced from each sample, although exhibiting the same collision cross section, were clearly different. Indeed, while the α-anomer actually present in the THF sample was electrosprayed with the ammonium adducted at the C2 acrylate, its homologue only observed when the DMAC sample was subjected to TWIMS hold the adducted ammonium at the C1 acrylate. These findings were explained by a β/α inter-conversion upon injection in the TWIMS cell, as supported by theoretical calculation and dynamic molecular modeling.

  12. Detection of Huanglongbing disease using differential mobility spectrometry.

    PubMed

    Aksenov, Alexander A; Pasamontes, Alberto; Peirano, Daniel J; Zhao, Weixiang; Dandekar, Abhaya M; Fiehn, Oliver; Ehsani, Reza; Davis, Cristina E

    2014-03-01

    The viability of the multibillion dollar global citrus industry is threatened by the "green menace", citrus greening disease (Huanglongbing, HLB), caused by the bacterial pathogen Candidatus Liberibacter. The long asymptomatic stage of HLB makes it challenging to detect emerging regional infections early to limit disease spread. We have established a novel method of disease detection based on chemical analysis of released volatile organic compounds (VOCs) that emanate from infected trees. We found that the biomarkers "fingerprint" is specific to the causal pathogen and could be interpreted using analytical methods such as gas chromatography/mass spectrometry (GC/MS) and gas chromatography/differential mobility spectrometry (GC/DMS). This VOC-based disease detection method has a high accuracy of ∼90% throughout the year, approaching 100% under optimal testing conditions, even at very early stages of infection where other methods are not adequate. Detecting early infection based on VOCs precedes visual symptoms and DNA-based detection techniques (real-time polymerase chain reaction, RT-PCR) and can be performed at a substantially lower cost and with rapid field deployment. PMID:24484549

  13. Analysis of explosives using corona discharge ionization combined with ion mobility spectrometry-mass spectrometry.

    PubMed

    Lee, Jihyeon; Park, Sehwan; Cho, Soo Gyeong; Goh, Eun Mee; Lee, Sungman; Koh, Sung-Suk; Kim, Jeongkwon

    2014-03-01

    Corona discharge ionization combined with ion mobility spectrometry-mass spectrometry (IMS-MS) was utilized to investigate five common explosives: cyclonite (RDX), trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), cyclotetramethylenetetranitramine (HMX), and 2,4-dinitrotoluene (DNT). The MS scan and the selected ion IMS analyses confirmed the identities of the existing ion species and their drift times. The ions observed were RDX·NO3(-), TNT(-), PETN·NO3(-), HMX·NO3(-), and DNT(-), with average drift times of 6.93 ms, 10.20 ms, 9.15 ms, 12.24 ms, 11.30 ms, and 8.89 ms, respectively. The reduced ion mobility values, determined from a standard curve calculated by linear regression of (normalized drift times)(-1) versus literature K0 values, were 2.09, 1.38, 1.55, 1.15, 1.25, and 1.60 cm(2) V(-1) s(-1), respectively. The detection limits were found to be 0.1 ng for RDX, 10 ng for TNT, 0.5 ng for PETN, 5.0 ng for HMX, and 10 ng for DNT. Simplified chromatograms were observed when nitrogen, as opposed to air, was used as the drift gas, but the detection limits were approximately 10 times worse (i.e., less sensitivity of detection). PMID:24468343

  14. Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry.

    PubMed

    Glover, Matthew S; Dilger, Jonathan M; Acton, Matthew D; Arnold, Randy J; Radivojac, Predrag; Clemmer, David E

    2016-05-01

    Ion mobility spectrometry-mass spectrometry (IMS-MS) techniques are used to study the general effects of phosphorylation on peptide structure. Cross sections for a library of 66 singly phosphorylated peptide ions from 33 pairs of positional isomers, and unmodified analogues were measured. Intrinsic size parameters (ISPs) derived from these measurements yield calculated collision cross sections for 85% of these phosphopeptide sequences that are within ±2.5% of experimental values. The average ISP for the phosphoryl group (0.64 ± 0.05) suggests that in general this moiety forms intramolecular interactions with the neighboring residues and peptide backbone, resulting in relatively compact structures. We assess the capability of ion mobility to separate positional isomers (i.e., peptide sequences that differ only in the location of the modification) and find that more than half of the isomeric pairs have >1% difference in collision cross section. Phosphorylation is also found to influence populations of structures that differ in the cis/trans orientation of Xaa-Pro peptide bonds. Several sequences with phosphorylated Ser or Thr residues located N-terminally adjacent to Pro residues show fewer conformations compared to the unmodified sequences. Graphical Abstract ᅟ. PMID:26860087

  15. Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Glover, Matthew S.; Dilger, Jonathan M.; Acton, Matthew D.; Arnold, Randy J.; Radivojac, Predrag; Clemmer, David E.

    2016-05-01

    Ion mobility spectrometry-mass spectrometry (IMS-MS) techniques are used to study the general effects of phosphorylation on peptide structure. Cross sections for a library of 66 singly phosphorylated peptide ions from 33 pairs of positional isomers, and unmodified analogues were measured. Intrinsic size parameters (ISPs) derived from these measurements yield calculated collision cross sections for 85% of these phosphopeptide sequences that are within ±2.5% of experimental values. The average ISP for the phosphoryl group (0.64 ± 0.05) suggests that in general this moiety forms intramolecular interactions with the neighboring residues and peptide backbone, resulting in relatively compact structures. We assess the capability of ion mobility to separate positional isomers (i.e., peptide sequences that differ only in the location of the modification) and find that more than half of the isomeric pairs have >1% difference in collision cross section. Phosphorylation is also found to influence populations of structures that differ in the cis/ trans orientation of Xaa-Pro peptide bonds. Several sequences with phosphorylated Ser or Thr residues located N-terminally adjacent to Pro residues show fewer conformations compared to the unmodified sequences.

  16. Structures of Metallosupramolecular Coordination Assemblies Can Be Obtained by Ion Mobility Spectrometry-Mass Spectrometry

    PubMed Central

    Brocker, Erin R.; Anderson, Stanley E.; Northrop, Brian H.; Stang, Peter J.; Bowers, Michael T.

    2010-01-01

    Rigid rectangular, cyclobis[(2,9-bis[trans-Pt(PEt3)2(PF6)]anthracene)(4,4′-dipyridyl)], triangular, cyclotris[(2,9-bis[trans-Pt(PEt3)2(PF6)]phenanthrene)(4,4′-dipyridyl)], and prismatic, cyclotris[bis-[cis-Pt(PEt3)2)(CF3SO3)2](tetrakis(4-pyridyl)cyclobutadienecyclopentadienylcobalt(I))] supramolecular assemblies, based on dipyridyl ligands and square planar platinum coordination, have been investigated by ion mobility spectrometry-mass spectrometry (IMS-MS). ESI-quadrupole and TOF spectra have been obtained and fragmentation pathways assigned. Ion mobility studies give cross sections that compare very well with cross sections of the supramolecular rectangle and triangle species based on X-ray bond distances. For the larger prism structures, agreement of experimental and calculated cross sections from molecular modeling is very good, indicating IMS-MS methods can be used to characterize complex self-assembled structures where X-ray or other spectroscopic structures are not available. PMID:20815390

  17. Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Glover, Matthew S.; Dilger, Jonathan M.; Acton, Matthew D.; Arnold, Randy J.; Radivojac, Predrag; Clemmer, David E.

    2016-02-01

    Ion mobility spectrometry-mass spectrometry (IMS-MS) techniques are used to study the general effects of phosphorylation on peptide structure. Cross sections for a library of 66 singly phosphorylated peptide ions from 33 pairs of positional isomers, and unmodified analogues were measured. Intrinsic size parameters (ISPs) derived from these measurements yield calculated collision cross sections for 85% of these phosphopeptide sequences that are within ±2.5% of experimental values. The average ISP for the phosphoryl group (0.64 ± 0.05) suggests that in general this moiety forms intramolecular interactions with the neighboring residues and peptide backbone, resulting in relatively compact structures. We assess the capability of ion mobility to separate positional isomers (i.e., peptide sequences that differ only in the location of the modification) and find that more than half of the isomeric pairs have >1% difference in collision cross section. Phosphorylation is also found to influence populations of structures that differ in the cis/trans orientation of Xaa-Pro peptide bonds. Several sequences with phosphorylated Ser or Thr residues located N-terminally adjacent to Pro residues show fewer conformations compared to the unmodified sequences.

  18. Ion mobility spectrometry for food quality and safety.

    PubMed

    Vautz, W; Zimmermann, D; Hartmann, M; Baumbach, J I; Nolte, J; Jung, J

    2006-11-01

    Ion mobility spectrometry is known to be a fast and sensitive technique for the detection of trace substances, and it is increasingly in demand not only for protection against explosives and chemical warfare agents, but also for new applications in medical diagnosis or process control. Generally, a gas phase sample is ionized by help of ultraviolet light, ss-radiation or partial discharges. The ions move in a weak electrical field towards a detector. During their drift they collide with a drift gas flowing in the opposite direction and, therefore, are slowed down depending on their size, shape and charge. As a result, different ions reach the detector at different drift times, which are characteristic for the ions considered. The number of ions reaching the detector are a measure of the concentration of the analyte. The method enables the identification and quantification of analytes with high sensitivity (ng l(-1) range). The selectivity can even be increased - as necessary for the analyses of complex mixtures - using pre-separation techniques such as gas chromatography or multi-capillary columns. No pre-concentration of the sample is necessary. Those characteristics of the method are preserved even in air with up to a 100% relative humidity rate. The suitability of the method for application in the field of food quality and safety - including storage, process and quality control as well as the characterization of food stuffs - was investigated in recent years for a number of representative examples, which are summarized in the following, including new studies as well: (1) the detection of metabolites from bacteria for the identification and control of their growth; (2) process control in food production - beer fermentation being an example; (3) the detection of the metabolites of mould for process control during cheese production, for quality control of raw materials or for the control of storage conditions; (4) the quality control of packaging materials during

  19. Fundamentals of Trapped Ion Mobility Spectrometry Part II: Fluid Dynamics

    NASA Astrophysics Data System (ADS)

    Silveira, Joshua A.; Michelmann, Karsten; Ridgeway, Mark E.; Park, Melvin A.

    2016-04-01

    Trapped ion mobility spectrometry (TIMS) is a new high resolution (R up to ~300) separation technique that utilizes an electric field to hold ions stationary against a moving gas. Recently, an analytical model for TIMS was derived and, in part, experimentally verified. A central, but not yet fully explored, component of the model involves the fluid dynamics at work. The present study characterizes the fluid dynamics in TIMS using simulations and ion mobility experiments. Results indicate that subsonic laminar flow develops in the analyzer, with pressure-dependent gas velocities between ~120 and 170 m/s measured at the position of ion elution. One of the key philosophical questions addressed is: how can mobility be measured in a dynamic system wherein the gas is expanding and its velocity is changing? We noted previously that the analytically useful work is primarily done on ions as they traverse the electric field gradient plateau in the analyzer. In the present work, we show that the position-dependent change in gas velocity on the plateau is balanced by a change in pressure and temperature, ultimately resulting in near position-independent drag force. That the drag force, and related variables, are nearly constant allows for the use of relatively simple equations to describe TIMS behavior. Nonetheless, we derive a more comprehensive model, which accounts for the spatial dependence of the flow variables. Experimental resolving power trends were found to be in close agreement with the theoretical dependence of the drag force, thus validating another principal component of TIMS theory.

  20. Fundamentals of Trapped Ion Mobility Spectrometry Part II: Fluid Dynamics.

    PubMed

    Silveira, Joshua A; Michelmann, Karsten; Ridgeway, Mark E; Park, Melvin A

    2016-04-01

    Trapped ion mobility spectrometry (TIMS) is a new high resolution (R up to ~300) separation technique that utilizes an electric field to hold ions stationary against a moving gas. Recently, an analytical model for TIMS was derived and, in part, experimentally verified. A central, but not yet fully explored, component of the model involves the fluid dynamics at work. The present study characterizes the fluid dynamics in TIMS using simulations and ion mobility experiments. Results indicate that subsonic laminar flow develops in the analyzer, with pressure-dependent gas velocities between ~120 and 170 m/s measured at the position of ion elution. One of the key philosophical questions addressed is: how can mobility be measured in a dynamic system wherein the gas is expanding and its velocity is changing? We noted previously that the analytically useful work is primarily done on ions as they traverse the electric field gradient plateau in the analyzer. In the present work, we show that the position-dependent change in gas velocity on the plateau is balanced by a change in pressure and temperature, ultimately resulting in near position-independent drag force. That the drag force, and related variables, are nearly constant allows for the use of relatively simple equations to describe TIMS behavior. Nonetheless, we derive a more comprehensive model, which accounts for the spatial dependence of the flow variables. Experimental resolving power trends were found to be in close agreement with the theoretical dependence of the drag force, thus validating another principal component of TIMS theory. Graphical Abstract ᅟ. PMID:26864793

  1. Electrospray Ionization Ion Mobility Mass Spectrometry of Human Brain Gangliosides.

    PubMed

    Sarbu, Mirela; Robu, Adrian C; Ghiulai, Roxana M; Vukelić, Željka; Clemmer, David E; Zamfir, Alina D

    2016-05-17

    The progress of ion mobility spectrometry (IMS), together with its association to mass spectrometry (MS), opened new directions for the identification of various metabolites in complex biological matrices. However, glycolipidomics of the human brain by IMS MS represents an area untouched up to now, because of the difficulties encountered in brain sampling, analyte extraction, and IMS MS method optimization. In this study, IMS MS was introduced in human brain ganglioside (GG) research. The efficiency of the method in clinical glycolipidomics was demonstrated on a highly complex mixture extracted from a normal fetal frontal lobe (FL37). Using this approach, a remarkably rich molecular ion pattern was discovered, which proved the presence of a large number of glycoforms and an unpredicted diversity of the ceramide chains. Moreover, the results showed for the first time the occurrence of GGs in the human brain with a much higher degree of sialylation than previously reported. Using IMS MS, the entire series starting from mono- up to octasialylated GGs was detected in FL37. These findings substantiate early clinical reports on the direct correlation between GG sialylation degree and brain developmental stage. Using IMS CID MS/MS, applied here for the first time to gangliosides, a novel, tetrasialylated O-GalNAc modified species with a potential biomarker role in brain development was structurally characterized. Under variable collision energy, a high number of sequence ions was generated for the investigated GalNAc-GQ1(d18:1/18:0) species. Several fragment ions documented the presence of the tetrasialo element attached to the inner Gal, indicating that GalNAc-GQ1(d18:1/18:0) belongs to the d series. PMID:27088833

  2. Dynamically multiplexed ion mobility time-of-flight mass spectrometry.

    PubMed

    Belov, Mikhail E; Clowers, Brian H; Prior, David C; Danielson, William F; Liyu, Andrei V; Petritis, Brianne O; Smith, Richard D

    2008-08-01

    Ion mobility spectrometry-time-of-flight mass spectrometry (IMS-TOFMS) has been increasingly used in analysis of complex biological samples. A major challenge is to transform IMS-TOFMS to a high-sensitivity, high-throughput platform, for example, for proteomics applications. In this work, we have developed and integrated three advanced technologies, including efficient ion accumulation in an ion funnel trap prior to IMS separation, multiplexing (MP) of ion packet introduction into the IMS drift tube, and signal detection with an analog-to-digital converter, into the IMS-TOFMS system for the high-throughput analysis of highly complex proteolytic digests of, for example, blood plasma. To better address variable sample complexity, we have developed and rigorously evaluated a novel dynamic MP approach that ensures correlation of the analyzer performance with an ion source function and provides the improved dynamic range and sensitivity throughout the experiment. The MP IMS-TOFMS instrument has been shown to reliably detect peptides at a concentration of 1 nM in the presence of a highly complex matrix, as well as to provide a 3 orders of magnitude dynamic range and a mass measurement accuracy of better than 5 ppm. When matched against human blood plasma database, the detected IMS-TOF features were found to yield approximately 700 unique peptide identifications at a false discovery rate (FDR) of approximately 7.5%. Accounting for IMS information gave rise to a projected FDR of approximately 4%. Signal reproducibility was found to be greater than 80%, while the variations in the number of unique peptide identifications were <15%. A single sample analysis was completed in 15 min that constitutes almost 1 order of magnitude improvement compared to a more conventional LC-MS approach. PMID:18582088

  3. Ion Mobility Spectrometry Reveals Duplex DNA Dissociation Intermediates

    NASA Astrophysics Data System (ADS)

    Burmistrova, Anastasia; Gabelica, Valérie; Duwez, Anne-Sophie; De Pauw, Edwin

    2013-11-01

    Electrospray ionization (ESI) soft desolvation is widely used to investigate fragile species such as nucleic acids. Tandem mass spectrometry (MS/MS) gives access to the gas phase energetics of the intermolecular interactions in the absence of solvent, by following the dissociation of mass-selected ions. Ion mobility mass spectrometry (IMS) provides indications on the tridimensional oligonucleotide structure by attributing a collision cross section (CCS) to the studied ion. Electrosprayed duplexes longer than eight bases pairs retain their helical structure in a solvent-free environment. However, the question of conformational changes under activation in MS/MS studies remains open. The objective of this study is to probe binding energetics and characterize the unfolding steps occurring prior to oligonucleotide duplex dissociation. Comparing the evolution of CCS with collision energy and breakdown curves, we characterize dissociation pathways involved in CID-activated DNA duplex separation into single strands, and we demonstrate here the existence of stable dissociation intermediates. At fixed duplex length, dissociation pathways were found to depend on the percentage of GC base pairs and on their position in the duplex. Our results show that pure GC sequences undergo a gradual compaction until reaching the dissociation intermediate: A-helix. Mixed AT-GC sequences were found to present at least two conformers: a classic B-helix and an extended structure where the GC tract is a B-helix and the AT tract(s) fray. The dissociation in single strands takes place from both conformers when the AT base pairs are enclosed between two GC tracts or only from the extended conformer when the AT tract is situated at the end(s) of the sequence.

  4. High-Sensitivity Ion Mobility Spectrometry/Mass Spectrometry Using Electrodynamic Ion Funnel Interfaces

    PubMed Central

    Tang, Keqi; Shvartsburg, Alexandre A.; Lee, Hak-No; Prior, David C.; Buschbach, Michael A.; Li, Fumin; Tolmachev, Aleksey; Anderson, Gordon A.; Smith, Richard D.

    2007-01-01

    The utility of ion mobility spectrometry (IMS) for separation of mixtures and structural characterization of ions has been demonstrated extensively, including in the biological and nanoscience contexts. A major attraction of IMS is its speed, several orders of magnitude greater than that of condensed-phase separations. Nonetheless, IMS combined with mass spectrometry (MS) has remained a niche technique, substantially because of limited sensitivity resulting from ion losses at the IMS-MS junction. We have developed a new electrospray ionization (ESI)-IMS-QToF MS instrument that incorporates electrodynamic ion funnels at both front ESI-IMS and rear IMS-QToF interfaces. The front funnel is of the novel “hourglass” design that efficiently accumulates ions and pulses them into the IMS drift tubes. Even for drift tubes of two meter length, ion transmission through IMS and on to QToF is essentially lossless across the range of ion masses relevant to most applications. The RF ion focusing at the IMS terminus does not degrade IMS resolving power, which exceeds 100 (for singly-charged ions) and is close to the theoretical limit. The overall sensitivity of present ESI-IMS-MS system is comparable to that of commercial ESI-MS, which should make IMS-MS suitable for analyses of complex mixtures with ultra-high sensitivity and exceptional throughput. PMID:15889926

  5. Profiling of phospholipids and related lipid structures using multidimensional ion mobility spectrometry-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Trimpin, Sarah; Tan, Bo; Bohrer, Brian C.; O'Dell, David K.; Merenbloom, Samuel I.; Pazos, Mauricio X.; Clemmer, David E.; Walker, J. Michael

    2009-10-01

    Increasingly comprehensive questions related to the biosynthesis of lipids relevant to understanding new signaling pathways have created daunting tasks for their chemical analysis. Here, ion mobility spectrometry (IMS) and mass spectrometry (MS) techniques combined with electrospray ionization have been used to examine mixtures of closely related lipid structures. The drift time distributions of sphingomyelins show baseline separations for ethylene chain length differences ([Delta] ~ 1.2 ms) and partial separations in single unsaturation differences ([Delta] ~ 0.3 ms) revealing that the most compact structures are observed with shorter chains and increasing unsaturation. Drift time distributions of different ionizations frequently fall into families with the same drift times (isodrifts) indicating that the ion attached to the lipid has little structural influence. The present data show that phospholipids, especially phosphatidylinositol, aggregate to form inverted micelles. Phospholipids (phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylinositol) are effectively separated according to their polar head groups. This method also provides information about the mixture composition of the chemically different lipids N-palmitoyl glycine, N-arachidonoyl ethanolamide, and phosphatidylcholine existing over an array of charge states and sizes (inverted micelles) depending on mixture concentration. Multidimensional IMS3-MS introduces an additional dimension to fragmentation analysis by separating the fragmented ions into groups related to size, shape and charge and allows determination of sn-1 and sn-2 substitution as is shown for phosphatidylglycerols. This contribution provides evidence for extending the targeted approach to global lipidomics analysis using the high-efficiency gas-phase separation afforded by multidimensional IMS-MS.

  6. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 1. Peptides to Proteins

    NASA Astrophysics Data System (ADS)

    Donohoe, Gregory C.; Khakinejad, Mahdiar; Valentine, Stephen J.

    2015-04-01

    Ion mobility spectrometry (IMS) coupled with hydrogen deuterium exchange (HDX)-mass spectrometry (MS) has been used to study the conformations of negatively-charged peptide and protein ions. Results are presented for ion conformers of angiotensin 1, a synthetic peptide (SP), bovine insulin, ubiquitin, and equine cytochrome c. In general, the SP ion conformers demonstrate a greater level of HDX efficiency as a greater proportion of the sites undergo HDX. Additionally, these ions exhibit the fastest rates of exchange. Comparatively, the angiotensin 1 ions exhibit a lower rate of exchange and HDX level presumably because of decreased accessibility of exchange sites by charge sites. The latter are likely confined to the peptide termini. Insulin ions show dramatically reduced HDX levels and exchange rates, which can be attributed to decreased conformational flexibility resulting from the disulfide bonds. For the larger ubiquitin and protein ions, increased HDX is observed for larger ions of higher charge state. For ubiquitin, a conformational transition from compact to more elongated species (from lower to higher charge states) is reflected by an increase in HDX levels. These results can be explained by a combination of interior site protection by compact conformers as well as decreased access by charge sites. The elongated cytochrome c ions provide the largest HDX levels where higher values correlate with charge state. These results are consistent with increased exchange site accessibility by additional charge sites. The data from these enhanced IMS-HDX experiments are described in terms of charge site location, conformer rigidity, and interior site protection.

  7. High-Sensitivity Ion Mobility Spectrometry/Mass Spectrometry Using Electrodynamic Ion Funnel Interfaces

    SciTech Connect

    Tang, Keqi; Shvartsburg, Alexandre A.; Lee, Hak-No; Prior, David C.; Buschbach, Michael A.; Li, Fumin; Tolmachev, Aleksey V.; Anderson, Gordon A.; Smith, Richard D.

    2005-05-15

    The utility of ion mobility spectrometry (IMS) for separation of mixtures and structural characterization of ions has been demonstrated extensively, including in the biological and nanoscience contexts. A major attraction of IMS is its speed, several orders of magnitude above that of condensed-phase separations. Nonetheless, IMS combined with mass spectrometry (MS) has remained a niche technique, substantially due to limited sensitivity resulting from ion losses at the IMS-MS junction. We have developed a new electrospray ionization (ESI)-IMS-QToF MS instrument that incorporates electrodynamic ion funnels at both front ESI-IMS and back IMS-QToF interfaces. The front funnel is of the novel ''hourglass'' design that efficiently accumulates ions and pulses them into the IMS drift tubes. Even for drift tubes of two meter length, ion transmission through IMS and on to QToF is essentially lossless across the range of ion masses relevant to most applications. The RF ion focusing at IMS terminus does not degrade IMS resolving power, which exceeds 100 (for singly-charged ions) and is close to the theoretical limit. The overall sensitivity of present ESI-IMS-MS system is shown to be comparable to that of commercial ESI-MS, which should make IMS-MS suitable for analyses of complex mixtures with ultra-high sensitivity and exceptional throughput.

  8. Detection and characterization of smokeless powders with ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Hernandez, Neiza M.; Rosario, Santa V.; Hernandez, Samuel P.; Mina, Nairmen

    2005-05-01

    Smokeless Powders are a class of propellants that were developed in the late 19th century to replace black powder; it has been used as an explosive in shotguns, rifles, firearms and many other larger caliber weapons. These propellants can be placed into one of three different classes according to the chemical composition of their primary energetic ingredients. Advance equipment have been designed and used for the detection of explosives devices and compounds potentially energetic. In this research we are developing an analytical methodology to detect different formulation of smokeless powders: Alliant-American Select, Alliant-Bullseye, and Alliant-Red Dot using the ion mobility spectrometry (IMS) technique. We used different surfaces like computer diskettes, CD"s, book covers and plastics to study their adsorption/desorption process. Using micropipettes, we delivered solutions with different amounts of Smokeless Powders from a 1000 ppm solution and deposit it on various types of filters to make a calibration curve. Several amounts of Smokeless Powder were deposited to the different surfaces and collected with filter paper. The samples were desorbed directly from the filter to the instrument inlet port. Subsequently, the percentage of explosive recovered was calculated.

  9. Towards metals analysis using corona discharge ionization ion mobility spectrometry.

    PubMed

    Jafari, Mohammad T; Saraji, Mohammad; Sherafatmand, Hossein

    2016-02-25

    For the first time, the capability of corona discharge ionization ion mobility spectrometry (CD-IMS) in the determination of metal complex was evaluated. The extreme simplicity of dispersive liquid-liquid microextraction (DLLME) coupled to the high sensitivity of CD-IMS measurement could make this combination really useful for simple, rapid, and sensitive determination of metals in different samples. In this regard, mercury, as a model metal, was complexed with diethyldithiocarbamate (DEDTC), and then extracted into the carbon tetrachloride using DLLME. Some parameters affecting the extraction efficiency, including the type and volume of the extraction solvent, the type and volume of the disperser solvent, the concentration of the chelating agent, salt addition and, pH were exhaustively investigated. Under the optimized condition, the enrichment factor was obtained to be 142. The linear range of 0.035-10.0 μg mL(-1) with r(2) = 0.997 and the detection limit of 0.010 μg mL(-1) were obtained. The relative standard deviation values were calculated to be lower than 4% and 8% for intra-day and inter-day, respectively. Finally, the developed method was successfully applied for the extraction and determination of mercury in various real samples. The satisfactory results revealed the capability of the proposed method in trace analysis without tedious derivatization or hydride generation. PMID:26851088

  10. Total residue analysis of swabs by ion mobility spectrometry.

    PubMed

    Strege, Mark A

    2009-06-01

    Ion mobility spectrometry (IMS) is a technique attractive for use within the pharmaceutical industry for at-line determination of residues on swabs taken from the surfaces of manufacturing equipment for the purposes of cleaning validation or verification. In this study, the development of a novel IMS method to provide a measurement of total residue present on a swab is described. The technique is based upon quantitation of charged atmospheric gas reactant ion consumption (RIC) within the instrument as a direct measure of the mass of total ionizable residue. Coupled with the conventional analysis of the active pharmaceutical ingredient within a single 2 min analysis, RIC determination provided the benefit of a single measure representative of the presence of multiple residue components or unknown components. To account for differences in response between components of a model drug product (Cymbalta) and its associated cleaning agents, a strategy was proposed to determine a "worst case" total residue test result based on RIC. A limitation of the IMS method was its incompatibility with cleaners containing a high concentration of inorganic components. The methodology provided a range from 5-50 microg per 25 cm(2) surface area and acceptable analyte recovery (50-100%). PMID:19476393

  11. Low-temperature plasma ionization differential ion mobility spectrometry.

    PubMed

    Kuklya, Andriy; Engelhard, Carsten; Uteschil, Florian; Kerpen, Klaus; Marks, Robert; Telgheder, Ursula

    2015-09-01

    A low-temperature plasma (LTP) was used as an ionization source for differential ion mobility spectrometry (DMS) for the first time. This ionization source enhances the potential of DMS as a miniaturized system for on-site rapid monitoring. The effects of experimental parameters (e.g., discharge/carrier gas composition and flow rate, applied voltage) on the analysis of model aromatic compounds were investigated and discussed. It was found that the nature of reactant ion positive (RIP) is dependent on the discharge/carrier gas composition. The best response to the analyte was achieved when pure nitrogen was used as the discharge/carrier gas. The ability to perform analysis with zero helium consumption is especially attractive in view of the potential application of LTP-DMS for online (and on-site) monitoring. Analytical performance was determined with six environmentally relevant model compounds (benzene, toluene, ethylbenzene, p-xylene, 1,2,4-trimethylbenzene, and naphthalene) using LTP and directly compared to APPI and APCI ((63)Ni) ionization sources. When LTP was coupled to DMS, calculated LOD values were found to be in the range of 35-257 ng L(-1) (concentration in the carrier gas). These values are competitive with those calculated for two DMS equipped with traditional ionization sources (APPI, (63)Ni). The obtained results are promising enough to ensure the potential of LTP as ionization source for DMS. PMID:26266836

  12. Characterization of triacetone triperoxide by ion mobility spectrometry and mass spectrometry following atmospheric pressure chemical ionization

    SciTech Connect

    Ewing, Robert G.; Waltman, Melanie J.; Atkinson, David A.

    2011-04-28

    The atmospheric pressure chemical ionization of triacetone triperoxide (TATP) with subsequent separation and detection by ion mobility spectrometry has been studied. Positive ionization with hydronium reactant ions produced only fragments of the TATP molecule, with m/z 91 ion being the most predominant species. Ionization with ammonium reactant ions produced a molecular adduct at m/z 240. The reduced mobility value of this ion was constant at 1.36 cm{sup 2}V{sup -1}s{sup -1} across the temperature range from 60 to 140 C. The stability of this ion was temperature dependent and did not exist at temperatures above 140 C, where only fragment ions were observed. The introduction of ammonia vapors with TATP resulted in the formation of m/z 58 ion. As the concentration of ammonia increased, this smaller ion appeared to dominate the spectra and the TATP-ammonium adduct decreased in intensity. The ion at m/z 58 has been noted by several research groups upon using ammonia reagents in chemical ionization, but the identity was unknown. Evidence presented here supports the formation of protonated 2-propanimine. A proposed mechanism involves the addition of ammonia to the TATP-ammonium adduct followed by an elimination reaction. A similar mechanism involving the chemical ionization of acetone with excess ammonia also showed the formation of m/z 58 ion. TATP vapors from a solid sample were detected with a hand-held ion mobility spectrometer operated at room temperature. The TATP-ammonium molecular adduct was observed in the presence of ammonia and TATP vapors with this spectrometer.

  13. Ion Mobility Mass Spectrometry Direct Isotope Abundance Analysis

    SciTech Connect

    Manuel J. Manard, Stephan Weeks, Kevin Kyle

    2010-05-27

    The nuclear forensics community is currently engaged in the analysis of illicit nuclear or radioactive material for the purposes of non-proliferations and attribution. One technique commonly employed for gathering nuclear forensics information is isotope analysis. At present, the state-of-the-art methodology for obtaining isotopic distributions is thermal ionization mass spectrometry (TIMS). Although TIMS is highly accurate at determining isotope distributions, the technique requires an elementally pure sample to perform the measurement. The required radiochemical separations give rise to sample preparation times that can be in excess of one to two weeks. Clearly, the nuclear forensics community is in need of instrumentation and methods that can expedite their decision making process in the event of a radiological release or nuclear detonation. Accordingly, we are developing instrumentation that couples a high resolution IM drift cell to the front end of a MS. The IM cell provides a means of separating ions based upon their collision cross-section and mass-to-charge ratio (m/z). Two analytes with the same m/z, but with different collision cross-sections (shapes) would exit the cell at different times, essentially enabling the cell to function in a similar manner to a gas chromatography (GC) column. Thus, molecular and atomic isobaric interferences can be effectively removed from the ion beam. The mobility selected chemical species could then be introduced to a MS for high-resolution mass analysis to generate isotopic distributions of the target analytes. The outcome would be an IM/MS system capable of accurately measuring isotopic distributions while concurrently eliminating isobaric interferences and laboratory radiochemical sample preparation. The overall objective of this project is developing instrumentation and methods to produce near real-time isotope distributions with a modular mass spectrometric system that performs the required gas-phase chemistry and

  14. Dynamically Multiplexed Ion Mobility Time-of-Flight Mass Spectrometry

    PubMed Central

    Belov, Mikhail E.; Clowers, Brian H.; Prior, David C.; Danielson, William F.; Liyu, Andrei V.; Petritis, Brianne O.; Smith, Richard D.

    2010-01-01

    Ion Mobility Spectrometry–Time-of-Flight Mass Spectrometry (IMS-TOFMS) has been increasingly used in analysis of complex biological samples. A major challenge is to transform IMS-TOFMS to a high-sensitivity high-throughput platform for e.g. proteomics applications. In this work, we have developed and integrated three advanced technologies, including efficient ion accumulation in the ion funnel trap prior to IMS separation, multiplexing (MP) of ion packet introduction into the IMS drift tube and signal detection with an analog-to-digital converter (ADC), into the IMS-TOFMS system for the high-throughput analysis of highly complex proteolytic digests of e.g. blood plasma. To better address variable sample complexity, we have developed and rigorously evaluated a novel dynamic MP approach that ensures correlation of the analyzer performance with an ion source function, and provides the improved dynamic range and sensitivity throughout the experiment. The MP IMS-TOF MS instrument has been shown to reliably detect peptides at a concentration of 1 nM in the presence of highly complex matrix, as well as to provide a three orders of magnitude dynamic range and a mass measurement accuracy of better than 5 ppm. When matched against human blood plasma database, the detected IMS-TOF features were found to yield ~ 700 unique peptide identifications at a false discovery rate (FDR) of ~ 7.5 %. Accounting for IMS information gave rise to a projected FDR of ~ 4 %. Signal reproducibility was found to be greater than 80 %, while the variations in the number of unique peptide identifications were < 15 %. A single sample analysis was completed in 15 min that constitutes almost an order of magnitude improvement compared to a more conventional LC-MS approach. PMID:18582088

  15. Dynamically Multiplexed Ion Mobility Time-of-Flight Mass Spectrometry

    SciTech Connect

    Belov, Mikhail E.; Clowers, Brian H.; Prior, David C.; Danielson, William F.; Liyu, Andrei V.; Petritis, Brianne O.; Smith, Richard D.

    2008-08-01

    Ion Mobility Spectrometry–Time-of-Flight Mass Spectrometry (IMS-TOFMS) has been increasingly used in analysis of complex biological samples. A major challenge is to transform IMS-TOFMS to a high-sensitivity high-throughput platform for e.g. proteomics applications. In this work, we have developed and integrated three advanced technologies, enabling (1) efficient ion accumulation in the ion funnel trap prior to IMS separation, (2) multiplexing (MP) of ion packet introduction into the IMS drift tube and (3) signal detection with an analog-to-digital converter (ADC), into the IMS-TOFMS system for the high-throughput analysis of highly complex proteolytic digests of e.g. blood plasma. To better address variable sample complexity, we have additionally developed and rigorously evaluated a new dynamic MP approach that ensures correlation of the analyzer performance with an ion source function, and provides the improved dynamic range and sensitivity. The MP IMS-TOF MS instrument has been shown to reliably detect peptides at a concentration of 1 nM in a highly complex matrix, as well as to provide a four orders of magnitude dynamic range and a mass measurement accuracy of better than 5 ppm. When matched against human blood plasma database, the detected IMS-TOF features yielded ~ 700 unique peptide identifications at a false discovery rate (FDR) of ~ 7.5 %. Accounting for IMS information gave rise to a projected FDR of ~ 4 %. Signal reproducibility was found to be greater than 80 %, while the variations in the number of unique peptide identifications were < 15 %. A single sample analysis was completed in 15 min, corresponding to approximately an order of magnitude improvement compared to a more conventional LC-MS approach.

  16. Differential mobility spectrometry of isomeric protonated dipeptides: modifier and field effects on ion mobility and stability.

    PubMed

    Blagojevic, Voislav; Chramow, Alexander; Schneider, Bradley B; Covey, Thomas R; Bohme, Diethard K

    2011-05-01

    The ability to resolve isomeric protonated dipeptides was investigated with the new technique of differential ion mobility mass spectrometry that uses "modifier" molecules to enhance differential mobility. Two pairs of protonated peptides [glycine-alanine (GlyAla) and alanine-glycine (AlaGly), glycine-serine (GlySer) and serine-glycine (SerGly)] and eight different modifiers (water, 2-propanol, 1,5-hexadiene, 2-chloropropane, chlorobenzene, dichloromethane, acetonitrile, and cyclohexane) were used in the initial study. Separation of the protonated peptides was found to be dependent on the mass and proton affinity of the modifier and combinations of functionalities present in the modifier and the analyte ion. Six of the eight modifiers (water, 2-propanol, chlorobenzene, cyclohexane, dichloromethane, and acetonitrile) were able to separate the protonated isomeric peptide pairs, and generally, modifiers with electron-rich groups performed the best. In the presence of some modifiers, a reduction of ion current was observed under the highest field conditions (>115 Td). Dopant-catalyzed isomerization, likely by proton-transport catalysis, and field-induced fragmentation may have contributed to these losses. Two high vapor pressure modifiers, 1,5-hexadiene and 2-chloropropane, significantly influenced ion formation leading to the formation of stable cluster populations that could be observed in the mass spectrometer. Although not a major concern, both fragmentation and influence of modifier evaporation warrant further studies in order to fully understand and possibly eliminate them. PMID:21504141

  17. Structurally selective imaging mass spectrometry by imaging ion mobility-mass spectrometry.

    PubMed

    McLean, John A; Fenn, Larissa S; Enders, Jeffrey R

    2010-01-01

    This chapter describes the utility of structurally based separations combined with imaging mass spectrometry (MS) by ion mobility-MS (IM-MS) approaches. The unique capabilities of combining rapid (mus-ms) IM separations with imaging MS are detailed for an audience ranging from new to potential practitioners in IM-MS technology. Importantly, imaging IM-MS provides the ability to rapidly separate and elucidate various types of endogenous and exogenous biomolecules (e.g., nucleotides, carbohydrates, peptides, and lipids), including isobaric species. Drift tube and traveling wave IM-MS instrumentation are described and specific protocols are presented for calculating ion-neutral collision cross sections (i.e., apparent ion surface area or structure) from experimentally obtained IM-MS data. Special emphasis is placed on the use of imaging IM-MS for the analysis of samples in life sciences research (e.g., thin tissue sections), including selective imaging for peptide/protein and lipid distributions. Future directions for rapid and multiplexed imaging IM-MS/MS are detailed. PMID:20680602

  18. Increasing Confidence of LC-MS Identifications by Utilizing Ion Mobility Spectrometry

    SciTech Connect

    Crowell, Kevin L.; Baker, Erin Shammel; Payne, Samuel H.; Ibrahim, Yehia M.; Monroe, Matthew E.; Slysz, Gordon W.; Lamarche, Brian L.; Petyuk, Vladislav A.; Piehowski, Paul D.; Danielson, William F.; Anderson, Gordon A.; Smith, Richard D.

    2013-09-05

    Ion mobility spectrometry in conjunction with liquid chromatography separations and mass spectrometry offers a range of new possibilities for analyzing complex biological samples. To fully utilize the information obtained from these three measurement dimensions, informatics tools based on the accurate mass and time tag methodology were modified to incorporate ion mobility spectrometry drift times for peptides observed in human serum. A reference human serum database was created using 12,139 peptides, tracking the monoisotopic mass, liquid chromatography normalized elution time, and ion mobility spectrometry drift time(s) for each peptide. We demonstrate that the use of three dimensions for peak matching during the peptide identification process resulted in increased numbers of identifications and lower false discovery rates relative to the use of only the mass and normalized elution time dimensions.

  19. Evaluation of Ion Mobility-Mass Spectrometry for Comparative Analysis of Monoclonal Antibodies.

    PubMed

    Ferguson, Carly N; Gucinski-Ruth, Ashley C

    2016-05-01

    Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics. Graphical Abstract ᅟ. PMID:26988372

  20. Evaluation of Ion Mobility-Mass Spectrometry for Comparative Analysis of Monoclonal Antibodies

    NASA Astrophysics Data System (ADS)

    Ferguson, Carly N.; Gucinski-Ruth, Ashley C.

    2016-05-01

    Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics.

  1. Fundamentals of ambient metastable-induced chemical ionization mass spectrometry and atmospheric pressure ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Harris, Glenn A.

    Chapter 1. Chapter 2 presents the first investigations into the atmospheric pressure ion transport phenomena during DART analysis. Chapter 3 provides a comparison on the internal energy deposition processes during DART and pneumatically assisted-ESI. Chapter 4 investigates the complex spatially-dependent sampling sensitivity, dynamic range and ion suppression effects present in most DART experiments. New implementations and applications with DART are shown in Chapters 5 and 6. In Chapter 5, DART is coupled to multiplexed drift tube ion mobility spectrometry as a potential fieldable platform for the detection of toxic industrial chemicals and chemical warfare agents simulants. In Chapter 6, transmission-mode DART is shown to be an effective method for reproducible sampling from materials which allow for gas to flow through it. Also, Chapter 6 provides a description of a MS imaging platform coupling infrared laser ablation and DART-like phenomena. Finally, in Chapter 7 I will provide perspective on the work completed with DART and the tasks and goals that future studies should focus on.

  2. Gas phase studies on terpenes by ion mobility spectrometry using different atmospheric pressure chemical ionization techniques

    NASA Astrophysics Data System (ADS)

    Borsdorf, H.; Stone, J. A.; Eiceman, G. A.

    2005-11-01

    The ionization pathways and drift behavior were determined for sets of constitutional isomeric and stereoisomeric non-polar hydrocarbons (unsaturated monocyclic terpenes, unsaturated and saturated bicyclic terpenes) using ion mobility spectrometry (IMS) with different techniques of atmospheric pressure chemical ionization (APCI) to assess how structural and stereochemical differences influence ion formation. Depending on the structural features, different ions were observed for constitutional isomers using ion mobility spectrometry with photoionization (PI) and corona discharge (CD) ionization. Photoionization provides ion mobility spectra containing one major peak for saturated compounds while at two peaks were observed for unsaturated compounds, which can be assigned to product ions related to monomer and dimer ions. However, differences in relative abundance of product ions were found depending on the position of the double bond. Although IMS using corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra are complex and differ from those obtained using photoionization. Additional cluster ions and fragment ions were detected. Only small differences in ion mobility spectra were observed for the diastereomers while the enantiomers provide identical spectra. The structure of the product ions formed was checked by investigations using the coupling of ion mobility spectrometry with mass spectrometry (IMS-MS).

  3. Multidimensional Separation of Natural Products Using Liquid Chromatography Coupled to Hadamard Transform Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Wenjie; Zhang, Xing; Knochenmuss, Richard; Siems, William F.; Hill, Herbert H.

    2016-05-01

    A high performance liquid chromatograph (HPLC)was interfaced to an atmospheric drift tube ion mobility time of flight mass spectrometry. The power of multidimensional separation was demonstrated using chili pepper extracts. The ambient pressure drift tube ion mobility provided high resolving powers up to 166 for the HPLC eluent. With implementation of Hadamard transform (HT), the duty cycle for the ion mobility drift tube was increased from less than 1% to 50%, and the ion transmission efficiency was improved by over 200 times compared with pulsed mode, improving signal to noise ratio 10 times. HT ion mobility and TOF mass spectrometry provide an additional dimension of separation for complex samples without increasing the analysis time compared with conventional HPLC.

  4. Multidimensional Separation of Natural Products Using Liquid Chromatography Coupled to Hadamard Transform Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Wenjie; Zhang, Xing; Knochenmuss, Richard; Siems, William F.; Hill, Herbert H.

    2016-02-01

    A high performance liquid chromatograph (HPLC)was interfaced to an atmospheric drift tube ion mobility time of flight mass spectrometry. The power of multidimensional separation was demonstrated using chili pepper extracts. The ambient pressure drift tube ion mobility provided high resolving powers up to 166 for the HPLC eluent. With implementation of Hadamard transform (HT), the duty cycle for the ion mobility drift tube was increased from less than 1% to 50%, and the ion transmission efficiency was improved by over 200 times compared with pulsed mode, improving signal to noise ratio 10 times. HT ion mobility and TOF mass spectrometry provide an additional dimension of separation for complex samples without increasing the analysis time compared with conventional HPLC.

  5. Multidimensional Separation of Natural Products Using Liquid Chromatography Coupled to Hadamard Transform Ion Mobility Mass Spectrometry.

    PubMed

    Liu, Wenjie; Zhang, Xing; Knochenmuss, Richard; Siems, William F; Hill, Herbert H

    2016-05-01

    A high performance liquid chromatograph (HPLC)was interfaced to an atmospheric drift tube ion mobility time of flight mass spectrometry. The power of multidimensional separation was demonstrated using chili pepper extracts. The ambient pressure drift tube ion mobility provided high resolving powers up to 166 for the HPLC eluent. With implementation of Hadamard transform (HT), the duty cycle for the ion mobility drift tube was increased from less than 1% to 50%, and the ion transmission efficiency was improved by over 200 times compared with pulsed mode, improving signal to noise ratio 10 times. HT ion mobility and TOF mass spectrometry provide an additional dimension of separation for complex samples without increasing the analysis time compared with conventional HPLC. Graphical Abstract ᅟ. PMID:26914233

  6. Rapid profiling and identification of anthocyanins in fruits with Hadamard transform ion mobility mass spectrometry.

    PubMed

    Liu, Wenjie; Zhang, Xing; Siems, William F; Hill, Herbert H; Yin, Dulin

    2015-06-15

    The use of Hadamard transform ion mobility mass spectrometry (HT-IMMS) in the profiling of anthocyanins from different fruits is presented. Samples extracted with acidic methanol and purified with solid phase extraction were analyzed with direct IMMS infusion. The separation of various anthocyanins was achieved within 30s with resolving powers up to 110. The ion mobility drift times correlated with their mass-to-charge ratios with a correlation coefficient of 0.979 to produce a trend line that was characteristic for anthocyanins. Isomers with the same anthocyanidin but different hexoses were differentiated by ion mobility spectrometry. Furthermore, mobility separated ions underwent collision induced dissociation at the IMMS interface to provide MS/MS spectra. These fragmentation spectra aided in the identification of anthocyanidins via the loss of the saccharide groups. IMMS appears to be a rapid and efficient approach for profiling and identifying anthocyanins. PMID:25660880

  7. Protein mixture analysis by MALDI/mobility/time-of-flight mass spectrometry

    NASA Astrophysics Data System (ADS)

    Russell, David H.; Gillig, Kent J.; Stone, Earle; Park, Zee-Yong; Fuhrer, K.; Gonon, M.; Schultz, A. J.

    2000-03-01

    Progress in the development of ion mobility (IM) orthogonal time-of-flight (oTOF) mass spectrometry for rapid analysis of biological samples is presented. The IM-oTOF apparatus described consists of a short drift tube (1 to 15 cm) designed for ion mobility measurement in the low-field limit and a low resolution linear (20 cm) TOF mass spectrometer. Proof of concept is demonstrated by analysis of peptide mixtures generated by proteolytic digestion of proteins.

  8. Analysis of Ultra-Pure Gases by Ion Mobility Spectrometry

    NASA Technical Reports Server (NTRS)

    Stimac, Robert M.; Wernlund, Roger F.; Cohen, Martin J.

    1995-01-01

    Work has continued with the evaluation of the Ion Mobility Spectrometer (IMS) for the analysis of gases having low parts-per-billion (10(exp -9)) water concentration. A modified PCP, inc. MMS-160 Mobility Mass Spectrometer System was used for the analysis of ultra-pure argon and nitrogen. The MMS-160 system permits the mass-identification of unique reactant and product ions observed in the reduced-water host gases. When the water is removed to low ppb levels, higher energy reactant ions are observed. In nitrogen, distinct odd- and even-numbered nitrogen cluster ion mobility peaks are observed, as well as adduct ion peaks from the trace contaminants in the gas. Argon also produces a cluster ion mobility peak and adduct ion peaks from trace components in the gas. Levels of contaminants in these ultra-pure gases can be determined from the ion mobility spectra. A calibrated source was used to provide variable known quantities of water to the pure gas supply of the IMS.

  9. Structural insights into interactions between ubiquitin specific protease 5 and its polyubiquitin substrates by mass spectrometry and ion mobility spectrometry

    PubMed Central

    Scott, Daniel; Layfield, Robert; Oldham, Neil J

    2015-01-01

    Nanoelectrospray ionization-mass spectrometry and ion mobility-mass spectrometry have been used to study the interactions of the large, multidomain, and conformationally flexible deubiquitinating enzyme ubiquitin specific protease 5 (USP5) with mono- and poly-ubiquitin (Ub) substrates. Employing a C335A active site mutant, mass spectrometry was able to detect the stable and cooperative binding of two mono-Ub molecules at the Zinc-finger ubiquitin binding protein (ZnF-UBP) and catalytic site domains of USP5. Tetra-ubiquitin, in contrast, bound to USP5 with a stoichiometry of 1 : 1, and formed additional interactions with USP5's two ubiquitin associated domains (UBAs). Charge-state distribution and ion mobility analysis revealed that both mono- and tetra-ubiquitin bound to the compact conformation of USP5 only, and that tetra-ubiquitin binding was able to shift the conformational distribution of USP5 from a mixture of extended and compact forms to a completely compact conformation. PMID:25970461

  10. Ion Mobility Mass Spectrometry Analysis of Isomeric Disaccharide Precursor, Product and Cluster Ions

    PubMed Central

    Li, Hongli; Bendiak, Brad; Siems, William F.; Gang, David R.; Hill, Herbert H.

    2015-01-01

    RATIONALE Carbohydrates are highly variable in structure owing to differences in their anomeric configurations, monomer stereochemistry, inter-residue linkage positions and general branching features. The separation of carbohydrate isomers poses a great challenge for current analytical techniques. METHODS The isomeric heterogeneity of disaccharide ions and monosaccharideglycolaldehyde product ions evaluated using electrospray traveling wave ion mobility mass spectrometry (Synapt G2 high definition mass spectrometer) in both positive and negative ion modes investigation. RESULTS The separation of isomeric disaccharide ions was observed but not fully achieved based on their mobility profiles. The mobilities of isomeric product ions, the monosaccharide-glycolaldehydes, derived from different disaccharide isomers were measured. Multiple mobility peaks were observed for both monosaccharide-glycolaldehyde cations and anions, indicating that there was more than one structural configuration in the gas phase as verified by NMR in solution. More importantly, the mobility patterns for isomeric monosaccharide-glycolaldehyde product ions were different, which enabled partial characterization of their respective disaccharide ions. Abundant disaccharide cluster ions were also observed. The Results showed that a majority of isomeric cluster ions had different drift times and, moreover, more than one mobility peak was detected for a number of specific cluster ions. CONCLUSIONS It is demonstrated that ion mobility mass spectrometry is an advantageous method to assess the isomeric heterogeneity of carbohydrate compounds. It is capable of differentiating different types of carbohydrate ions having identical m/z values as well as multiple structural configurations of single compounds. PMID:24591031

  11. Development of rapid methodologies for the isolation and quantitation of drug metabolites by differential mobility spectrometry – mass spectrometry

    PubMed Central

    Coy, Stephen L.; Nazarov, Erkinjon; Vouros, Paul

    2013-01-01

    Clinical and forensic toxicology laboratories are inundated with thousands of samples requiring lengthy chromatographic separations prior to mass spectrometry. Here, we employ differential mobility spectrometry (DMS) interfaced to nano-electrospray ionization-mass spectrometry to provide a rapid ion filtration technique for the separation of ions in gas phase media prior to mass spectral analysis on a DMS-integrated AB SCIEX API 3000 triple-quadrupole mass spectrometer. DMS is efficient at the rapid separation of ions under ambient conditions and provides many advantages when used as an ion filtration technique in tandem with mass spectrometry (MS) and MS/MS. Our studies evaluated DMS-MS/MS as a rapid, quantitative platform for the analysis of drug metabolites isolated from urine samples. In targeted applications, five metabolites of common drugs of abuse were effectively and rapidly separated using isopropanol and ethyl acetate as transport gas modifiers, eliminating the gas chromatography or liquid chromatography-based separations commonly employed in clinical and forensic toxicology laboratories. Calibration curves were prepared for the selected drug metabolites utilizing deuterated internal standards for quantitative purposes. The feasibility of separating and quantitating drug metabolites in a rapid fashion was evaluated by compensation voltage stepping followed by multiple reaction monitoring (MRM) detection. Rapid profiling of clinical and forensic toxicology samples could help to address an urgent need within the scientific community by developing high-throughput analytical methodologies, which could reduce significant case backlogs present within these laboratories. PMID:24311968

  12. MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness.

    PubMed

    Planells-Ferrer, L; Urresti, J; Soriano, A; Reix, S; Murphy, D M; Ferreres, J C; Borràs, F; Gallego, S; Stallings, R L; Moubarak, R S; Segura, M F; Comella, J X

    2014-01-01

    Neuroblastoma (NBL) is the most common solid tumor in infants and accounts for 15% of all pediatric cancer deaths. Several risk factors predict NBL outcome: age at the time of diagnosis, stage, chromosome alterations and MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-Derived Homolog) amplification, which characterizes the subset of the most aggressive NBLs with an overall survival below 30%. MYCN-amplified tumors develop exceptional chemoresistance and metastatic capacity. These properties have been linked to defects in the apoptotic machinery, either by silencing components of the extrinsic apoptotic pathway (e.g. caspase-8) or by overexpression of antiapoptotic regulators (e.g. Bcl-2, Mcl-1 or FLIP). Very little is known on the implication of death receptors and their antagonists in NBL. In this work, the expression levels of several death receptor antagonists were analyzed in multiple human NBL data sets. We report that Lifeguard (LFG/FAIM2 (Fas apoptosis inhibitory molecule 2)/NMP35) is downregulated in the most aggressive and undifferentiated tumors. Intringuingly, although LFG has been initially characterized as an antiapoptotic protein, we have found a new association with NBL differentiation. Moreover, LFG repression resulted in reduced cell adhesion, increased sphere growth and enhanced migration, thus conferring a higher metastatic capacity to NBL cells. Furthermore, LFG expression was found to be directly repressed by MYCN at the transcriptional level. Our data, which support a new functional role for a hitherto undiscovered MYCN target, provide a new link between MYCN overexpression and increased NBL metastatic properties. PMID:25188511

  13. Recent developments in ion mobility spectrometry detection technology

    NASA Astrophysics Data System (ADS)

    Ritchie, Robert K.; Kuja, Frank J.; Jackson, Ronald A.; Loveless, Arthur J.; Danylewich-May, Lucy L.

    1994-03-01

    Barringer's new IONSCANTM model 350 provides improved operational flexibility, reliability, and effectiveness in the rapid on-site detection and identification of narcotics and explosives. The model 350 is a modular integrated design, with DC-power capabilities, and wheels or vehicle mounts to facilitate transportation to and operation in a variety of operational locations. Recent developments in IONSCAN ion mobility spectrometer (IMS) technology in the model 350 include a long-life air dryer/purification system and new software for improved substance detection and false alarm rate performance. New multiple peak detection capabilities for more reliable substance identification are described. Studies on IMS temperature and pressure effects are reported and their possible future use to further improve peak detection performance are discussed. Some recent applications in narcotics interdiction are described.

  14. Proton-bound cluster ions in ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Ewing, R. G.; Eiceman, G. A.; Stone, J. A.

    1999-01-01

    Gaseous oxygen and nitrogen bases, both singly and as binary mixtures, have been introduced into ion mobility spectrometers to study the appearance of protonated molecules, and proton-bound dimers and trimers. At ambient temperature it was possible to simultaneously observe, following the introduction of molecule A, comparable intensities of peaks ascribable to the reactant ion (H2O)nH+, the protonated molecule AH+ and AH+ H2O, and the symmetrical proton bound dimer A2H+. Mass spectral identification confirmed the identifications and also showed that the majority of the protonated molecules were hydrated and that the proton-bound dimers were hydrated to a much lesser extent. No significant peaks ascribable to proton-bound trimers were obtained no matter how high the sample concentration. Binary mixtures containing molecules A and B, in some cases gave not only the peaks unique to the individual compounds but also peaks due to asymmetrical proton bound dimers AHB+. Such ions were always present in the spectra of mixtures of oxygen bases but were not observed for several mixtures of oxygen and nitrogen bases. The dimers, which were not observable, notable for their low hydrogen bond strengths, must have decomposed in their passage from the ion source to the detector, i.e. in a time less than approximately 5 ms. When the temperature was lowered to -20 degrees C, trimers, both homogeneous and mixed, were observed with mixtures of alcohols. The importance of hydrogen bond energy, and hence operating temperature, in determining the degree of solvation of the ions that will be observed in an ion mobility spectrometer is stressed. The possibility is discussed that a displacement reaction involving ambient water plays a role in the dissociation.

  15. Atmospheric pressure chemical ionization of fluorinated phenols in atmospheric pressure chemical ionization mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Eiceman, G. A.; Bergloff, J. F.; Rodriguez, J. E.; Munro, W.; Karpas, Z.

    1999-01-01

    Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) for fluorinated phenols (C6H5-xFxOH Where x = 0-5) in nitrogen with Cl- as the reagent ion yielded product ions of M Cl- through ion associations or (M-H)- through proton abstractions. Proton abstraction was controllable by potentials on the orifice and first lens, suggesting that some proton abstraction occurs through collision induced dissociation (CID) in the interface region. This was proven using CID of adduct ions (M Cl-) with Q2 studies where adduct ions were dissociated to Cl- or proton abstracted to (M-H)-. The extent of proton abstraction depended upon ion energy and structure in order of calculated acidities: pentafluorophenol > tetrafluorophenol > trifluorophenol > difluorophenol. Little or no proton abstraction occurred for fluorophenol, phenol, or benzyl alcohol analogs. Ion mobility spectrometry was used to determine if proton abstraction reactions passed through an adduct intermediate with thermalized ions and mobility spectra for all chemicals were obtained from 25 to 200 degrees C. Proton abstraction from M Cl- was not observed at any temperature for phenol, monofluorophenol, or difluorophenol. Mobility spectra for trifluorophenol revealed the kinetic transformations to (M-H)- either from M Cl- or from M2 Cl- directly. Proton abstraction was the predominant reaction for tetra- and penta-fluorophenols. Consequently, the evidence suggests that proton abstraction occurs from an adduct ion where the reaction barrier is reduced with increasing acidity of the O-H bond in C6H5-xFxOH.

  16. Modulation of hippocampal neuroplasticity by Fas/CD95 regulatory protein 2 (Faim2) in the course of bacterial meningitis.

    PubMed

    Tauber, Simone C; Harms, Kristian; Falkenburger, Björn; Weis, Joachim; Sellhaus, Bernd; Nau, Roland; Schulz, Jörg B; Reich, Arno

    2014-01-01

    Fas-apoptotic inhibitory molecule 2 (Faim2) is a neuron-specific membrane protein and a member of the evolutionary conserved lifeguard apoptosis regulatory gene family. Its neuroprotective effect in acute neurological diseases has been demonstrated in an in vivo model of focal cerebral ischemia. Here we show that Faim2 is physiologically expressed in the human brain with a changing pattern in cases of infectious meningoencephalitis.In Faim2-deficient mice, there was increased caspase-associated hippocampal apoptotic cell death and an increased extracellular signal-regulated kinase pattern during acute bacterial meningitis induced by subarachnoid infection with Streptococcus pneumoniae type 3 strain. However, after rescuing the animals by antibiotic treatment, Faim2 deficiency led to increased hippocampal neurogenesis at 7 weeks after infection. This was associated with improved performance of Faim2-deficient mice compared to wild-type littermates in the Morris water maze, a paradigm for hippocampal spatial learning and memory. Thus, Faim2 deficiency aggravated degenerative processes in the acute phase but induced regenerative processes in the repair phase of a mouse model of pneumococcal meningitis. Hence, time-dependent modulation of neuroplasticity by Faim2 may offer a new therapeutic approach for reducing hippocampal neuronal cell death and improving cognitive deficits after bacterial meningitis. PMID:24335530

  17. Structural Characterization of Unsaturated Phosphatidylcholines Using Traveling Wave Ion Mobility Spectrometry

    PubMed Central

    Kim, Hugh I.; Kim, Hyungjun; Pang, Eric S.; Ryu, Ernest K.; Beegle, Luther W.; Loo, Joseph A.; Goddard, William A.; Kanik, Isik

    2009-01-01

    A number of phosphatidylcholine (PC) cations spanning a mass range of 400 to 1000 Da are investigated using electrospray ionization mass spectrometry coupled with traveling wave ion mobility spectrometry (TWIMS). A high correlation between mass and mobility is demonstrated with saturated phosphatidylcholine cations in N2. A significant deviation from this mass-mobility correlation line is observed for the unsaturated PC cation. We found that the double bond in the acyl chain causes a 5% reduction in drift time. The drift time is reduced at a rate of ~1% for each additional double bond. Theoretical collision cross sections of PC cations exhibit good agreement with experimentally evaluated values. Collision cross sections are determined using the recently derived relationship between mobility and drift time in TWIMS stacked ring ion guide (SRIG) and compared to estimate collision cross-sections using empiric calibration method. Computational analysis was performed using the modified trajectory (TJ) method with nonspherical N2 molecules as the drift gas. The difference between estimated collision cross-sections and theoretical collision cross-sections of PC cations is related to the sensitivity of the PC cation collision cross-sections to the details of the ion-neutral interactions. The origin of the observed correlation and deviation between mass and mobility of PC cations is discussed in terms of the structural rigidity of these molecules using molecular dynamic simulations. PMID:19764704

  18. Ion Mobility-Mass Spectrometry Analysis of Serum N-linked Glycans from Esophageal Adenocarcinoma Phenotypes

    PubMed Central

    Gaye, M. M.; Valentine, S. J.; Hu, Y.; Mirjankar, N.; Hammoud, Z. T.; Mechref, Y.; Lavine, B. K.; Clemmer, D. E.

    2012-01-01

    Three disease phenotypes, Barrett’s esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS) and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including: 7 characterized as BE, 12 as HGD, 56 as EAC and 61 as NC. In typical datasets it was possible to assign ~20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for eleven N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution. PMID:23126309

  19. Ion mobility spectrometry-mass spectrometry (IMS-MS) for on- and offline analysis of atmospheric gas and aerosol species

    NASA Astrophysics Data System (ADS)

    Krechmer, Jordan E.; Groessl, Michael; Zhang, Xuan; Junninen, Heikki; Massoli, Paola; Lambe, Andrew T.; Kimmel, Joel R.; Cubison, Michael J.; Graf, Stephan; Lin, Ying-Hsuan; Budisulistiorini, Sri H.; Zhang, Haofei; Surratt, Jason D.; Knochenmuss, Richard; Jayne, John T.; Worsnop, Douglas R.; Jimenez, Jose-Luis; Canagaratna, Manjula R.

    2016-07-01

    Measurement techniques that provide molecular-level information are needed to elucidate the multiphase processes that produce secondary organic aerosol (SOA) species in the atmosphere. Here we demonstrate the application of ion mobility spectrometry-mass spectrometry (IMS-MS) to the simultaneous characterization of the elemental composition and molecular structures of organic species in the gas and particulate phases. Molecular ions of gas-phase organic species are measured online with IMS-MS after ionization with a custom-built nitrate chemical ionization (CI) source. This CI-IMS-MS technique is used to obtain time-resolved measurements (5 min) of highly oxidized organic molecules during the 2013 Southern Oxidant and Aerosol Study (SOAS) ambient field campaign in the forested SE US. The ambient IMS-MS signals are consistent with laboratory IMS-MS spectra obtained from single-component carboxylic acids and multicomponent mixtures of isoprene and monoterpene oxidation products. Mass-mobility correlations in the 2-D IMS-MS space provide a means of identifying ions with similar molecular structures within complex mass spectra and are used to separate and identify monoterpene oxidation products in the ambient data that are produced from different chemical pathways. Water-soluble organic carbon (WSOC) constituents of fine aerosol particles that are not resolvable with standard analytical separation methods, such as liquid chromatography (LC), are shown to be separable with IMS-MS coupled to an electrospray ionization (ESI) source. The capability to use ion mobility to differentiate between isomers is demonstrated for organosulfates derived from the reactive uptake of isomers of isoprene epoxydiols (IEPOX) onto wet acidic sulfate aerosol. Controlled fragmentation of precursor ions by collisionally induced dissociation (CID) in the transfer region between the IMS and the MS is used to validate MS peak assignments, elucidate structures of oligomers, and confirm the

  20. Ion mobility tandem mass spectrometry enhances performance of bottom-up proteomics.

    PubMed

    Helm, Dominic; Vissers, Johannes P C; Hughes, Christopher J; Hahne, Hannes; Ruprecht, Benjamin; Pachl, Fiona; Grzyb, Arkadiusz; Richardson, Keith; Wildgoose, Jason; Maier, Stefan K; Marx, Harald; Wilhelm, Mathias; Becher, Isabelle; Lemeer, Simone; Bantscheff, Marcus; Langridge, James I; Kuster, Bernhard

    2014-12-01

    One of the limiting factors in determining the sensitivity of tandem mass spectrometry using hybrid quadrupole orthogonal acceleration time-of-flight instruments is the duty cycle of the orthogonal ion injection system. As a consequence, only a fraction of the generated fragment ion beam is collected by the time-of-flight analyzer. Here we describe a method utilizing postfragmentation ion mobility spectrometry of peptide fragment ions in conjunction with mobility time synchronized orthogonal ion injection leading to a substantially improved duty cycle and a concomitant improvement in sensitivity of up to 10-fold for bottom-up proteomic experiments. This enabled the identification of 7500 human proteins within 1 day and 8600 phosphorylation sites within 5 h of LC-MS/MS time. The method also proved powerful for multiplexed quantification experiments using tandem mass tags exemplified by the chemoproteomic interaction analysis of histone deacetylases with Trichostatin A. PMID:25106551

  1. Ion Mobility Tandem Mass Spectrometry Enhances Performance of Bottom-up Proteomics

    PubMed Central

    Helm, Dominic; Vissers, Johannes P. C.; Hughes, Christopher J.; Hahne, Hannes; Ruprecht, Benjamin; Pachl, Fiona; Grzyb, Arkadiusz; Richardson, Keith; Wildgoose, Jason; Maier, Stefan K.; Marx, Harald; Wilhelm, Mathias; Becher, Isabelle; Lemeer, Simone; Bantscheff, Marcus; Langridge, James I.; Kuster, Bernhard

    2014-01-01

    One of the limiting factors in determining the sensitivity of tandem mass spectrometry using hybrid quadrupole orthogonal acceleration time-of-flight instruments is the duty cycle of the orthogonal ion injection system. As a consequence, only a fraction of the generated fragment ion beam is collected by the time-of-flight analyzer. Here we describe a method utilizing postfragmentation ion mobility spectrometry of peptide fragment ions in conjunction with mobility time synchronized orthogonal ion injection leading to a substantially improved duty cycle and a concomitant improvement in sensitivity of up to 10-fold for bottom-up proteomic experiments. This enabled the identification of 7500 human proteins within 1 day and 8600 phosphorylation sites within 5 h of LC-MS/MS time. The method also proved powerful for multiplexed quantification experiments using tandem mass tags exemplified by the chemoproteomic interaction analysis of histone deacetylases with Trichostatin A. PMID:25106551

  2. Fundamental studies of gas phase ionic reactions by ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Giles, K.; Knighton, W. B.; Sahlstrom, K. E.; Grimsrud, E. P.

    1995-01-01

    Ion mobility spectrometry (IMS) provides a promising approach to the study of gas phase ionic reactions in buffer gases at unusually high pressures. This point is illustrated here by studies of the Sn2 nucleophilic displacement reaction, Cl(-) + CH3Br yields Br + CH3Br, using IMS at atmospheric pressure. The equilibrium clustering reaction, Cl(-)(CHCI3)(n - 1) + CHCI3 yields Cl(-)(CHCI3)(n), where n = 1 and 2, and the effect of clustering on the Sn2 reaction with CH3Br have also been characterized by this IMS-based kinetic method. Present problems and anticipated improvements in the application of ion mobility spectrometry to studies of other gas phase ionic processes are discussed.

  3. Tandem mass spectrometry and ion mobility mass spectrometry for the analysis of molecular sequence and architecture of hyperbranched glycopolymers

    PubMed Central

    Liu, Xiumin; Cool, Lydia R.; Lin, Kenneth; Kasko, Andrea M.; Wesdemiotis, Chrys

    2015-01-01

    Multidimensional mass spectrometry techniques, combining matrix-assisted laser desorption/ionization (MALDI) or electrospray ionization (ESI) with tandem mass spectrometry (MS2), multistage mass spectrometry (MSn) or ion mobility mass spectrometry (IM-MS), have been employed to gain precise structural insight on the compositions, sequences and architectures of small oligomers of a hyperbranched glycopolymer, prepared by atom transfer radical copolymerization of an acrylate monomer (A) and an acrylate inimer (B), both carrying mannose ester pendants. The MS data confirmed the incorporation of multiple inimer repeat units, which ultimately lead to the hyperbranched material. The various possible structures of n-mers with the same composition were subsequently elucidated based on MS2 and MSn studies. The characteristic elimination of bromomethane molecule provided definitive information about the comonomer connectivity in the copolymeric AB2 trimer and A2B2 tetramer, identifying as present only one of the three possible trimeric isomers (viz. sequence BBA) and only two of the six possible tetrameric isomers (viz. sequences BBA2 and BABA). Complementary IM-MS studies confirmed that only one of the tetrameric structures is formed. Comparison of the experimentally determined collision cross-section of the detected isomer with those predicted by molecular simulations for the two possible sequences ascertained BBA2 as the predominant tetrameric architecture. The multidimensional MS approaches presented provide connectivity information at the atomic level without requiring high product purity (due to the dispersive nature of MS) and, hence, should be particularly useful for the microstructure characterization of novel glycopolymers and other types of complex copolymers. PMID:25519163

  4. Advances in ion mobility spectrometry–mass spectrometry reveal key insights into amyloid assembly☆

    PubMed Central

    Woods, L.A.; Radford, S.E.; Ashcroft, A.E.

    2013-01-01

    Interfacing ion mobility spectrometry to mass spectrometry (IMS–MS) has enabled mass spectrometric analyses to extend into an extra dimension, providing unrivalled separation and structural characterization of lowly populated species in heterogeneous mixtures. One biological system that has benefitted significantly from such advances is that of amyloid formation. Using IMS–MS, progress has been made into identifying transiently populated monomeric and oligomeric species for a number of different amyloid systems and has led to an enhanced understanding of the mechanism by which small molecules modulate amyloid formation. This review highlights recent advances in this field, which have been accelerated by the commercial availability of IMS–MS instruments. This article is part of a Special Issue entitled: Mass spectrometry in structural biology. PMID:23063533

  5. Overtone Mobility Spectrometry: Part 5. Simulations and Analytical Expressions Describing Overtone Limits

    PubMed Central

    Ewing, Michael A.; Zucker, Steven M.; Valentine, Stephen J.; Clemmer, David E.

    2015-01-01

    Mathematical expressions for the analytical duty cycle associated with different overtones in overtone mobility spectrometry are derived from the widths of the transmitted packets of ions under different instrumental operating conditions. Support for these derivations is provided through ion trajectory simulations. The outcome of the theory and simulations indicates that under all operating conditions there exists a limit or maximum observable overtone that will result in ion transmission. Implications of these findings on experimental design are discussed. PMID:23468094

  6. Using gas modifiers to significantly improve sensitivity and selectivity in a cylindrical FAIMS device.

    PubMed

    Purves, Randy W; Ozog, Allison R; Ambrose, Stephen J; Prasad, Satendra; Belford, Michael; Dunyach, Jean-Jacques

    2014-07-01

    Recent reports describing enhanced performance when using gas additives in a DMS device (planar electrodes) have indicated that comparable benefits are not attainable using FAIMS (cylindrical electrodes), owing to the non-homogeneous electric fields within the analyzer region. In this study, a FAIMS system (having cylindrical electrodes) was modified to allow for controlled delivery of gas additives. An experiment was carried out that illustrates the important distinction between gas modifiers present as unregulated contaminants and modifiers added in a controlled manner. The effect of contamination was simulated by adjusting the ESI needle position to promote incomplete desolvation, thereby permitting ESI solvent vapor into the FAIMS analyzer region, causing signal instability and irreproducible CV values. However, by actively controlling the delivery of the gas modifier, reproducible CV spectra were obtained. The effects of adding different gas modifiers were examined using 15 positive ions having mass-to-charge (m/z) values between 90 and 734. Significant improvements in peak capacity and increases in ion transmission were readily attained by adding acetonitrile vapor, even at trace levels (≤0.1%). Increases in signal intensity were greatest for the low m/z ions; for the six lowest molecular weight species, signal intensities increased by ∼10- to over 100-fold compared with using nitrogen without gas additives, resulting in equivalent or better signal intensities compared with ESI without FAIMS. These results confirm that analytical benefits derived from the addition of gas modifiers reported with a uniform electric field (DMS) also are observed using a non-homogenous electric field (FAIMS) in the analyser region. PMID:24796261

  7. Using a Buffer Gas Modifier to Change Separation Selectivity in Ion Mobility Spectrometry

    PubMed Central

    Fernández-Maestre, Roberto; Wu, Ching; Hill, Herbert H.

    2010-01-01

    The mobilities of a set of common α-amino acids, four tetraalkylammonium ions, 2,4-dimethyl pyridine (2,4-lutidine), 2,6-di-tert-butyl pyridine (DTBP), and valinol were determined using electrospray ionization-ion mobility spectrometry-quadrupole mass spectrometry (ESI-IMS-QMS) while introducing 2-butanol into the buffer gas. The mobilities of the test compounds decreased by varying extents with 2-butanol concentration in the mobility spectrometer. When the concentration of 2-butanol increased from 0.0 to 6.8 mmol m−3 (2.5×102 ppmv), percentage reductions in mobilities were: 13.6% (serine), 12.2% (threonine), 10.4% (methionine), 10.3% (tyrosine), 9.8% (valinol), 9.2% (phenylalanine), 7.8% (tryptophan), 5.6% (2,4-lutidine), 2.2% (DTBP), 1.0% (tetramethylammonium ion, TMA, and tetraethylammonium ion, TEA), 0.0% (tetrapropylammonium ion, TPA), and 0.3% (tetrabutylammonium ion, TBA). These variations in mobility depended on the size and steric hindrance on the charge of the ions, and were due to formation of large ion-2-butanol clusters. This selective variation in mobilities was applied to the resolution of a mixture of compounds with similar reduced mobilities such as serine and valinol, which overlapped in N2-only buffer gas in the IMS spectrum. The relative insensitivity of tetraalkylammonium ions and DTBP to the introduction of 2-butanol into the buffer gas was explained by steric hindrance of the four alkyl substituents in tetraalkylammonium ions and the two tert-butyl groups in DTBP, which shielded the positive charge of the ion from the attachment of 2-butanol molecules. Low buffer gas temperatures (100 °C) produced the largest reductions in mobilities by increasing ion-2-butanol interactions and formation of clusters; high temperatures (250 °C) prevented the formation of clusters, and no reduction in ion mobility was obtained with the introduction of 2-butanol into the buffer gas. Low temperatures and high concentrations of 2-butanol produced a series of

  8. Modular calibrant sets for the structural analysis of nucleic acids by ion mobility spectrometry mass spectrometry.

    PubMed

    Lippens, Jennifer L; Ranganathan, Srivathsan V; D'Esposito, Rebecca J; Fabris, Daniele

    2016-06-20

    This study explored the use of modular nucleic acid (NA) standards to generate calibration curves capable of translating primary ion mobility readouts into corresponding collision cross section (CCS) data. Putative calibrants consisted of single- (ss) and double-stranded (ds) oligo-deoxynucleotides reaching up to ∼40 kDa in size (i.e., 64 bp) and ∼5700 Å(2) in CCS. To ensure self-consistency among reference CCS values, computational data obtained in house were preferred to any experimental or computational data from disparate sources. Such values were obtained by molecular dynamics (MD) simulations and either the exact hard sphere scattering (EHSS) or the projection superposition approximation (PSA) methods, and then plotted against the corresponding experimental values to generate separate calibration curves. Their performance was evaluated on the basis of their correlation coefficients and ability to provide values that matched the CCS of selected test samples mimicking typical unknowns. The results indicated that the predictive power benefited from the exclusion of higher charged species that were more susceptible to the destabilizing effects of Coulombic repulsion. The results revealed discrepancies between EHSS and PSA data that were ascribable to the different approximations used to describe the ion mobility process. Within the boundaries defined by these approximations and the challenges of modeling NA structure in a solvent-free environment, the calibrant sets enabled the experimental determination of CCS with excellent reproducibility (precision) and error (accuracy), which will support the analysis of progressively larger NA samples of biological significance. PMID:27152369

  9. Identity Efficiency for High-Performance Ambient Pressure Ion Mobility Spectrometry.

    PubMed

    Kanu, A Bakarr; Leal, Anne

    2016-03-15

    A new approach to reduce the false-positive responses commonly encountered in the field when drugs and explosives are detected is reported for an electrospray ionization high-performance ion mobility spectrometry (ESI-HPIMS). In this article, we report on the combination of reduced mobility and the width-at-half-height of a peak to give a new parameter called conditional reduced mobility (CRM). It was found that the CRM was capable of differentiating between real drugs peaks from that of a false-positive peak and may help to reduce false-positive rates. This effect was demonstrated using 11 drugs (amphetamine, cannabidiol, cocaine, codeine, heroine, methamphetamine, morphine, phentermine, L-phenylepherine, proglitazone, and rosiglitazone) and seven interferences chosen from off-the-shelf products. This report determined and compared CRM, resolving power (R(m)), and diffusion-limited conditional theoretical reduced mobility (DLCTRM) for ESI-HPIMS. The most important parameters for determining CRM are reduced mobility and width-at-half-height of a peak. There is a specific optimum voltage, gate pulse width, resolving power, and now CRM for each ion. DLCTRM indicate the optimum reduced mobility that is not normally possible under field conditions. CRM predicts the condition at which a target compound can be differentiated from a false-positive response. This was possible because different ions exhibits different drifting patterns and hence a different peak broadening phenomenon inside an ion mobility tube. Reduced mobility for target compounds reported were reproducible to within 2% for ESI-HPIMS. The estimated resolving power for the ESI-HPIMS used in this study was 61 ± 0.22. Conditional reduced mobility introduced in this paper show differences between target compounds and false-positive peaks as high as 74%, as was the case for cannabidiol and interference #1 at 70 μs gate pulse width. PMID:26919030

  10. Sizing Large Proteins and Protein Complexes by Electrospray Ionization Mass Spectrometry and Ion Mobility

    PubMed Central

    Kaddis, Catherine S.; Lomeli, Shirley H.; Yin, Sheng; Berhane, Beniam; Apostol, Marcin I.; Kickhoefer, Valerie A.; Rome, Leonard H.; Loo, Joseph A.

    2009-01-01

    Mass spectrometry (MS) and ion mobility with electrospray ionization (ESI) have the capability to measure and detect large noncovalent protein-ligand and protein-protein complexes. Using an ion mobility method termed GEMMA (Gas-Phase Electrophoretic Mobility Molecular Analysis), protein particles representing a range of sizes can be separated by their electrophoretic mobility in air. Highly charged particles produced from a protein complex solution using electrospray can be manipulated to produce singly charged ions which can be separated and quantified by their electrophoretic mobility. Results from ESI-GEMMA analysis from our laboratory and others were compared to other experimental and theoretically determined parameters, such as molecular mass and cryoelectron microscopy and x-ray crystal structure dimensions. There is a strong correlation between the electrophoretic mobility diameter determined from GEMMA analysis and the molecular mass for protein complexes up to 12 MDa, including the 93 kDa enolase dimer, the 480 kDa ferritin 24-mer complex, the 4.6 MDa cowpea chlorotic mottle virus (CCMV), and the 9 MDa MVP-vault assembly. ESI-GEMMA is used to differentiate a number of similarly sized vault complexes that are composed of different N-terminal protein tags on the MVP subunit. The average effective density of the proteins and protein complexes studied was 0.6 g/cm3. Moreover, there is evidence that proteins and protein complexes collapse or become more compact in the gas phase in the absence of water. PMID:17434746

  11. Corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry for monitoring of volatile organic compounds.

    PubMed

    Sabo, Martin; Matejčík, Štefan

    2012-06-19

    We demonstrate the application of corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry (CD IMS-oaTOF) for volatile organic compounds (VOCs) monitoring. Two-dimensional (2D) IMS-oaTOF spectra of VOCs were recorded in nearly real time. The corona discharge atmospheric pressure chemical ionization (APCI) source was operated in positive mode in nitrogen and air. The CD ion source generates in air H(3)O(+)(H(2)O)(n) and NO(+). The NO(+) offers additional possibility for selective ionization and for an increase of the sensitivity of monoaromatic compounds. In addition to H(3)O(+)(H(2)O)(n) and NO(+), we have carried out ionization of VOCs using acetone as dopant gas ((CH(3))(2)COH(+)). Sixteen model VOCs (tetrahydrofuran, butanol, n-propanol, iso-propano, acetone, methanol, ethanol, toluene, benzene, amomnia, dioxan, triethylamine, acetonitrile, formaldehyde, m-xylene, 2,2,2-trifluoroethylamine) were tested using these ionization techniques. PMID:22594852

  12. Structural Elucidation of Enzymatically Synthesized Galacto-oligosaccharides Using Ion-Mobility Spectrometry-Tandem Mass Spectrometry.

    PubMed

    Carević, Milica; Bezbradica, Dejan; Banjanac, Katarina; Milivojević, Ana; Fanuel, Mathieu; Rogniaux, Hélène; Ropartz, David; Veličković, Dušan

    2016-05-11

    Galacto-oligosaccharides (GOS) represent a diverse group of well-characterized prebiotic ingredients derived from lactose in a reaction catalyzed with β-galactosidases. Enzymatic transgalactosylation results in a mixture of compounds of various degrees of polymerization and types of linkages. Because structure plays an important role in terms of prebiotic activity, it is of crucial importance to provide an insight into the mechanism of transgalactosylation reaction and occurrence of different types of β-linkages during GOS synthesis. Our study proved that a novel one-step method, based on ion-mobility spectrometry-tandem mass spectrometry (IMS-MS/MS), enables complete elucidation of GOS structure. It has been shown that β-galactosidase from Aspergillus oryzae has the highest affinity toward formation of β-(1→3) or β-(1→6) linkages. Additionally, it was observed that the occurrence of different linkages varies during the reaction course, indicating that tailoring favorable GOS structures with improved prebiotic activity can be achieved by adequate control of enzymatic synthesis. PMID:27109424

  13. Resolving Structural Isomers of Monosaccharide Methyl Glycosides Using Drift Tube and Traveling Wave Ion Mobility Mass Spectrometry

    PubMed Central

    Li, Hongli; Giles, Kevin; Bendiak, Brad; Kaplan, Kimberly; Siems, William F.; Hill, Herbert H.

    2013-01-01

    Monosaccharide structural isomers including sixteen methyl-D-glycopyranosides and four methyl-N-acetylhexosamines were subjected to ion mobility measurements by electrospray ion mobility mass spectrometry. Two ion mobility-MS systems were employed: atmospheric pressure drift tube ion mobility time-of-flight mass spectrometry and a Synapt G2 HDMS system which incorporates a low pressure traveling wave ion mobility separator. All the compounds were investigated as [M+Na]+ ions in the positive mode. A majority of the monosaccharide structural isomers exhibited different mobility drift times in either system, depending on differences in their anomeric and stereochemical configurations. In general, drift time patterns (relative drift times of isomers) matched between the two instruments. Higher resolving power was observed using the atmospheric pressure drift tube. Collision cross section values of monosaccharide structural isomers were directly calculated from the atmospheric pressure ion mobility experiments and a collision cross section calibration curve was made for the traveling wave ion mobility instrument. Overall, it was demonstrated that ion mobility-mass spectrometry using either drift tube or traveling wave ion mobility is a valuable technique for resolving subtle variations in stereochemistry among the sodium adducts of monosaccharide methyl glycosides. PMID:22339760

  14. Analysis of heterogeneous uptake by nanoparticles via differential mobility analysis-drift tube ion mobility spectrometry.

    PubMed

    Oberreit, Derek R; McMurry, Peter H; Hogan, Christopher J

    2014-04-21

    Improved methods are needed to study sorption of vapor molecules by particles in the gas phase (heterogeneous uptake), which is an important process in both natural and engineered environments. Here, a new measurement system, composed of a differential mobility analyzer (DMA) and drift tube ion mobility spectrometer (DTIMS) in series, is used to examine the heterogeneous uptake of water vapor by 2.85-7.6 nm particles composed of lithium and sodium iodide. The extent of heterogeneous uptake is determined by controlling the relative humidity of the drift region in the DTIMS in the 0-30% range (in air at atmospheric pressure and room temperature), and is quantified via the dimensionless growth factor (GF), i.e. the ratio of the mobility diameter of particles at a prescribed relative humidity relative to their mobility diameter under dry conditions. The precision in GF estimation of the DMA-DTIMS system is shown to be below 0.2%. An analytical equation to calculate the growth factor, based upon predictions of the equilibrium constants for the successive uptake of vapor molecules by particles, is also presented. While the equation is sufficiently general to enable comparison between measured GFs and predictions from any theoretical expression for equilibrium constants, we specifically compare measurements to GF predictions based on the classical Kelvin-Thomson-Raoult (KTR) model for the vapor pressure of a small particle, with consideration of the influence of the ion-dipole potential on water vapor-nanoparticle collisions. It is shown that KTR calculations drastically underpredict the extent of heterogeneous uptake for the examined nanoparticles. PMID:24600691

  15. Structural Characterization of Anticancer Drug Paclitaxel and Its Metabolites Using Ion Mobility Mass Spectrometry and Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Hong Hee; Hong, Areum; Cho, Yunju; Kim, Sunghwan; Kim, Won Jong; Kim, Hugh I.

    2016-02-01

    Paclitaxel (PTX) is a popular anticancer drug used in the treatment of various types of cancers. PTX is metabolized in the human liver by cytochrome P450 to two structural isomers, 3'- p-hydroxypaclitaxel (3 p-OHP) and 6α-hydroxypaclitaxel (6α-OHP). Analyzing PTX and its two metabolites, 3 p-OHP and 6α-OHP, is crucial for understanding general pharmacokinetics, drug activity, and drug resistance. In this study, electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) and collision induced dissociation (CID) are utilized for the identification and characterization of PTX and its metabolites. Ion mobility distributions of 3 p-OHP and 6α-OHP indicate that hydroxylation of PTX at different sites yields distinct gas phase structures. Addition of monovalent alkali metal and silver metal cations enhances the distinct dissociation patterns of these structural isomers. The differences observed in the CID patterns of metalated PTX and its two metabolites are investigated further by evaluating their gas-phase structures. Density functional theory calculations suggest that the observed structural changes and dissociation pathways are the result of the interactions between the metal cation and the hydroxyl substituents in PTX metabolites.

  16. Ultrasensitive Identification of Localization Variants of Modified Peptides Using Ion Mobility Spectrometry

    PubMed Central

    Ibrahim, Yehia M.; Shvartsburg, Alexandre A.; Smith, Richard D.; Belov, Mikhail E.

    2011-01-01

    Localization of the modification sites on peptides is challenging, particularly when multiple modifications or mixtures of localization isomers (variants) are involved. Such variants commonly coelute in liquid chromatography and may be undistinguishable in tandem mass spectrometry (MS/MS) for lack of unique fragments. Here, we have resolved the variants of singly and doubly phosphorylated peptides employing drift tube ion mobility spectrometry (IMS) coupled to time-of-flight mass spectrometry. Even with a moderate IMS resolving power of ~80, substantial separation was achieved for both 2+ and 3+ ions normally generated by electrospray ionization, including for the variant indistinguishable by MS/MS. Variants often exhibit a distribution of 3-D conformers, which can be adjusted for optimum IMS separation by prior field heating of ions in a funnel trap. The peak assignments were confirmed using MS/MS after IMS separation, but known species could be identified using just the ion mobility ‘tag”. Avoiding the MS/MS step lowers the detection limit of localization variants to <100 attomoles, an order of magnitude better than that provided by electron transfer dissociation in an Orbitrap MS. PMID:21692493

  17. Ultrasensitive Identification of Localization Variants of Modified Peptides Using Ion Mobility Spectrometry

    SciTech Connect

    Ibrahim, Yehia M.; Shvartsburg, Alexandre A.; Smith, Richard D.; Belov, Mikhail E.

    2011-05-28

    Localization of the modification sites on peptides is challenging, particularly when multiple modifications or mixtures of localization isomers (variants) are involved. Such variants commonly coelute in liquid chromatography and may be undistinguishable in tandem mass spectrometry (MS/MS) for lack of unique fragments. Here, we have resolved the variants of singly and doubly phosphorylated peptides employing drift tube ion mobility spectrometry (IMS) coupled to time-of-flight mass spectrometry. Even with a moderate IMS resolving power of ~80, substantial separation was achieved for both 2+ and 3+ ions normally generated by electrospray ionization, including for the variant indistinguishable by MS/MS. Variants often exhibit a distribution of 3-D conformers, which can be adjusted for optimum IMS separation by prior field heating of ions in a funnel trap. The peak assignments were confirmed using MS/MS after IMS separation, but known species could be identified using just the ion mobility "tag". Avoiding the MS/MS step lowers the detection limit of localization variants to <100 attomoles, an order of magnitude better than provided by electron transfer dissociation in an Orbitrap MS.

  18. Spatial Ion Peak Compression and its Utility in Ion Mobility Spectrometry

    PubMed Central

    Garimella, Sandilya V. B.; Ibrahim, Yehia M.; Tang, Keqi; Webb, Ian K.; Baker, Erin S.; Tolmachev, Aleksey V.; Chen, Tsung-Chi; Anderson, Gordon A.; Smith, Richard D.

    2016-01-01

    A novel concept for ion spatial peak compression is described, and discussed primarily in the context of ion mobility spectrometry (IMS). Using theoretical and numerical methods, the effects of using non-constant (e.g., linearly varying) electric fields on ion distributions (e.g., an ion mobility peak) is evaluated both in the physical and temporal domains. The application of linearly decreasing electric field in conjunction with conventional drift field arrangements is shown to lead to a reduction in IMS physical peak width. When multiple ion packets (i.e. peaks) in a selected mobility window are simultaneously subjected to such fields, there is ion packet compression, i.e., a reduction in peak widths for all species. This peak compression occurs with only a modest reduction of resolution, and which can be quickly recovered as ions drift in a constant field after the compression event. Compression also yields a significant increase in peak intensities. Ion mobility peak compression can be particularly useful for mitigating diffusion driven peak spreading over very long path length separations (e.g., in cyclic multi-pass arrangements), and for achieving higher S/N and IMS resolution over a selected mobility range. PMID:27052738

  19. Spatial Ion Peak Compression and its Utility in Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Garimella, Sandilya V. B.; Ibrahim, Yehia M.; Tang, Keqi; Webb, Ian K.; Baker, Erin S.; Tolmachev, Aleksey V.; Chen, Tsung-Chi; Anderson, Gordon A.; Smith, Richard D.

    2016-06-01

    A novel concept for ion spatial peak compression is described, and discussed primarily in the context of ion mobility spectrometry (IMS). Using theoretical and numerical methods, the effects of using non-constant (e.g., linearly varying) electric fields on ion distributions (e.g., an ion mobility peak) is evaluated both in the physical and temporal domains. The application of a linearly decreasing electric field in conjunction with conventional drift field arrangements is shown to lead to a reduction in IMS physical peak width. When multiple ion packets (i.e., peaks) in a selected mobility window are simultaneously subjected to such fields, there is ion packet compression (i.e., a reduction in peak widths for all species). This peak compression occurs with only a modest reduction of resolution, which can be quickly recovered as ions drift in a constant field after the compression event. Compression also yields a significant increase in peak intensities. Ion mobility peak compression can be particularly useful for mitigating diffusion-driven peak broadening over very long path length separations (e.g., in cyclic multi-pass arrangements), and for achieving higher S/N and IMS resolution over a selected mobility range.

  20. Spatial Ion Peak Compression and its Utility in Ion Mobility Spectrometry.

    PubMed

    Garimella, Sandilya V B; Ibrahim, Yehia M; Tang, Keqi; Webb, Ian K; Baker, Erin S; Tolmachev, Aleksey V; Chen, Tsung-Chi; Anderson, Gordon A; Smith, Richard D

    2016-06-01

    A novel concept for ion spatial peak compression is described, and discussed primarily in the context of ion mobility spectrometry (IMS). Using theoretical and numerical methods, the effects of using non-constant (e.g., linearly varying) electric fields on ion distributions (e.g., an ion mobility peak) is evaluated both in the physical and temporal domains. The application of a linearly decreasing electric field in conjunction with conventional drift field arrangements is shown to lead to a reduction in IMS physical peak width. When multiple ion packets (i.e., peaks) in a selected mobility window are simultaneously subjected to such fields, there is ion packet compression (i.e., a reduction in peak widths for all species). This peak compression occurs with only a modest reduction of resolution, which can be quickly recovered as ions drift in a constant field after the compression event. Compression also yields a significant increase in peak intensities. Ion mobility peak compression can be particularly useful for mitigating diffusion-driven peak broadening over very long path length separations (e.g., in cyclic multi-pass arrangements), and for achieving higher S/N and IMS resolution over a selected mobility range. Graphical Abstract ᅟ. PMID:27052738

  1. Spatial Ion Peak Compression and its Utility in Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Garimella, Sandilya V. B.; Ibrahim, Yehia M.; Tang, Keqi; Webb, Ian K.; Baker, Erin S.; Tolmachev, Aleksey V.; Chen, Tsung-Chi; Anderson, Gordon A.; Smith, Richard D.

    2016-04-01

    A novel concept for ion spatial peak compression is described, and discussed primarily in the context of ion mobility spectrometry (IMS). Using theoretical and numerical methods, the effects of using non-constant (e.g., linearly varying) electric fields on ion distributions (e.g., an ion mobility peak) is evaluated both in the physical and temporal domains. The application of a linearly decreasing electric field in conjunction with conventional drift field arrangements is shown to lead to a reduction in IMS physical peak width. When multiple ion packets (i.e., peaks) in a selected mobility window are simultaneously subjected to such fields, there is ion packet compression (i.e., a reduction in peak widths for all species). This peak compression occurs with only a modest reduction of resolution, which can be quickly recovered as ions drift in a constant field after the compression event. Compression also yields a significant increase in peak intensities. Ion mobility peak compression can be particularly useful for mitigating diffusion-driven peak broadening over very long path length separations (e.g., in cyclic multi-pass arrangements), and for achieving higher S/N and IMS resolution over a selected mobility range.

  2. Fast detection of narcotics by single photon ionization mass spectrometry and laser ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Laudien, Robert; Schultze, Rainer; Wieser, Jochen

    2010-10-01

    In this contribution two analytical devices for the fast detection of security-relevant substances like narcotics and explosives are presented. One system is based on an ion trap mass spectrometer (ITMS) with single photon ionization (SPI). This soft ionization technique, unlike electron impact ionization (EI), reduces unwanted fragment ions in the mass spectra allowing the clear determination of characteristic (usually molecular) ions. Their enrichment in the ion trap and identification by tandem MS investigations (MS/MS) enables the detection of the target substances in complex matrices at low concentrations without time-consuming sample preparation. For SPI an electron beam pumped excimer light source of own fabrication (E-Lux) is used. The SPI-ITMS system was characterized by the analytical study of different drugs like cannabis, heroin, cocaine, amphetamines, and some precursors. Additionally, it was successfully tested on-site in a closed illegal drug laboratory, where low quantities of MDMA could be directly detected in samples from floors, walls and lab equipments. The second analytical system is based on an ion mobility (IM) spectrometer with resonant multiphoton ionization (REMPI). With the frequency quadrupled Nd:YAG laser (266 nm), used for ionization, a selective and sensitive detection of aromatic compounds is possible. By application of suited aromatic dopants, in addition, also non-aromatic polar compounds are accessible by ion molecule reactions like proton transfer or complex formation. Selected drug precursors could be successfully detected with this device as well, qualifying it to a lower-priced alternative or useful supplement of the SPI-ITMS system for security analysis.

  3. Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

    SciTech Connect

    Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.; Diamond, Deborah L.; Brown, Roslyn N.; Ibrahim, Yehia M.; Orton, Daniel J.; Piehowski, Paul D.; Purdy, David E.; Moore, Ronald J.; Danielson, William F.; Monroe, Matthew E.; Crowell, Kevin L.; Slysz, Gordon W.; Gritsenko, Marina A.; Sandoval, John D.; Lamarche, Brian L.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Simons, Brenna C.; McMahon, Brian J.; Bhattacharya, Renuka; Perkins, James D.; Carithers, Robert L.; Strom, Susan; Self, Steven; Katze, Michael G.; Anderson, Gordon A.; Smith, Richard D.

    2014-04-01

    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is an imperative goal for the field of medicine. While mass spectrometry (MS)-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry (IMS) separations [1, 2] with liquid chromatography (LC) and MS to dramatically increase measurement sensitivity and throughput, further enabling future MS-based clinical applications. An initial application of the LC-IMS-MS platform for the analysis of blood serum samples from stratified post-liver transplant patients with recurrent fibrosis progression illustrates its potential utility for disease characterization and use in personalized medicine [3, 4].

  4. Site-Specific Mapping of Sialic Acid Linkage Isomers by Ion Mobility Spectrometry.

    PubMed

    Guttman, Miklos; Lee, Kelly K

    2016-05-17

    Detailed structural elucidation of protein glycosylation is a tedious process often involving several techniques. Glycomics and glycoproteomics approaches with mass spectrometry offer a rapid platform for glycan profiling but are limited by the inability to resolve isobaric species such as linkage and positional isomers. Recently, ion mobility spectrometry (IMS) has been shown to effectively resolve isobaric oligosaccharides, but the utility of IMS to obtain glycan structural information on a site-specific level with proteomic analyses has yet to be investigated. Here, we report that the addition of IMS to conventional glycoproteomics platforms adds additional information regarding glycan structure and is particularly useful for differentiation of sialic acid linkage isomers on both N- and O-linked glycopeptides. With further development IMS may hold the potential for rapid and complete structural elucidation of glycan chains at a site-specific level. PMID:27089023

  5. Applicability of ion mobility spectrometry for detection of quarantine pests in wood

    NASA Astrophysics Data System (ADS)

    Ewing, K. J.; Sanghera, J.; Myers, S. W.; Ervin, A. M.; Carey, C.; Gleason, G.; Mosser, L.; Levy, L.; Hennessey, M. K.; Bulluck, R.

    2016-05-01

    Visual inspection is the most commonly used method for detecting quarantine pests in agricultural cargo items at ports. For example, solid wood packing material (SWPM) at ports may be a pathway for wood pests and is a frequent item of inspection at ports. The inspection process includes examination of the external surface of the item and often destructive sampling to detect internal pest targets. There are few tools available to inspectors to increase the efficiency of inspection and reduce the labor involved. Ion mobility spectrometry (IMS) has promise as an aid for inspection. Because pests emit volatile organic compounds (VOCs) such as hormone like substances, Ion Mobility Spectrometry (IMS) was investigated for possible utility for detecting pests during inspection. SWPM is a major pest pathway in trade, and fumigation of many kinds of wood, including SWPM, with methyl bromide (MeBr) following a published schedule1 is regularly conducted for phytosanitary reasons prior to shipment to the United States. However, the question remains as to how long the methyl bromide remains in the wood samples after fumigation such that it could act as an interferent to the detection of pest related VOC emissions. This work investigates the capability of ion mobility spectrometry to detect the presence of residual methyl bromide in fumigated maple and poplar wood samples at different times post fumigation up to 118 days after fumigation. Data show that MeBr can be detected in the less dense poplar wood up to 118 days after fumigation while MeBr can be detected in the denser maple wood 55 days after fumigation.

  6. Gas phase ion chemistry of an ion mobility spectrometry based explosive trace detector elucidated by tandem mass spectrometry.

    PubMed

    Kozole, Joseph; Levine, Lauren A; Tomlinson-Phillips, Jill; Stairs, Jason R

    2015-08-01

    The gas phase ion chemistry for an ion mobility spectrometer (IMS) based explosive detector has been elucidated using tandem mass spectrometry. The IMS system, which is operated with hexachloroethane and isobutyramide reagent gases and an ion shutter type gating scheme, is connected to the atmospheric pressure interface of a triple quadrupole mass spectrometer (MS/MS). Product ion masses, daughter ion masses, and reduced mobility values for a collection of nitro, nitrate, and peroxide explosives measured with the IMS/MS/MS instrument are reported. The mass and mobility data together with targeted isotopic labeling experiments and information about sample composition and reaction environment are leveraged to propose molecular formulas, structures, and ionization pathways for the various product ions. The major product ions are identified as [DNT-H](-) for DNT, [TNT-H](-) for TNT, [RDX+Cl](-) and [RDX+NO2](-) for RDX, [HMX+Cl](-) and [HMX+NO2](-) for HMX, [NO3](-) for EGDN, [NG+Cl](-) and [NG+NO3](-) for NG, [PETN+Cl](-) and [PETN+NO3](-) for PETN, [HNO3+NO3](-) for NH4NO3, [NO2](-) for DMNB, [HMTD-NC3H6O3+H+Cl](-) and [HMTD+H-CH2O-H2O2](+) for HMTD, and [(CH3)3CO2](+) for TATP. In general, the product ions identified for the IMS system studied here are consistent with the product ions reported previously for an ion trap mobility spectrometer (ITMS) based explosive trace detector, which is operated with dichloromethane and ammonia reagent gases and an ion trap type gating scheme. Differences between the explosive trace detectors include the [NG+Cl](-) and [PETN+Cl](-) product ions being major ions in the IMS system compared to minor ions in the ITMS system as well as the major product ion for TATP being [(CH3)3CO2](+) for the IMS system and [(CH3)2CNH2](+) for the ITMS system. PMID:26048817

  7. Ion mobility-mass spectrometry strategies for untargeted systems, synthetic, and chemical biology

    PubMed Central

    May, Jody C.; Goodwin, Cody R.; McLean, John A.

    2014-01-01

    Contemporary strategies that concentrate on only one or a handful of molecular targets limits the utility of the information gained for diagnostic and predictive purposes. Recent advances in the sensitivity, speed, and precision of measurements obtained from ion mobility coupled to mass spectrometry (IM-MS) have accelerated the utility of IM-MS in untargeted, discovery-driven studies in biology. Perhaps most evident is the impact that such wide-scale discovery capabilities have yielded in the areas of systems, synthetic, and chemical biology, where the need for comprehensive, hypothesis-driving studies from multidimensional and unbiased data is required. PMID:25462629

  8. Demonstrated Potential of Ion Mobility Spectrometry for Detection of Adulterated Perfumes and Plant Speciation

    SciTech Connect

    Clark, Jared Matthew; Daum, Keith Alvin; Kalival, J. H.

    2003-01-01

    This initial study evaluates the use of ion mobility spectrometry (IMS) as a rapid test procedure for potential detection of adulterated perfumes and speciation of plant life. Sample types measured consist of five genuine perfumes, two species of sagebrush, and four species of flowers. Each sample type is treated as a separate classification problem. It is shown that discrimination using principal component analysis with K-nearest neighbors can distinguish one class from another. Discriminatory models generated using principal component regressions are not as effective. Results from this examination are encouraging and represent an initial phase demonstrating that perfumes and plants possess characteristic chemical signatures that can be used for reliable identification.

  9. Design and implementation of embedded ion mobility spectrometry instrument based on SOPC

    NASA Astrophysics Data System (ADS)

    Zhang, Genwei; Zhao, Jiang; Yang, Liu; Liu, Bo; Jiang, Yanwei; Yang, Jie

    2015-02-01

    On the hardware platform with single CYCLONE IV FPGA Chip based on SOPC technology, the control functions of IP cores of a Ion Mobility Spectrometry instrument was tested, including 32 bit Nios II soft-core processor, high-voltage module, ion gate switch, gas flow, temperature and pressure sensors, signal acquisition and communication protocol. Embedded operating system μCLinux was successfully transplanted to the hardware platform, used to schedule all the tasks, such as system initialization, parameter setting, signal processing, recognition algorithm and results display. The system was validated using the IMS diagram of Acetone reagent, and the instrument was proved to have a strong signal resolution.

  10. Dual mode ion mobility spectrometer and method for ion mobility spectrometry

    DOEpatents

    Scott, Jill R [Idaho Falls, ID; Dahl, David A [Idaho Falls, ID; Miller, Carla J [Idaho Falls, ID; Tremblay, Paul L [Idaho Falls, ID; McJunkin, Timothy R [Idaho Falls, ID

    2007-08-21

    Ion mobility spectrometer apparatus may include an ion interface that is operable to hold positive and negative ions and to simultaneously release positive and negative ions through respective positive and negative ion ports. A first drift chamber is operatively associated with the positive ion port of the ion interface and encloses an electric field therein. A first ion detector operatively associated with the first drift chamber detects positive ions from the first drift chamber. A second drift chamber is operatively associated with the negative ion port of the ion interface and encloses an electric field therein. A second ion detector operatively associated with the second drift chamber detects negative ions from said second drift chamber.

  11. A novel approach to increasing cocaine detection confidence utilizing ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Jadamec, J. Richard; Su, Chih-Wu; Rigdon, Stephen; Norwood, Lavan

    1995-01-01

    When a positive detection of a narcotic occurs during the search of a vessel, a decision has to be made whether further intensive search is warranted. In terms of unwarranted delays of vessels and possible property damage, the accuracy of the analytical determination is very important. Analytical accuracy becomes critical when the data may be used in court actions as evidence. For this purpose, the U.S. Coast Guard has been investigating several confirmatory ion mobility spectrometry (IMS) field methods for the detection and identification of cocaine. This paper presents the findings of our investigations on the use of catalytic pyrolysis and base hydrolysis as confirmatory methods. The catalytic effects of various metals on the pyrolysis reaction are reported. In addition, the effects of several different ion mobility spectrometer sample transfer mediums and varying laboratory conditions on the base hydrolysis of the cocaine molecule are also be reported.

  12. Measurement of drug facilitated sexual assault agents in simulated sweat by ion mobility spectrometry.

    PubMed

    Demoranville, Leonard T; Verkouteren, Jennifer R

    2013-03-15

    Ion mobility spectrometry has found widespread use for the detection of explosives and illicit drugs. The technique offers rapid results with high sensitivity and little sample preparation. As such, it is well suited for field deployed screening settings. Here the response of ion mobility spectrometers for three drug-facilitated sexual assault (DFSA) agents - flunitrazepam, ketamine, and MDMA - and related metabolites has been studied in the presence of a simulated sweat. While all three DFSA agents present certain challenges for qualitative identification, IMS can provide useful information to guide the early treatment and investigation of sexual assault cases. Used as a presumptive test, the identification of DFSA agents would later require confirmatory analysis by other techniques. PMID:23598140

  13. Detection of Radiation-Exposure Biomarkers by Differential Mobility Prefiltered Mass Spectrometry (DMS-MS)

    PubMed Central

    Coy, Stephen L.; Krylov, Evgeny V.; Schneider, Bradley B.; Covey, Thomas R.; Brenner, David J.; Tyburski, John B.; Patterson, Andrew D.; Krausz, Kris W.; Fornace, Albert J.; Nazarov, Erkinjon G.

    2010-01-01

    Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH / NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry – mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential-mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from nearly-isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly-isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation-treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation. PMID:20305793

  14. Separation and Identification of Isomeric Glycans by Selected Accumulation-Trapped Ion Mobility Spectrometry-Electron Activated Dissociation Tandem Mass Spectrometry.

    PubMed

    Pu, Yi; Ridgeway, Mark E; Glaskin, Rebecca S; Park, Melvin A; Costello, Catherine E; Lin, Cheng

    2016-04-01

    One of the major challenges in structural characterization of oligosaccharides is the presence of many structural isomers in most naturally occurring glycan mixtures. Although ion mobility spectrometry (IMS) has shown great promise in glycan isomer separation, conventional IMS separation occurs on the millisecond time scale, largely restricting its implementation to fast time-of-flight (TOF) analyzers which often lack the capability to perform electron activated dissociation (ExD) tandem MS analysis and the resolving power needed to resolve isobaric fragments. The recent development of trapped ion mobility spectrometry (TIMS) provides a promising new tool that offers high mobility resolution and compatibility with high-performance Fourier transform ion cyclotron resonance (FTICR) mass spectrometers when operated under the selected accumulation-TIMS (SA-TIMS) mode. Here, we present our initial results on the application of SA-TIMS-ExD-FTICR MS to the separation and identification of glycan linkage isomers. PMID:26959868

  15. Machine learning based prediction for peptide drift times in ion mobility spectrometry

    PubMed Central

    Shah, Anuj R.; Agarwal, Khushbu; Baker, Erin S.; Singhal, Mudita; Mayampurath, Anoop M.; Ibrahim, Yehia M.; Kangas, Lars J.; Monroe, Matthew E.; Zhao, Rui; Belov, Mikhail E.; Anderson, Gordon A.; Smith, Richard D.

    2010-01-01

    Motivation: Ion mobility spectrometry (IMS) has gained significant traction over the past few years for rapid, high-resolution separations of analytes based upon gas-phase ion structure, with significant potential impacts in the field of proteomic analysis. IMS coupled with mass spectrometry (MS) affords multiple improvements over traditional proteomics techniques, such as in the elucidation of secondary structure information, identification of post-translational modifications, as well as higher identification rates with reduced experiment times. The high throughput nature of this technique benefits from accurate calculation of cross sections, mobilities and associated drift times of peptides, thereby enhancing downstream data analysis. Here, we present a model that uses physicochemical properties of peptides to accurately predict a peptide's drift time directly from its amino acid sequence. This model is used in conjunction with two mathematical techniques, a partial least squares regression and a support vector regression setting. Results: When tested on an experimentally created high confidence database of 8675 peptide sequences with measured drift times, both techniques statistically significantly outperform the intrinsic size parameters-based calculations, the currently held practice in the field, on all charge states (+2, +3 and +4). Availability: The software executable, imPredict, is available for download from http:/omics.pnl.gov/software/imPredict.php Contact: rds@pnl.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20495001

  16. Amyloid-β / Neuropeptide Interactions Assessed by Ion Mobility-Mass Spectrometry

    PubMed Central

    Soper, Molly T.; DeToma, Alaina S.; Hyung, Suk-Joon; Lim, Mi Hee; Ruotolo, Brandon T.

    2013-01-01

    Recently, small peptides have been shown to modulate aggregation and toxicity of the amyloid-β protein (Aβ). As such, these new scaffolds may help discover a new class of biotherapeutics useful in the treatment of Alzheimer's disease. Many of these inhibitory peptide sequences have been derived from natural sources or from Aβ itself (e.g., C-terminal Aβ fragments). In addition, much earlier work indicates that tachykinins, a broad class of neuropeptides, display neurotrophic properties, presumably through direct interactions with either Aβ or its receptors. Based on this work, we undertook a limited screen of neuropeptides using ion mobility-mass spectrometry to search for similar such peptides with direct Aβ binding properties. Our results reveal that the neuropeptides leucine enkephalin (LE) and galanin interact with both the monomeric and small oligomeric forms of Aβ1-40 to create a range of complexes having diverse stoichiometries, while some tachyknins (i.e., substance P) do not. LE interacts with Aβ more strongly than galanin, and we utilized ion mobility-mass spectrometry, molecular dynamics simulations, gel electrophoresis/Western blot, and transmission electron microscopy to study the influence of this peptide on the structure of Aβ monomer, small Aβ oligomers, as well as the eventual formation of Aβ fibrils. We find that LE binds selectively within a region of Aβ between its N-terminal tail and hydrophobic core. Furthermore, our data indicate that LE modulates fibril generation, producing shorter fibrillar aggregates when added in stoichiometric excess relative to Aβ. PMID:23612608

  17. Electrospray ion mobility mass spectrometry of positively charged sodium bis[2-ethythexyl)sulfosuccinate aggregates.

    PubMed

    Bongiorno, David; Indelicato, Serena; Giorgi, Gianluca; Scarpella, Simona; Liveri, Vincenzo Turco; Ceraulo, Leopoldo

    2014-01-01

    Collision cross-sections (CCS) of positively singly and multiply charged aggregates of the surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) in the gas phase have been measured by quadrupole ion mobility time-of-flight mass spectrometry. Calibration of the observed drift times to the CCS of the AOTNa non-covalent aggregates was achieved by collecting, under the same experimental conditions, the drift times of a range of singly and multiply charged polyalanine peptides whose CCS had been obtained by conventional ion mobility spectrometry. Together with an obvious increase of the aggregate cross-section with the aggregation number, it was found that the aggregate cross-section increases with the charge state due to the sodium counterions steric effect and the augmented electrostatic repulsion. This finding is consistent with the result of a previous molecular dynamics study on positively charged AOTNa aggregates in the gas phase showing that, by increasing the charge state, the aggregates become progressively more oblate; implying a rise of their CCS. Moreover, the occurrence at each aggregation number and extra charge of a unique value of cross section points toward aggregates whose conformations do not show discernible shape change in the experiment time scale. PMID:24895777

  18. Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry.

    PubMed

    Campbell, J Larry; Yang, Amy Meng-Ci; Melo, Luke R; Hopkins, W Scott

    2016-07-01

    In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogen-deuterium exchange (HDX)-a probe of ion structure in mass spectrometry-actually altered analyte ion structure by tautomerization. For the N- and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D2O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D2O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the O-protonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH3OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS. Graphical Abstract ᅟ. PMID:27094827

  19. Analysis of new synthetic drugs by ion mobility time-of-flight mass spectrometry.

    PubMed

    Sysoev, Alexey A; Poteshin, Sergey S; Chernyshev, Denis M; Karpov, Alexander V; Tuzkov, Yuriy B; Kyzmin, Vyacheslav V; Sysoev, Alexander A

    2014-01-01

    Characteristic ion mobility mass spectrometry data, reduced mobility, and limits of detection (signal-to-noise ratio = 3) were determined for six synthetic drugs and cocaine by ion mobility time-of-flight mass spectrometry (IM-TOF-MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). The studied synthetic illicit drugs recently appeared on the recreational drug market as designer drugs and were methylone, 4-MEC (4'-methylethcathinone), 3,4-MDPV (3,4-methylenedioxypyrovalerone), JWH-210 [4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone], JWH-250 [2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone], and JWH-203 [1-pentyl-3-(2'-chlorophenylacetyl) indole]. Absolute reduced mobilities in nitrogen were 1.35, 1.28, 1.41, 1.30, 1.18, 0.98, 1.09, and 1.07 cm2V(-1)s(-1), for methylone [M-H]+, methylone [M+H]+, 4-MEC [M-H]+, 4-MEC [M+H]+, 3,4-MDPV [M+H]+, JWH-210 [M+H]+, JWH-250 [M+H]+, and JWH-203 [M+H]+, respectively. Selected illicit drugs are easily identified by IM-TOF-MS during a 100s analysis. Relative Limits of detection ranged from 4 to 400 nM are demonstrated for these compounds. Such relative limits of detection correspond to 14 pg to 2 ng absolute limits of detection. Better detection limits are obtained in APCI mode for all the illicit drugs except cocaine. ESI mode was found to be preferable for the IM-TOF-MS detection of cocaine at trace levels. A single sample analysis is completed in an order of magnitude less time than that for conventional liquid chromatography/mass spectrometry approach. The application allows one to consider IM-TOF-MS as a good candidate for a method to determine quickly the recently surfaced designer drugs marketed on the internet as "bath salts," "spice," and "herbal blends". PMID:24895779

  20. T-wave Ion Mobility-mass Spectrometry: Basic Experimental Procedures for Protein Complex Analysis

    PubMed Central

    Michaelevski, Izhak; Kirshenbaum, Noam; Sharon, Michal

    2010-01-01

    Ion mobility (IM) is a method that measures the time taken for an ion to travel through a pressurized cell under the influence of a weak electric field. The speed by which the ions traverse the drift region depends on their size: large ions will experience a greater number of collisions with the background inert gas (usually N2) and thus travel more slowly through the IM device than those ions that comprise a smaller cross-section. In general, the time it takes for the ions to migrate though the dense gas phase separates them, according to their collision cross-section (Ω). Recently, IM spectrometry was coupled with mass spectrometry and a traveling-wave (T-wave) Synapt ion mobility mass spectrometer (IM-MS) was released. Integrating mass spectrometry with ion mobility enables an extra dimension of sample separation and definition, yielding a three-dimensional spectrum (mass to charge, intensity, and drift time). This separation technique allows the spectral overlap to decrease, and enables resolution of heterogeneous complexes with very similar mass, or mass-to-charge ratios, but different drift times. Moreover, the drift time measurements provide an important layer of structural information, as Ω is related to the overall shape and topology of the ion. The correlation between the measured drift time values and Ω is calculated using a calibration curve generated from calibrant proteins with defined cross-sections1. The power of the IM-MS approach lies in its ability to define the subunit packing and overall shape of protein assemblies at micromolar concentrations, and near-physiological conditions1. Several recent IM studies of both individual proteins2,3 and non-covalent protein complexes4-9, successfully demonstrated that protein quaternary structure is maintained in the gas phase, and highlighted the potential of this approach in the study of protein assemblies of unknown geometry. Here, we provide a detailed description of IMS-MS analysis of protein

  1. Ultrahigh-Resolution Differential Ion Mobility Separations of Conformers for Proteins above 10 kDa: Onset of Dipole Alignment?

    SciTech Connect

    Shvartsburg, Alexandre A.

    2014-11-04

    Biomacromolecules tend to assume numerous structures in solution or the gas phase. It has been possible to resolve disparate conformational families but not unique geometries within each, and drastic peak broadening has been the bane of protein analyses by chromatography, electrophoresis, and ion mobility spectrometry (IMS). The new differential IMS (FAIMS) approach using hydrogen-rich gases was recently found to separate conformers of a small protein ubiquitin with same peak width and resolving power up to ~400 as for peptides. Present work explores the reach of this approach for larger proteins, exemplified by cytochrome c and myoglobin. Resolution similar to that for ubiquitin was largely achieved with longer separations, while the onset of peak broadening and coalescence with shorter separations suggests the limitation of present technique to proteins under ~20 kDa. This capability may enable distinguishing whole proteins with differing residue sequences or localizations of posttranslational modifications. Small features at negative compensation voltages that markedly grow from cytochrome c to myoglobin indicate the dipole alignment of rare conformers in accord with theory, further supporting the concept of pendular macroions in FAIMS.

  2. Real-time 2D separation by LC × differential ion mobility hyphenated to mass spectrometry.

    PubMed

    Varesio, Emmanuel; Le Blanc, J C Yves; Hopfgartner, Gérard

    2012-03-01

    The liquid chromatography-mass spectrometry (LC-MS) analysis of complex samples such as biological fluid extracts is widespread when searching for new biomarkers as in metabolomics. The success of this hyphenation resides in the orthogonality of both separation techniques. However, there are frequent cases where compounds are co-eluting and the resolving power of mass spectrometry (MS) is not sufficient (e.g., isobaric compounds and interfering isotopic clusters). Different strategies are discussed to solve these cases and a mixture of eight compounds (i.e., bromazepam, chlorprothixene, clonapzepam, fendiline, flusilazol, oxfendazole, oxycodone, and pamaquine) with identical nominal mass (i.e., m/z 316) is taken to illustrate them. Among the different approaches, high-resolution mass spectrometry or liquid chromatography (i.e., UHPLC) can easily separate these compounds. Another technique, mostly used with low resolving power MS analyzers, is differential ion mobility spectrometry (DMS), where analytes are gas-phase separated according to their size-to-charge ratio. Detailed investigations of the addition of different polar modifiers (i.e., methanol, ethanol, and isopropanol) into the transport gas (nitrogen) to enhance the peak capacity of the technique were carried out. Finally, a complex urine sample fortified with 36 compounds of various chemical properties was analyzed by real-time 2D separation LC×DMS-MS(/MS). The addition of this orthogonal gas-phase separation technique in the LC-MS(/MS) hyphenation greatly improved data quality by resolving composite MS/MS spectra, which is mandatory in metabolomics when performing database generation and search. PMID:22006241

  3. LC-IMS-MS Feature Finder. Detecting Multidimensional Liquid Chromatography, Ion Mobility, and Mass Spectrometry Features in Complex Datasets

    SciTech Connect

    Crowell, Kevin L.; Slysz, Gordon W.; Baker, Erin Shammel; Lamarche, Brian L.; Monroe, Matthew E.; Ibrahim, Yehia M.; Payne, Samuel H.; Anderson, Gordon A.; Smith, Richard D.

    2013-09-05

    We introduce a command line software application LC-IMS-MS Feature Finder that searches for molecular ion signatures in multidimensional liquid chromatography-ion mobility spectrometry-mass spectrometry (LC-IMS-MS) data by clustering deisotoped peaks with similar monoisotopic mass, charge state, LC elution time, and ion mobility drift time values. The software application includes an algorithm for detecting and quantifying co-eluting chemical species, including species that exist in multiple conformations that may have been separated in the IMS dimension.

  4. Quantitative determination of residual active pharmaceutical ingredients and intermediates on equipment surfaces by ion mobility spectrometry.

    PubMed

    Qin, C; Granger, A; Papov, V; McCaffrey, J; Norwood, D L

    2010-01-01

    Ion mobility spectrometry (IMS) is an analytical technique that separates ions based on their gas phase mobility at atmospheric pressure. Since gas phase ion mobility is a function of the shape and structure of the ion, this technique has the potential to provide unique specificity and selectivity. Furthermore, IMS is very sensitive (subnanogram detection limits for many small molecules), and a single analysis is typically completed within 1 min. In principle, these features of IMS should make it an ideal choice for use in cleaning verification analysis of pharmaceutical manufacturing equipment. This report describes the successful development and validation of three different equipment cleaning verification methods using IMS. The methods were developed for a specific intermediate (Compound A) in the synthetic route for a drug substance as well as for final drug substances (active pharmaceutical ingredients Compounds B and C). The cleaning verification methods were validated with respect to specificity, linearity, precision, accuracy, stability, and limit-of-quantitation. In all cases, the limits-of-quantitation were determined to be at the nanogram or sub-nanogram level. Both swab and rinse samples collected from the equipment surfaces were successfully analyzed and manufacturing equipment down-time was significantly minimized due to the reduction in cleaning verification analysis time (for example, the total analysis time for more than 30 samples using IMS was reduced to less than 2h). PMID:19758781

  5. Digitally-multiplexed nanoelectrospray ionization atmospheric pressure drift tube ion mobility spectrometry.

    PubMed

    Kwasnik, Mark; Caramore, Joe; Fernández, Facundo M

    2009-02-15

    One of the shortcomings of atmospheric pressure drift tube ion mobility spectrometry (DTIMS) is its intrinsically low duty cycle (approximately 0.04-1%) caused by the rapid pulsing of the ion gate (25-400 micros) followed by a comparatively long drift time (25-100 ms), which translates into a loss of sensitivity. Multiplexing approaches via Hadamard and Fourier-type gating techniques have been reported for increasing the sensitivity of DTIMS. Here, we report an extended multiplexing approach which encompasses arbitrary binary ion injection waveforms with variable duty cycles ranging from 0.5 to 50%. In this approach, ion mobility spectra can be collected using conventional signal averaging, arbitrary, standard Hadamard and/or "extended" Hadamard operation modes. Initial results indicate signal-to-noise gains ranging from 2-7-fold for both arbitrary and "extended" Hadamard sequences. Standard Hadamard transform IMS provided increased sensitivity, with gains ranging from 9-12-fold, however, mobility spectra suffered from defects that appeared as false peaks, which were reduced or eliminated when using arbitrary or "extended" Hadamard waveforms for multiplexing. Digital multiplexing enables variation of the duty cycle in a continuous manner, minimizing the contribution of imperfect modulation on spectral defects without the need for complex spectral correction methods. By reducing the frequency of gating events employed in the variable duty cycle sequences, the contributions of factors such as ion depletion prior to gating, interaction of successively injected ion packets, and the cumulative effect of imperfect gating events were mitigated. PMID:19133785

  6. Ion mobility spectrometry for the rapid analysis of over-the-counter drugs and beverages

    PubMed Central

    Fernández-Maestre, Roberto

    2009-01-01

    In the pharmaceutical industry, there are increasing requirements for analytical methods in quality assessment for the production of drugs. In this investigation, ion mobility spectrometry (IMS) was used for the rapid qualitative separation and identification of active ingredients in generic over-the-counter drugs and food additives in beverages. The active ingredients determined in drugs were acetaminophen, aspartame, bisacodyl, caffeine, dextromethorphan, diphenhydramine, famotidine, glucosamine, guaifenesin, loratadine, niacin, phenylephrine, pyridoxine, thiamin, and tetrahydrozoline. Aspartame and caffeine were determined in beverages. Fourteen over-the-counter drugs and beverages were analyzed. Analysis times below 10 s were obtained for IMS, and reduced mobilities were reported for the first time for 12 compounds. A quadrupole mass spectrometer coupled to a mobility spectrometer was used to assure a correct peak assignation. The combination of fast analysis, low cost, and inexpensive maintenance of IMS instruments makes IMS an attractive technique for the qualitative determination of the active ingredients in over-the-counter drugs and food additives in manufacture quality control and cleaning verification for the drug and food industries. PMID:20835390

  7. Direct analysis of pharmaceutical drug formulations using ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry combined with desorption electrospray ionization.

    PubMed

    Weston, Daniel J; Bateman, Robert; Wilson, Ian D; Wood, Tim R; Creaser, Colin S

    2005-12-01

    A novel approach to the rapid analysis of pharmaceutical drug formulations using hyphenated ion mobility spectrometry (IMS) and time-of-flight mass spectrometry (ToF-MS) that requires no sample pretreatment or chromatographic separation is described. A modified quadrupole time-of-flight mass spectrometer containing an ion mobility drift cell was used for gas-phase electrophoretic separation of ions prior to ToF-MS detection. The generation of sample ions directly from tablets and cream formulations was effected by desorption electrospray ionization (DESI) using a modified electrospray ion source. The analysis of a range of over-the-counter and prescription tablet formulations is described, including histamine H2 receptor antagonist (ranitidine), analgesic (paracetamol), opiate (codeine), and aromatase inhibitor anticancer (anastrozole) drugs. The successful determination of active drugs from soft formulations, such as an antiseptic cream (chlorhexidine) and a nicotine-containing skin patch, is also presented. Limits of detection for the active drugs using the DESI/IMS/ToF-MS method fell within the high-picomole to nanomole range. In all cases, the use of ion mobility drift tube separation showed increased selectivity for active drug responses (present as low as 0.14% w/w) over excipient responses such as poly(ethylene glycol). Tandem mass spectrometric analysis of precursor ions separated by IMS allowed positive confirmation of active drugs with little loss of ion mobility efficiency. The ability to analyze hard or soft pharmaceutical formulations directly by DESI combined with ion mobility spectrometry/mass spectrometry in approximately 2 min demonstrates the potential applicability of this novel method to pharmaceutical screening of low-molecular-weight drug formulations with high selectivity over the formulation vehicle. PMID:16316164

  8. Laser desorption with corona discharge ion mobility spectrometry for direct surface detection of explosives.

    PubMed

    Sabo, M; Malásková, M; Matejčík, S

    2014-10-21

    We present a new highly sensitive technique for the detection of explosives directly from the surface using laser desorption-corona discharge-ion mobility spectrometry (LD-CD-IMS). We have developed LD based on laser diode modules (LDM) and the technique was tested using three different LDM (445, 532 and 665 nm). The explosives were detected directly from the surface without any further preparation. We discuss the mechanism of the LD and the limitations of this technique such as desorption time, transport time and desorption area. After the evaluation of experimental data, we estimated the potential limits of detection of this method to be 0.6 pg for TNT, 2.8 pg for RDX and 8.4 pg for PETN. PMID:25118619

  9. Direct determination of ammoniacal nitrogen in water samples using corona discharge ion mobility spectrometry.

    PubMed

    Jafari, M T; Khayamian, T

    2008-09-15

    In this study, direct determination of ammoniacal nitrogen residues in water samples using corona discharge ion mobility spectrometry (CD-IMS) was investigated. Pyridine was used as an alternate reagent gas to enhance selectivity and sensitivity of the method. The results indicate that the limit of detection (LOD) was about 9.2x10(-3)mugmL(-1) and the linear dynamic range was obtained from 0.03 to 2.00mugmL(-1). The relative standard deviation was about 11%. Furthermore, this method was successfully applied to the direct determination of ammoniacal nitrogen in river and tap water samples and the results were compared with the Nessler method. The comparison of the results validates the potential of the proposed method as an alternative technique for the analysis of the ammoniacal nitrogen in water samples. PMID:18761176

  10. Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements

    DOE PAGESBeta

    Prost, Spencer A.; Crowell, Kevin L.; Baker, Erin Shammel; Ibrahim, Yehia M.; Clowers, Brian H.; Monroe, Matthew E.; Anderson, Gordon A.; Smith, Richard D.; Payne, Samuel H.

    2014-05-06

    Applying Hadamard transform multiplexing to ion mobility separations (IMS) can significantly improve the signal-to-noise ratio and throughput for IMS coupled mass spectrometry (MS) measurements by increasing the ion utilization efficiency. However, it has been determined that both fluctuations in ion intensity as well as spatial shifts in the multiplexed data lower the signal-to-noise ratios and appear as noise in downstream processing of the data. To address this problem, we have developed a novel algorithm that discovers and eliminates data artifacts. The algorithm uses knowledge of the true signal peaks derived from the encoded data and allows for both artifacts andmore » noise to be removed with high confidence, decreasing the likelihood of false identifications in subsequent data processing. The result is that IMS-MS can be applied to increase measurement sensitivity while avoiding artifacts that have previously limited its utility.« less

  11. Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements

    NASA Astrophysics Data System (ADS)

    Prost, Spencer A.; Crowell, Kevin L.; Baker, Erin S.; Ibrahim, Yehia M.; Clowers, Brian H.; Monroe, Matthew E.; Anderson, Gordon A.; Smith, Richard D.; Payne, Samuel H.

    2014-12-01

    Applying Hadamard transform multiplexing to ion mobility separations (IMS) can significantly improve the signal-to-noise ratio and throughput for IMS coupled mass spectrometry (MS) measurements by increasing the ion utilization efficiency. However, it has been determined that fluctuations in ion intensity as well as spatial shifts in the multiplexed data lower the signal-to-noise ratios and appear as noise in downstream processing of the data. To address this problem, we have developed a novel algorithm that discovers and eliminates data artifacts. The algorithm employs an analytical approach to identify and remove artifacts from the data, decreasing the likelihood of false identifications in subsequent data processing. Following application of the algorithm, IMS-MS measurement sensitivity is greatly increased and artifacts that previously limited the utility of applying the Hadamard transform to IMS are avoided. [Figure not available: see fulltext.

  12. Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements

    SciTech Connect

    Prost, Spencer A.; Crowell, Kevin L.; Baker, Erin Shammel; Ibrahim, Yehia M.; Clowers, Brian H.; Monroe, Matthew E.; Anderson, Gordon A.; Smith, Richard D.; Payne, Samuel H.

    2014-12-01

    Applying Hadamard transform multiplexing to ion mobility separations (IMS) can significantly improve the signal-to-noise ratio and throughput for IMS coupled mass spectrometry (MS) measurements by increasing the ion utilization efficiency. However, it has been determined that both fluctuations in ion intensity as well as spatial shifts in the multiplexed data lower the signal-to-noise ratios and appear as noise in downstream processing of the data. To address this problem, we have developed a novel algorithm that discovers and eliminates data artifacts. The algorithm uses knowledge of the true signal peaks derived from the encoded data and allows for both artifacts and noise to be removed with high confidence, decreasing the likelihood of false identifications in subsequent data processing. The result is that IMS-MS can be applied to increase measurement sensitivity while avoiding artifacts that have previously limited its utility.

  13. Ion mobility spectrometry fingerprints: A rapid detection technology for adulteration of sesame oil.

    PubMed

    Zhang, Liangxiao; Shuai, Qian; Li, Peiwu; Zhang, Qi; Ma, Fei; Zhang, Wen; Ding, Xiaoxia

    2016-02-01

    A simple and rapid detection technology was proposed based on ion mobility spectrometry (IMS) fingerprints to determine potential adulteration of sesame oil. Oil samples were diluted by n-hexane and analyzed by IMS for 20s. Then, chemometric methods were employed to establish discriminant models for sesame oils and four other edible oils, pure and adulterated sesame oils, and pure and counterfeit sesame oils, respectively. Finally, Random Forests (RF) classification model could correctly classify all five types of edible oils. The detection results indicated that the discriminant models built by recursive support vector machine (R-SVM) method could identify adulterated sesame oil samples (⩾ 10%) with an accuracy value of 94.2%. Therefore, IMS was shown to be an effective method to detect the adulterated sesame oils. Meanwhile, IMS fingerprints work well to detect the counterfeit sesame oils produced by adding sesame oil essence into cheaper edible oils. PMID:26304320

  14. Resolving Interferences in Negative Mode Ion Mobility Spectrometry Using Selective Reactant Ion Chemistry

    SciTech Connect

    Daum, Keith Alvin; Atkinson, David Alan; Ewing, Robert Gordon; Knighton, W. B.; Grimsrud, E. P

    2001-04-01

    During the investigation of the degradation products of 2,4,6-trinitrotoluene (TNT) using ion mobility spectrometry (IMS), 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4-dichlorophenol (DCP) were found to have IMS responses which overlapped those of the TNT degradation products. It was observed that the Cl- reactant ion chemistry, often used for explosives analysis, was not always successful in resolving peak overlap of analytes and interferents. It is shown here that resolution of the analytes and interferences can sometimes be achieved using only air for the formation of reactant ions, at other times through the use of Br- as an alternative to Cl- for producing reactant ions, and also through the promotion of adduct stability by lowering the IMS temperature.

  15. The use of difference spectra with a filtered rolling average background in mobile gamma spectrometry measurements

    NASA Astrophysics Data System (ADS)

    Cresswell, A. J.; Sanderson, D. C. W.

    2009-08-01

    The use of difference spectra, with a filtering of a rolling average background, as a variation of the more common rainbow plots to aid in the visual identification of radiation anomalies in mobile gamma spectrometry systems is presented. This method requires minimal assumptions about the radiation environment, and is not computationally intensive. Some case studies are presented to illustrate the method. It is shown that difference spectra produced in this manner can improve signal to background, estimate shielding or mass depth using scattered spectral components, and locate point sources. This approach could be a useful addition to the methods available for locating point sources and mapping dispersed activity in real time. Further possible developments of the procedure utilising more intelligent filters and spatial averaging of the background are identified.

  16. Atmospheric Pressure Chemical Ionization Sources Used in The Detection of Explosives by Ion Mobility Spectrometry

    SciTech Connect

    Waltman, Melanie J.

    2010-05-01

    Explosives detection is a necessary and wide spread field of research. From large shipping containers to airline luggage, numerous items are tested for explosives every day. In the area of trace explosives detection, ion mobility spectrometry (IMS) is the technique employed most often because it is a quick, simple, and accurate way to test many items in a short amount of time. Detection by IMS is based on the difference in drift times of product ions through the drift region of an IMS instrument. The product ions are created when the explosive compounds, introduced to the instrument, are chemically ionized through interactions with the reactant ions. The identity of the reactant ions determines the outcomes of the ionization process. This research investigated the reactant ions created by various ionization sources and looked into ways to manipulate the chemistry occurring in the sources.

  17. Ion mobility spectrometry as a high-throughput analytical tool in occupational pyrethroid exposure.

    PubMed

    Armenta, S; Blanco, M

    2012-08-01

    The capabilities of ion mobility spectrometry (IMS) as a high throughput and green analytical tool in the occupational health and safety control, using pyrethroids as models has been evidenced. The method used for dermal and inhalation exposure assessment is based on the passive pyrethroid sampling using Teflon membranes, direct thermal extraction of the pyrethroids, and measurement of the vaporized analytes by IMS without reagent and solvent consumption. The IMS signatures of the studied synthetic pyrethroids under atmospheric pressure chemical ionization by investigating the formed negative ion products have been obtained. The main advantages of the proposed procedure are related to the obtained limits of detection, ranging from 0.08 to 5 ng, the simplicity of measurement, the lack of sample treatment, and therefore, solvent consumption and waste generation, and finally, the speed of analysis. PMID:22159370

  18. Field screening of soils contaminated with explosives using ion mobility spectrometry

    SciTech Connect

    Crockett, A.B.; Atkinson, D.A.; Jenkins, T.F.

    1996-09-01

    Soils contaminated with explosives constitute a problem at DOE facilities and Army installations. Because explosives in soil are often heterogeneously distributed and require high density sampling, field screening is essential to characterize sites more quickly, economically and accurately. Current immunoassay and colorimetric field screening procedures have proven useful, but have significant per sample costs and limited throughput. At present, several field screening are available for TNT in soil, three procedures for RDX, and one procedure for 2,4-DNTand ammonium picrate/picric acid (AP/PA). Ion mobility spectrometry (IMS) has been used to detect explosives in air at ppt levels, but limited work has been done to apply the technique to quantify explosives in soils. The objective of this study has been to evaluate the utility of IMS as a screening technique for quantifying explosive residues in soils.

  19. Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements

    SciTech Connect

    Prost, Spencer A.; Crowell, Kevin L.; Baker, Erin Shammel; Ibrahim, Yehia M.; Clowers, Brian H.; Monroe, Matthew E.; Anderson, Gordon A.; Smith, Richard D.; Payne, Samuel H.

    2014-05-06

    Applying Hadamard transform multiplexing to ion mobility separations (IMS) can significantly improve the signal-to-noise ratio and throughput for IMS coupled mass spectrometry (MS) measurements by increasing the ion utilization efficiency. However, it has been determined that both fluctuations in ion intensity as well as spatial shifts in the multiplexed data lower the signal-to-noise ratios and appear as noise in downstream processing of the data. To address this problem, we have developed a novel algorithm that discovers and eliminates data artifacts. The algorithm uses knowledge of the true signal peaks derived from the encoded data and allows for both artifacts and noise to be removed with high confidence, decreasing the likelihood of false identifications in subsequent data processing. The result is that IMS-MS can be applied to increase measurement sensitivity while avoiding artifacts that have previously limited its utility.

  20. GlycoMob: an ion mobility-mass spectrometry collision cross section database for glycomics.

    PubMed

    Struwe, Weston B; Pagel, Kevin; Benesch, Justin L P; Harvey, David J; Campbell, Matthew P

    2016-06-01

    Ion mobility mass spectrometry (IM-MS) is a promising analytical technique for glycomics that separates glycan ions based on their collision cross section (CCS) and provides glycan precursor and fragment masses. It has been shown that isomeric oligosaccharide species can be separated by IM and identified on basis of their CCS and fragmentation. These results indicate that adding CCSs information for glycans and glycan fragments to searchable databases and analysis pipelines will increase identification confidence and accuracy. We have developed a freely accessible database, GlycoMob ( http://www.glycomob.org ), containing over 900 CCSs values of glycans, oligosaccharide standards and their fragments that will be continually updated. We have measured the absolute CCSs of calibration standards, biologically derived and synthetic N-glycans ionized with various adducts in positive and negative mode or as protonated (positive ion) and deprotonated (negative ion) ions. PMID:26314736

  1. Ion Mobility-Mass Spectrometry Reveals the Energetics of Intermediates that Guide Polyproline Folding.

    PubMed

    Shi, Liuqing; Holliday, Alison E; Glover, Matthew S; Ewing, Michael A; Russell, David H; Clemmer, David E

    2016-01-01

    Proline favors trans-configured peptide bonds in native proteins. Although cis/trans configurations vary for non-native and unstructured states, solvent also influences these preferences. Water induces the all-cis right-handed polyproline-I (PPI) helix of polyproline to fold into the all-trans left-handed polyproline-II (PPII) helix. Our recent work has shown that this occurs via a sequential mechanism involving six resolved intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702-12711 (2014)]. Here, we use ion mobility-mass spectrometry to make the first detailed thermodynamic measurements of the folding intermediates, which inform us about how and why this transition occurs. It appears that early intermediates are energetically favorable because of the hydration of the peptide backbone, whereas late intermediates are enthalpically unfavorable. However, folding continues, as the entropy of the system increases upon successive formation of each new structure. When PPII is immersed in 1-propanol, the PPII→PPI transition occurs, but this reaction occurs through a very different mechanism. Early on, the PPII population splits onto multiple pathways that eventually converge through a late intermediate that continues on to the folded PPI helix. Nearly every step is endothermic. Folding results from a stepwise increase in the disorder of the system, allowing a wide-scale search for a critical late intermediate. Overall, the data presented here allow us to establish the first experimentally determined energy surface for biopolymer folding as a function of solution environment. PMID:26362047

  2. High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel

    DOEpatents

    Smith, Richard D.; Tang, Keqi; Shvartsburg, Alexandre A.

    2005-11-22

    A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing a device for transmitting ions from an ion source which allows the transmission of ions without significant delay to an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.

  3. High-Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel

    DOEpatents

    Smith, Richard D.; Tang, Keqi; Shvartsburg, Alexandre A.

    2004-11-16

    A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.

  4. Ion Mobility-Mass Spectrometry Reveals the Energetics of Intermediates that Guide Polyproline Folding

    NASA Astrophysics Data System (ADS)

    Shi, Liuqing; Holliday, Alison E.; Glover, Matthew S.; Ewing, Michael A.; Russell, David H.; Clemmer, David E.

    2016-01-01

    Proline favors trans-configured peptide bonds in native proteins. Although cis/ trans configurations vary for non-native and unstructured states, solvent also influences these preferences. Water induces the all- cis right-handed polyproline-I (PPI) helix of polyproline to fold into the all- trans left-handed polyproline-II (PPII) helix. Our recent work has shown that this occurs via a sequential mechanism involving six resolved intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702-12711 (2014)]. Here, we use ion mobility-mass spectrometry to make the first detailed thermodynamic measurements of the folding intermediates, which inform us about how and why this transition occurs. It appears that early intermediates are energetically favorable because of the hydration of the peptide backbone, whereas late intermediates are enthalpically unfavorable. However, folding continues, as the entropy of the system increases upon successive formation of each new structure. When PPII is immersed in 1-propanol, the PPII→PPI transition occurs, but this reaction occurs through a very different mechanism. Early on, the PPII population splits onto multiple pathways that eventually converge through a late intermediate that continues on to the folded PPI helix. Nearly every step is endothermic. Folding results from a stepwise increase in the disorder of the system, allowing a wide-scale search for a critical late intermediate. Overall, the data presented here allow us to establish the first experimentally determined energy surface for biopolymer folding as a function of solution environment.

  5. Site-Specific Characterization of d-Amino Acid Containing Peptide Epimers by Ion Mobility Spectrometry

    PubMed Central

    2013-01-01

    Traditionally, the d-amino acid containing peptide (DAACP) candidate can be discovered by observing the differences of biological activity and chromatographic retention time between the synthetic peptides and naturally occurring peptides. However, it is difficult to determine the exact position of d-amino acid in the DAACP candidates. Herein, we developed a novel site-specific strategy to rapidly and precisely localize d-amino acids in peptides by ion mobility spectrometry (IMS) analysis of mass spectrometry (MS)-generated epimeric fragment ions. Briefly, the d/l-peptide epimers were separated by online reversed-phase liquid chromatography and fragmented by collision-induced dissociation (CID), followed by IMS analysis. The epimeric fragment ions resulting from d/l-peptide epimers exhibit conformational differences, thus showing different mobilities in IMS. The arrival time shift between the epimeric fragment ions was used as criteria to localize the d-amino acid substitution. The utility of this strategy was demonstrated by analysis of peptide epimers with different molecular sizes, [d-Trp]-melanocyte-stimulating hormone, [d-Ala]-deltorphin, [d-Phe]-achatin-I, and their counterparts that contain all-l amino acids. Furthermore, the crustacean hyperglycemia hormones (CHHs, 8.5 kDa) were isolated from the American lobster Homarus americanus and identified by integration of MS-based bottom-up and top-down sequencing approaches. The IMS data acquired using our novel site-specific strategy localized the site of isomerization of l- to d-Phe at the third residue of the CHHs from the N-terminus. Collectively, this study demonstrates a new method for discovery of DAACPs using IMS technique with the ability to localize d-amino acid residues. PMID:24328107

  6. Determination of N-linked glycosylation in viral glycoproteins by negative ion mass spectrometry and ion mobility

    PubMed Central

    Bitto, David; Harvey, David J.; Halldorsson, Steinar; Doores, Katie J.; Pritchard, Laura K.; Huiskonen, Juha T.; Bowden, Thomas A.; Crispin, Max

    2016-01-01

    Summary Glycan analysis of virion-derived glycoproteins is challenging due to the difficulties in glycoprotein isolation and low sample abundance. Here, we describe how ion mobility mass spectrometry can be used to obtain spectra from virion samples. We also describe how negative ion fragmentation of glycans can be used to probe structural features of virion glycans. PMID:26169737

  7. Shift reagents in ion mobility spectrometry: the effect of the number of interaction sites, size and interaction energies on the mobilities of valinol and ethanolamine.

    PubMed

    Fernández-Maestre, Roberto; Meza-Morelos, Dairo; Wu, Ching

    2016-05-01

    Overlapping peaks interfere in ion mobility spectrometry (IMS), but they are separated introducing mobility shift reagents (SR) in the buffer gas forming adducts with different collision cross-sections (size). IMS separations using SR depend on the ion mobility shifts which are governed by adduct's size and interaction energies (stabilities). Mobility shifts of valinol and ethanolamine ions were measured by electrospray-ionization ion mobility-mass spectrometry (MS). Methyl-chloro propionate (M) was used as SR; 2-butanol (B) and nitrobenzene (N) were used for comparison. Density functional theory was used for calculations. B produced the smallest mobility shifts because of its small size. M and N have two strong interaction sites (oxygen atoms) and similar molecular mass, and they should produce similar shifts. For both ethanolamine and valinol ions, stabilities were larger for N adducts than those of M. With ethanolamine, M produced a 68% shift, large compared to that using N, 61%, because M has a third weak interaction site on the chlorine atom and, therefore, M has more interaction possibilities than N. This third site overrode the oxygen atoms' interaction energy that favored the adduction of ethanolamine with N over that with M. On the contrary, with valinol mobility shifts were larger with N than with M (21 vs 18%) because interaction energy favored even more adduction of valinol with N than with M; that is, the interaction energy difference between adducts of valinol with M and N was larger than that between those adducts with ethanolamine, and the third M interaction could not override this larger difference. Mobility shifts were explained based on the number of SR's interaction sites, size of ions and SR, and SR-ion interaction energies. This is the first time that the number of interaction sites is used to explain mobility shifts in SR-assisted IMS. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27194523

  8. Multi-Capillary Column-Ion Mobility Spectrometry of Volatile Metabolites Emitted by Saccharomyces Cerevisiae

    PubMed Central

    Halbfeld, Christoph; Ebert, Birgitta E.; Blank, Lars M.

    2014-01-01

    Volatile organic compounds (VOCs) produced during microbial fermentations determine the flavor of fermented food and are of interest for the production of fragrances or food additives. However, the microbial synthesis of these compounds from simple carbon sources has not been well investigated so far. Here, we analyzed the headspace over glucose minimal salt medium cultures of Saccharomyces cerevisiae using multi-capillary column-ion mobility spectrometry (MCC-IMS). The high sensitivity and fast data acquisition of the MCC-IMS enabled online analysis of the fermentation off-gas and 19 specific signals were determined. To four of these volatile compounds, we could assign the metabolites ethanol, 2-pentanone, isobutyric acid, and 2,3-hexanedione by MCC-IMS measurements of pure standards and cross validation with thermal desorption–gas chromatography-mass spectrometry measurements. Despite the huge biochemical knowledge of the biochemistry of the model organism S. cerevisiae, only the biosynthetic pathways for ethanol and isobutyric acid are fully understood, demonstrating the considerable lack of research of volatile metabolites. As monitoring of VOCs produced during microbial fermentations can give valuable insight into the metabolic state of the organism, fast and non-invasive MCC-IMS analyses provide valuable data for process control. PMID:25197771

  9. Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Campbell, J. Larry; Yang, Amy Meng-Ci; Melo, Luke R.; Hopkins, W. Scott

    2016-04-01

    In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogen-deuterium exchange (HDX)—a probe of ion structure in mass spectrometry—actually altered analyte ion structure by tautomerization. For the N- and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D2O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D2O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the O-protonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH3OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS.

  10. Early stages of insulin fibrillogenesis examined with ion mobility mass spectrometry and molecular modelling.

    PubMed

    Cole, Harriet; Porrini, Massimiliano; Morris, Ryan; Smith, Tom; Kalapothakis, Jason; Weidt, Stefan; Mackay, C Logan; MacPhee, Cait E; Barran, Perdita E

    2015-10-21

    A prevalent type of protein misfolding causes the formation of β-sheet-rich structures known as amyloid fibrils. Research into the mechanisms of fibril formation has implications for both disease prevention and nanoscale templating technologies. This investigation into the aggregation of insulin utilises ion mobility mass spectrometry coupled with molecular modelling to identify and characterise oligomers formed during the 'lag' phase that precedes fibril growth. High resolution mass spectrometry and collision induced dissociation is used to unequivocally assign species as m/z coincident multimers or confomers, providing a robust analytical approach that supports the use of molecular dynamics to atomistically resolve the observed oligomers. We show that insulin oligomerises to form species In where 2 ≤ n ≤ 12 and within this set of oligomers we delineate over 60 distinct conformations, the most dominant of which are compact species. Modelling trained with experimental data suggests that the dominant compact dimers are enriched in β-sheet secondary structure and dominated by hydrophobic interactions, and provides a linear relationship between Rg and collision cross section. This approach provides detailed insight to the early stages of assembly of this much studied amyloidogenic protein, and can be used to inform models of nucleation and growth. PMID:26369607

  11. Lipid Analysis and Lipidomics by Structurally Selective Ion Mobility-Mass Spectrometry

    PubMed Central

    Kliman, Michal; May, Jody C.

    2012-01-01

    Recent advances in mass spectrometry approaches to the analysis of lipids include the ability to incorporate both lipid class identification with lipid structural information for increased characterization capabilities. The detailed examination of lipids and their biosynthetic and biochemical pathways made possible by novel instrumental and bioinformatics approaches is advancing research in fundamental cellular and medical studies. Recently, high-throughput structural analysis has been demonstrated through the use of rapid gas-phase separation on the basis of the ion mobility (IM) analytical technique combined with mass spectrometry (IM-MS). While IM-MS has been extensively utilized in biochemical research for peptide, protein and small molecule analysis, the role of IM-MS in lipid research is still an active area of development. In this review of lipid-based IM-MS research, we begin with an overview of three contemporary IM techniques which show great promise in being applied towards the analysis of lipids. Fundamental concepts regarding the integration of IM-MS are reviewed with emphasis on the applications of IM-MS towards simplifying and enhancing complex biological sample analysis. Finally, several recent IM-MS lipid studies are highlighted and the future prospects of IM-MS for integrated omics studies and enhanced spatial profiling through imaging IM-MS are briefly described. PMID:21708282

  12. Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Campbell, J. Larry; Yang, Amy Meng-Ci; Melo, Luke R.; Hopkins, W. Scott

    2016-07-01

    In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogen-deuterium exchange (HDX)—a probe of ion structure in mass spectrometry—actually altered analyte ion structure by tautomerization. For the N- and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D2O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D2O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the O-protonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH3OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS.

  13. Differential mobility spectrometry with nanospray ion source as a compact detector for small organics and inorganics

    PubMed Central

    Coy, Stephen L.; Krylov, Evgeny V.; Nazarov, Erkinjon G.; Fornace, Albert J.; Kidd, Richard D.

    2013-01-01

    Electrospray ionization (ESI) is an important tool in chemical and biochemical survey and targeted analysis in many applications. For chemical detection and identification electrospray is usually used with mass spectrometry (MS). However, for screening and monitoring of chemicals of interest in light, low power field-deployable instrumentation, an alternative detection technology with chemical selectivity would be highly useful, especially since small, lightweight, chip-based gas and liquid chromatographic technologies are being developed. Our initial list of applications requiring portable instruments includes chemical surveys on Mars, medical diagnostics based on metabolites in biological samples, and water quality analysis. In this report, we evaluate ESI-Differential Mobility Spectrometry (DMS) as a compact, low-power alternative to MS detection. Use of DMS for chemically-selective detection of ESI suffers in comparison with mass spectrometry because portable MS peak capacity is greater than that of DMS by 10X or more, but the development of light, fast chip chromatography offers compensating resolution. Standalone DMS provides the chemical selectivity familiar from DMS-MS publications, and exploits the sensitivity of ion detection. We find that sub-microliter-per-minute flows and a correctly-designed interface prepare a desolvated ion stream that enables DMS to act as an effective ion filter. Results for a several small organic biomarkers and metabolites, including citric acid, azelaic acid, n-hexanoylglycine, thymidine, and caffeine, as well as compounds such as dinitrotoluene and others, have been characterized and demonstrate selective detection. Water-quality-related halogen-containing anions, fluoride through bromate, contained in liquid samples are also isolated by DMS. A reaction-chamber interface is highlighted as most practical for portable ESI-DMS instrumentation. PMID:23914140

  14. Atmospheric pressure chemical ionization studies of non-polar isomeric hydrocarbons using ion mobility spectrometry and mass spectrometry with different ionization techniques

    NASA Technical Reports Server (NTRS)

    Borsdorf, H.; Nazarov, E. G.; Eiceman, G. A.

    2002-01-01

    The ionization pathways were determined for sets of isomeric non-polar hydrocarbons (structural isomers, cis/trans isomers) using ion mobility spectrometry and mass spectrometry with different techniques of atmospheric pressure chemical ionization to assess the influence of structural features on ion formation. Depending on the structural features, different ions were observed using mass spectrometry. Unsaturated hydrocarbons formed mostly [M - 1]+ and [(M - 1)2H]+ ions while mainly [M - 3]+ and [(M - 3)H2O]+ ions were found for saturated cis/trans isomers using photoionization and 63Ni ionization. These ionization methods and corona discharge ionization were used for ion mobility measurements of these compounds. Different ions were detected for compounds with different structural features. 63Ni ionization and photoionization provide comparable ions for every set of isomers. The product ions formed can be clearly attributed to the structures identified. However, differences in relative abundance of product ions were found. Although corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra detected are complex and differ from those obtained with 63Ni ionization and photoionization. c. 2002 American Society for Mass Spectrometry.

  15. Cryogenic Ion Mobility-Mass Spectrometry: Tracking Ion Structure from Solution to the Gas Phase.

    PubMed

    Servage, Kelly A; Silveira, Joshua A; Fort, Kyle L; Russell, David H

    2016-07-19

    Electrospray ionization (ESI) combined with ion mobility-mass spectrometry (IM-MS) is adding new dimensions, that is, structure and dynamics, to the field of biological mass spectrometry. There is increasing evidence that gas-phase ions produced by ESI can closely resemble their solution-phase structures, but correlating these structures can be complicated owing to the number of competing effects contributing to structural preferences, including both inter- and intramolecular interactions. Ions encounter unique hydration environments during the transition from solution to the gas phase that will likely affect their structure(s), but many of these structural changes will go undetected because ESI-IM-MS analysis is typically performed on solvent-free ions. Cryogenic ion mobility-mass spectrometry (cryo-IM-MS) takes advantage of the freeze-drying capabilities of ESI and a cryogenically cooled IM drift cell (80 K) to preserve extensively solvated ions of the type [M + xH](x+)(H2O)n, where n can vary from zero to several hundred. This affords an experimental approach for tracking the structural evolution of hydrated biomolecules en route to forming solvent-free gas-phase ions. The studies highlighted in this Account illustrate the varying extent to which dehydration can alter ion structure and the overall impact of cryo-IM-MS on structural studies of hydrated biomolecules. Studies of small ions, including protonated water clusters and alkyl diammonium cations, reveal structural transitions associated with the development of the H-bond network of water molecules surrounding the charge carrier(s). For peptide ions, results show that water networks are highly dependent on the charge-carrying species within the cluster. Specifically, hydrated peptide ions containing lysine display specific hydration behavior around the ammonium ion, that is, magic number clusters with enhanced stability, whereas peptides containing arginine do not display specific hydration around the

  16. Specific O₂⁻ generation in corona discharge for ion mobility spectrometry.

    PubMed

    Sabo, Martin; Matúška, Ján; Matejčík, Stefan

    2011-07-15

    This study deals with O(2)(-) generation in corona discharge (CD) in point to plane geometry for single flow ion mobility spectrometry (IMS) with gas outlet located behind the ionization source. We have designed CD of special geometry in order to achieve the high O(2)(-) yield. Using this ion source we have achieved in zero air conditions that up to 74% all negative ions were O(2)(-) or O(2)(-)(H(2)O). It has been demonstrated that the non-electronegative nitrogen positively influences the efficiency of O(2)(-) generation in O(2)/N(2) mixtures. The reduced ion mobility of 2.27 cm(2)V(-1)s(-1) has been measured for O(2)(-)/O(2)(-)(H(2)O) ions in zero air. Additional ions detected in zero air (less than 200 ppb CO(2)) using the mass spectrometric and IMS technique were, NO(2)(-), N(2)O(2)(-) (2.37 cm(2)V(-1)s(-1)), NO(3)(-), N(2)O(3)(-) and N(2)O(3)(-)(H(2)O). The CO(3)(-) and CO(4)(-) ions have been detected after the introduction of 5 ppm CO(2) into zero air. PMID:21645716

  17. Multiplicative effects model with internal standard in mobile phase for quantitative liquid chromatography-mass spectrometry.

    PubMed

    Song, Mi; Chen, Zeng-Ping; Chen, Yao; Jin, Jing-Wen

    2014-07-01

    Liquid chromatography-mass spectrometry assays suffer from signal instability caused by the gradual fouling of the ion source, vacuum instability, aging of the ion multiplier, etc. To address this issue, in this contribution, an internal standard was added into the mobile phase. The internal standard was therefore ionized and detected together with the analytes of interest by the mass spectrometer to ensure that variations in measurement conditions and/or instrument have similar effects on the signal contributions of both the analytes of interest and the internal standard. Subsequently, based on the unique strategy of adding internal standard in mobile phase, a multiplicative effects model was developed for quantitative LC-MS assays and tested on a proof of concept model system: the determination of amino acids in water by LC-MS. The experimental results demonstrated that the proposed method could efficiently mitigate the detrimental effects of continuous signal variation, and achieved quantitative results with average relative predictive error values in the range of 8.0-15.0%, which were much more accurate than the corresponding results of conventional internal standard method based on the peak height ratio and partial least squares method (their average relative predictive error values were as high as 66.3% and 64.8%, respectively). Therefore, it is expected that the proposed method can be developed and extended in quantitative LC-MS analysis of more complex systems. PMID:24840455

  18. Application of a nonradioactive pulsed electron source for ion mobility spectrometry.

    PubMed

    Gunzer, Frank; Zimmermann, Stefan; Baether, Wolfgang

    2010-05-01

    Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. Common ion mobility spectrometers work by employing a radioactive source to provide electrons with high energy to ionize analytes in a series of chemical reactions. General security as well as regulatory concerns related to radioactivity result in the need for a different ionization source which on the other hand produces ions in a similar manner as a radioactive source since the ion chemistry is well-known. Here we show the application of a novel nonradioactive source that produces spectra similar to those obtained with radioactive tritium sources. Using this source in a pulsed mode offers the additional advantage of selecting certain analytes by their recombination time and thus significantly increasing the selectivity. The successful isolation of a target signal in the presence of contaminants using a pulsed electron beam or more precisely the difference in recombination times will be demonstrated for the case of dimethyl-methylphosphonate (DMMP) showing the potential of this source to reduce the possibility for false-positive detection of corresponding chemical warfare agents (CWA) by IMS. PMID:20353158

  19. Spectroscopic characterization of a microplasma used as ionization source for ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Michels, Antje; Tombrink, Sven; Vautz, Wolfgang; Miclea, Manuela; Franzke, Joachim

    2007-11-01

    We report a miniaturized excitation source for soft ionization of molecules based on a dielectric barrier discharge. An atmospheric plasma is established at the end of a 500 μm diameter capillary using He as buffer gas. The plasma jet which comes out of the capillary is dependent on the gas flow rate. The mechanism of the production of N 2+ outside the capillary, which is relevant for the protonation of molecules and sustains the production of primary ions, is investigated by spatially resolved spectroscopic measurements throughout the plasma. Possible application of such miniaturized plasmas is the ionization of gaseous compounds under atmospheric pressure as an alternative to traditional APCI (atmospheric pressure chemical ionization). The miniaturized plasma was applied as ionization source for ion mobility spectrometry where the common sources are radioactive, thus limiting the place of installation. First measurements of gaseous compounds with such a plasma ion mobility spectrometer with promising results showed detection limits comparable or even better than those obtained using common radioactive ionization sources.

  20. Native mass spectrometry and ion mobility characterize the orange carotenoid protein functional domains.

    PubMed

    Zhang, Hao; Liu, Haijun; Lu, Yue; Wolf, Nathan R; Gross, Michael L; Blankenship, Robert E

    2016-06-01

    Orange Carotenoid Protein (OCP) plays a unique role in protecting many cyanobacteria from light-induced damage. The active form of OCP is directly involved in energy dissipation by binding to the phycobilisome (PBS), the major light-harvesting complex in cyanobacteria. There are two structural modules in OCP, an N-terminal domain (NTD), and a C-terminal domain (CTD), which play different functional roles during the OCP-PBS quenching cycle. Because of the quasi-stable nature of active OCP, structural analysis of active OCP has been lacking compared to its inactive form. In this report, partial proteolysis was used to generate two structural domains, NTD and CTD, from active OCP. We used multiple native mass spectrometry (MS) based approaches to interrogate the structural features of the NTD and the CTD. Collisional activation and ion mobility analysis indicated that the NTD releases its bound carotenoid without forming any intermediates and the CTD is resistant to unfolding upon collisional energy ramping. The unfolding intermediates observed in inactive intact OCP suggest that it is the N-terminal extension and the NTD-CTD loop that lead to the observed unfolding intermediates. These combined approaches extend the knowledge of OCP photo-activation and structural features of OCP functional domains. Combining native MS, ion mobility, and collisional activation promises to be a sensitive new approach for studies of photosynthetic protein-pigment complexes. PMID:26921809

  1. Oversampling Selective Accumulation Trapped Ion Mobility Spectrometry Coupled to FT-ICR MS: Fundamentals and Applications.

    PubMed

    Benigni, Paolo; Fernandez-Lima, Francisco

    2016-07-19

    In the present paper, we describe the fundamentals and analytical advantages of Oversampling Selective Accumulation Trapped Ion Mobility Spectrometry (OSA-TIMS) when coupled to ultrahigh resolution mass analyzers (e.g., FT-ICR MS). During TIMS analysis, ion packages are spatially resolved based on their mobilities along the TIMS analyzer axis and multiple strategies can be utilized during the trapping and elution of the ion population of interest. In the case of OSA-TIMS-FT-ICR MS, the TIMS operation sequence, trapping conditions, and operations are optimized to increase the signal-to-noise and the number of points across the mobility domain, which leads to more accurate mobility and mass measurements. Experimental results show that accurate ion-neutral collision cross sections (<1%) can be measured using OSA-TIMS-FT-ICR MS with high mobility resolving powers (RIMS up to 250), high mass accuracy (<1 ppm), and ultrahigh mass resolution (RMS up to 600-1200k at m/z 400) in a single analysis. The analytical advantages of OSA-TIMS over SA-TIMS were illustrated for the analysis of structural peptide isomers (SDGRG and GRGDS [M + H](+)), conformational isomers (AT-hook peptide 3 KRGRGRPRK [M + 2H](+2)), and a complex mixture of polyaromatic hydrocarbons (PAH) from coal tar. Baseline separation of the structural peptide isomers SDGRG and GRGDS, [M + H](+), was observed, and three conformations were identified for the AT-hook peptide 3 KRGRGRPRK [M + 2H](+2) during OSA-TIMS-FT-ICR MS. A 2-fold increase in the number of molecular features and a 2-6-fold signal-to-noise increase was observed for OSA-TIMS when compared with SA-TIMS during the PAH analysis. This work provides the proof-of-principle for further application of OSA-TIMS-FT-ICR MS for the unsupervised analysis of complex mixtures based on the characterization of the conformational space and the assignment of chemical formulas in a single analysis. PMID:27340830

  2. A Critical Review of Ion Mobility Spectrometry for the Detection of Explosives and Explosive Related Compounds

    SciTech Connect

    Ewing, Robert Gordon; Atkinson, David Alan; Eiceman, G. A.; Ewing, G. J.

    2001-05-01

    Ion mobility spectrometry has become the most successful and widely used technology for the detection of trace levels of nitro-organic explosives on handbags and carry on-luggage in airports throughout the US. The low detection limits are provided by the efficient ionization process, namely, atmospheric pressure chemical ionization (APCI) reactions in negative polarity. An additional level of confidence in a measurement is imparted by characterization of ions for mobilities in weak electric fields of a drift tube at ambient pressure. Findings from over 30 years of investigations into IMS response to these explosives have been collected and assessed to allow a comprehensive view of the APCI reactions characteristic of nitro-organic explosives. Also, the drift tube conditions needed to obtain particular mobility spectra have been summarized. During the past decade, improvements have occurred in IMS on the understanding of reagent gas chemistries, the influence of temperature on ion stability, and sampling methods. In addition, commercial instruments have been refined to provide fast and reliable measurements for on-site detection of explosives. The gas phase ion chemistry of most explosives is mediated by the fragile C---ONO2 bonds or the acidity of protons. Thus, M- or M·Cl- species are found with only a few explosives and loss of NO2, NO3 and proton abstraction reactions are common and complicating pathways. However, once ions are formed, they appear to have stabilities on time scales equal to or longer than ion drift times from 5–20 ms. As such, peak shapes in IMS are suitable for high selectivity and sensitivity.

  3. Optimization of a Differential Ion Mobility Spectrometry-Tandem Mass Spectrometry Method for High-Throughput Analysis of Nicotine and Related Compounds: Application to Electronic Cigarette Refill Liquids.

    PubMed

    Regueiro, Jorge; Giri, Anupam; Wenzl, Thomas

    2016-06-21

    Fast market penetration of electronic cigarettes is leading to an exponentially growing number of electronic refill liquids with different nicotine contents and an endless list of flavors. Therefore, rapid and simple methods allowing a fast screening of these products are necessary to detect harmful substances which can negatively impact the health of consumers. In this regard, the present work explores the capabilities of differential ion mobility spectrometry coupled to tandem mass spectrometry for high-throughput analysis of nicotine and 11 related compounds in commercial refill liquids for electronic cigarettes. The influence of main factors affecting the ion mobility separation, such as modifier types and concentration, separation voltage, and temperature, was systematically investigated. Despite small molecular weight differences among the studied compounds, a good separation was achieved in the ion mobility cell under the optimized conditions, which involved the use of ethanol as a polar gas-phase chemical modifier. Indeed, differential ion mobility was able to resolve (resolution >4) nicotine from its structural isomer anabasine without the use of any chromatographic separation. The quantitative performance of the proposed method was then evaluated, showing satisfactory precision (RSD ≤ 16%) and recoveries ranging from 85 to 100% for nicotine, and from 84 to 126% for the rest of the target analytes. Several commercial electronic cigarette refill liquids were analyzed to demonstrate the applicability of the method. In some cases, significant differences were found between labeled and measured levels of nicotine. Anatabine, cotinine, myosmine, and nornicotine were also found in some of the analyzed samples. PMID:27173877

  4. Chemical Effects in the Separation Process of a Differential Mobility / Mass Spectrometer System

    PubMed Central

    Schneider, Bradley B.; Covey, Thomas R.; Coy, Stephen L.; Krylov, Evgeny V.; Nazarov, Erkinjon G.

    2013-01-01

    In differential mobility spectrometry (DMS, also referred to as high field asymmetric waveform ion mobility spectrometry, FAIMS), ions are separated on the basis of the difference in their mobility under high and low electric fields. The addition of polar modifiers to the gas transporting the ions through a DMS enhances the formation of clusters in a field-dependent way and thus amplifies the high and low field mobility difference resulting in increased peak capacity and separation power. Observations of the increase in mobility field dependence are consistent with a cluster formation model, also referred to as the dynamic cluster-decluster model. The uniqueness of chemical interactions that occur between an ion and cluster-forming neutrals increases the selectivity of the separation and the depression of low-field mobility relative to high-field mobility increases the compensation voltage and peak capacity. The effect of polar modifiers on the peak capacity across a broad range of chemicals has been investigated. We discuss the theoretical underpinnings which explain the observed effects. In contrast to the result from polar modifiers, we find that using mixtures of inert gases as the transport gas improve resolution by reducing peak width but has very little effect on peak capacity or selectivity. Inert gases do not cluster and thus do not reduce low field mobility relative to high-field mobility. The observed changes in the differential mobility α parameter exhibited by different classes of compounds when the transport gas contains polar modifiers or has a significant fraction of inert gas can be explained on the basis of the physical mechanisms involved in the separation processes. PMID:20121077

  5. An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1

    NASA Astrophysics Data System (ADS)

    Schenauer, Matthew R.; Leary, Julie A.

    2009-10-01

    In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility spectrometry-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt(TM)). Through investigation of the 9+ charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5+ monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9+ dimer, were then compared with ATDs obtained for the 5+ MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra(TM); the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non

  6. Understanding gas phase modifier interactions in rapid analysis by Differential Mobility-Tandem Mass Spectrometry

    PubMed Central

    Kafle, Amol; Coy, Stephen L.; Wong, Bryan M.; Fornace, Albert J.; Glick, James J.; Vouros, Paul

    2014-01-01

    A systematic study involving the use and optimization of gas phase modifiers in quantitative differential mobility- mass spectrometry (DMS-MS) analysis is presented using mucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 106 normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab-initio thermochemical results we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry in mobility differences, but at lower temperatures multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects. PMID:24452298

  7. Nanomaterial size distribution analysis via liquid nebulization coupled with ion mobility spectrometry (LN-IMS).

    PubMed

    Jeon, Seongho; Oberreit, Derek R; Van Schooneveld, Gary; Hogan, Christopher J

    2016-02-21

    We apply liquid nebulization (LN) in series with ion mobility spectrometry (IMS, using a differential mobility analyzer coupled to a condensation particle counter) to measure the size distribution functions (the number concentration per unit log diameter) of gold nanospheres in the 5-30 nm range, 70 nm × 11.7 nm gold nanorods, and albumin proteins originally in aqueous suspensions. In prior studies, IMS measurements have only been carried out for colloidal nanoparticles in this size range using electrosprays for aerosolization, as traditional nebulizers produce supermicrometer droplets which leave residue particles from non-volatile species. Residue particles mask the size distribution of the particles of interest. Uniquely, the LN employed in this study uses both online dilution (with dilution factors of up to 10(4)) with ultra-high purity water and a ball-impactor to remove droplets larger than 500 nm in diameter. This combination enables hydrosol-to-aerosol conversion preserving the size and morphology of particles, and also enables higher non-volatile residue tolerance than electrospray based aerosolization. Through LN-IMS measurements we show that the size distribution functions of narrowly distributed but similarly sized particles can be distinguished from one another, which is not possible with Nanoparticle Tracking Analysis in the sub-30 nm size range. Through comparison to electron microscopy measurements, we find that the size distribution functions inferred via LN-IMS measurements correspond to the particle sizes coated by surfactants, i.e. as they persist in colloidal suspensions. Finally, we show that the gas phase particle concentrations inferred from IMS size distribution functions are functions of only of the liquid phase particle concentration, and are independent of particle size, shape, and chemical composition. Therefore LN-IMS enables characterization of the size, yield, and polydispersity of sub-30 nm particles. PMID:26750519

  8. Micro-machined planar field asymmetric ion mobility spectrometer as a gas chromatographic detector

    NASA Technical Reports Server (NTRS)

    Eiceman, G. A.; Nazarov, E. G.; Miller, R. A.; Krylov, E. V.; Zapata, A. M.

    2002-01-01

    A planar high field asymmetric waveform ion mobility spectrometer (PFAIMS) with a micro-machined drift tube was characterized as a detector for capillary gas chromatography. The performance of the PFAIMS was compared directly to that of a flame ionization detector (FID) for the separation of a ketone mixture from butanone to decanone. Effluent from the column was continuously sampled by the detector and mobility scans could be obtained throughout the chromatographic analysis providing chemical inforrmation in mobility scans orthogonal to retention time. Limits of detection were approximately I ng for measurement of positive ions and were comparable or slightly better than those for the FID. Direct comparison of calibration curves for the FAIMS and the FID was possible over four orders of magnitude with a semi-log plot. The concentration dependence of the PFAIMS mobility scans showed the dependence between ion intensity and ion clustering, evident in other mobility spectrometers and atmospheric pressure ionization technologies. Ions were identified using mass spectrometry as the protonated monomer and the proton bound dimer of the ketones. Residence time for column effluent in the PFAIMS was calculated as approximately 1 ms and a 36% increase in extra-column broadening versus the FID occurred with the PFAIMS.

  9. Structural Characterization of Methylenedianiline Regioisomers by Ion Mobility-Mass Spectrometry, Tandem Mass Spectrometry, and Computational Strategies: I. Electrospray Spectra of 2-Ring Isomers

    PubMed Central

    2015-01-01

    Purified methylenedianiline (MDA) regioisomers were structurally characterized and differentiated using tandem mass spectrometry (MS/MS), ion mobility-mass spectrometry (IM-MS), and IM-MS/MS in conjunction with computational methods. It was determined that protonation sites on the isomers can vary depending on the position of amino groups, and the resulting protonation sites play a role in the gas-phase stability of the isomer. We also observed differences in the relative distributions of protonated conformations depending on experimental conditions and instrumentation, which is consistent with previous studies on aniline in the gas phase. This work demonstrates the utility of a multifaceted approach for the study of isobaric species and elucidates why previous MDA studies may have been unable to detect and/or differentiate certain isomers. Such analysis may prove useful in the characterization of larger MDA multimeric species, industrial MDA mixtures, and methylene diphenyl diisocyanate (MDI) mixtures used in polyurethane synthesis. PMID:24678803

  10. Direct analysis of human breath ammonia using corona discharge ion mobility spectrometry.

    PubMed

    Jazan, Elham; Mirzaei, Hadi

    2014-01-01

    In this study, ammonia in human breath was directly determined using corona discharge ionization ion mobility spectrometry (CD-IMS) technique with several important advantages including high sensitivity, low cost, high speed, and ease of maintenance. The temperature effect on the ammonia signal was evaluated too. The results indicated that the best temperature for the investigation of breath ammonia was 150°C. The analytical results showed that the linear dynamic range was between 12 and 810ppb and the detection limit was 6.6ppb. The relative standard deviation (RSD) was obtained to be 5, 3, and 3 for 290, 348, and 522ppb, respectively. The amounts of ammonia in breath of eight healthy volunteers were measured. The values were between 236 and 1218ppb. Also, the inequality in breath ammonia levels was scrutinized over a 6h working day for three healthy volunteers. The results showed a drop in breath ammonia from the morning amount to the mid-day measurement and then, a progressive increase while the day continued. In addition, the amounts of ammonia were determined to be 1494-1553ppb in exhaled breath of two renal failure patients. The results obtained in this work revealed that the method was conveniently established without any considerable sample pretreatment for direct analysis of ammonia in human breath. PMID:24120979

  11. Design for gas chromatography-corona discharge-ion mobility spectrometry.

    PubMed

    Jafari, Mohammad T; Saraji, Mohammad; Sherafatmand, Hossein

    2012-11-20

    A corona discharge ionization-ion mobility spectrometry (CD-IMS) with a novel sample inlet system was designed and constructed as a detector for capillary gas chromatography. In this design, a hollow needle was used instead of a solid needle which is commonly used for corona discharge creation, helping us to have direct axial interfacing for GC-IMS. The capillary column was passed through the needle, resulting in a reaction of effluents with reactant ions on the upstream side of the corona discharge ionization source. Using this sample introduction design, higher ionization efficiency was achieved relative to the entrance direction through the side of the drift tube. In addition, the volume of the ionization region was reduced to minimize the resistance time of compounds in the ionization source, increasing chromatographic resolution of the instrument. The effects of various parameters such as drift gas flow, makeup gas flow, and column tip position inside the needle were investigated. The designed instrument was exhaustively validated in terms of sensitivity, resolution, and reproducibility by analyzing the standard solutions of methyl isobutyl ketone, heptanone, nonanone, and acetophenone as the test compounds. The results obtained by CD-IMS detector were compared with those of the flame ionization detector, which revealed the capability of the proposed GC-IMS for two-dimensional separation (based on the retention time and drift time information) and identification of an analyte in complex matrixes. PMID:23083064

  12. Simultaneous determination of 2-furfural and 5-methyl-2-furfural using corona discharge ion mobility spectrometry.

    PubMed

    Jafari, M T; Khayamian, T

    2009-06-01

    A novel technique, corona discharge ion mobility spectrometry (CD-IMS), was developed for the qualitative and quantitative determination of 2-furfural (F) and 5-methyl-2-furfural (MF) in aqueous solutions. The limits of detection (LODs) were 5.3 x 10(-3) microg/mL for F and 6.7 x 10(-3) microg/mL for MF. The linear dynamic ranges of 1.16 x 10(-2) to 1.04 microg/mL and 2.20 x 10(-2) to 1.10 microg/mL were obtained for F and MF, respectively. The relative standard deviation was below 12% for both compounds. In addition to analysis of the individual compound, simultaneous determination of F and MF was also investigated. It was realized that F imposes a matrix effect on the MF signal and vice versa. The standard addition method was used to deal with the matrix effect. The recovery of the compounds in the synthetic samples validates the capability of the method. PMID:19531891

  13. Gas-Phase Dopant-Induced Conformational Changes Monitored with Transversal Modulation Ion Mobility Spectrometry.

    PubMed

    Meyer, Nicole Andrea; Root, Katharina; Zenobi, Renato; Vidal-de-Miguel, Guillermo

    2016-02-16

    The potential of a Transversal Modulation Ion Mobility Spectrometry (TMIMS) instrument for protein analysis applications has been evaluated. The Collision Cross Section (CCS) of cytochrome c measured with the TMIMS is in agreement with values reported in the literature. Additionally, it enables tandem IMS-IMS prefiltration in dry gas and in vapor doped gas. The chemical specificity of the different dopants enables interesting studies on the structure of proteins as CCS changed strongly depending on the specific dopant. Hexane produced an unexpectedly high CCS shift, which can be utilized to evaluate the exposure of hydrophobic parts of the protein. Alcohols produced higher shifts with a dual behavior: an increase in CCS due to vapor uptake at specific absorption sites, followed by a linear shift typical for unspecific and unstable vapor uptake. The molten globule +8 shows a very specific transition. Initially, its CCS follows the trend of the compact folded states, and then it rapidly increases to the levels of the unfolded states. This strong variation suggests that the +8 charge state undergoes a dopant-induced conformational change. Interestingly, more sterically demanding alcohols seem to unfold the protein more effectively also in the gas phase. This study shows the capabilities of the TMIMS device for protein analysis and how tandem IMS-IMS with dopants could provide better understanding of the conformational changes of proteins. PMID:26845079

  14. Geodetic Mobile Solar Spectrometry: Description of the New Spectrometer GEMOSS and First Measurements

    NASA Astrophysics Data System (ADS)

    Somieski, A.; Buerki, B.; Kahle, H.-G.; Becker-Ross, H.; Florek, S.; Okruss, M.

    2003-04-01

    In former scientific research projects of the Geodesy and Geodynamic Laboratory (GGL) the method of solar spectrometry has demonstrated its performance as a remote sensing technique for determination of integrated precipitable water vapor (IPWV). A first prototype, named Solar Atmospheric MOnitoring Spectrometer (SAMOS), was developed at GGL in cooperation with the Institute of Spectrochemistry and Applied Spectroscopy (ISAS) in Berlin. A new type of solar spectrometer for geodetic applications is currently under development. In this project the construction of the first prototype GEMOSS I (Geodetic MObile Solar Spectrometer) has been completed. It provides simultaneous measurements of water vapor absorption lines in the range from 730 nm to 910 nm with a spectral resolution of 10-15 pm. This technique allows a compact design, low weight as well as high time resolution and accuracy of IPWV at a relatively low level of costs. First measurements were carried out to verify the system stability under field conditions and the data quality. The presentation will highlight the technical innovations of GEMOSS I and will show results of first measurements.

  15. Fast detection of coliform bacteria by means of gas chromatography-differential mobility spectrometry.

    PubMed

    Saptalena, Lena Ganda; Kuklya, Andriy; Telgheder, Ursula

    2016-05-01

    In this study, we demonstrate that the combination of an enzymatic method (based on Colilert-18 medium) and gas chromatography-differential mobility spectrometry (GC-DMS) can reduce the time required for detection of coliform bacteria (including Escherichia coli) from 18 to 2.5 h. The presented method includes the incubation (~2.5 h) of the sample containing coliform bacteria in Colilert-18 medium. The incubation time of 2.5 h is required for the activation of the β-galactosidase enzyme. Produced during the incubation biomarker o-nitrophenol (ONP) can be detected by means of GC-DMS within just 200 s. The detection limit for ONP was 45 ng (on-column). The method developed in this work provides significantly shorter analysis time compared with standard methods, and can be potentially adapted to the field conditions. Therefore, this method is a promising tool for an early detection of coliform bacteria (including E. coli). Graphical Abstract Fast detection of coliform bacteria by means of GC-DMS. PMID:27002609

  16. Off-line coupling of multidimensional immunoaffinity chromatography and ion mobility spectrometry: A promising partnership.

    PubMed

    Armenta, Sergio; de la Guardia, Miguel; Abad-Fuentes, Antonio; Abad-Somovilla, Antonio; Esteve-Turrillas, Francesc A

    2015-12-24

    The extreme specificity of immunoaffinity chromatography (IAC) columns coupled to the high sensitivity of ion mobility spectrometry (IMS) measurements makes this combination really useful for rapid, selective, and sensitive determination of a high variety of analytes in different samples. The capabilities of the IAC-IMS coupling have been highlighted under three different scenarios: (i) multiclass residue analysis using a single IAC column, (ii) multiclass residue analysis using stacked IAC columns, and (iii) isomer analysis. In the first case, the determination of three strobilurin fungicides - azoxystrobin, picoxystrobin, and pyraclostrobin - in water and strawberry juice was considered, obtaining limits of quantification (LOQs) from 11 to 63μgL(-1). Recoveries from 96 to 106% for water, and from 67 to 104% for strawberry juice were obtained. In the second case, anilinopyrimidine compounds, including two analytes with similar drift time, were selectively retained in different IAC columns and analyzed after independent elution in commercial wine samples by IMS. LOQ values of 16, 14 and 12μgL(-1) were obtained for pyrimethanil, mepanipyrim, and cyprodinil, respectively. The obtained recoveries for wine samples spiked with 25 and 100μgL(-1) were from 82 to 123%. Additionally, the stacked IAC columns concept was applied to the separation of Z and E isomers of azoxystrobin that were selectively retained in specific IAC columns and quantified by IMS. Recoveries between 91 and 94% were obtained for both isomers in water samples. PMID:26654255

  17. Elucidation of Drug Metabolite Structural Isomers Using Molecular Modeling Coupled with Ion Mobility Mass Spectrometry.

    PubMed

    Reading, Eamonn; Munoz-Muriedas, Jordi; Roberts, Andrew D; Dear, Gordon J; Robinson, Carol V; Beaumont, Claire

    2016-02-16

    Ion mobility-mass spectrometry (IM-MS) in combination with molecular modeling offers the potential for small molecule structural isomer identification by measurement of their gas phase collision cross sections (CCSs). Successful application of this approach to drug metabolite identification would facilitate resource reduction, including animal usage, and may benefit other areas of pharmaceutical structural characterization including impurity profiling and degradation chemistry. However, the conformational behavior of drug molecules and their metabolites in the gas phase is poorly understood. Here the gas phase conformational space of drug and drug-like molecules has been investigated as well as the influence of protonation and adduct formation on the conformations of drug metabolite structural isomers. The use of CCSs, measured from IM-MS and molecular modeling information, for the structural identification of drug metabolites has also been critically assessed. Detection of structural isomers of drug metabolites using IM-MS is demonstrated and, in addition, a molecular modeling approach has been developed offering rapid conformational searching and energy assessment of candidate structures which agree with experimental CCSs. Here it is illustrated that isomers must possess markedly dissimilar CCS values for structural differentiation, the existence and extent of CCS differences being ionization state and molecule dependent. The results present that IM-MS and molecular modeling can inform on the identity of drug metabolites and highlight the limitations of this approach in differentiating structural isomers. PMID:26752623

  18. Detection of metabolites of trapped humans using ion mobility spectrometry coupled with gas chromatography.

    PubMed

    Vautz, Wolfgang; Slodzynski, Rafael; Hariharan, Chandrasekhara; Seifert, Luzia; Nolte, Jürgen; Fobbe, Rita; Sielemann, Stefanie; Lao, Bolan C; Huo, Ran; Thomas, C L Paul; Hildebrand, Lars

    2013-02-19

    For the first time, ion mobility spectrometry coupled with rapid gas chromatography, using multicapillary columns, was applied for the development of a pattern of signs of life for the localization of entrapped victims after disaster events (e.g., earthquake, terroristic attack). During a simulation experiment with entrapped volunteers, 12 human metabolites could be detected in the air of the void with sufficient sensitivity to enable a valid decision on the presence of a living person. Using a basic normalized summation of the measured concentrations, all volunteers involved in the particular experiments could be recognized only few minutes after they entered the simulation void and after less than 3 min of analysis time. An additional independent validation experiment enabled the recognition of a person in a room of ∼25 m(3) after ∼30 min with sufficiently high sensitivity to detect even a person briefly leaving the room. Undoubtedly, additional work must be done on analysis time and weight of the equipment, as well as on validation during real disaster events. However, the enormous potential of the method as a significantly helpful tool for search-and-rescue operations, in addition to trained canines, could be demonstrated. PMID:23249433

  19. Gas chromatography/ion mobility spectrometry as a hyphenated technique for improved explosives detection and analysis

    NASA Technical Reports Server (NTRS)

    Mercado, AL; Marsden, Paul

    1995-01-01

    Ion Mobility Spectrometry (IMS) is currently being successfully applied to the problem of on-line trace detection of plastic and other explosives in airports and other facilities. The methods of sample retrieval primarily consist of batch sampling for particulate residue on a filter card for introduction into the IMS. The sample is desorbed into the IMS using air as the carrier and negative ions of the explosives are detected, some as an adduct with a reagent ion such as Cl(-). Based on studies and tests conducted by different airport authorities, this method seems to work well for low vapor pressure explosives such as RDX and PETN, as well as TNT that are highly adsorptive and can be found in nanogram quantities on contaminated surfaces. Recently, the changing terrorist threat and the adoption of new marking agents for plastic explosives has meant that the sample introduction and analysis capabilities of the IMS must be enhanced in order to keep up with other detector developments. The IMS has sufficient analytical resolution for a few threat compounds but the IMS Plasmogram becomes increasingly more difficult to interpret when the sample mixture gets more complex.

  20. Separation and characterization of oxidized isomeric lipid-peptide adducts by ion mobility mass spectrometry.

    PubMed

    Milic, Ivana; Kipping, Marc; Hoffmann, Ralf; Fedorova, Maria

    2015-12-01

    Phospholipids are major components of cell membranes and lipoprotein complexes. They are prone to oxidation by endogenous and exogenous reactive oxygen species yielding a large variety of modified lipids including small aliphatic and phospholipid bound aldehydes and ketones. These carbonyls are strong electrophiles that can modify proteins and, thereby, alter their structures and functions triggering various pathophysiological conditions. The analysis of lipid-protein adducts by liquid chromatography-MS is challenged by their mixed chemical nature (polar peptide and hydrophobic lipid), low abundance in biological samples, and formation of multiple isomers. Thus, we investigated traveling wave ion mobility mass spectrometry (TWIMS) to analyze lipid-peptide adducts generated by incubating model peptides corresponding to the amphipathic β1 sheet sequence of apolipoprotein B-100 with 1-palmitoyl-2-(oxo-nonanoyl)-sn-glycerophosphatidylcholine (PONPC). The complex mixture of peptides, lipids, and peptide-lipid adducts was separated by TWIMS, which was especially important for the identification of two mono-PONPC-peptide isomers containing Schiff bases at different lysine residues. Moreover, TWIMS separated structural conformers of one peptide-lipid adduct possessing most likely different orientations of the hydrophobic sn-1 fatty acyl residue and head group of PONPC, relative to the peptide backbone. PMID:26634972

  1. Separation of catechin epimers by complexation using ion mobility mass spectrometry.

    PubMed

    Troć, Anna; Zimnicka, Magdalena; Danikiewicz, Witold

    2015-03-01

    Ion mobility coupled with mass spectrometry provides a fast and repeatable method to separate catechin epimers by previous complexation with selected chiral modifiers and transition metals. Several combinations with chiral ligands such as D- and L-amino acids and/or additional metal cations, chiral crown ethers, tartaric acid and heptakis(2,6-di-O-methyl)-β-cyclodextrin were screened for their ability to affect the separation efficiency. The clusters having the form of [2M + D-amino acid + Cu(2+) - 3H](-) (M stands for (-)-epicatechin or (+)-catechin) showed improvement in stereodifferentiation between two epimeric catechins in comparison to the analysis of pure epimers, where no separation was observed or the separation was hampered by the formation of mixed dimer complexes. Among various examined D-amino acids only those possessing hydrophobic side chains induced the improvement of separation efficiency. The best peak-to-peak resolution (Rp-p) was determined to be 0.71 for [2M + D-Leucine + Cu(2+) - 3H](-) clusters. PMID:25800190

  2. Membrane-Extraction Ion Mobility Spectrometry for In-Situ Detection of Chlorinated Hydrocarbons in Water

    SciTech Connect

    Du, Yongzhai; Zhang, Wei; Whitten, William B; Li, Haiyang; Watson, David B; Xu, Jun

    2010-01-01

    Membrane-extraction ion mobility spectrometry (ME-IMS) has been developed for in-situ sampling and analysis of trace chlorinated hydrocarbons in water in a single procedure. The sampling is configured so that aqueous contaminants permeate through a spiral hollow polydimethylsiloxane (PDMS) membrane and are carried away by a vapor flow through the membrane tube. The extracted analyte flows into an atmospheric pressure chemical ionization (APCI) chamber and is analyzed in a home-made IMS analyzer. PDMS membrane is found to effectively extract chlorinated hydrocarbon solvents from liquid phase to vapor. The specialized IMS analyzer has been found to have resolutions of R=33 and 41, respectively, for negative- and positive-modes and is capable of detecting aqueous tetrachloroethylene (PCE) and trichloroethylene (TCE) as low as 80 g/L and 74 g/L in negative ion mode, respectively. The time-dependent characteristics of sampling and detection of TCE are both experimentally and theoretically studied for various concentrations, membrane lengths, and flow rates. These characteristics demonstrate that membrane-extraction IMS is feasible for the continuous monitoring of chlorinated hydrocarbons in water.

  3. Transport Modeling of Membrane Extraction of Chlorinated Hydrocarbon from Water for Ion Mobility Spectrometry

    SciTech Connect

    Zhang, Wei; Du, Yongzhai; Feng, Zhili; Xu, Jun

    2010-01-01

    Membrane-extraction Ion Mobility Spectrometry (ME-IMS) is a feasible technique for the continuous monitoring of chlorinated hydrocarbons in water. This work studies theoretically the time-dependent characteristics of sampling and detection of trichloroethylene (TCE). The sampling is configured so that aqueous contaminants permeate through a hollow polydimethylsiloxane (PDMS) membrane and are carried away by a transport gas flowing through the membrane tube into IMS analyzer. The theoretical study is based on a two-dimensional transient fluid flow and mass transport model. The model describes the TCE mixing in the water, permeation through the membrane layer, and convective diffusion in the air flow inside membrane tube. The effect of various transport gas flow rates on temporal profiles of IMS signal intensity is investigated. The results show that fast time response and high transport yield can be achieved for ME-IMS by controlling the flow rate in the extraction membrane tube. These modeled time-response profiles are important for determining duty cycles of field-deployable sensors for monitoring chlorinated hydrocarbons in water.

  4. Simultaneous determination of three azo dyes in food product by ion mobility spectrometry.

    PubMed

    Jiao, Jiandong; Wang, Jinfeng; Li, Mingfeng; Li, Junqing; Li, Qihong; Quan, Qinbo; Chen, Jinquan

    2016-07-01

    Color is an important property for food evaluation. Synthetic azo dyes are usually used in food product to obtain better appearance because of their stability and low cost. However, such dyes should be strictly controlled because of their potential threat to human health. A simple, rapid and sensitive method has been developed to determine orange II, allura red, and para red simultaneously by ion mobility spectrometry. The three dyes could be separated at the same time and the migration time of orange II, allura red, and para red are 12.070±0.010, 8.180±0.015, and 11.037±0.016ms, respectively. The effects of different parameters, such as pH, solvent, percentage of water, were investigated to establish the optimal condition. The detection limits were 0.1, 0.05, and 0.2μg/mL for orange II, allura red, and para red, respectively. The recoveries of the three azo dyes from jellies were all higher than 81%. The developed method is fast and accurate for the detection of the three synthetic dyes. PMID:27235999

  5. Mapping of explosive contamination using GC/chemiluminescence and ion mobility spectrometry techniques

    NASA Astrophysics Data System (ADS)

    Miller, Carla J.; Glenn, D. F.; Hartenstein, Steven D.; Hallowell, Susan F.

    1998-12-01

    Recent efforts at the Idaho National Engineering and Environmental Laboratory (INEEL) have included mapping explosive contamination resulting from manufacturing and carrying improvised explosive devices (IEDs). Two types of trace detection equipment were used to determine levels of contamination from designated sampling areas. A total of twenty IEDs were constructed: ten using TNT and ten using C-4. Two test scenarios were used. The first scenario tracked the activities of a manufacturer who straps the device onto an independent courier. The courier then performed a series of activities to simulate waiting in an airport. The second scenario tracked the activities of a manufacturer who also served as the courier. A sample set for each test consisted of thirty samples from various locations on each IED manufacturer, thirty from each IED courier, twenty-five from the manufacturing area, and twenty-five from the courier area. Pre-samples and post-samples were collected for analysis with each detection technique. Samples analyzed by gc/chemiluminescence were taken by swiping a teflon- coated sampling swipe across the surface of the sampling area to pick up any explosive particles. Samples analyzed by ion mobility spectrometry (IMS) were taken from the clothing of the manufacturer and courier by vacuuming the surface and collecting particulates on a fiberglass filter. Samples for IMS analysis from the manufacturing and courier rooms were taken by wiping a cotton sampling swipe across the surface area. Currently, building IEDs and monitoring the explosive contamination is being directed toward detection with portal monitors.

  6. Improved Quantitative Analysis of Ion Mobility Spectrometry by Chemometric Multivariate Calibration

    SciTech Connect

    Fraga, Carlos G.; Kerr, Dayle; Atkinson, David A.

    2009-09-01

    Traditional peak-area calibration and the multivariate calibration methods of principle component regression (PCR) and partial least squares (PLS), including unfolded PLS (U-PLS) and multi-way PLS (N-PLS), were evaluated for the quantification of 2,4,6-trinitrotoluene (TNT) and cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX) in Composition B samples analyzed by temperature step desorption ion mobility spectrometry (TSD-IMS). The true TNT and RDX concentrations of eight Composition B samples were determined by high performance liquid chromatography with UV absorbance detection. Most of the Composition B samples were found to have distinct TNT and RDX concentrations. Applying PCR and PLS on the exact same IMS spectra used for the peak-area study improved quantitative accuracy and precision approximately 3 to 5 fold and 2 to 4 fold, respectively. This in turn improved the probability of correctly identifying Composition B samples based upon the estimated RDX and TNT concentrations from 11% with peak area to 44% and 89% with PLS. This improvement increases the potential of obtaining forensic information from IMS analyzers by providing some ability to differentiate or match Composition B samples based on their TNT and RDX concentrations.

  7. Development of ion-mobility and mass spectrometry for probing the reactivity of nanoparticles and nanocomposites

    NASA Astrophysics Data System (ADS)

    Zhou, Lei

    2009-12-01

    Aerosols of diameter smaller than 100 nm, usually are referred as nanoparticles or ultrafines, have received considerable interests lately as a source of building blocks to novel materials. However, our capabilities for charactering these materials are greatly limited by lack of appropriate diagnostic tools. The objective of this work is to develop new aerosol-based techniques for the characterization of nanoparticles and nanocomposites. Though the scope of this dissertation is focused on probing the reactivity of metal based nanoparticles/nanocomposites and their applications in energetic materials, the methods provide generic approaches for understanding the intrinsic reactivity of nanoparticles. Real-time single particle mass spectrometry (SPMS) has been used to study the reactivity of aluminum nanoparticles. The SPMS is a powerful tool due to its ability to obtain quantitative information at the single particle level. Here in this work, we conducted extensive investigations on the quantification of the SPMS. Particle morphology and composition biases on quantifying the composition of nanoparticles were observed experimentally, was related to the high non-linear properties of the laser-particle interaction. To understand pulsed laser interaction with nanoparticles, as it applied to the implementation and quantification of SPMS, we employed a one-dimensional hydrodynamic model to determine the characteristic behavior of ions produced from the particle. In the simulation, the temporal evolution of the ionization state and energy were evaluated as a function of aluminum particle size that were heated and ionized by a nanosecond laser. The results are shown to be consistent with our experimental observation, and suggest that particle size-dependent energetic ions led to the power law relationship between peak area and particle size observed in our single particle mass spectrometer. Another approach to probe the reactivity of the nanoparticles is an ion-mobility

  8. Mobility-Resolved Ion Selection in Uniform Drift Field Ion Mobility Spectrometry/Mass Spectrometry; Dynamic Switching in Structures for Lossless Ion Manipulations

    SciTech Connect

    Webb, Ian K.; Garimella, Venkata BS; Tolmachev, Aleksey V.; Chen, Tsung-Chi; Zhang, Xinyu; Cox, Jonathan T.; Norheim, Randolph V.; Prost, Spencer A.; Lamarche, Brian L.; Anderson, Gordon A.; Ibrahim, Yehia M.; Smith, Richard D.

    2014-10-07

    A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a “Tee” configuration and allows switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be deflected to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 torr. In the “dynamic mode” we show that mobility-selected ions can be switched into the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. This development also provides the basis for e.g. the selection of specific mobilities for storage and accumulation, and key modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.

  9. Ion mobility mass spectrometry of peptide, protein, and protein complex ions using a radio-frequency confining drift cell.

    PubMed

    Allen, Samuel J; Giles, Kevin; Gilbert, Tony; Bush, Matthew F

    2016-02-01

    Ion mobility mass spectrometry experiments enable the characterization of mass, assembly, and shape of biological molecules and assemblies. Here, a new radio-frequency confining drift cell is characterized and used to measure the mobilities of peptide, protein, and protein complex ions. The new drift cell replaced the traveling-wave ion mobility cell in a Waters Synapt G2 HDMS. Methods for operating the drift cell and determining collision cross section values using this experimental set up are presented within the context of the original instrument control software. Collision cross sections for 349 cations and anions are reported, 155 of which are for ions that have not been characterized previously using ion mobility. The values for the remaining ions are similar to those determined using a previous radio-frequency confining drift cell and drift tubes without radial confinement. Using this device under 2 Torr of helium gas and an optimized drift voltage, denatured and native-like ions exhibited average apparent resolving powers of 14.2 and 16.5, respectively. For ions with high mobility, which are also low in mass, the apparent resolving power is limited by contributions from ion gating. In contrast, the arrival-time distributions of low-mobility, native-like ions are not well explained using only contributions from ion gating and diffusion. For those species, the widths of arrival-time distributions are most consistent with the presence of multiple structures in the gas phase. PMID:26739109

  10. Liquid Nebulization-Ion Mobility Spectrometry Based Quantification of Nanoparticle-Protein Conjugate Formation.

    PubMed

    Jeon, Seongho; Oberreit, Derek R; Van Schooneveld, Gary; Hogan, Christopher J

    2016-08-01

    Despite the importance of examining the formation of nanoparticle-protein conjugates, there is a dearth of routine techniques for nanoparticle-protein conjugate characterization. The most prominent change to a nanoparticle population upon conjugate formation is a shift in the nanoparticle size distribution function. However, commonly employed dynamic light scattering based approaches for size distribution characterization are ineffective for nonmonodisperse samples, and further they are relatively insensitive to size shifts of only several nanometers, which are common during conjugate formation. Conversely, gas phase ion mobility spectrometry (IMS) techniques can be used to reliably examine polydisperse samples, and are sensitive to ∼1 nm size distribution function shifts; the challenge with IMS is to convert nanoparticle-protein conjugates to aerosol particles without bringing about nonspecific aggregation or conjugate formation. Except in limited circumstances, electrospray based aerosolization has proven difficult to apply for this purpose. Here we show that via liquid nebulization (LN) with online, high-flow-rate dilution (with dilution factors up to 10 000) it is possible to aerosolize nanoparticle-protein conjugates, enabling IMS measurements of their conjugate size distribution functions. We specifically employ the LN-IMS system to examine bovine serum albumin binding to gold nanoparticles. Inferred maximum protein surface coverages (∼0.025 nm(-2)) from measurements are shown to be in excellent agreement with reported values for gold from quartz crystal microbalance measurements. It is also shown that LN-IMS measurements can be used to detect size distribution function shifts on the order of 1 nm, even in circumstances where the size distribution function itself has a standard deviation of ∼5 nm. In total, the reported measurements suggest that LN-IMS is a potentially simple and robust technique for nanoparticle-protein conjugate characterization

  11. Optimization of curved drift tubes for ultraviolet-ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Ni, Kai; Ou, Guangli; Zhang, Xiaoguo; Yu, Zhou; Yu, Quan; Qian, Xiang; Wang, Xiaohao

    2015-08-01

    Ion mobility spectrometry (IMS) is a key trace detection technique for toxic pollutants and explosives in the atmosphere. Ultraviolet radiation photoionization source is widely used as an ionization source for IMS due to its advantages of high selectivity and non-radioactivity. However, UV-IMS bring problems that UV rays will be launched into the drift tube which will cause secondary ionization and lead to the photoelectric effect of the Faraday disk. So air is often used as working gas to reduce the effective distance of UV rays, but it will limit the application areas of UV-IMS. In this paper, we propose a new structure of curved drift tube, which can avoid abnormally incident UV rays. Furthermore, using curved drift tube may increase the length of drift tube and then improve the resolution of UV-IMS according to previous research. We studied the homogeneity of electric field in the curved drift tube, which determined the performance of UV-IMS. Numerical simulation of electric field in curved drift tube was conducted by SIMION in our study. In addition, modeling method and homogeneity standard for electric field were also presented. The influences of key parameters include radius of gyration, gap between electrode as well as inner diameter of curved drift tube, on the homogeneity of electric field were researched and some useful laws were summarized. Finally, an optimized curved drift tube is designed to achieve homogenous drift electric field. There is more than 98.75% of the region inside the curved drift tube where the fluctuation of the electric field strength along the radial direction is less than 0.2% of that along the axial direction.

  12. Understanding Gas Phase Modifier Interactions in Rapid Analysis by Differential Mobility-Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kafle, Amol; Coy, Stephen L.; Wong, Bryan M.; Fornace, Albert J.; Glick, James J.; Vouros, Paul

    2014-07-01

    A systematic study involving the use and optimization of gas-phase modifiers in quantitative differential mobility-mass spectrometry (DMS-MS) analysis is presented using nucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes, and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 106 normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab initio thermochemical results, we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry, but at lower temperatures, multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.

  13. Peak Detection Method Evaluation for Ion Mobility Spectrometry by Using Machine Learning Approaches

    PubMed Central

    Hauschild, Anne-Christin; Kopczynski, Dominik; D’Addario, Marianna; Baumbach, Jörg Ingo; Rahmann, Sven; Baumbach, Jan

    2013-01-01

    Ion mobility spectrometry with pre-separation by multi-capillary columns (MCC/IMS) has become an established inexpensive, non-invasive bioanalytics technology for detecting volatile organic compounds (VOCs) with various metabolomics applications in medical research. To pave the way for this technology towards daily usage in medical practice, different steps still have to be taken. With respect to modern biomarker research, one of the most important tasks is the automatic classification of patient-specific data sets into different groups, healthy or not, for instance. Although sophisticated machine learning methods exist, an inevitable preprocessing step is reliable and robust peak detection without manual intervention. In this work we evaluate four state-of-the-art approaches for automated IMS-based peak detection: local maxima search, watershed transformation with IPHEx, region-merging with VisualNow, and peak model estimation (PME). We manually generated a gold standard with the aid of a domain expert (manual) and compare the performance of the four peak calling methods with respect to two distinct criteria. We first utilize established machine learning methods and systematically study their classification performance based on the four peak detectors’ results. Second, we investigate the classification variance and robustness regarding perturbation and overfitting. Our main finding is that the power of the classification accuracy is almost equally good for all methods, the manually created gold standard as well as the four automatic peak finding methods. In addition, we note that all tools, manual and automatic, are similarly robust against perturbations. However, the classification performance is more robust against overfitting when using the PME as peak calling preprocessor. In summary, we conclude that all methods, though small differences exist, are largely reliable and enable a wide spectrum of real-world biomedical applications. PMID:24957992

  14. Electrospray Ionization Mechanisms for Large Polyethylene Glycol Chains Studied Through Tandem Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Larriba, Carlos; de la Mora, Juan Fernandez; Clemmer, David E.

    2014-08-01

    Ion mobility mass spectrometry (IMS-MS) is used to investigate the abundance pattern, n z (m) of Poly-(ethyleneglycol) (PEG) electrosprayed from water/methanol as a function of mass and charge state. We examine n z (m) patterns from a diversity of solution cations, primarily dimethylammonium and triethylammonium. The ability of PEG chains to initially attach to various cations in the spraying chamber, and to retain them (or not) on entering the MS, provide valuable clues on the ionization mechanism. Single chains form in highly charged and extended shapes in most buffers. But the high initial charge they hold under atmospheric pressure is lost on transit to the vacuum system for large cations. In contrast, aggregates of two or more chains carry in all buffers at most the Rayleigh charge of a water drop of the same volume. This shows either that they form via Dole's charge residue mechanism, or that highly charged and extended aggregates are ripped apart by Coulombic repulsion. IMS-IMS experiments in He confirm these findings, and provide new mechanistic insights on the stability of aggregates. When collisionally activated, initially globular dimers are stable. However, slightly nonglobular dimers projecting out a linear appendix are segregated into two monomeric chains. The breakup of a charged dimer is therefore a multi-step process, similar to the Fenn-Consta polymer extrusion mechanism. The highest activation barrier is associated to the first step, where a short chain segment carrying a single charge escapes (ion-evaporates) from a charged drop, leading then to gradual field extrusion of the whole chain out of the drop.

  15. Dissociation Enthalpies of Chloride Adducts of Nitrate and Nitrite Explosives Determined by Ion Mobility Spectrometry.

    PubMed

    Rajapakse, Maneeshin Y; Fowler, Peter E; Eiceman, Gary A; Stone, John A

    2016-02-11

    The kinetics for thermal dissociations of the chloride adducts of the nitrate explosives 1,3-dinitroglycerin (1,3-NG), 1,2-dinitroglycerin (1,2-NG), the nitrite explosive 3,4-dinitrotoluene (3,4-DNT), and the explosive taggant 2,3-dimethyl-2,3-dinitrobutane (DMNB) have been studied by atmospheric pressure ion mobility spectrometry. Both 1,3-NG·Cl(-) and1,2-NG·Cl(-) decompose in a gas-phase SN2 reaction in which Cl(-) displaces NO3(-) while 3,4-DNT·Cl(-) and DMNB·Cl(-) decompose by loss of Cl(-). The determined activation energy (kJ mol(-1)) and pre-exponential factor (s(-1)) values for the dissociations respectively are 1,3-NG·Cl(-), 86 ± 2 and 2.2 × 10(12); 1,2-NG·Cl(-), 97 ± 2 and 3.5 × 10(12); 3,4-DNT·Cl(-), 81 ± 2 and 4.8 × 10(13); and DMNB·Cl(-), 68 ± 2 and 9.7 × 10(11). Calculations by density functional theory show the structures of the nitrate ester adducts involve three hydrogen bonds: one from the hydroxyl group and the other two from the two nitrated carbons. The relative Cl(-) dissociation energies of the nitrates together with the previously reported smaller value for glycerol trinitrate and the calculated highest value for glycerol 1-mononitrate are explicable in terms of the number of hydroxyl hydrogen bond participants. The theoretical enthalpy changes for the nitrate ester displacement reactions are in agreement with those derived from the experimental activation energies but considerably higher for the nitro compounds. PMID:26777731

  16. Probing the stability of insulin oligomers using electrospray ionization ion mobility mass spectrometry.

    PubMed

    Boga Raja, Uday Kumar; Injeti, Srilakshmi; Culver, Tiffany; McCabe, Jacob W; Angel, Laurence A

    2015-01-01

    The peptide hormone insulin is central to regulating carbohydrate and fat metabolism in the body by controlling blood sugar levels. Insulin's most active form is the monomer and the extent of insulin oligomerization is related to insulin's activity of controlling blood sugar levels. Electrospray ionization (ESI) of human insulin produced a series of oligomers from the monomer to the undecamer identified using quadrupole ion mobility time-of-flight mass spectrometry. Previous research suggested that only the monomer, dimer and hexamer are native forms of insulin in solution and the range of oligomers observed in the gas-phase are ESI artifacts. Here the properties of three distinct oligomer bands I, II and III, where both the charge state and number of insulin units of the oligomer increase incrementally, were investigated. When Zn(ii) was added to the insulin sample the same oligomers were observed but with 0-6 Zn(ii) ions bound to each of the oligomers. The oligomers of bands I, II and III were characterized by comparing their drift times, collision cross- sections, relative intensities, collision-induced dissociation (CID) patterns and relative breakdown energies. Insulin oligomers of band I dissociated primarily by releasing either the 2+ or 3+ monomer accompanied by an oligomer that conserved the mass, charge and Zn(ii) of the precursor. Insulin oligomers of bands II and III dissociated primarily by releasing the 2+ monomer accompanied by an oligomer which conserved the mass, charge and Zn(ii) of the precursor. Comparison of CID patterns and breakdown energies showed all the oligomers in band II required higher collision energies to dissociate than the oligomers in band I, and the oligomers of band III required higher energies to dissociate than oligomers of band II. These results show that the amount of excess charge on the oligomer in respect to the number of insulin monomers in the oligomer affects their stability. PMID:26764306

  17. Electrothermal Vaporization Sample Introduction for Spaceflight Water Quality Monitoring via Gas Chromatography-Differential Mobility Spectrometry.

    PubMed

    Wallace, William T; Gazda, Daniel B; Limero, Thomas F; Minton, John M; Macatangay, Ariel V; Dwivedi, Prabha; Fernández, Facundo M

    2015-06-16

    In the history of manned spaceflight, environmental monitoring has relied heavily on archival sampling. However, with the construction of the International Space Station (ISS) and the subsequent extension in mission duration up to one year, an enhanced, real-time method for environmental monitoring is necessary. The station air is currently monitored for trace volatile organic compounds (VOCs) using gas chromatography-differential mobility spectrometry (GC-DMS) via the Air Quality Monitor (AQM), while water is analyzed to measure total organic carbon and biocide concentrations using the Total Organic Carbon Analyzer (TOCA) and the Colorimetric Water Quality Monitoring Kit (CWQMK), respectively. As mission scenarios extend beyond low Earth orbit, a convergence in analytical instrumentation to analyze both air and water samples is highly desirable. Since the AQM currently provides quantitative, compound-specific information for air samples and many of the targets in air are also common to water, this platform is a logical starting point for developing a multimatrix monitor. Here, we report on the interfacing of an electrothermal vaporization (ETV) sample introduction unit with a ground-based AQM for monitoring target analytes in water. The results show that each of the compounds tested from water have similar GC-DMS parameters as the compounds tested in air. Moreover, the ETV enabled AQM detection of dimethlsilanediol (DMSD), a compound whose analysis had proven challenging using other sample introduction methods. Analysis of authentic ISS water samples using the ETV-AQM showed that DMSD could be successfully quantified, while the concentrations obtained for the other compounds also agreed well with laboratory results. PMID:25971650

  18. Selective quantitation of the neurotoxin BMAA by use of hydrophilic-interaction liquid chromatography-differential mobility spectrometry-tandem mass spectrometry (HILIC-DMS-MS/MS).

    PubMed

    Beach, Daniel G; Kerrin, Elliott S; Quilliam, Michael A

    2015-11-01

    The neurotoxin β-N-methylamino-L-alanine (BMAA) has been reported in cyanobacteria and shellfish, raising concerns about widespread human exposure. However, inconsistent results for BMAA analysis have led to controversy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the most appropriate method for analysis of BMAA, but the risk of interference from isomers, other sample components, and the electrospray background is still present. We have investigated differential mobility spectrometry (DMS) as an ion filter to improve selectivity in the hydrophilic interaction liquid chromatographic (HILIC)-MS/MS determination of BMAA. We obtained standards for two BMAA isomers not previously analyzed by HILIC-MS, β-amino-N-methylalanine and 3,4-diaminobutanoic acid, and the typically used 2,4-diaminobutanoic acid and N-(2-aminoethyl)glycine. DMS separation of BMAA from these isomers was achieved and optimized conditions were used to develop a sensitive and highly selective multidimensional HILIC-DMS-MS/MS method. This work revealed current technical limitations of DMS for trace quantitation, and practical solutions were implemented. Accurate control of low levels of DMS carrier gas modifier was essential, but required external metering. The linearity of our optimized method was excellent from 0.01 to 6 μmol L(-1). The instrumental LOD was 0.4 pg BMAA injected on-column and the estimated method LOD was 20 ng g(-1) dry weight for BMAA in sample matrix. The method was used to analyze cycad plant tissue, a cyanobacterial reference material, and mussel tissues, by use of isotope-dilution quantitation with deuterated BMAA. This confirmed the presence of BMAA and several of its isomers in cycad and mussel tissues, including commercially available mussel tissue reference materials certified for other biotoxins. Graphical Abstract Differential Mobility Spectrometry is used to increases the selectivity of BMAA analysis by HILIC-MS/MS. PMID:26396078

  19. Confirmation of diosmetin 3-O-glucuronide as major metabolite of diosmin in humans, using micro-liquid-chromatography-mass spectrometry and ion mobility mass spectrometry.

    PubMed

    Silvestro, Luigi; Tarcomnicu, Isabela; Dulea, Constanta; Attili, Nageswara Rao B N; Ciuca, Valentin; Peru, Dan; Rizea Savu, Simona

    2013-10-01

    Diosmin is a flavonoid often administered in the treatment of chronic venous insufficiency, hemorrhoids, and related affections. Diosmin is rapidly hydrolized in the intestine to its aglicone, diosmetin, which is further metabolized to conjugates. In this study, the development and validations of three new methods for the determination of diosmetin, free and after enzymatic deconjugation, and of its potential glucuronide metabolites, diosmetin-3-O-glucuronide, diosmetin-7-O-glucuronide, and diosmetin-3,7-O-glucuronide from human plasma and urine are presented. First, the quantification of diosmetin, free and after deconjugation, was carried out by high-performance liquid chromatography coupled with tandem mass spectrometry, on an Ascentis RP-Amide column (150 × 2.1 mm, 5 μm), in reversed-phase conditions, after enzymatic digestion. Then glucuronide metabolites from plasma were separated by micro-liquid chromatography coupled with tandem mass spectrometry on a HALO C18 (50 × 0.3 mm, 2.7 μm, 90 Å) column, after solid-phase extraction. Finally, glucuronides from urine were measured using a Discovery HSF5 (100 × 2.1 mm, 5 μm) column, after simple dilution with mobile phase. The methods were validated by assessing linearity, accuracy, precision, low limit of quantification, selectivity, extraction recovery, stability, and matrix effects; results in agreement with regulatory (Food and Drug Administration and European Medicines Agency) guidelines acceptance criteria were obtained in all cases. The methods were applied to a pharmacokinetic study with diosmin (450 mg orally administered tablets). The mean C max of diosmetin in plasma was 6,049.3 ± 5,548.6 pg/mL. A very good correlation between measured diosmetin and glucuronide metabolites concentrations was obtained. Diosmetin-3-O-glucuronide was identified as a major circulating metabolite of diosmetin in plasma and in urine, and this finding was confirmed by supplementary experiments with differential ion-mobility

  20. Correlation of mass spectrometry identified bacterial biomarkers from a fielded pyrolysis-gas chromatography-ion mobility spectrometry biodetector with the microbiological gram stain classification scheme.

    PubMed

    Snyder, A Peter; Dworzanski, Jacek P; Tripathi, Ashish; Maswadeh, Waleed M; Wick, Charles H

    2004-11-01

    A pyrolysis-gas chromatography-ion mobility spectrometry (Py-GC-IMS) briefcase system has been shown to detect and classify deliberately released bioaerosols in outdoor field scenarios. The bioaerosols included Gram-positive and Gram-negative bacteria, MS-2 coliphage virus, and ovalbumin protein species. However, the origin and structural identities of the pyrolysate peaks in the GC-IMS data space, their microbiological information content, and taxonomic importance with respect to biodetection have not been determined. The present work interrogates the identities of the peaks by inserting a time-of-flight mass spectrometry system in parallel with the IMS detector through a Tee connection in the GC module. Biological substances producing ion mobility peaks from the pyrolysis of microorganisms were identified by their GC retention time, matching of their electron ionization mass spectra with authentic standards, and the National Institutes for Standards and Technology mass spectral database. Strong signals from 2-pyridinecarboxamide were identified in Bacillus samples including Bacillus anthracis, and its origin was traced to the cell wall peptidoglycan macromolecule. 3-Hydroxymyristic acid is a component of lipopolysaccharides in the cell walls of Gram-negative organisms. The Gram-negative Escherichia coli organism showed significant amounts of 3-hydroxymyristic acid derivatives and degradation products in Py-GC-MS analyses. Some of the fatty acid derivatives were observed in very low abundance in the ion mobility spectra, and the higher boiling lipid species were absent. Evidence is presented that the Py-GC-ambient temperature and pressure-IMS system generates and detects bacterial biochemical information that can serve as components of a biological classification scheme directly correlated to the Gram stain reaction in microorganism taxonomy. PMID:15516146

  1. ATP and autophosphorylation driven conformational changes of HipA kinase revealed by ion mobility and crosslinking mass spectrometry.

    PubMed

    Wen, Yurong; Sobott, Frank; Devreese, Bart

    2016-08-01

    Toxin-antitoxin systems are genetic modules involved in a broad range of bacterial cellular processes including persistence, multidrug resistance and tolerance, biofilm formation, and pathogenesis. In type II toxin-antitoxin systems, both the toxin and antitoxin are proteins. In the prototypic Escherichia coli HipA-HipB module, the antitoxin HipB forms a complex with the protein kinase HipA and sequesters it in the nucleoid. HipA is then no longer able to phosphorylate glutamyl-tRNA-synthetase and this prevents the initiation of the forthcoming stringent response. Here we investigated the assembly of the Shewanella oneidensis MR-1 HipA-HipB complex using native electrospray ion mobility-mass spectrometry and chemical crosslinking combined with mass spectrometry. We revealed that the HipA autophosphorylation was accompanied by a large conformational change, and confirmed structural evidence that S. oneidensis MR-1 HipA-HipB assembly was distinct from the prototypic E. coli HipA-HipB complex. Graphical abstract Ion mobility mass spectrometry shows a two phase transition from unstructured HipA to a compact folded phosphorylated protein. PMID:27325463

  2. Stable compositions and geometrical structures of titanium oxide cluster cations and anions studied by ion mobility mass spectrometry.

    PubMed

    Ohshimo, Keijiro; Norimasa, Naoya; Moriyama, Ryoichi; Misaizu, Fuminori

    2016-05-21

    Geometrical structures of titanium oxide cluster cations and anions have been investigated by ion mobility mass spectrometry and quantum chemical calculations based on density functional theory. Stable cluster compositions with respect to collision induced dissociation were also determined by changing ion injection energy to an ion drift cell for mobility measurements. The TinO2n-1 (+) cations and TinO2n (-) anions were predominantly observed at high injection energies, in addition to TinO2n (+) for cations and TinO2n+1 (-) for anions. Collision cross sections of TinO2n (+) and TinO2n+1 (-) for n = 1-7, determined by ion mobility mass spectrometry, were compared with those obtained theoretically as orientation-averaged cross sections for the optimized structures by quantum chemical calculations. All of the geometrical structures thus assigned have three-dimensional structures, which are in marked contrast with other oxides of late transition metals. One-oxygen atom dissociation processes from TinO2n (+) and TinO2n+1 (-) by collisions were also explained by analysis of spin density distributions. PMID:27208947

  3. Stable compositions and geometrical structures of titanium oxide cluster cations and anions studied by ion mobility mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ohshimo, Keijiro; Norimasa, Naoya; Moriyama, Ryoichi; Misaizu, Fuminori

    2016-05-01

    Geometrical structures of titanium oxide cluster cations and anions have been investigated by ion mobility mass spectrometry and quantum chemical calculations based on density functional theory. Stable cluster compositions with respect to collision induced dissociation were also determined by changing ion injection energy to an ion drift cell for mobility measurements. The TinO2n-1+ cations and TinO2n- anions were predominantly observed at high injection energies, in addition to TinO2n+ for cations and TinO2n+1- for anions. Collision cross sections of TinO2n+ and TinO2n+1- for n = 1-7, determined by ion mobility mass spectrometry, were compared with those obtained theoretically as orientation-averaged cross sections for the optimized structures by quantum chemical calculations. All of the geometrical structures thus assigned have three-dimensional structures, which are in marked contrast with other oxides of late transition metals. One-oxygen atom dissociation processes from TinO2n+ and TinO2n+1- by collisions were also explained by analysis of spin density distributions.

  4. Atmospheric Solid Analysis Probe-Ion Mobility Mass Spectrometry: An Original Approach to Characterize Grafting on Cyclic Olefin Copolymer Surfaces.

    PubMed

    Vieillard, Julien; Hubert-Roux, Marie; Brisset, Florian; Soulignac, Cecile; Fioresi, Flavia; Mofaddel, Nadine; Morin-Grognet, Sandrine; Afonso, Carlos; Le Derf, Franck

    2015-12-01

    A cyclic olefin copolymer (COC) was grafted with aryl layers from aryldiazonium salts, and then we combined infrared spectrometry, atomic force microscopy (AFM), and ion mobility mass spectrometry with atmospheric solid analysis probe ionization (ASAP-IM-MS) to characterize the aryl layers. ASAP is a recent atmospheric ionization method dedicated to the direct analysis of solid samples. We demonstrated that ASAP-IM-MS is complementary to other techniques for characterizing bromine and sulfur derivatives of COC on surfaces. ASAP-IM-MS was useful for optimizing experimental grafting conditions and to elucidate hypotheses around aryl layer formation during the grafting process. Thus, ASAP-IM-MS is a good candidate tool to characterize covalent grafting on COC surfaces. PMID:26556473

  5. Collision-Induced Dissociation Ion Mobility Mass Spectrometry for the Elucidation of Unknown Structures in Strained Polycyclic Aromatic Hydrocarbon Macrocycles.

    PubMed

    Zhang, Wen; Quernheim, Martin; Räder, Hans Joachim; Müllen, Klaus

    2016-01-01

    Structure determination of unexpected products obtained during synthesis of large carbon nanotube sidewall segments with more than 200 carbon atoms represents a challenging task for traditional analytical methods. Herein, we investigate a homologous series of four products having the same number of carbon atoms but slightly different hydrogen numbers ranging from 168 to 162. We demonstrate that the combination of mass spectrometry, ion mobility separation, and collision-induced dissociation (CID) can be used to finally elucidate the complete structures with high certainty. The postulated 1,2-phenyl shift as origin for the side reaction could be proven by changes in the minimum fragment sizes. A combination of CID and ion mobility spectrometry was applied for the first time to prove the cyclic nature of all molecules by the significant size increase upon ring opening. Thereby, also, more compact molecules were discovered in the gas phase with thus far unknown structures. Finally, the potential presence of numerous isomers could be ruled out by drift time measurements and molecular modeling together with theoretical collision cross-section (CCS) calculations. Surprisingly, only one defined structure could be assigned to each macrocycle in the homologous series, most likely as a result of natural selection rules driven by ring strain and steric hindrance. With a decreasing hydrogen content, the macrocycles undergo a stepwise transition from a cylindrical to conical shape. Overall, ion mobility mass spectrometry together with molecular modeling shows great potential to analyze unknown structures, especially in cases where structure determination by X-ray single-crystal analysis is not applicable. PMID:26613508

  6. Matrix-Assisted Ionization-Ion Mobility Spectrometry-Mass Spectrometry: Selective Analysis of a Europium-PEG Complex in a Crude Mixture

    NASA Astrophysics Data System (ADS)

    Fischer, Joshua L.; Lutomski, Corinne A.; El-Baba, Tarick J.; Siriwardena-Mahanama, Buddhima N.; Weidner, Steffen M.; Falkenhagen, Jana; Allen, Matthew J.; Trimpin, Sarah

    2015-12-01

    The analytical utility of a new and simple to use ionization method, matrix-assisted ionization (MAI), coupled with ion mobility spectrometry (IMS) and mass spectrometry (MS) is used to characterize a 2-armed europium(III)-containing poly(ethylene glycol) (Eu-PEG) complex directly from a crude sample. MAI was used with the matrix 1,2-dicyanobenzene, which affords low chemical background relative to matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). MAI provides high ion abundance of desired products in comparison to ESI and MALDI. Inductively coupled plasma-MS measurements were used to estimate a maximum of 10% of the crude sample by mass was the 2-arm Eu-PEG complex, supporting evidence of selective ionization of Eu-PEG complexes using the new MAI matrix, 1,2-dicyanobenzene. Multiply charged ions formed in MAI enhance the IMS gas-phase separation, especially relative to the singly charged ions observed with MALDI. Individual components are cleanly separated and readily identified, allowing characterization of the 2-arm Eu-PEG conjugate from a mixture of the 1-arm Eu-PEG complex and unreacted starting materials. Size-exclusion chromatography, liquid chromatography at critical conditions, MALDI-MS, ESI-MS, and ESI-IMS-MS had difficulties with this analysis, or failed.

  7. Effects of Select Anions from the Hofmeister Series on the Gas-Phase Conformations of Protein Ions Measured with Traveling-Wave Ion Mobility Spectrometry/Mass Spectrometry

    PubMed Central

    Merenbloom, Samuel I.; Flick, Tawnya G.; Daly, Michael P.; Williams, Evan R.

    2011-01-01

    The gas-phase conformations of ubiquitin, cytochrome c, lysozyme, and ↦-lactalbumin ions, formed by electrospray ionization (ESI) from aqueous solutions containing 5 mM ammonium perchlorate, ammonium iodide, ammonium sulfate, ammonium chloride, ammonium thiocyanate, or guanidinium chloride, are examined using traveling-wave ion mobility spectrometry (TWIMS) coupled to time-of-flight (TOF) mass spectrometry (MS). For ubiquitin, cytochrome c, and ↦-lactalbumin, adduction of multiple acid molecules results in no significant conformational changes to the highest and lowest charge states formed from aqueous solutions, whereas the intermediate charge states become more compact. The transition to more compact conformers for the intermediate charge states occurs with fewer bound H2SO4 molecules than HClO4 or HI molecules, suggesting ion-ion or salt-bridge interactions are stabilizing more compact forms of the gaseous protein. However, the drift time distributions for protein ions of the same net charge with the highest levels of adduction of each acid are comparable, indicating that these protein ions all adopt similarly compact conformations or families of conformers. No change in conformation is observed upon the adduction of multiple acid molecules to charge states of lysozyme. These results show that the attachment of HClO4, HI, or H2SO4 to multiply protonated proteins can induce compact conformations in the resulting gas-phase protein ions. In contrast, differing Hofmeister effects are observed for the corresponding anions in solution at higher concentrations. PMID:21952780

  8. Aqueous phase oligomerization of α,β-unsaturated carbonyls and acids investigated using ion mobility spectrometry coupled to mass spectrometry (IMS-MS)

    NASA Astrophysics Data System (ADS)

    Renard, Pascal; Tlili, Sabrine; Ravier, Sylvain; Quivet, Etienne; Monod, Anne

    2016-04-01

    One of the current essential issues to unravel our ability to forecast future climate change and air quality, implies a better understanding of natural processes leading to secondary organic aerosol (SOA) formation, and in particular the formation and fate of oligomers. The difficulty in characterizing macromolecules is to discern between large oxygenated molecules from series of oligomers containing repeated small monomers of diverse structures. In the present study, taking advantage from previously established radical vinyl oligomerization of methyl vinylketone (MVK) in the aqueous phase, where relatively simple oligomers containing up to 14 monomers were observed, we have investigated the same reactivity on several other unsaturated water soluble organic compounds (UWSOCs) and on a few mixtures of these precursor compounds. The technique used to characterize the formed oligomers was a traveling wave ion mobility spectrometry coupled to a hybrid quadrupole - time of flight mass spectrometer (IMS-MS) fitted with an electrospray source and ultra-high performance liquid chromatography (UPLC). The technique allows for an additional separation, especially for large ions, containing long carbon chains. We have shown the efficiency of the IMS-mass spectrometry technique to detect oligomers derived from MVK photooxidation in the aqueous phase. The results were then compared to other oligomers, derived from ten other individual biogenic UWSOCs. The technique allowed distinguishing between different oligomers arising from different precursors. It also clearly showed that compounds bearing a non-conjugated unsaturation did not provide oligomerization. Finally, it was shown that the IMS-mass spectrometry technique, applied to mixtures of unsaturated conjugated precursors, exhibited the ability of these precursors to co-oligomerize, i.e. forming only one complex oligomer system bearing monomers of different structures. The results are discussed in terms of atmospheric

  9. Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Chen, Zhidan; Coy, Stephen L.; Pannkuk, Evan L.; Laiakis, Evagelia C.; Hall, Adam B.; Fornace, Albert J.; Vouros, Paul

    2016-07-01

    Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure.

  10. Carbohydrate Structure Characterization by Tandem Ion Mobility Mass Spectrometry (IMMS)2

    PubMed Central

    Li, Hongli; Bendiak, Brad; Siems, William F.; Gang, David R.; Hill, Herbert H.

    2013-01-01

    A high resolution ion mobility spectrometer was interfaced to a Synapt G2 high definition mass spectrometer (HDMS) to produce IMMS-IMMS analysis. The hybrid instrument contained an electro-spray ionization source, two ion gates, an ambient pressure linear ion mobility drift tube, a quadrupole mass filter, a traveling wave ion mobility spectrometer (TWIMS) and a time of flight mass spectrometer. The dual gate drift tube ion mobility spectrometer (DTIMS) could be used to acquire traditional IMS spectra, but also could selectively transfer specific mobility selected precursor ions to the Synapt G2 HDMS for mass filtration (quadrupole). The mobility and mass selected ions could then be introduced into a collision cell for fragmentation followed by mobility separation of the fragment ions with the traveling wave ion mobility spectrometer. These mobility separated fragment ions are finally mass analyzed using a time-of-flight mass spectrometer. This results in an IMMS-IMMS analysis and provides a method to evaluate the isomeric heterogeneity of precursor ions by both DTIMS and TWIMS, to acquire a mobility-selected and mass-filtered fragmentation pattern and to additionally obtain traveling wave ion mobility spectra of the corresponding product ions. This new IMMS2 instrument enables the structural diversity of carbohydrates to be studied in greater detail. The physical separation of isomeric oligosaccharide mixtures was achieved by both DTIMS and TWIMS, with DTIMS demonstrating higher resolving power (70~80) than TWIMS (30~40). Mobility selected MS/MS spectra were obtained, and TWIMS evaluation of product ions showed that isomeric forms of fragment ions existed for identical m/z values. PMID:23330948

  11. Carbohydrate structure characterization by tandem ion mobility mass spectrometry (IMMS)2.

    PubMed

    Li, Hongli; Bendiak, Brad; Siems, William F; Gang, David R; Hill, Herbert H

    2013-03-01

    A high resolution ion mobility spectrometer was interfaced to a Synapt G2 high definition mass spectrometer (HDMS) to produce IMMS-IMMS analysis. The hybrid instrument contained an electrospray ionization source, two ion gates, an ambient pressure linear ion mobility drift tube, a quadrupole mass filter, a traveling wave ion mobility spectrometer (TWIMS), and a time-of-flight mass spectrometer. The dual gate drift tube ion mobility spectrometer (DTIMS) could be used to acquire traditional IMS spectra but also could selectively transfer specific mobility selected precursor ions to the Synapt G2 HDMS for mass filtration (quadrupole). The mobility and mass selected ions could then be introduced into a collision cell for fragmentation followed by mobility separation of the fragment ions with the traveling wave ion mobility spectrometer. These mobility separated fragment ions are finally mass analyzed using a time-of-flight mass spectrometer. This results in an IMMS-IMMS analysis and provides a method to evaluate the isomeric heterogeneity of precursor ions by both DTIMS and TWIMS to acquire a mobility-selected and mass-filtered fragmentation pattern and to additionally obtain traveling wave ion mobility spectra of the corresponding product ions. This new IMMS(2) instrument enables the structural diversity of carbohydrates to be studied in greater detail. The physical separation of isomeric oligosaccharide mixtures was achieved by both DTIMS and TWIMS, with DTIMS demonstrating higher resolving power (70-80) than TWIMS (30-40). Mobility selected MS/MS spectra were obtained, and TWIMS evaluation of product ions showed that isomeric forms of fragment ions existed for identical m/z values. PMID:23330948

  12. Secondary ionization of chemical warfare agent simulants: atmospheric pressure ion mobility time-of-flight mass spectrometry.

    PubMed

    Steiner, Wes E; Clowers, Brian H; Haigh, Paul E; Hill, Herbert H

    2003-11-15

    For the first time, the use of a traditional ionization source for ion mobility spectrometry (radioactive nickel ((63)Ni) beta emission ionization) and three alternative ionization sources (electrospray ionization (ESI), secondary electrospray ionization (SESI), and electrical discharge (corona) ionization (CI)) were employed with an atmospheric pressure ion mobility orthogonal reflector time-of-flight mass spectrometer (IM(tof)MS) to detect chemical warfare agent (CWA) simulants from both aqueous- and gas-phase samples. For liquid-phase samples, ESI was used as the sample introduction and ionization method. For the secondary ionization (SESI, CI, and traditional (63)Ni ionization) of vapor-phase samples, two modes of sample volatilization (heated capillary and thermal desorption chamber) were investigated. Simulant reference materials, which closely mimic the characteristic chemical structures of CWA as defined and described by Schedule 1, 2, or 3 of the Chemical Warfare Convention treaty verification, were used in this study. A mixture of four G/V-type nerve simulants (dimethyl methylphosphonate, pinacolyl methylphosphonate, diethyl phosphoramidate, and 2-(butylamino)ethanethiol) and one S-type vesicant simulant (2-chloroethyl ethyl sulfide) were found in each case (sample ionization and introduction methods) to be clearly resolved using the IM(tof)MS method. In many cases, reduced mobility constants (K(o)) were determined for the first time. Ion mobility drift times, flight times, relative signal intensities, and fragmentation product signatures for each of the CWA simulants are reported for each of the methods investigated. PMID:14615983

  13. A strategy for identification and structural characterization of compounds from Gardenia jasminoides by integrating macroporous resin column chromatography and liquid chromatography-tandem mass spectrometry combined with ion-mobility spectrometry.

    PubMed

    Wang, Lu; Liu, Shu; Zhang, Xueju; Xing, Junpeng; Liu, Zhiqiang; Song, Fengrui

    2016-06-24

    In this paper, an analysis strategy integrating macroporous resin (AB-8) column chromatography and high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) combined with ion mobility spectrometry (IMS) was proposed and applied for identification and structural characterization of compounds from the fruits of Gardenia jasminoides. The extracts of G. jasminoides were separated by AB-8 resin column chromatography combined with reversed phase liquid chromatography (C18 column) and detected by electrospray ionization tandem mass spectrometry. Additionally, ion mobility spectrometry (IMS) was employed as a supplementary separation technique to discover previously undetected isomers from the fruits of G. jasminoides. A total of 71 compounds, including iridoids, flavonoids, triterpenes, monoterpenoids, carotenoids and phenolic acids were identified by the characteristic high resolution mass spectrometry and the ESI-MS/MS fragmentations. In conclusion, the IMS-MS technique achieved the separation of isomers in crocin-3 and crocin-4 according to their acquired mobility drift times differing from classical analysis by mass spectrometry. The proposed strategy can be used as a highly sensitive and efficient procedure for identification and separation isomeric components in extracts of herbal medicines. PMID:27208986

  14. Description of Gas-Phase Ion/Neutral Interactions in Differential Ion Mobility Spectrometry: CV Prediction Using Calibration Runs

    NASA Astrophysics Data System (ADS)

    Auerbach, David; Aspenleiter, Julia; Volmer, Dietrich A.

    2014-09-01

    Differential ion mobility spectrometry (DMS) coupled to mass spectrometry is increasingly used in both quantitative analyses of biological samples and as a means of removing background interferences for enhanced selectivity and improved quality of mass spectra. However, DMS separation efficiency using dry inert gases often lacks the required selectivity to achieve baseline separation. Polar gas-phase modifiers such as alcohols are therefore frequently employed to improve selectivity via clustering/declustering processes. The choice of an optimal modifier currently relies on trial and error experiments, making method development a tedious activity. It was the goal of this study to establish a means of CV prediction for compounds using a homologous series of alcohols as gas-phase modifiers. This prediction was based on linear regression of compensation voltages of two calibration runs for the alcohols with the lowest and the highest molecular weights and readily available descriptors such as proton affinity and gas phase acidity of the modifier molecules. All experiments were performed on a commercial quadrupole linear ion trap mass spectrometer equipped with a DMS device between electrospray ionization source and entrance quadrupole lens. We evaluated our approach using a homologous series of 4-alkylbenzoic acids and a selection of 23 small molecules of high chemical diversity. Predicted CV values typically deviated from the experimentally determined values by less than 0.5 V. Several test compounds changed their ion mobility behavior for the investigated gas phase modifiers (e.g., from type B to type A) and thus could thus not be evaluated.

  15. An effective approach for coupling direct analysis in real time with atmospheric pressure drift tube ion mobility spectrometry.

    PubMed

    Keelor, Joel D; Dwivedi, Prabha; Fernández, Facundo M

    2014-09-01

    Drift tube ion mobility spectrometry (DTIMS) has evolved as a robust analytical platform routinely used for screening small molecules across a broad suite of chemistries ranging from food and pharmaceuticals to explosives and environmental toxins. Most modern atmospheric pressure IM detectors employ corona discharge, photoionization, radioactive, or electrospray ion sources for efficient ion production. Coupling standalone DTIMS with ambient plasma-based techniques, however, has proven to be an exceptional challenge. Device sensitivity with near-ground ambient plasma sources is hindered by poor ion transmission at the source-instrument interface, where ion repulsion is caused by the strong electric field barrier of the high potential ion mobility spectrometry (IMS) inlet. To overcome this shortfall, we introduce a new ion source design incorporating a repeller point electrode used to shape the electric field profile and enable ion transmission from a direct analysis in real time (DART) plasma ion source. Parameter space characterization studies of the DART DTIMS setup were performed to ascertain the optimal configuration for the source assembly favoring ion transport. Preliminary system capabilities for the direct screening of solid pharmaceuticals are briefly demonstrated. PMID:24903510

  16. An Effective Approach for Coupling Direct Analysis in Real Time with Atmospheric Pressure Drift Tube Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Keelor, Joel D.; Dwivedi, Prabha; Fernández, Facundo M.

    2014-09-01

    Drift tube ion mobility spectrometry (DTIMS) has evolved as a robust analytical platform routinely used for screening small molecules across a broad suite of chemistries ranging from food and pharmaceuticals to explosives and environmental toxins. Most modern atmospheric pressure IM detectors employ corona discharge, photoionization, radioactive, or electrospray ion sources for efficient ion production. Coupling standalone DTIMS with ambient plasma-based techniques, however, has proven to be an exceptional challenge. Device sensitivity with near-ground ambient plasma sources is hindered by poor ion transmission at the source-instrument interface, where ion repulsion is caused by the strong electric field barrier of the high potential ion mobility spectrometry (IMS) inlet. To overcome this shortfall, we introduce a new ion source design incorporating a repeller point electrode used to shape the electric field profile and enable ion transmission from a direct analysis in real time (DART) plasma ion source. Parameter space characterization studies of the DART DTIMS setup were performed to ascertain the optimal configuration for the source assembly favoring ion transport. Preliminary system capabilities for the direct screening of solid pharmaceuticals are briefly demonstrated.

  17. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 3. Estimating Surface Area Exposure by Deuterium Uptake.

    PubMed

    Khakinejad, Mahdiar; Kondalaji, Samaneh Ghassabi; Donohoe, Gregory C; Valentine, Stephen J

    2016-03-01

    Gas-phase hydrogen deuterium exchange (HDX), collision cross section (CCS) measurement, and molecular dynamics simulation (MDS) techniques were utilized to develop and compare three methods for estimating the relative surface area exposure of separate peptide chains within bovine insulin ions. Electrosprayed [M - 3H](3-) and [M - 5H](5-) insulin ions produced a single conformer type with respective collision cross sections of 528 ± 5 Å(2) and 808 ± 2 Å(2). [M - 4H](4-) ions were comprised of more compact (Ω = 676 ± 3 Å(2)) and diffuse (i.e., more elongated, Ω = 779 ± 3 Å(2)) ion conformer types. Ions were subjected to HDX in the drift tube using D2O as the reagent gas. Collision-induced dissociation was used to fragment mobility-selected, isotopically labeled [M - 4H](4-) and [M - 5H](5-) ions into the protein subchains. Deuterium uptake levels of each chain can be explained by limited inter-chain isotopic scrambling upon collisional activation. Using nominal ion structures from MDS and a hydrogen accessibility model, the deuterium uptake for each chain was correlated to its exposed surface area. In separate experiments, the per-residue deuterium content for the protonated and deprotonated ions of the synthetic peptide KKDDDDDIIKIIK were compared. The differences in deuterium content indicated the regional HDX accessibility for cations versus anions. Using ions of similar conformational type, this comparison highlights the complementary nature of HDX data obtained from positive- and negative-ion analysis. PMID:26620531

  18. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 3. Estimating Surface Area Exposure by Deuterium Uptake

    NASA Astrophysics Data System (ADS)

    Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Donohoe, Gregory C.; Valentine, Stephen J.

    2016-03-01

    Gas-phase hydrogen deuterium exchange (HDX), collision cross section (CCS) measurement, and molecular dynamics simulation (MDS) techniques were utilized to develop and compare three methods for estimating the relative surface area exposure of separate peptide chains within bovine insulin ions. Electrosprayed [M - 3H]3- and [M - 5H]5- insulin ions produced a single conformer type with respective collision cross sections of 528 ± 5 Å2 and 808 ± 2 Å2. [M - 4H]4- ions were comprised of more compact (Ω = 676 ± 3 Å2) and diffuse (i.e., more elongated, Ω = 779 ± 3 Å2) ion conformer types. Ions were subjected to HDX in the drift tube using D2O as the reagent gas. Collision-induced dissociation was used to fragment mobility-selected, isotopically labeled [M - 4H]4- and [M - 5H]5- ions into the protein subchains. Deuterium uptake levels of each chain can be explained by limited inter-chain isotopic scrambling upon collisional activation. Using nominal ion structures from MDS and a hydrogen accessibility model, the deuterium uptake for each chain was correlated to its exposed surface area. In separate experiments, the per-residue deuterium content for the protonated and deprotonated ions of the synthetic peptide KKDDDDDIIKIIK were compared. The differences in deuterium content indicated the regional HDX accessibility for cations versus anions. Using ions of similar conformational type, this comparison highlights the complementary nature of HDX data obtained from positive- and negative-ion analysis.

  19. A new approach for detection of explosives based on ion mobility spectrometry and laser desorption/ionization on porous silicon

    NASA Astrophysics Data System (ADS)

    Kuzishchin, Yury; Kotkovskii, Gennadii; Martynov, Igor; Dovzhenko, Dmitriy; Chistyakov, Alexander

    2016-05-01

    We demonstrate a new way for detection ultralow concentration of explosives in this study. It combines an ion mobility spectrometry (IMS) and a promising method of laser desorption/ionization on silicon (DIOS). The DIOS is widely used in mass spectrometry due to the possibility of small molecule detection and high sensitivity. It is known that IMS based on laser ion source is a power method for the fast detection of ultralow concentration of organic molecules. However requirement of using high energy pulse ultraviolet laser increases weight and size of the device. The use of DIOS in an ion source of IMS could decrease energy pulse requirements and allows one to construct both compact and high sensitive device for analyzing gas and liquid probes. On the other hand mechanisms of DIOS in gas media is poorly studied, especially in case of nitroaromatic compounds. The investigation of the desorption/ionization on porous silicon (pSi) surface of nitroaromatic compounds has been carried out for 2,4,6-trinitrotoluene (TNT) using IMS and mass spectrometry (MS). It has been demonstrated that TNT ion formation in a gas medium is a complicated process and includes both an electron emission from the pSi surface with subsequent ion-molecular reactions in a gas phase and a proton transfer between pSi surface and TNT molecule.

  20. Rapid, in situ detection of cocaine residues based on paper spray ionization coupled with ion mobility spectrometry.

    PubMed

    Li, Ming; Zhang, Jingjing; Jiang, Jie; Zhang, Jing; Gao, Jing; Qiao, Xiaolin

    2014-04-01

    In this paper, a novel approach based on paper spray ionization coupled with ion mobility spectrometry (PSI-IMS) was developed for rapid, in situ detection of cocaine residues in liquid samples and on various surfaces (e.g. glass, marble, skin, wood, fingernails), without tedious sample pretreatment. The obvious advantages of PSI are its low cost, easy operation and simple configuration without using nebulizing gas or discharge gas. Compared with mass spectrometry, ion mobility spectrometry (IMS) takes advantage of its low cost, easy operation, and simple configuration without requiring a vacuum system. Therefore, IMS is a more congruous detection method for PSI in the case of rapid, in situ analysis. For the analysis of cocaine residues in liquid samples, dynamic responses from 5 μg mL(-1) to 200 μg mL(-1) with a linear coefficient (R(2)) of 0.992 were obtained. In this case, the limit of detection (LOD) was calculated to be 2 μg mL(-1) as signal to noise (S/N) was 3 with a relative standard deviation (RSD) of 6.5% for 11 measurements (n = 11). Cocaine residues on various surfaces such as metal, glass, marble, wood, skin, and fingernails were also directly analyzed before wiping the surfaces with a piece of paper. The LOD was calculated to be as low as 5 ng (S/N = 3, RSD = 6.3%, n = 11). This demonstrates the capability of the PSI-IMS method for direct detection of cocaine residues at scenes of cocaine administration. Our results show that PSI-IMS is a simple, sensitive, rapid and economical method for in situ detection of this illicit drug, which could help governments to combat drug abuse. PMID:24563903

  1. Ion mobility spectrometry–mass spectrometry (IMS–MS) for on- and offline analysis of atmospheric gas and aerosol species

    DOE PAGESBeta

    Krechmer, Jordan E.; Groessl, Michael; Zhang, Xuan; Junninen, Heikki; Massoli, Paola; Lambe, Andrew T.; Kimmel, Joel R.; Cubison, Michael J.; Graf, Stephan; Lin, Ying-Hsuan; et al

    2016-07-25

    Measurement techniques that provide molecular-level information are needed to elucidate the multiphase processes that produce secondary organic aerosol (SOA) species in the atmosphere. Here we demonstrate the application of ion mobility spectrometry-mass spectrometry (IMS–MS) to the simultaneous characterization of the elemental composition and molecular structures of organic species in the gas and particulate phases. Molecular ions of gas-phase organic species are measured online with IMS–MS after ionization with a custom-built nitrate chemical ionization (CI) source. This CI–IMS–MS technique is used to obtain time-resolved measurements (5 min) of highly oxidized organic molecules during the 2013 Southern Oxidant and Aerosol Study (SOAS) ambientmore » field campaign in the forested SE US. The ambient IMS–MS signals are consistent with laboratory IMS–MS spectra obtained from single-component carboxylic acids and multicomponent mixtures of isoprene and monoterpene oxidation products. Mass-mobility correlations in the 2-D IMS–MS space provide a means of identifying ions with similar molecular structures within complex mass spectra and are used to separate and identify monoterpene oxidation products in the ambient data that are produced from different chemical pathways. Water-soluble organic carbon (WSOC) constituents of fine aerosol particles that are not resolvable with standard analytical separation methods, such as liquid chromatography (LC), are shown to be separable with IMS–MS coupled to an electrospray ionization (ESI) source. The capability to use ion mobility to differentiate between isomers is demonstrated for organosulfates derived from the reactive uptake of isomers of isoprene epoxydiols (IEPOX) onto wet acidic sulfate aerosol. Controlled fragmentation of precursor ions by collisionally induced dissociation (CID) in the transfer region between the IMS and the MS is used to validate MS peak assignments, elucidate structures of

  2. Detection and classification of explosive compounds utilizing laser ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Langmeier, A.; Heep, W.; Oberhuettinger, C.; Oberpriller, H.; Kessler, M.; Goebel, J.; Mueller, G.

    2009-05-01

    Detection of explosives by ion mobility spectroscopy has become common in recent years. We demonstrate explosive detection with a novel Laser Ion Mobility Spectrometer (LIMS) developed at EADS Innovation Works. A Laser operating at 266nm was used for the two-photon ionisation of dopant and calibrant substances. Quantitative measurements of trace residues of explosives have been performed to quantify the sensitivity of the LIMS system. Findings demonstrate the suitability of this technique as a screening tool for explosive compounds.

  3. DISCRIMINATION OF COMBUSTION FUEL SOURCES USING GAS CHROMATOGRAPY-PLANAR FIELD ASYMETRIC WAVEFORM ION MOBILITY SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Smoke plumes from cotton, paper, grass and cigarettes and emissions from a gasoline engine were sampled using solid-phase microextraction (SPME) and samples were analyzed for volatile organic compounds(VOC) using gas chromatography-mass spectrometry (GC-MS). Chemical compositions were sufficiently ...

  4. Gas-phase separation of drugs and metabolites using modifier-assisted differential ion mobility spectrometry hyphenated to liquid extraction surface analysis and mass spectrometry.

    PubMed

    Porta, Tiffany; Varesio, Emmanuel; Hopfgartner, Gérard

    2013-12-17

    The present work describes an alternative generic approach to LC-MS for the analysis of drugs of abuse as well as their metabolites in post-mortem tissue samples. The platform integrates liquid extraction surface analysis (LESA) for analytes tissue extraction followed by differential ion mobility spectrometry (DMS) mass spectrometry for analytes gas phase separation. Detection is performed on a triple quadrupole linear ion trap using the selected reaction monitoring mode for quantification as well as product ion scan mode for structural confirmatory analyses. The major advantages of the platform are that neither chromatographic separation nor extensive sample preparation are required. In DMS the combination of a high separation voltage (i.e., up to 4 kV) together with organic modifiers (e.g., alcohols, acetonitrile, acetone) added in the drift gas is required to achieve the separation of isomeric metabolites, such as the ones of cocaine and tramadol. DMS also separates morphine from its glucuronide metabolites, which allows for preventing the overestimation of morphine in case of fragmentation of the glucuronides in the atmospheric-to-vacuum interface of the mass spectrometer. Cocaine, opiates, opioids, amphetamines, benzodiazepines and several of their metabolites could be identified in post-mortem human kidney and muscle tissue based on simultaneous screening and confirmatory analysis in data-dependent acquisition mode using an analyte-dependent compensation voltage to selectively transmit ions through the DMS cell to the mass analyzer. Quantitative performance of the LESA-DMS-MS platform was evaluated for cocaine and two of its metabolites spotted onto a tissue section using deuterated internal standard. Analyte's responses were linear from 2 to 1000 pg on tissue corresponding to a limit of detection in the order of nanograms of analyte per gram of tissue. Accuracy and precision based on QC sample was found to be less than 10%. Replicate analyses of cocaine and

  5. The Influence of Drift Gas Composition on the Separation Mechanism in Traveling Wave Ion Mobility Spectrometry: Insight from Electrodynamic Simulations

    PubMed Central

    May, Jody C.; McLean, John A.

    2013-01-01

    The influence of three different drift gases (helium, nitrogen, and argon) on the separation mechanism in traveling wave ion mobility spectrometry is explored through ion trajectory simulations which include considerations for ion diffusion based on kinetic theory and the electrodynamic traveling wave potential. The model developed for this work is an accurate depiction of a second-generation commercial traveling wave instrument. Three ion systems (cocaine, MDMA, and amphetamine) whose reduced mobility values have previously been measured in different drift gases are represented in the simulation model. The simulation results presented here provide a fundamental understanding of the separation mechanism in traveling wave, which is characterized by three regions of ion motion: (1) ions surfing on a single wave, (2) ions exhibiting intermittent roll-over onto subsequent waves, and (3) ions experiencing a steady state roll-over which repeats every few wave cycles. These regions of ion motion are accessed through changes in the gas pressure, wave amplitude, and wave velocity. Resolving power values extracted from simulated arrival times suggest that momentum transfer in helium gas is generally insufficient to access regions (2) and (3) where ion mobility separations occur. Ion mobility separations by traveling wave are predicted to be effectual for both nitrogen and argon, with slightly lower resolving power values observed for argon as a result of band-broadening due to collisional scattering. For the simulation conditions studied here, the resolving power in traveling wave plateaus between regions (2) and (3), with further increases in wave velocity contributing only minor improvements in separations. PMID:23888124

  6. Analysis of testosterone in human urine using molecularly imprinted solid-phase extraction and corona discharge ion mobility spectrometry.

    PubMed

    Mirmahdieh, Shiva; Mardihallaj, Azam; Hashemian, Zahra; Razavizadeh, Jalal; Ghaziaskar, Hassan; Khayamian, Taghi

    2011-01-01

    Analysis of testosterone was accomplished using corona discharge ion mobility spectrometry. Molecular imprinted polymer was used for the extraction and pre-concentration of testosterone. Analytical parameters including precision, dynamic range and detection limit were obtained. The linear dynamic range was from 10 to 250 ng/mL and the limit of detection was 0.9 ng/mL. The proposed method was used for analysis of testosterone in urine samples. A urine sample from a 3-year-old girl was used as the blank. The RSD was below 10%. The obtained results from the method were also compared with the standard method for analysis of testosterone using SPE-HPLC analysis. The results demonstrate the accuracy of the method. PMID:21171183

  7. External second-gate Fourier transform ion mobility spectrometry: parametric optimization for detection of weapons of mass destruction

    NASA Astrophysics Data System (ADS)

    Tarver, Edward E.

    2004-09-01

    Ion mobility spectrometry (IMS) is recognized as one of the most sensitive and robust techniques for the detection of narcotics, explosives and chemical warfare agents. IMS is widely used in forensic, military and security applications. Increasing threat of terrorist attacks, the proliferation of narcotics, Chemical Weapons Convention (CWC) treaty verification as well as humanitarian de-mining efforst have mandated that equal importance be placed on the time required to obtain results as well as the quality of the analytical data. In this regard IMS is virtually unrivaled when both speed of response and sensitivity have to be considered. The problem with conventional (signal averaging) IMS systems is the fixed duty cycle of the entrance gate that restricts to less than 1%, the number of available ions contributing to the measured signal. Furthermore, the signal averaging process incorporates scan-to-scan variations that degrade the spectral resolution contributing to misidentifications and false positives.

  8. [Detection of 1,4-dioxane in water by membrane extraction-gas chromiatgraphy/differential mobility spectrometry].

    PubMed

    Liang, Xixi; Chen, Chuang; Wang, Weiguo; Li, Haiyang

    2014-08-01

    The method of detecting trace 1,4-dioxane in water using membrane extraction coupled with gas chromatography/differential mobility spectrometry (GC/DMS) was developed. The parameters including radio frequency voltage, sampling flow rate, permeation time and trapping time were optimized to 1000 V, 50 mL/min, 30 min and 150 s, respectively. The linear range for dioxane was obtained from 2.0 μg/L to 20.0 μg/L. The LOD was found to be 0. 67 μg/L. The specificity towards 1,4-dioxane in the presence of five chlorinated hydrocarbons was improved by using two-dimensional GC separation with optimized DMS compensation voltage. This method paves a way for developing field-deployable sensors for real-time monitoring contaminants in groundwater. PMID:25434119

  9. Comparing equilibrium and kinetic protein unfolding using time-resolved electrospray-coupled ion mobility mass spectrometry.

    PubMed

    Liuni, Peter; Deng, Bin; Wilson, Derek J

    2015-10-21

    Protein unfolding intermediates are thought to play a critical role in conformational pathogenesis, acting as a 'gateway' to inactivation or pathogenic aggregation. Unfolding intermediates have long been studied either by populating partially-folded species at equilibrium using incresingly denaturing conditions, or by transiently populating 'kinetic' intermediates under fully denaturing conditions using a time-resolved approach (e.g. stopped-flow fluorescence). However, it is not clear that the folding intermediates populated under equilibrium conditions are comparable to intermediates transiently populated in kinetic experiments. In this work, we combine time-resolved electrospray (TRESI) with travelling wave Ion Mobility Spectrometry (IMS) for the first time to directly compare equilibrium and kinetic unfolding intermediates of cytochrome c. Our results show a high degree of correlation between all species populated under these substantially different regimes. PMID:26115375

  10. Selective pretreatment and determination of phenazopyridine using an imprinted polymer-electrospray ionization ion mobility spectrometry system.

    PubMed

    Rezaei, B; Jafari, M T; Rahmanian, O

    2011-01-15

    In this research, selective separation and determination of phenazopyridine (PAP) is demonstrated using molecular imprinted polymer (MIP) coupled with electrospray ionization ion mobility spectrometry (ESI-IMS). In the non-covalent approach, selective MIP produced using PAP and methacrylic acid (MAA) as a template molecule and monomer, respectively. The created polymer is utilized as a media for solid-phase extraction (SPE), revealing selective binding properties for the analyte from pharmaceutical and serum samples. A coupled MIP-IMS makes it possible to quantitize PAP in the range of 1-100 ng mL(-1) and with a 0.2 ng mL(-1) detection limit. Furthermore, the MIP selectivity is evaluated by application of some substances with analogous and different molecular structures to that of PAP. This method is successfully applied for the determination of PAP in pharmaceutical and serum samples. PMID:21147318

  11. Building biomarker libraries with novel chemical sensors: correlating differential mobility spectrometer signal outputs with mass spectrometry data

    NASA Astrophysics Data System (ADS)

    Schivo, Michael; Aksenov, Alexander A.; Bardaweel, Hamzeh; Zhao, Weixiang; Kenyon, Nicholas J.; Davis, Cristina E.

    2011-10-01

    Gas chromatography/mass spectrometry (GC/MS) is a widely used analytic tool for qualitative and quantitative analysis of volatile and semi-volatile compounds. However, GC/MS use is limited by its large size, lack of portability, high cost and inherent complexity. Smaller instruments capable of high-throughput analysis of volatile compounds have the potential of combining MS-like sensitivity with portability. The micromachined differential mobility spectrometer (DMS) is a miniature sensor capable of registering volatile compounds in sub-parts-per-million (ppm) concentrations. It is small, portable, and can be coupled with multiple other compound separation methods. Here we describe paired volatile sample analyses using both GC/MS and GC/DMS which show that the DMS is capable of registering known compounds as verified by MS. Furthermore, we show that MS can be used to help build a library for our unique DMS sensor outputs and detect compounds in chemically complex backgrounds.

  12. Utility of Ion Mobility Mass Spectrometry for Drug-to-Antibody Ratio Measurements in Antibody-Drug Conjugates

    NASA Astrophysics Data System (ADS)

    Huang, Richard Y.-C.; Deyanova, Ekaterina G.; Passmore, David; Rangan, Vangipuram; Deshpande, Shrikant; Tymiak, Adrienne A.; Chen, Guodong

    2015-06-01

    Antibody-drug conjugates (ADCs) are emerging modalities in the pharmaceutical industry. Characterization of ADC's drug-to-antibody ratio (DAR) becomes a key assessment because of its importance in ADC efficacy and safety. DAR characterization by conventional intact protein MS analysis, however, is challenging because of high heterogeneity of ADC samples. The analysis often requires protein deglycosylation, disulfide-bond reduction, or partial fragmentation. In this study, we illustrate the practical utility of ion mobility mass spectrometry (IM-MS) in a routine LC/MS workflow for DAR measurements. This strategy allows analyte "cleanup" in the gas phase, providing significant improvement of signal-to-noise ratios of ADC intact mass spectra for accurate DAR measurements. In addition, protein drift time analysis offers a new dimension in monitoring the changes of DAR in lot-to-lot analysis.

  13. Mercury-induced fragmentation of n-decane and n-undecane in positive mode ion mobility spectrometry.

    PubMed

    Gunzer, F

    2015-09-21

    Ion mobility spectrometry is a well-known technique for trace gas analysis. Using soft ionization techniques, fragmentation of analytes is normally not observed, with the consequence that analyte spectra of single substances are quite simple, i.e. showing in general only one peak. If the concentration is high enough, an extra cluster peak involving two analyte molecules can often be observed. When investigating n-alkanes, different results regarding the number of peaks in the spectra have been obtained in the past using this spectrometric technique. Here we present results obtained when analyzing n-alkanes (n-hexane to n-undecane) with a pulsed electron source, which show no fragmentation or clustering at all. However, when investigating a mixture of mercury and an n-alkane, a situation quite typical in the oil and gas industry, a strong fragmentation and cluster formation involving these fragments has been observed exclusively for n-decane and n-undecane. PMID:26247063

  14. EVALUATION OF GAS CHROMATOGRAPHY COUPLED WITH ION MOBILITY SPECTROMETRY FOR MONITORING VINYL CHLORIDE AND OTHER CHLORINATED AND AROMATIC COMPOUNDS IN AIR SAMPLES

    EPA Science Inventory

    The objective of this research was to evaluate, in the laboratory, the potential of gas chromatography/ion mobility spectrometry (GC/IMS) for monitoring vinyl chloride and other organic compounds in air samples in the field. It was determined that GC/IMS has the potential to dire...

  15. Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An ultra-high performance liquid chromatography-ion mobility- quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF-MS) method was developed for profiling the indole alkaloids in yohimbe bark. Many indole alkaloids with the yohimbine core structure, plus methylated, oxidized, and reduced speci...

  16. Combined corona discharge and UV photoionization source for ion mobility spectrometry.

    PubMed

    Bahrami, Hamed; Tabrizchi, Mahmoud

    2012-08-15

    An ion mobility spectrometer is described which is equipped with two non-radioactive ion sources, namely an atmospheric pressure photoionization and a corona discharge ionization source. The two sources cannot only run individually but are additionally capable of operating simultaneously. For photoionization, a UV lamp was mounted parallel to the axis of the ion mobility cell. The corona discharge electrode was mounted perpendicular to the UV radiation. The total ion current from the photoionization source was verified as a function of lamp current, sample flow rate, and drift field. Simultaneous operation of the two ionization sources was investigated by recording ion mobility spectra of selected samples. The design allows one to observe peaks from either the corona discharge or photoionization individually or simultaneously. This makes it possible to accurately compare peaks in the ion mobility spectra from each individual source. Finally, the instrument's capability for discriminating two peaks appearing in approximately identical drift times using each individual ionization source is demonstrated. PMID:22841099

  17. Ion mobility spectrometry of hydrazine, monomethylhydrazine, and ammonia in air with 5-nonanone reagent gas

    NASA Technical Reports Server (NTRS)

    Eiceman, G. A.; Salazar, M. R.; Rodriguez, M. R.; Limero, T. F.; Beck, S. W.; Cross, J. H.; Young, R.; James, J. T.

    1993-01-01

    Hydrazine (HZ) and monomethylhydrazine (MMH) in air were monitored continuously using a hand-held ion mobility spectrometer equipped with membrane inlet, 63Ni ion source, acetone reagent gas, and ambient temperature drift tube. Response characteristics included detection limit, 6 ppb; linear range, 10-600 ppb; saturated response, >2 ppm; and stable response after 15-30 min. Ammonia interfered in hydrazines detection through a product ion with the same drift time as that for MMH and HZ. Acetone reagent gas was replaced with 5-nonanone to alter drift times of product ions and separate ammonia from MMH and HZ. Patterns in mobility spectra, ion identifications from mass spectra, and fragmentation cross-sections from collisional-induced dissociations suggest that drift times are governed by ion-cluster equilibria in the drift region of the mobility spectrometer. Practical aspects including calibration, stability, and reproducibility are reported from the use of a hand-held mobility spectrometer on the space shuttle Atlantis during mission STS-37.

  18. Metabolic Profiling of Human Blood by High Resolution Ion Mobility Mass Spectrometry (IM-MS)

    PubMed Central

    Dwivedi, Prabha; Schultz, Albert J.; Hill, Herbert H.

    2010-01-01

    A high resolution ion mobility time-of-flight mass spectrometer with electrospray ionization source (ESI-IM-MS) was evaluated as an analytical method for rapid analysis of complex biological samples such as human blood metabolome was investigated. The hybrid instrument (IM-MS) provided an average ion mobility resolving power of ~90 and a mass resolution of ~1500 (at m/z 100). A few µL of whole blood was extracted with methanol, centrifuged and infused into the IM-MS via an electrospray ionization source. Upon IM-MS profiling of the human blood metabolome approximately 1,100 metabolite ions were detected and 300 isomeric metabolites separated in short analyses time (30 minutes). Estimated concentration of the metabolites ranged from the low micromolar to the low nanomolar level. Various classes of metabolites (amino acids, organic acids, fatty acids, carbohydrates, purines and pyrimidines etc) were found to form characteristic mobility-mass correlation curves (MMCC) that aided in metabolite identification. Peaks corresponding to various sterol derivatives, estrogen derivatives, phosphocholines, prostaglandins, and cholesterol derivatives detected in the blood extract were found to occupy characteristic two dimensional IM-MS space. Low abundance metabolite peaks that can be lost in MS random noise were resolved from noise peaks by differentiation in mobility space. In addition, the peak capacity of MS increased six fold by coupling IMS prior to MS analysis. PMID:21113320

  19. Differential Ion Mobility Separations in up to 100% Helium Using Microchips

    SciTech Connect

    Shvartsburg, Alexandre A.; Ibrahim, Yehia M.; Smith, Richard D.

    2014-01-09

    The performance of differential IMS (FAIMS) analyzers is much enhanced by gases comprising He, especially He/N2 buffers. However, electrical breakdown has limited the He fraction in those mixtures to ~50 - 75%, depending on the field strength. By Paschen law, the threshold field for breakdown increases at shorter distances. This allows FAIMS using chips with microscopic channels to utilize much stronger field intensities (E) than “full-size” analyzers with wider gaps. Here we show that those chips can employ higher He fractions up to 100%. Use of He-rich gases improves the resolution and resolution/sensitivity balance substantially, although less than for full-size analyzers. The optimum He fraction is ~80%, in line with first-principles theory. Hence one can now measure the dependences of ion mobility on E in pure He, where ion-molecule cross section calculations are much more tractable than in other gases that form deeper and more complex interaction potentials. This capability may facilitate quantitative modeling of high-field ion mobility behavior and thus FAIMS separation properties, which would enable a priori extraction of structural information about the ions from FAIMS data.

  20. Feasibility of corona discharge ion mobility spectrometry for direct analysis of samples extracted by dispersive liquid-liquid microextraction.

    PubMed

    Jafari, Mohammad T; Riahi, Farhad

    2014-05-23

    The capability of corona discharge ionization ion mobility spectrometry (CD-IMS) for direct analysis of the samples extracted by dispersive liquid-liquid microextraction (DLLME) was investigated and evaluated, for the first time. To that end, an appropriate new injection port was designed and constructed, resulting in possibility of direct injection of the known sample volume, without tedious sample preparation steps (e.g. derivatization, solvent evaporation, and re-solving in another solvent…). Malathion as a test compound was extracted from different matrices by a rapid and convenient DLLME method. The positive ion mobility spectra of the extracted malathion were obtained after direct injection of carbon tetrachloride or methanol solutions. The analyte responses were compared and the statistical results revealed the feasibility of direct analysis of the extracted samples in carbon tetrachloride, resulting in a convenient methodology. The coupled method of DLLME-CD-IMS was exhaustively validated in terms of sensitivity, dynamic range, recovery, and enrichment factor. Finally, various real samples of apple, river and underground water were analyzed, all verifying the feasibility and success of the proposed method for the easy extraction of the analyte using DLLME separation before the direct analysis by CD-IMS. PMID:24742534

  1. Evaluation of Collision Cross Section Calibrants for Structural Analysis of Lipids by Traveling Wave Ion Mobility-Mass Spectrometry.

    PubMed

    Hines, Kelly M; May, Jody C; McLean, John A; Xu, Libin

    2016-07-19

    Collision cross section (CCS) measurement of lipids using traveling wave ion mobility-mass spectrometry (TWIM-MS) is of high interest to the lipidomics field. However, currently available calibrants for CCS measurement using TWIM are predominantly peptides that display quite different physical properties and gas-phase conformations from lipids, which could lead to large CCS calibration errors for lipids. Here we report the direct CCS measurement of a series of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in nitrogen using a drift tube ion mobility (DTIM) instrument and an evaluation of the accuracy and reproducibility of PCs and PEs as CCS calibrants for phospholipids against different classes of calibrants, including polyalanine (PolyAla), tetraalkylammonium salts (TAA), and hexakis(fluoroalkoxy)phosphazines (HFAP), in both positive and negative modes in TWIM-MS analysis. We demonstrate that structurally mismatched calibrants lead to larger errors in calibrated CCS values while the structurally matched calibrants, PCs and PEs, gave highly accurate and reproducible CCS values at different traveling wave parameters. Using the lipid calibrants, the majority of the CCS values of several classes of phospholipids measured by TWIM are within 2% error of the CCS values measured by DTIM. The development of phospholipid CCS calibrants will enable high-accuracy structural studies of lipids and add an additional level of validation in the assignment of identifications in untargeted lipidomics experiments. PMID:27321977

  2. Application of Ion Mobility Mass Spectrometry for Detection and Identification of Oxidized Organic Species during SOAS 2013

    NASA Astrophysics Data System (ADS)

    Canagaratna, M. R.; Krechmer, J.; Kimmel, J.; Junninen, H.; Knochenmuss, R.; Cubison, M.; Massoli, P.; Stark, H.; Jayne, J. T.; Jimenez, J. L.; Worsnop, D. R.

    2013-12-01

    We present results obtained with a chemical ionization ion mobility time-of-flight mass spectrometer (CI-IMS-TOF) that was deployed during the Southern Oxidant and Aerosol Study (SOAS) at the Supersite in Centreville, AL. This two dimensional technique, which separates ions on the basis of their interactions with buffer gases before analysis by high-resolution time-of-flight mass spectrometry, allows for detailed separation and identification of isomeric and isobaric species. During SOAS the IMS-TOF was coupled to a chemical ionization source that utilized NO3- as the reagent ion. The NO3- reagent ion clusters with highly oxidized species and allows for a unique means of directly detecting particle phase precursors in the gas phase. Gas phase molecules corresponding to oxidized products of isoprene and terpenes were detected throughout the campaign with a time resolution of 5 minutes. Ion mobility separation and trends observed for several of these key species are discussed. In addition to ambient sampling, the CI-IMS-TOF was also operated behind a potential aerosol mass (PAM) flow reactor which exposed ambient air to high levels of OH radical. Ambient CI-IMS-TOF spectra obtained with and without the flow reactor are presented and compared with laboratory flow reactor spectra generated from isoprene and terpene precursors.

  3. A simple template-based transfer method to fabricate Bradbury–Nielsen gates with uniform tension for ion mobility spectrometry

    SciTech Connect

    Kai, Ni Jingran, Guo; Guangli, Ou; Yu, Lei; Quan, Yu; Xiang, Qian; Xiaohao, Wang

    2014-08-15

    A Bradbury–Nielsen gate (BNG) consists of two interleaved and electrically isolated sets of wires. It is usually used to gate or modulate ion beams. Uniformly tense wires can remain parallel, equidistant, and coplanar over a wide working temperature range, which is critical to reliable BNG performance. Hence, this study analyzes the non-uniform tension of wires wound using traditional sequential winding methods in which the elastic modulus of the metal wire is much larger than that of the insulation substrate. To address this problem, a simple and reliable template-based transfer method is developed. First, a template with large elastic modulus is used to fabricate a wire mesh with uniform tension. The mesh is then transferred to the substrate. Theoretically, this method reduces the non-uniformity of the tension in wires to less than 2%; therefore, it is used to construct a BNG with stainless steel wire, a stainless steel template, and a printed circuit board substrate. The BNG was installed in our homebuilt ion mobility spectrometer. To confirm that the performance of the BNG meets the requirements of portable ion mobility spectrometry, signal intensity and resolution (approximately 30) were experimentally determined.

  4. Theoretical evaluation of peak capacity improvements by use of liquid chromatography combined with drift tube ion mobility-mass spectrometry.

    PubMed

    Causon, Tim J; Hann, Stephan

    2015-10-16

    In the domain of liquid phase separations, the quality of separation obtainable is most readily gauged by consideration of classical chromatographic peak capacity theory. Column-based multidimensional strategies for liquid chromatography remain the most attractive and practical route for increasing the number of spatially resolved components in order to reduce stress on necessary mass spectrometric detection. However, the stress placed on a chromatographic separation step as a second dimension in a comprehensive online methodology (i.e. online LC×LC) is rather high. As an alternative to online LC×LC combinations, coupling of HPLC with ion mobility spectrometry hyphenated to mass spectrometry (IMS-MS) has emerged as an attractive approach to permit comprehensive sampling of first dimension chromatographic peaks and subsequent introduction to an orthogonal IMS separation prior to measurement of ions by a mass spectrometer. In the present work, utilization of classical peak capacity and ion mobility theory allows theoretical assessment of the potential of two- (LC×IMS-MS) or even three-dimensional (LC×LC×IMS-MS) experimental setups to enhance peak capacity and, therefore, the number of correctly annotated features within the framework of complex, non-targeted analysis problems frequently addressed using HPLC-MS strategies. Theoretical calculations indicate that newly-available drift tube IMS-MS instrumentation can yield peak capacities of between 10 and 40 using nitrogen drift gas for typical non-targeted metabolomic, lipidomic and proteomic applications according to the expected reduced mobilities of components in the respective samples. Theoretically, this approach can significantly improve the overall peak capacity of conventional HPLC-(MS) methodologies to in excess of 10(4) depending upon the column length and gradient time employed. A more elaborate combination of LC×LC×IMS-MS would improve the ion suppression limitation and possibly allow access to

  5. Traveling Wave Ion Mobility Mass Spectrometry and Ab Initio Calculations of Phosphoric Acid Clusters

    NASA Astrophysics Data System (ADS)

    Lavanant, Hélène; Tognetti, Vincent; Afonso, Carlos

    2014-04-01

    Positive and negative ion electrospray mass spectra obtained from 50 mM phosphoric acid solutions presented a large number of phosphoric acid clusters: [(H3PO4)n + zH] z+ or [(H3PO4)n - zH] z- , with n up to 200 and z up to 4 for positively charged clusters, and n up to 270 and z up to 7 for negatively charged cluster ions. Ion mobility experiments allowed very explicit separation of the different charge states. Because of the increased pressures involved in ion mobility experiments, dissociation to smaller clusters was observed both in the trap and transfer areas. Voltages along the ion path could be optimized so as to minimize this effect, which can be directly associated with the cleavage of hydrogen bonds. Having excluded the ion mobility times that resulted from dissociated ions, each cluster ion appeared at a single drift time. These drift times showed a linear progression with the number of phosphoric atoms for cluster ions of the same charge state. Cross section calculations were carried out with MOBCAL on DFT optimized geometries with different hydrogen locations and with three types of atomic charges. DFT geometry optimizations yielded roughly spherical structures. Our results for nitrogen gas interaction cross sections showed that values were dependent on the atomic charges definition used in the MOBCAL calculation. This pinpointed the necessity to define a clear theoretical framework before any comparative interpretations can be attempted with uncharacterized compounds.

  6. Targeting the untargeted in molecular phenomics with structurally-selective ion mobility-mass spectrometry.

    PubMed

    May, Jody Christopher; Gant-Branum, Randi Lee; McLean, John Allen

    2016-06-01

    Systems-wide molecular phenomics is rapidly expanding through technological advances in instrumentation and bioinformatics. Strategies such as structural mass spectrometry, which utilizes size and shape measurements with molecular weight, serve to characterize the sum of molecular expression in biological contexts, where broad-scale measurements are made that are interpreted through big data statistical techniques to reveal underlying patterns corresponding to phenotype. The data density, data dimensionality, data projection, and data interrogation are all critical aspects of these approaches to turn data into salient information. Untargeted molecular phenomics is already having a dramatic impact in discovery science from drug discovery to synthetic biology. It is evident that these emerging techniques will integrate closely in broad efforts aimed at precision medicine. PMID:27132126

  7. Application of Ion Mobility Spectrometry (IMS) in forensic chemistry and toxicology with focus on biological matrices

    NASA Technical Reports Server (NTRS)

    Bernhard, Werner; Keller, Thomas; Regenscheit, Priska

    1995-01-01

    The IMS (Ion Mobility Spectroscopy) instrument 'Ionscan' takes advantage of the fact that trace quantities of illicit drugs are adsorbed on dust particles on clothes, in cars and on other items of evidence. The dust particles are collected on a membrane filter by a special attachment on a vacuum cleaner. The sample is then directly inserted into the spectrometer and can be analyzed immediately. We show casework applications of a forensic chemistry and toxicology laboratory. One new application of IMS in forensic chemistry is the detection of psilocybin in dried mushrooms without any further sample preparation.

  8. Ion Mobility-Mass Spectrometry Analysis of Cross-Linked Intact Multiprotein Complexes: Enhanced Gas-Phase Stabilities and Altered Dissociation Pathways.

    PubMed

    Samulak, Billy M; Niu, Shuai; Andrews, Philip C; Ruotolo, Brandon T

    2016-05-17

    Analysis of protein complexes by ion mobility-mass spectrometry is a valuable method for the rapid assessment of complex composition, binding stoichiometries, and structures. However, capturing labile, unknown protein assemblies directly from cells remains a challenge for the technology. Furthermore, ion mobility-mass spectrometry measurements of complexes, subcomplexes, and subunits are necessary to build complete models of intact assemblies, and such data can be difficult to acquire in a comprehensive fashion. Here, we present the use of novel mass spectrometry cleavable cross-linkers and tags to stabilize intact protein complexes for ion mobility-mass spectrometry. Our data reveal that tags and linkers bearing permanent charges are superior stabilizers relative to neutral cross-linkers, especially in the context of retaining compact forms of the assembly under a wide array of activating conditions. In addition, when cross-linked protein complexes are collisionally activated in the gas phase, a larger proportion of the product ions produced are often more compact and reflect native protein subcomplexes when compared with unmodified complexes activated in the same fashion, greatly enabling applications in structural biology. PMID:27078797

  9. Ambient pressure laser desorption and laser-induced acoustic desorption ion mobility spectrometry detection of explosives.

    PubMed

    Ehlert, Sven; Walte, Andreas; Zimmermann, Ralf

    2013-11-19

    The development of fast, mobile, and sensitive detection systems for security-relevant substances is of enormous importance. Because of the low vapor pressures of explosives and improvised explosive devices, adequate sampling procedures are crucial. Ion mobility spectrometers (IMSs) are fast and sensitive instruments that are used as detection systems for explosives. Ambient pressure laser desorption (APLD) and ambient pressure laser-induced acoustic desorption (AP-LIAD) are new tools suitable to evaporate explosives in order to detect them in the vapor phase. Indeed, the most important advantage of APLD or AP-LIAD is the capability to sample directly from the surface of interest without any transfer of the analyte to other surfaces such as wipe pads. A much more gentle desorption, compared to classical thermal-based desorption, is possible with laser-based desorption using very short laser pulses. With this approach the analyte molecules are evaporated in a very fast process, comparable to a shock wave. The thermal intake is reduced considerably. The functionality of APLD and AP-LIAD techniques combined with a hand-held IMS system is shown for a wide range of common explosives such as EGDN (ethylene glycol dinitrate), urea nitrate, PETN (pentaerythritol tetranitrate), HMTD (hexamethylene triperoxide diamine), RDX (hexogen), tetryl (2,4,6-trinitrophenylmethylnitramine), and TNT (trinitrotoluene). Detection limits down to the low nanogram range are obtained. The successful combination of IMS detection and APLD/AP-LIAD sampling is shown. PMID:24116702

  10. Fast detection of toxic industrial compounds by laser ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Oberhuettinger, Carola; Langmeier, Andreas; Oberpriller, Helmut; Kessler, Matthias; Goebel, Johann; Mueller, Gerhard

    2009-05-01

    Trace detection of toxic industrial compounds has been investigated with the help of a laser ion mobility spectrometer (LIMS). The LIMS was equipped with a tuneable UV laser source for enabling two-photon ionization of the analyte gases and an ion drift tube for the measurement of the ion mobility. Different aromatic and aliphatic hydrocarbons as well as amines were investigated. We find that the first class of molecules can be well ionized due to the delocalization of their valence electron shells and the second due to the presence of non-bonding electrons in lone-pair orbitals. Selectivity of detection is attained on the basis of molecule-specific photo-ionization and drift time spectra. Ion currents were found to scale linearly with the substance concentration over several orders of magnitude down to the detection limits in the ppt range. As besides toxic industrial compounds, similar electron configurations also occur in illicit drugs, toxins and pharmaceutical substances, LIMS can be applied in a variety of fields ranging from environmental analysis, air pollution monitoring, drug detection and chemical process monitoring.

  11. Electron-capture dissociation and ion mobility mass spectrometry for characterization of the hemoglobin protein assembly

    PubMed Central

    Cui, Weidong; Zhang, Hao; Blankenship, Robert E; Gross, Michael L

    2015-01-01

    Native spray has the potential to probe biophysical properties of protein assemblies. Here we report an investigation using both ECD top-down sequencing with an FTICR mass spectrometer and ion mobility (IM) measurements on a Q-TOF to investigate the collisionally induced unfolding of a native-like heterogeneous tetrameric assembly, human hemoglobin (hHb), in the gas phase. To our knowledge, this is the first report combining ECD and ion-mobility data on the same target protein assembly to delineate the effects of collisional activation on both assembly size and the extent and location of fragmentation. Although the collision-induced unfolding of the hemoglobin assembly is clearly seen by both IMMS and ECD, the latter delineates the regions that increasingly unfold as the collision energy is increased. The results are consistent with previous outcomes for homogeneous protein assemblies and reinforce our interpretation that activation opens the structure of the protein assembly from the flexible regions to make available ECD fragmentation, without dissociating the component proteins. PMID:26032343

  12. Mobile field data acquisition in geosciences

    NASA Astrophysics Data System (ADS)

    Golodoniuc, Pavel; Klump, Jens; Reid, Nathan; Gray, David

    2016-04-01

    The Discovering Australia's Mineral Resources Program of CSIRO is conducting a study to develop novel methods and techniques to reliably define distal footprints of mineral systems under regolith cover in the Capricorn Orogen - the area that lies between two well-known metallogenic provinces of Pilbara and Yilgarn Cratons in Western Australia. The multidisciplinary study goes beyond the boundaries of a specific discipline and aims at developing new methods to integrate heterogeneous datasets to gain insight into the key indicators of mineralisation. The study relies on large regional datasets obtained from previous hydrogeochemical, regolith, and resistate mineral studies around known deposits, as well as new data obtained from the recent field sampling campaigns around areas of interest. With thousands of water, vegetation, rock and soil samples collected over the past years, it has prompted us to look at ways to standardise field sampling procedures and review the data acquisition process. This process has evolved over the years (Golodoniuc et al., 2015; Klump et al., 2015) and has now reached the phase where fast and reliable collection of scientific data in remote areas is possible. The approach is backed by a unified discipline-agnostic platform - the Federated Archaeological Information Management System (FAIMS). FAIMS is an open source framework for mobile field data acquisition, developed at the University of New South Wales for archaeological field data collection. The FAIMS framework can easily be adapted to a diverse range of scenarios, different kinds of samples, each with its own peculiarities, integration with GPS, and the ability to associate photographs taken with the device embedded camera with captured data. Three different modules have been developed so far, dedicated to geochemical water, plant and rock sampling. All modules feature automatic date and position recording, and reproduce the established data recording workflows. The rock sampling

  13. Characterization of an Ion Mobility-Multiplexed Collision Induced Dissociation-Tandem Time-of-Flight Mass Spectrometry Approach

    PubMed Central

    Ibrahim, Yehia M.; Prior, David C.; Baker, Erin S.; Smith, Richard D.; Belov, Mikhail E.

    2010-01-01

    The confidence in peptide (and protein) identifications with ion mobility spectrometry time-of-flight mass spectrometry (IMS-TOFMS) is expected to drastically improve with the addition of information from an efficient ion dissociation step prior to MS detection. High throughput IMS-TOFMS analysis imposes a strong need for multiplexed ion dissociation approaches where multiple precursor ions yield complex sets of fragment ions that are often intermingled with each other in both the drift time and m/z domains. We have developed and evaluated an approach for collision-induced dissociation (CID) using IMS-TOFMS instrument. It has been shown that precursor ions activated inside an rf-device with an axial dc-electric field produce abundant fragment ions which are radially confined with the rf-field and collisionally cooled at an elevated pressure, resulting in high CID efficiencies comparable or higher than those measured in triple-quadrupole instruments. We have also developed an algorithm for deconvoluting these complex multiplexed tandem MS spectra by clustering both the precursor and fragment ions into matching drift time profiles and by utilizing the high mass measurement accuracy achievable with TOFMS. In a single IMS separation from direct infusion of tryptic digest of bovine serum albumin (BSA), we have reliably identified 20 unique peptides using a multiplexed CID approach downstream of the IMS separation. Peptides were identified based upon the correlation between the precursor and fragment drift time profiles and by matching the profile representative masses to those of in silico BSA tryptic peptides and their fragments. The false discovery rate (FDR) of peptide identifications from multiplexed MS/MS spectra was less than 1%. PMID:20596241

  14. Ion mobility spectrometry: A personal view of its development at UCSB

    PubMed Central

    Bowers, Michael T.

    2014-01-01

    Ion mobility is not a newly discovered phenomenon. It has roots going back to Langevin at the beginning of the 20th century. Our group initially got involved by accident around 1990 and this paper is a brief account of what has transpired here at UCSB the past 25 years in response to this happy accident. We started small, literally, with transition metal atomic ions and transitioned to carbon clusters, synthetic polymers, most types of biological molecules and eventually peptide and protein oligomeric assembly. Along the way we designed and built several generations of instruments, a process that is still ongoing. And perhaps most importantly we have incorporated theory with experiment from the beginning; a necessary wedding that allows an atomistic face to be put on the otherwise interesting but not fully informative cross section measurements. PMID:25147478

  15. Ion mobility mass spectrometry of proteins in a modified commercial mass spectrometer

    NASA Astrophysics Data System (ADS)

    Thalassinos, K.; Slade, S. E.; Jennings, K. R.; Scrivens, J. H.; Giles, K.; Wildgoose, J.; Hoyes, J.; Bateman, R. H.; Bowers, M. T.

    2004-08-01

    Ion mobility has emerged as an important technique for determining biopolymer conformations in solvent free environments. These experiments have been nearly exclusively performed on home built systems. In this paper we describe modifications to a commercial high performance mass spectrometer, the Waters UK "Ultima" Q-Tof, that allows high sensitivity measurement of peptide and protein cross sections. Arrival time distributions are obtained for a series of peptides (bradykinin, LHRH, substance P, bombesin) and proteins (bovine and equine cytochrome c, myoglobin, [alpha]-lactalbumin) with good agreement found with literature cross sections where available. In complex ATD's, mass spectra can be obtained for each feature confirming assignments. The increased sensitivity of the commercial instrument is retained along with the convenience of the data system, crucial features for analysis of protein misfolding systems.

  16. Determination of C1-C4 alkanes by ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Kojiro, Daniel R.; Cohen, Martin J.; Stimac, Robert M.; Wernlund, Roger F.; Humphry, Donald E.; Takeuchi, Norishige

    1991-01-01

    Results are presented from a comparison between two ion-mobility-spectrometer (IMS) methods of sample ionisation: a conventional IMS with very dry helium and an IMS using metastable helium ionization. As one of the tests, a mixture of several hydrocarbons expected to be the components of Titan's atmosphere (made of ethane, ethylene, acetylene, propane, n-butane, isobutane, and propyne in concentrations from 20 to 200 ppm) was analyzed by both methods. Results from the dry-He IMS showed that the dry-helium approach was more adequate for the analysis of these gases than the metastable-helium IMS approach. In the metastable-He approach, in which several versions of He ionization reaction were tested, the spectra produced were not as clear as the conventional IMS spectra, due to the fact that the strong electric field introduced in the reaction region to generate metastable helium affected the gating, resolution, and collection of the ions.

  17. Electrospray-Differential Mobility Hyphenated with Single Particle Inductively Coupled Plasma Mass Spectrometry for Characterization of Nanoparticles and Their Aggregates.

    PubMed

    Tan, Jiaojie; Liu, Jingyu; Li, Mingdong; El Hadri, Hind; Hackley, Vincent A; Zachariah, Michael R

    2016-09-01

    The novel hyphenation of electrospray-differential mobility analysis with single particle inductively coupled plasma mass spectrometry (ES-DMA-spICPMS) was demonstrated with the capacity for real-time size, mass, and concentration measurement of nanoparticles (NPs) on a particle-to-particle basis. In this proof-of-concept study, the feasibility of this technique was validated through both concentration and mass calibration using NIST gold NP reference materials. A detection limit of 10(5) NPs mL(-1) was determined under current experimental conditions, which is about 4 orders of magnitude lower in comparison to that of a traditional ES-DMA setup using a condensation particle counter as detector. Furthermore, independent and simultaneous quantification of both size and mass of NPs provides information regarding NP aggregation states. Two demonstrative applications include gold NP mixtures with a broad size range (30-100 nm), and aggregated gold NPs with a primary size of 40 nm. Finally, this technique was shown to be potentially useful for real-world samples with high ionic background due to its ability to remove dissolved ions yielding a cleaner background. Overall, we demonstrate the capacity of this new hyphenated technique for (1) clearly resolving NP populations from a mixture containing a broad size range; (2) accurately measuring a linear relationship, which should inherently exist between mobility size and one-third power of ICPMS mass for spherical NPs; (3) quantifying the early stage propagation of NP aggregation with well-characterized oligomers; and (4) differentiating aggregated NPs and nonaggregated states based on the "apparent density" derived from both DMA size and spICPMS mass. PMID:27479448

  18. Mass spectrometry and ion mobility spectrometry of G-quadruplexes. A study of solvent effects on dimer formation and structural transitions in the telomeric DNA sequence d(TAGGGTTAGGGT).

    PubMed

    Ferreira, Rubén; Marchand, Adrien; Gabelica, Valérie

    2012-05-01

    We survey here state of the art mass spectrometry methodologies for investigating G-quadruplexes, and will illustrate them with a new study on a simple model system: the dimeric G-quadruplex of the 12-mer telomeric DNA sequence d(TAGGGTTAGGGT), which can adopt either a parallel or an antiparallel structure. We will discuss the solution conditions compatible with electrospray ionisation, the quantification of complexes using ESI-MS, the interpretation of ammonium ion preservation in the complexes in the gas phase, and the use of ion mobility spectrometry to resolve ambiguities regarding the strand stoichiometry, or separate and characterise different structural isomers. We also describe that adding electrospray-compatible organic co-solvents (methanol, ethanol, isopropanol or acetonitrile) to aqueous ammonium acetate increases the stability and rate of formation of dimeric G-quadruplexes, and causes structural transitions to parallel structures. Structural changes were probed by circular dichroism and ion mobility spectrometry, and the excellent correlation between the two techniques validates the use of ion mobility to investigate G-quadruplex folding. We also demonstrate that parallel G-quadruplex structures are easier to preserve in the gas phase than antiparallel structures. PMID:22465284

  19. Urban increments of gaseous and aerosol pollutants and their sources using mobile aerosol mass spectrometry measurements

    NASA Astrophysics Data System (ADS)

    Elser, Miriam; Bozzetti, Carlo; El-Haddad, Imad; Maasikmets, Marek; Teinemaa, Erik; Richter, Rene; Wolf, Robert; Slowik, Jay G.; Baltensperger, Urs; Prévôt, André S. H.

    2016-06-01

    Air pollution is one of the main environmental concerns in urban areas, where anthropogenic emissions strongly affect air quality. This work presents the first spatially resolved detailed characterization of PM2.5 (particulate matter with aerodynamic equivalent diameter daero ≤ 2.5 µm) in two major Estonian cities, Tallinn and Tartu. The measurements were performed in March 2014 using a mobile platform. In both cities, the non-refractory (NR)-PM2.5 was characterized by a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) using a recently developed lens which increases the transmission of super-micron particles. Equivalent black carbon (eBC) and several trace gases including carbon monoxide (CO), carbon dioxide (CO2), and methane (CH4) were also measured. The chemical composition of PM2.5 was found to be very similar in the two cities. Organic aerosol (OA) constituted the largest fraction, explaining on average about 52 to 60 % of the PM2.5 mass. Four sources of OA were identified using positive matrix factorization (PMF): hydrocarbon-like OA (HOA, from traffic emissions), biomass burning OA (BBOA, from biomass combustion), residential influenced OA (RIOA, probably mostly from cooking processes with possible contributions from waste and coal burning), and oxygenated OA (OOA, related to secondary aerosol formation). OOA was the major OA source during nighttime, explaining on average half of the OA mass, while during daytime mobile measurements the OA was affected by point sources and dominated by the primary fraction. A strong increase in the secondary organic and inorganic components was observed during periods with transport of air masses from northern Germany, while the primary local emissions accumulated during periods with temperature inversions. Mobile measurements offered the identification of different source regions within the urban areas and the assessment of the extent to which pollutants concentrations exceeded regional background

  20. Note: Design and construction of a simple and reliable printed circuit board-substrate Bradbury-Nielsen gate for ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Du, Yongzhai; Cang, Huaiwen; Wang, Weiguo; Han, Fenglei; Chen, Chuang; Li, Lin; Hou, Keyong; Li, Haiyang

    2011-08-01

    A less laborious, structure-simple, and performance-reliable printed circuit board (PCB) based Bradbury-Nielsen gate for high-resolution ion mobility spectrometry was introduced and investigated. The gate substrate was manufactured using a PCB etching process with small holes (Φ 0.1 mm) drilled along the gold-plated copper lines. Two interdigitated sets of rigid stainless steel spring wire (Φ 0.1 mm) that stands high temperature and guarantees performance stability were threaded through the holes. Our homebuilt ion mobility spectrometer mounted with the gate gave results of about 40 for resolution while keeping a signal intensity of over 0.5 nano-amperes.

  1. Protein Structural Studies by Traveling Wave Ion Mobility Spectrometry: A Critical Look at Electrospray Sources and Calibration Issues.

    PubMed

    Sun, Yu; Vahidi, Siavash; Sowole, Modupeola A; Konermann, Lars

    2016-01-01

    The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Ω) measured by ion mobility spectrometry (IMS) with Ω values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Ω values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments. ᅟ PMID:26369778

  2. Computational Methods for Metabolomic Data Analysis of Ion Mobility Spectrometry Data—Reviewing the State of the Art

    PubMed Central

    Hauschild, Anne-Christin; Schneider, Till; Pauling, Josch; Rupp, Kathrin; Jang, Mi; Baumbach, Jörg Ingo; Baumbach, Jan

    2012-01-01

    Ion mobility spectrometry combined with multi-capillary columns (MCC/IMS) is a well known technology for detecting volatile organic compounds (VOCs). We may utilize MCC/IMS for scanning human exhaled air, bacterial colonies or cell lines, for example. Thereby we gain information about the human health status or infection threats. We may further study the metabolic response of living cells to external perturbations. The instrument is comparably cheap, robust and easy to use in every day practice. However, the potential of the MCC/IMS methodology depends on the successful application of computational approaches for analyzing the huge amount of emerging data sets. Here, we will review the state of the art and highlight existing challenges. First, we address methods for raw data handling, data storage and visualization. Afterwards we will introduce de-noising, peak picking and other pre-processing approaches. We will discuss statistical methods for analyzing correlations between peaks and diseases or medical treatment. Finally, we study up-to-date machine learning techniques for identifying robust biomarker molecules that allow classifying patients into healthy and diseased groups. We conclude that MCC/IMS coupled with sophisticated computational methods has the potential to successfully address a broad range of biomedical questions. While we can solve most of the data pre-processing steps satisfactorily, some computational challenges with statistical learning and model validation remain. PMID:24957760

  3. Determination of vinyl chloride in soil-gas samples by gas chromatography coupled with ion mobility spectrometry

    SciTech Connect

    Jones, T.L.; Hill, H.; Simpson, G.; Klasmeier, M.; Lopez-Avila, V.; Radolovich, G.

    1995-12-31

    The advantages of ion mobility spectrometry (IMS), such as ambient pressure operation, simplicity of design, high sensitivity, speed of response, spectral output, and ability to respond to a large number of compounds, make IMS technology attractive for a variety of field monitoring applications. A quantitative, multicompound field detector based on IMS technology has not been successful, however, because of technology limitations. For multicomponent samples, multiple ion-molecule reactions result in confusing spectral information. Varying humidity can result in ion-water clusters that cause errors in both the identification and quantification of the target analyte. These limitations could be overcome through the addition of gas chromatography (GC) prior to high-temperature IMS. When coupling GC to IMS, the following need to be considered: (a) currently available IMS cells have a relatively large internal volume (> 20 mL), reducing the chromatographic resolution; (b) smaller IMS cells are not capable of operating above 100 C; (c) the radioactive ionization cell limits the dynamic range of the device to 2 to 3 orders of magnitude; and (d) most standard miniature cells have a membrane inlet that does not allow direct interface with a GC column. The authors have overcome some of these difficulties by interfacing GC with Fourier Transform IMS (FTIMS). They will present data on determining vinyl chloride in soil-gas samples by GC-FTIMS.

  4. Laser desorption-ion mobility spectrometry as a useful tool for imaging of thin layer chromatography surface.

    PubMed

    Ilbeigi, Vahideh; Sabo, Martin; Valadbeigi, Younes; Matejcik, Stefan; Tabrizchi, Mahmoud

    2016-08-12

    We present a novel method for coupling thin layer chromatography (TLC) with ion mobility spectrometry (IMS) using laser desorption technique (LD). After separation of the compounds by TLC, the TLC surface was sampled by the LD-IMS without any further manipulation or preparation. The position of the laser was fixed and the TLC plate was moved in desired directions by the motorized micro-positioning stage. The method was successfully applied to analyze the TLC plates containing explosives (tri nitro toluene, 1,3,5-trinitro- 1,3,5-triazacyclohexane, pentaerythritol tetranitrate, 2,4-dinitro toluene and 3,4-dinitro toluene), amino acids (alanine, proline and isoleucine), nicotine and diphenylamine mixtures and detection limits for these compounds were determined. Combination of TLC with LD-IMS technique offers additional separation dimension, allowing separation of overlapping TLC analytes. The time for TLC sampling by LD-IMS was less than 80s. The scan rate for LD is adjustable so that fast and effective analysis of the mixtures is possible with the proposed method. PMID:27397925

  5. Determination of benzene, toluene and xylene concentration in humid air using differential ion mobility spectrometry and partial least squares regression.

    PubMed

    Maziejuk, M; Szczurek, A; Maciejewska, M; Pietrucha, T; Szyposzyńska, M

    2016-05-15

    Benzene, toluene and xylene (BTX compounds) are chemicals of greatest concern due to their impact on humans and the environment. In many cases, quantitative information about each of these compounds is required. Continuous, fast-response analysis, performed on site would be desired for this purpose. Several methods have been developed to detect and quantify these compounds in this way. Methods vary considerably in sensitivity, accuracy, ease of use and cost-effectiveness. The aim of this work is to show that differential ion mobility spectrometry (DMS) may be applied for determining concentration of BTX compounds in humid air. We demonstrate, this goal is achievable by applying multivariate analysis of the measurement data using partial least squares (PLS) regression. The approach was tested at low concentrations of these compounds in the range of 5-20ppm and for air humidity in a range 0-12g/kg. These conditions correspond to the foreseeable application of the developed approach in occupational health and safety measurements. The average concentration assessment error was about 1ppm for each: benzene, toluene and xylene. We also successfully determined water vapor content in air. The error achieved was 0.2g/kg. The obtained results are very promising regarding further development of DMS technique as well as its application. PMID:26992504

  6. Thermal Solid Sample Introduction-Fast Gas Chromatography-Low Flow Ion Mobility Spectrometry as a field screening detection system.

    PubMed

    Hajialigol, Saeed; Ghorashi, Seyed Alireza; Alinoori, Amir Hossein; Torabpour, Amir; Azimi, Mehdi

    2012-12-14

    The potential of Thermal Solid Sample Introduction (TSSI)-Fast Gas Chromatography (GC)-Low Flow Ion Mobility Spectrometry (LF-IMS) having been designed and constructed in Engineering Research Center of Esfahan, detector group was investigated for chemical detection capabilities. Customizing the configuration of fast GC-IMS as a high technology, provides unique solutions for rapid detection of a broad range of chemical mixtures in many operational environments. TSSI configuration provides fast and easily applied method for direct detection with no additional sample preparation or extraction. The time required for total analysis, less than 265 s, was determined by the wide range of solid matrixes, including nitrate esters, nitroaromatics, and a nitramine. The fast extraction together with the short separation time limits degradation of the thermally labile compounds and decreases the peak widths, which results in larger peak intensities and a simultaneous improvement in detection limits. For signal-to-noise ratio equals to 5, the detection limits for instrument for TNT, DNT and RDX were attained 15, 10 and 50 ng/μl respectively. The combination of short analysis time and low detection limits make this instrument a potential candidate for field screening techniques. PMID:23141709

  7. Detection and quantification of natural contaminants of wine by gas chromatography-differential ion mobility spectrometry (GC-DMS).

    PubMed

    Camara, Malick; Gharbi, Nasser; Lenouvel, Audrey; Behr, Marc; Guignard, Cédric; Orlewski, Pierre; Evers, Danièle

    2013-02-01

    Rapid and direct, in situ headspace screening for odoriferous volatile organic compounds (VOCs) present in fresh grapes and in wines is a very promising method for quality control because the economic value of a wine is closely related to its aroma. Long used for the detection of VOCs in complex mixtures, miniature differential ion mobility spectrometry (DMS) seems therefore adequate for in situ trace detection of many kinds of VOCs of concern appearing in the headspace of selected foodstuffs. This work aims at a rapid detection, identification, and quantification of some natural and volatile contaminants of wine such as geosmin, 2-methylisoborneol (2-MIB), 1-octen-3-ol, 1-octen-3-one, and pyrazines (2-isopropyl-3-methoxypyrazine, IPMP, and 3-isobutyl-2-methoxypyrazine, IBMP). In the present study, these compounds were spiked at a known concentration in wine and analyzed with a hyphenated trap-GC-DMS device. The detection of all target compounds at concentrations below the human olfactory threshold was demonstrated. PMID:23356506

  8. Neuronal metabolomics by ion mobility mass spectrometry in cocaine self-administering rats after early and late withdrawal.

    PubMed

    Zhang, Xing; Chiu, Veronica M; Todd, Ryan P; Sorg, Barbara A; Hill, Herbert H

    2016-06-01

    The neuronal metabolomes in rat striatum (STR), prefrontal cortex (PFC), and nucleus accumbens (NAC) were analyzed by Hadamard transform ion mobility mass spectrometry (HT-IMMS) in order to reveal global and specific metabolic changes induced by cocaine self-administration after 1-day or 3-week withdrawal. Metabolite features were comprehensively separated and detected using HPLC-IMMS within minutes. Global metabolic differences were observed by PCA for comparisons between cocaine and saline treatments at 1-day withdrawal time. Metabolite features that were significantly changed were selected using PCA loadings' plot and unpaired LLL test and then tentatively identified by accurate m/z, yielding a complete profile of metabolic changes induced by cocaine self-administration. The majority of these changes were found at the 1-day withdrawal time, but several of them endured even after 3-week withdrawal from cocaine, and these changes were generally brain region specific. Putatively identified metabolites associated with oxidative stress and energy metabolism were also specifically investigated. We discovered that the dysregulation of creatine/creatinine was different between the STR and NAC, demonstrating that metabolic alterations are brain region specific. Glutathione and adenosine were also changed in their abundance, and the results agreed with previous studies. In general, this study provided a high-throughput analytical platform to perform metabolomics analyses with putative identifications for altered metabolite features induced by cocaine treatment, therefore revealing additional metabolic targets of cocaine-induced changes after early and extended withdrawal times. PMID:27108279

  9. Fragmentation of molecular ions in differential mobility spectrometry as a method for identification of chemical warfare agents.

    PubMed

    Maziejuk, M; Puton, J; Szyposzyńska, M; Witkiewicz, Z

    2015-11-01

    The subject of the work is the use of differential mobility spectrometry (DMS) for the detection of chemical warfare agents (CWA). Studies were performed for mustard gas, i.e., bis(2-chloroethyl)sulfide (HD), sarin, i.e., O-isopropyl methylphosphonofluoridate (GB) and methyl salicylate (MS) used as test compounds. Measurements were conducted with two ceramic DMS analyzers of different constructions allowing the generation of an electric field with an intensity of more than 120 Td. Detector signals were measured for positive and negative modes of operation in a temperature range from 0 to 80 °C. Fragmentations of ions containing analyte molecules were observed for all tested compounds. The effective temperatures of fragmentation estimated on the basis of dispersion plots were equal from about 148 °C for GB to 178 °C for MS. It was found that values of separation voltage (SV) and compensation voltage (CV) at which the fragmentation of sample ions is observed may be the parameters improving the certainty of detection for different analytes. The DMS analyzers enabling the observation of ion fragmentation can be successfully used for effective CWA detection. PMID:26452948

  10. Online Measurement of Exhaled NO Concentration and Its Production Sites by Fast Non-equilibrium Dilution Ion Mobility Spectrometry

    PubMed Central

    Peng, Liying; Jiang, Dandan; Wang, Zhenxin; Liu, Jiwei; Li, Haiyang

    2016-01-01

    Exhaled nitric oxide (NO) is one of the most promising breath markers for respiratory diseases. Its profile for exhalation and the respiratory NO production sites can provide useful information for medical disease diagnosis and therapeutic procedures. However, the high-level moisture in exhaled gas always leads to the poor selectivity and sensitivity for ion spectrometric techniques. Herein, a method based on fast non-equilibrium dilution ion mobility spectrometry (NED-IMS) was firstly proposed to directly monitor the exhaled NO profile on line. The moisture interference was eliminated by turbulently diluting the original moisture to 21% of the original with the drift gas and dilution gas. Weak enhancement was observed for humid NO response and its limit of detection at 100% relative humidity was down to 0.58 ppb. The NO concentrations at multiple exhalation flow rates were measured, while its respiratory production sites were determined by using two-compartment model (2CM) and Högman and Meriläinen algorithm (HMA). Last but not the least, the NO production sites were analyzed hourly to tentatively investigate the daily physiological process of NO. The results demonstrated the capacity of NED-IMS in the real-time analysis of exhaled NO and its production sites for clinical diagnosis and assessment. PMID:26975333

  11. Identification of volatile chemical signatures from plastic explosives by SPME-GC/MS and detection by ion mobility spectrometry.

    PubMed

    Lai, Hanh; Leung, Alfred; Magee, Matthew; Almirall, José R

    2010-04-01

    This study demonstrates the use of solid-phase microextraction (SPME) to extract and pre-concentrate volatile signatures from static air above plastic explosive samples followed by detection using ion mobility spectrometry (IMS) optimized to detect the volatile, non-energetic components rather than the energetic materials. Currently, sample collection for detection by commercial IMS analyzers is conducted through swiping of suspected surfaces for explosive particles and vapor sampling. The first method is not suitable for sampling inside large volume areas, and the latter method is not effective because the low vapor pressure of some explosives such as RDX and PETN make them not readily available in the air for headspace sampling under ambient conditions. For the first time, headspace sampling and detection of Detasheet, Semtex H, and C-4 is reported using SPME-IMS operating under one universal setting with limits of detection ranging from 1.5 to 2.5 ng for the target volatile signatures. The target signature compounds n-butyl acetate and the taggant DMNB are associated with untagged and tagged Detasheet explosives, respectively. Cyclohexanone and DMNB are associated with tagged C-4 explosives. DMNB is associated with tagged Semtex H explosives. Within 10 to 60 s of sampling, the headspace inside a glass vial containing 1 g of explosive, more than 20 ng of the target signatures can be extracted by the SPME fiber followed by IMS detection. PMID:20229010

  12. Protein Structural Studies by Traveling Wave Ion Mobility Spectrometry: A Critical Look at Electrospray Sources and Calibration Issues

    NASA Astrophysics Data System (ADS)

    Sun, Yu; Vahidi, Siavash; Sowole, Modupeola A.; Konermann, Lars

    2016-01-01

    The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Ω) measured by ion mobility spectrometry (IMS) with Ω values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Ω values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments.

  13. Ion Mobility-Mass Spectrometry as a Tool for the Structural Characterization of Peptides Bearing Intramolecular Disulfide Bond(s)

    NASA Astrophysics Data System (ADS)

    Massonnet, Philippe; Haler, Jean R. N.; Upert, Gregory; Degueldre, Michel; Morsa, Denis; Smargiasso, Nicolas; Mourier, Gilles; Gilles, Nicolas; Quinton, Loïc; De Pauw, Edwin

    2016-08-01

    Disulfide bonds are post-translationnal modifications that can be crucial for the stability and the biological activities of natural peptides. Considering the importance of these disulfide bond-containing peptides, the development of new techniques in order to characterize these modifications is of great interest. For this purpose, collision cross cections (CCS) of a large data set of 118 peptides (displaying various sequences) bearing zero, one, two, or three disulfide bond(s) have been measured in this study at different charge states using ion mobility-mass spectrometry. From an experimental point of view, CCS differences (ΔCCS) between peptides bearing various numbers of disulfide bonds and peptides having no disulfide bonds have been calculated. The ΔCCS calculations have also been applied to peptides bearing two disulfide bonds but different cysteine connectivities (Cys1-Cys2/Cys3-Cys4; Cys1-Cys3/Cys2-Cys4; Cys1-Cys4/Cys2-Cys3). The effect of the replacement of a proton by a potassium adduct on a peptidic structure has also been investigated.

  14. Analyzing slowly exchanging protein conformations by ion mobility mass spectrometry: study of the dynamic equilibrium of prolyl oligopeptidase.

    PubMed

    López, Abraham; Vilaseca, Marta; Madurga, Sergio; Varese, Monica; Tarragó, Teresa; Giralt, Ernest

    2016-07-01

    Ion mobility mass spectrometry (IMMS) is a biophysical technique that allows the separation of isobaric species on the basis of their size and shape. The high separation capacity, sensitivity and relatively fast time scale measurements confer IMMS great potential for the study of proteins in slow (µs-ms) conformational equilibrium in solution. However, the use of this technique for examining dynamic proteins is still not generalized. One of the major limitations is the instability of protein ions in the gas phase, which raises the question as to what extent the structures detected reflect those in solution. Here, we addressed this issue by analyzing the conformational landscape of prolyl oligopeptidase (POP) - a model of a large dynamic enzyme in the µs-ms range - by native IMMS and compared the results obtained in the gas phase with those obtained in solution. In order to interpret the experimental results, we used theoretical simulations. In addition, the stability of POP gaseous ions was explored by charge reduction and collision-induced unfolding experiments. Our experiments disclosed two species of POP in the gas phase, which correlated well with the open and closed conformations in equilibrium in solution; moreover, a gas-phase collapsed form of POP was also detected. Therefore, our findings not only support the potential of IMMS for the study of multiple co-existing conformations of large proteins in slow dynamic equilibrium in solution but also stress the need for careful data analysis to avoid artifacts. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27434808

  15. Online Measurement of Exhaled NO Concentration and Its Production Sites by Fast Non-equilibrium Dilution Ion Mobility Spectrometry.

    PubMed

    Peng, Liying; Jiang, Dandan; Wang, Zhenxin; Liu, Jiwei; Li, Haiyang

    2016-01-01

    Exhaled nitric oxide (NO) is one of the most promising breath markers for respiratory diseases. Its profile for exhalation and the respiratory NO production sites can provide useful information for medical disease diagnosis and therapeutic procedures. However, the high-level moisture in exhaled gas always leads to the poor selectivity and sensitivity for ion spectrometric techniques. Herein, a method based on fast non-equilibrium dilution ion mobility spectrometry (NED-IMS) was firstly proposed to directly monitor the exhaled NO profile on line. The moisture interference was eliminated by turbulently diluting the original moisture to 21% of the original with the drift gas and dilution gas. Weak enhancement was observed for humid NO response and its limit of detection at 100% relative humidity was down to 0.58 ppb. The NO concentrations at multiple exhalation flow rates were measured, while its respiratory production sites were determined by using two-compartment model (2CM) and Högman and Meriläinen algorithm (HMA). Last but not the least, the NO production sites were analyzed hourly to tentatively investigate the daily physiological process of NO. The results demonstrated the capacity of NED-IMS in the real-time analysis of exhaled NO and its production sites for clinical diagnosis and assessment. PMID:26975333

  16. Identification of novel isomeric pectic oligosaccharides using hydrophilic interaction chromatography coupled to traveling-wave ion mobility mass spectrometry.

    PubMed

    Leijdekkers, Antonius G M; Huang, Jie-Hong; Bakx, Edwin J; Gruppen, Harry; Schols, Henk A

    2015-03-01

    Separation and characterization of complex mixtures of pectic oligosaccharides still remains challenging and often requires the use of multiple analytical techniques, especially when isomeric structures are present. In this work, it is demonstrated that the coupling of hydrophilic interaction chromatography (HILIC) to traveling-wave ion mobility mass spectrometry (TWIMMS) enabled the simultaneous separation and characterization of complex mixtures of various isomeric pectic oligosaccharides. Labeling of oligosaccharides with 3-aminoquinoline (3-AQ) improved MS-ionization efficiency of the oligosaccharides and reduced the complexity of the product ion mass spectra, without losing resolution of the HILIC separation. In addition, labeling enabled quantification of oligosaccharides on molar basis using in-line fluorescence detection. Isomeric structures were distinguished using TWIMMS. The 3-AQ-HILIC-TWIMMS method was used to characterize a series of isomeric sugar beet rhamnogalacturonan I derived oligosaccharides carrying a glucuronic acid substituent. Thereby, some novel structural features were identified for the first time: glucuronic acid was attached to O-3 or to O-2 of galacturonic acid residues and a single galacturonic acid residue within an oligomer could contain both an acetyl group and a glucuronic acid substituent. PMID:25647688

  17. Estimating collision cross sections of negatively charged N-glycans using traveling wave ion mobility-mass spectrometry.

    PubMed

    Hofmann, Johanna; Struwe, Weston B; Scarff, Charlotte A; Scrivens, James H; Harvey, David J; Pagel, Kevin

    2014-11-01

    Glycosylation is one of the most common post-translational modifications occurring in proteins. A detailed structural characterization of the involved carbohydrates, however, is still one of the greatest challenges in modern glycoproteomics, since multiple regio- and stereoisomers with an identical monosaccharide composition may exist. Recently, ion mobility-mass spectrometry (IM-MS), a technique in which ions are separated according to their mass, charge, and shape, has evolved as a promising technique for the separation and structural analysis of complex carbohydrates. This growing interest is based on the fact that the measured drift times can be converted into collision cross sections (CCSs), which can be compared, implemented into databases, and used as additional search criteria for structural identification. However, most of the currently used commercial IM-MS instruments utilize a nonuniform traveling wave field to propel the ions through the IM cell. As a result, CCS measurements cannot be performed directly and require calibration. Here, we present a calibration data set consisting of over 500 reference CCSs for negatively charged N-glycans and their fragments. Moreover, we show that dextran, already widely used as a calibrant in high performance liquid chromatography, is also a suitable calibrant for CCS estimations. Our data also indicate that a considerably increased error has to be taken into account when reference CCSs acquired in a different drift gas are used for calibration. PMID:25268221

  18. Identification and separation of saxitoxins using hydrophilic interaction liquid chromatography coupled to traveling wave ion mobility-mass spectrometry.

    PubMed

    Poyer, Salomé; Loutelier-Bourhis, Corinne; Coadou, Gaël; Mondeguer, Florence; Enche, Julien; Bossée, Anne; Hess, Philipp; Afonso, Carlos

    2015-01-01

    The aim of this work was to develop a reliable and efficient analytical method to characterise and differentiate saxitoxin analogues (STX), including sulphated (gonyautoxins, GTX) and non-sulphated analogues. For this purpose, hydrophilic interaction liquid chromatography (HILIC) was used to separate sulphated analogues. We also resorted to ion mobility spectrometry to differentiate the STX analogues because this technique adds a new dimension of separation based on ion gas phase conformation. Positive and negative ionisation modes were used for gonyautoxins while positive ionisation mode was used for non-sulphated analogues. Subsequently, the coupling of these three complementary techniques, HILIC-IM-MS, permitted the separation and identification of STX analogues; isomer differentiation was achieved in HILIC dimension while non-sulphated analogues were separated in the IM-MS dimension. Additional structural characteristics concerning the conformation of STXs could be obtained using IM-MS measurements. Thus, the collision cross sections (CCS) of STXs are reported for the first time in the positive ionisation mode. These experimental CCSs correlated well with the calculated CCS values using the trajectory method. PMID:25601690

  19. Molecular Insights into the Thermal Stability of mAbs with Variable-Temperature Ion-Mobility Mass Spectrometry.

    PubMed

    Pacholarz, Kamila J; Peters, Shirley J; Garlish, Rachel A; Henry, Alistair J; Taylor, Richard J; Humphreys, David P; Barran, Perdita E

    2016-01-01

    The aggregation of protein-based therapeutics such as monoclonal antibodies (mAbs) can affect the efficacy of the treatment and can even induce effects that are adverse to the patient. Protein engineering is used to shift the mAb away from an aggregation-prone state by increasing the thermodynamic stability of the native fold, which might in turn alter conformational flexibility. We have probed the thermal stability of three types of intact IgG molecules and two Fc-hinge fragments by using variable-temperature ion-mobility mass spectrometry (VT-IM-MS). We observed changes in the conformations of isolated proteins as a function of temperature (300-550 K). The observed differences in thermal stability between IgG subclasses can be rationalized in terms of changes to higher-order structural organization mitigated by the hinge region. VT-IM-MS provides insights into mAbs structural thermodynamics and is presented as a promising tool for thermal-stability studies for proteins of therapeutic interest. PMID:26534882

  20. Direct coupling of packed column supercritical fluid chromatography to continuous corona discharge ion mobility spectrometry.

    PubMed

    Rahmanian, A; Ghaziaskar, H S; Khayamian, T

    2013-01-11

    In this study, packed column supercritical fluid chromatography (SFC) was directly coupled to a continuous corona discharge (CD) ion mobility spectrometer (IMS) with several modifications. The main advantage of the developed detector is its capability to introduce full column effluent up to 2000 mL min(-1) CO(2) gas directly into the IMS cell relative to 40 mL min(-1) CO(2) gas as a maximum tolerance, reported for the previous IMS detectors. This achievement was made possible because of using corona discharge instead of (63)Ni as an ionization source and locating the inlet and outlet of the CO(2) gas in the counter electrode of the CD in opposite direction. In addition, a heated interface was placed between back pressure regulator (BPR) and the IMS cell to heat the output of the BPR for introducing sample as the gas phase into the IMS cell. Furthermore, a make-up methanol flow was introduced between the column outlet and BPR to provide a more uniform flow through the BPR and also to prevent freezing and deposition of the analytes in the BPR. The performance of the SFC-CD-IMS was evaluated by analysis of testosterone, medroxyprogesterone, caffeine, and theophylline as test compounds and figures of merit for these compounds have been calculated. PMID:23261285

  1. Using corona discharge-ion mobility spectrometry for detection of 2,4,6-Trichloroanisole.

    PubMed

    Lichvanová, Zuzana; Ilbeigi, Vahideh; Sabo, Martin; Tabrizchi, Mahmoud; Matejčík, Stefan

    2014-09-01

    In this work possible application of the corona discharge-ion mobility spectrometer (CD-IMS) for detection of 2,4,6-Trichloroanisole (TCA) has been investigated. We applied CD-IMS interfaced with orthogonal acceleration time of flight mass spectrometer (CD-IMS-oaTOF) to study the ion processes within the CD-IMS technique. The CD-IMS instrument was operated in two modes, (i) standard and (ii) reverse flow modes resulting in different chemical ionisation schemes by NO3(-)(HNO3)n (n=0,1,2) and O2(-)(H2O)n (n=0,1,2), respectively. The O2(-)(H2O)n ionisation was associated with formation of Cl(-) and (TCA-CH3)(-) ions from TCA. The NO3(-)(HNO3)n ionisation, resulted in formation of NO3(-)(HNO3)(TCA-Cl) adduct ions. Limit of detection (LOD) for TCA was determined in gas (100 ppb) and solid phases (150 ng). PMID:24913882

  2. The Predictive Power of SIMION/SDS Simulation Software for Modeling Ion Mobility Spectrometry Instruments

    SciTech Connect

    Hanh Lai; Timothy R. McJunkin; Carla J. Miller; Jill R. Scott; Jose R. Almirall

    2008-09-01

    The combined use of SIMION 7.0 and the statistical diffusion simulation (SDS) user program in conjunction with SolidWorks® with COSMSOFloWorks® fluid dynamics software to model a complete, commercial ion mobility spectrometer (IMS) was demonstrated for the first time and compared to experimental results for tests using compounds of immediate interest in the security industry (e.g., 2,4,6-trinitrotoluene and cocaine). The effort of this research was to evaluate the predictive power of SIMION/SDS for application to IMS instruments. The simulation was evaluated against experimental results in three studies: 1) a drift:carrier gas flow rates study assesses the ability of SIMION/SDS to correctly predict the ion drift times; 2) a drift gas composition study evaluates the accuracy in predicting the resolution; and 3) a gate width study compares the simulated peak shape and peak intensity with the experimental values. SIMION/SDS successfully predicted the correct drift time, intensity, and resolution trends for the operating parameters studied. Despite the need for estimations and assumptions in the construction of the simulated instrument, SIMION/SDS was able to predict the resolution between two ion species in air within 3% accuracy. The preliminary success of IMS simulations using SIMION/SDS software holds great promise for the design of future instruments with enhanced performance.

  3. The predictive power of SIMION/SDS simulation software for modeling ion mobility spectrometry instruments

    NASA Astrophysics Data System (ADS)

    Lai, Hanh; McJunkin, Timothy R.; Miller, Carla J.; Scott, Jill R.; Almirall, José R.

    2008-09-01

    The combined use of SIMION 7.0 and the statistical diffusion simulation (SDS) user program in conjunction with SolidWorks® with COSMSOSFloWorks® fluid dynamics software to model a complete, commercial ion mobility spectrometer (IMS) was demonstrated for the first time and compared to experimental results for tests using compounds of immediate interest in the security industry (e.g., 2,4,6-trinitrotoluene, 2,7-dinitrofluorene, and cocaine). The effort of this research was to evaluate the predictive power of SIMION/SDS for application to IMS instruments. The simulation was evaluated against experimental results in three studies: (1) a drift:carrier gas flow rates study assesses the ability of SIMION/SDS to correctly predict the ion drift times; (2) a drift gas composition study evaluates the accuracy in predicting the resolution; (3) a gate width study compares the simulated peak shape and peak intensity with the experimental values. SIMION/SDS successfully predicted the correct drift time, intensity, and resolution trends for the operating parameters studied. Despite the need for estimations and assumptions in the construction of the simulated instrument, SIMION/SDS was able to predict the resolution between two ion species in air within 3% accuracy. The preliminary success of IMS simulations using SIMION/SDS software holds great promise for the design of future instruments with enhanced performance.

  4. Improved Isobaric Tandem Mass Tag Quantification by Ion Mobility-Mass Spectrometry

    PubMed Central

    Li, Lingjun

    2014-01-01

    Isobaric tandem mass tags are an attractive alternative to mass difference tags and label free approaches for quantitative proteomics due to the high degree of multiplexing that can be performed with their implementation. A drawback of tandem mass tags are that the co-isolation and co-fragmentation of labeled peptide precursors can result in chimeric MS/MS spectra that can underestimate the fold-change expression of each peptide. Two methods (QuantMode and MS3) have addressed this concern for ion trap and orbitrap instruments, but there is still a need to solve this problem for quadrupole time-of-flight (Q-TOF) instruments. Ion mobility (IM) separations coupled to Q-TOF instruments have the potential to mitigate MS/MS spectra chimeracy since IM-MS has the ability to separate ions based on charge, m/z, and collision cross section (CCS). This work presents results that showcase the power of IM-MS to improve tandem mass tag peptide quantitation accuracy by resolving co-isolated differently charged and same charged peptides prior to MS/MS fragmentation. PMID:24677527

  5. The use of ion mobility spectrometry and gas chromatography/mass spectrometry for the detection of illicit drugs on clandestine records

    NASA Technical Reports Server (NTRS)

    Donnelly, Brian; Jourdan, Thomas; Fetterolf, Dean D.; Beasley, James O., II

    1995-01-01

    the records. The detection of trace drug residue on surfaces by ion mobility spectrometry (IMS) is well documented in literature. The following procedure will deal primarily with the newer techniques of trace drug analysis and drug record analysis developed by the Chemistry/Toxicology Unit of the FBI Laboratory since the more traditional techniques of latent finger print analysis and document analysis are well known.

  6. Optimized thermal desorption for improved sensitivity in trace explosives detection by ion mobility spectrometry.

    PubMed

    Najarro, Marcela; Dávila Morris, Melissa E; Staymates, Matthew E; Fletcher, Robert; Gillen, Greg

    2012-06-01

    In this work we evaluate the influence of thermal desorber temperature on the analytical response of a swipe-based thermal desorption ion mobility spectrometer (IMS) for detection of trace explosives. IMS response for several common high explosives ranging from 0.1 ng to 100 ng was measured over a thermal desorber temperature range from 60 °C to 280 °C. Most of the explosives examined demonstrated a well-defined maximum IMS signal response at a temperature slightly below the melting point. Optimal temperatures, giving the highest IMS peak intensity, were 80 °C for trinitrotoluene (TNT), 100 °C for pentaerythritol tetranitrate (PETN), 160 °C for cyclotrimethylenetrinitramine (RDX) and 200 °C for cyclotetramethylenetetranitramine (HMX). By modifying the desorber temperature, we were able to increase cumulative IMS signal by a factor of 5 for TNT and HMX, and by a factor of 10 for RDX and PETN. Similar signal enhancements were observed for the same compounds formulated as plastic-bonded explosives (Composition 4 (C-4), Detasheet, and Semtex). In addition, mixtures of the explosives exhibited similar enhancements in analyte peak intensities. The increases in sensitivity were obtained at the expense of increased analysis times of up to 20 seconds. A slow sample heating rate as well as slower vapor-phase analyte introduction rate caused by low-temperature desorption enhanced the analytical sensitivity of individual explosives, plastic-bonded explosives, and explosives mixtures by IMS. Several possible mechanisms that can affect IMS signal response were investigated such as thermal degradation of the analytes, ionization efficiency, competitive ionization from background, and aerosol emission. PMID:22498665

  7. The Role of Oxygen in the Formation of TNT Product Ions in Ion Mobility Spectrometry

    SciTech Connect

    Daum, Keith Alvin; Atkinson, David Alan; Ewing, Robert Gordon

    2002-03-01

    The atmospheric pressure ionization of 2,4,6-trinitrotoluene (TNT) in air yields the (TNT-H)- product ion. It is generally accepted that this product ion is formed by the direct proton abstraction of neutral TNT by O2- reactant ions. Data presented here demonstrate the reaction involves the formation of an intermediate (TNT·O2)-, from the association of either TNT+O2- or TNT-+O2. This intermediate has two subsequent reaction branches. One of these branches involves simple dissociation of the intermediate to TNT-; the other branch is a terminal reaction that forms the typically observed (TNT-H)- ion via proton abstraction. The dissociation reaction involving electron transfer to TNT- appeared to be kinetically favored and prevailed at low concentrations of oxygen (less than 2%). The presence of significant amounts of oxygen, however, resulted in the predominant formation of the (TNT-H)- ion by the terminal reaction branch. With TNT- in the system, either from direct electron attachment or by simple dissociation of the intermediate, increasing levels of oxygen in the system will continue to reform the intermediate, allowing the cycle to continue until proton abstraction occurs. Key to understanding this complex reaction pathway is that O2- was observed to transfer an electron directly to neutral TNT to form the TNT-. At oxygen levels of less than 2%, the TNT- ion intensity increased with increasing levels of oxygen (and O2-) and was larger than the (TNT-H)- ion intensity. As the oxygen level increased from 2 to 10%, the (TNT-H)- product ion became predominant. The potential reaction mechanisms were investigated with an ion mobility spectrometer, which was configured to independently evaluate the ionization pathways.

  8. Comparative A/B testing a mobile data acquisition app for hydrogeochemistry

    NASA Astrophysics Data System (ADS)

    Klump, Jens; Golodoniuc, Pavel; Reid, Nathan; Gray, David; Ross, Shawn

    2015-04-01

    In the context of a larger study on the Capricorn Orogen of Western Australia, the CSIRO Mineral Discovery Program is conducting a regional study of the hydrogeochemistry on water from agricultural and other bores. Over time, the sampling process was standardised and a form for capturing metadata and data from initial measurements was developed. In 2014 an extensive technology review was conducted with an aim to automate field data acquisition process. A prototype hydrogeochemistry data capture form was implemented as a mobile application for Windows Mobile devices. This version of the software was a standalone application with an interface to export data as CSV files. A second candidate version of the hydrogeochemistry data capture form was implemented as an Android mobile application in the FAIMS framework. FAIMS is a framework for mobile field data capture, originally developed by at the University of New South Wales for archaeological field data collection. A benefit of the FAIMS application was the ability to associate photographs taken with the device's embedded camera with the captured data. FAIMS also allows networked collaboration within a field team, using the mobile applications as asynchronous rich clients. The network infrastructure can be installed in the field ("FAIMS in a Box") to supply data synchronisation, backup and transfer. This aspect will be tested in the next field season. A benefit of the FAIMS application was the ability to associate photographs taken with the device's embedded camera with the captured data. Having two data capture applications available allowed us to conduct an A/B test, comparing two different implementations for the same task. Both applications were trialled in the field by different field crews and user feedback will be used to improve the usability of the app for the next field season. A key learning was that the ergonomics of the app is at paramount importance to gain the user acceptance. This extends from general

  9. A Mobile App for Geochemical Field Data Acquisition

    NASA Astrophysics Data System (ADS)

    Klump, J. F.; Reid, N.; Ballsun-Stanton, B.; White, A.; Sobotkova, A.

    2015-12-01

    We have developed a geochemical sampling application for use on Android tablets. This app was developed together with the Federated Archaeological Information Management Systems (FAIMS) at Macquarie University and is based on the open source FAIMS mobile platform, which was originally designed for archaeological field data collection. The FAIMS mobile platform has proved valuable for hydrogeochemical, biogeochemical, soil and rock sample collection due to the ability to customise data collection methodologies for any field research. The module we commissioned allows for using inbuilt or external GPS to locate sample points, it incorporates standard and incremental sampling names which can be easily fed into the International Geo-Sample Number (IGSN). Sampling can be documented not only in metadata, but also accompanied by photographic documentation and sketches. The module is augmented by dropdown menus for fields specific for each sample type and user defined tags. The module also provides users with an overview of all records from a field campaign in a records viewer. We also use basic mapping functionality, showing the current location, sampled points overlaid on preloaded rasters, and allows for drawing of points and simple polygons to be later exported as shape files. A particular challenge is the remoteness of the sampling locations, hundreds of kilometres away from network access. The first trial raised the issue of backup without access to the internet, so in collaboration with the FAIMS team and Solutions First, we commissioned a vehicle mounted portable server. This server box is constantly syncing with the tablets in the field via Wi-Fi, it has an uninterruptible power supply that can run for up to 45 minutes when the vehicle is turned off, and a 1TB hard drive for storage of all data and photographs. The server can be logged into via any of the field tablets or laptop to download all the data collected to date or to just view it on the server.

  10. Coupling laser ablation/desorption electrospray ionization to atmospheric pressure drift tube ion mobility spectrometry for the screening of antimalarial drug quality.

    PubMed

    Harris, Glenn A; Graf, Stephan; Knochenmuss, Richard; Fernández, Facundo M

    2012-07-01

    Significant developments in the field of ambient desorption/ionization mass spectrometry (MS) have led to high-throughput direct analysis and imaging capabilities. However, advances in coupling ambient ionization techniques with standalone drift tube ion mobility spectrometry (DTIMS) have been comparatively slower, despite the attractive ruggedness and simplicity of IMS. In this study, we have developed and characterized a laser ablation/desorption electrospray ionization (LADESI) DTIMS platform, and applied it to the detection of active pharmaceutical ingredients (APIs) in antimalarial tablets collected in developing countries. The overarching goal of this work was to perform an initial evaluation of LADESI DTIMS as a technique with the potential for constituting the core of a portable drug quality-testing platform. The set-up consisted of an IR laser for desorption and an electrospray ionizer for capturing the ablated plume coupled to a high-resolution monolithic resistive glass drift tube ion mobility spectrometer. For more confident API identification, tablet extracts were also investigated via electrospray IM MS to correlate LADESI DTIMS reduced mobility (K(0)) values to m/z values. Overall, it was found that the IR LADESI DTIMS platform provided distinct ion mobility spectral fingerprints that could be used to detect the presence of the expected APIs, helping to distinguish counterfeit drugs from their genuine counterparts. PMID:22606690

  11. Coupling a branch enclosure with differential mobility spectrometry to isolate and measure plant volatiles in contained greenhouse settings.

    PubMed

    McCartney, Mitchell M; Spitulski, Sierra L; Pasamontes, Alberto; Peirano, Daniel J; Schirle, Michael J; Cumeras, Raquel; Simmons, Jason D; Ware, Jeffrey L; Brown, Joshua F; Poh, Alexandria J Y; Dike, Seth C; Foster, Elizabeth K; Godfrey, Kristine E; Davis, Cristina E

    2016-01-01

    Volatile organic compounds (VOCs) are off-gassed from all living organisms and represent end products of metabolic pathways within the system. In agricultural systems, these VOCs can provide important information on plant health and can ordinarily be measured non-invasively without harvesting tissue from the plants. Previously we reported a portable gas chromatography/differential mobility spectrometry (GC/DMS) system that could distinguish VOC profiles of pathogen-infected citrus from healthy trees before visual symptoms of disease were present. These measurements were taken directly from canopies in the field, but the sampling and analysis protocol did not readily transfer to a controlled greenhouse study where the ambient background air was saturated with volatiles contained in the facility. In this study, we describe for the first time a branch enclosure uniquely coupled with GC/DMS to isolate and measure plant volatiles. To test our system, we sought to replicate our field experiment within a contained greenhouse and distinguish the VOC profiles of healthy versus citrus infected with Candidatus Liberibacter asiaticus. We indeed confirm the ability to track infection-related trace biogenic VOCs using our sampling system and method and we now show this difference in Lisbon lemons (Citrus×limon L. Burm. f.), a varietal not previously reported. Furthermore, the system differentiates the volatile profiles of Lisbon lemons from Washington navels [Citrus sinensis (L.) Osbeck] and also from Tango mandarins (Citrus reticulata Blanco). Based on this evidence, we believe this enclosure-GC/DMS system is adaptable to other volatile-based investigations of plant diseases in greenhouses or other contained settings, and this system may be helpful for basic science research studies of infection mechanisms. PMID:26695246

  12. Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

    PubMed Central

    2015-01-01

    Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data. PMID:25360896

  13. Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI.

    PubMed

    Xu, Libin; Kliman, Michal; Forsythe, Jay G; Korade, Zeljka; Hmelo, Anthony B; Porter, Ned A; McLean, John A

    2015-06-01

    Profiling and imaging of cholesterol and its precursors by mass spectrometry (MS) are important in a number of cholesterol biosynthesis disorders, such as in Smith-Lemli-Opitz syndrome (SLOS), where 7-dehydrocholesterol (7-DHC) is accumulated in affected individuals. SLOS is caused by defects in the enzyme that reduces 7-DHC to cholesterol. However, analysis of sterols is challenging because these hydrophobic olefins are difficult to ionize for MS detection. We report here sputtered silver matrix-assisted laser desorption/ionization (MALDI)-ion mobility-MS (IM-MS) analysis of cholesterol and 7-DHC. In comparison with liquid-based AgNO3 and colloidal Ag nanoparticle (AgNP), sputtered silver NP (10-25 nm) provided the lowest limits-of-detection based on the silver coordinated [cholesterol + Ag](+) and [7-DHC + Ag](+) signals while minimizing dehydrogenation products ([M + Ag-2H](+)). When analyzing human fibroblasts that were directly grown on poly-L-lysine-coated ITO glass plates with this technique, in situ, the 7-DHC/cholesterol ratios for both control and SLOS human fibroblasts are readily obtained. The m/z of 491 (specific for [7-DHC + (107)Ag](+)) and 495 (specific for [cholesterol + (109)Ag](+)) were subsequently imaged using MALDI-IM-MS. MS images were co-registered with optical images of the cells for metabolic ratio determination. From these comparisons, ratios of 7-DHC/cholesterol for SLOS human fibroblasts are distinctly higher than in control human fibroblasts. Thus, this strategy demonstrates the utility for diagnosing/assaying the severity of cholesterol biosynthesis disorders in vitro. PMID:25822928

  14. Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.

    PubMed

    Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

    2015-08-01

    Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. PMID:25694334

  15. Profiling and Imaging Ion Mobility-Mass Spectrometry Analysis of Cholesterol and 7-Dehydrocholesterol in Cells Via Sputtered Silver MALDI

    NASA Astrophysics Data System (ADS)

    Xu, Libin; Kliman, Michal; Forsythe, Jay G.; Korade, Zeljka; Hmelo, Anthony B.; Porter, Ned A.; McLean, John A.

    2015-06-01

    Profiling and imaging of cholesterol and its precursors by mass spectrometry (MS) are important in a number of cholesterol biosynthesis disorders, such as in Smith-Lemli-Opitz syndrome (SLOS), where 7-dehydrocholesterol (7-DHC) is accumulated in affected individuals. SLOS is caused by defects in the enzyme that reduces 7-DHC to cholesterol. However, analysis of sterols is challenging because these hydrophobic olefins are difficult to ionize for MS detection. We report here sputtered silver matrix-assisted laser desorption/ionization (MALDI)-ion mobility-MS (IM-MS) analysis of cholesterol and 7-DHC. In comparison with liquid-based AgNO3 and colloidal Ag nanoparticle (AgNP), sputtered silver NP (10-25 nm) provided the lowest limits-of-detection based on the silver coordinated [cholesterol + Ag]+ and [7-DHC + Ag]+ signals while minimizing dehydrogenation products ([M + Ag-2H]+). When analyzing human fibroblasts that were directly grown on poly-L-lysine-coated ITO glass plates with this technique, in situ, the 7-DHC/cholesterol ratios for both control and SLOS human fibroblasts are readily obtained. The m/z of 491 (specific for [7-DHC + 107Ag]+) and 495 (specific for [cholesterol + 109Ag]+) were subsequently imaged using MALDI-IM-MS. MS images were co-registered with optical images of the cells for metabolic ratio determination. From these comparisons, ratios of 7-DHC/cholesterol for SLOS human fibroblasts are distinctly higher than in control human fibroblasts. Thus, this strategy demonstrates the utility for diagnosing/assaying the severity of cholesterol biosynthesis disorders in vitro.

  16. Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate

    PubMed Central

    Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

    2015-01-01

    Antibody–drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla®). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin®), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. PMID:25694334

  17. On-site quantitation of arsenic in drinking water by disk solid-phase extraction/mobile X-ray fluorescence spectrometry.

    PubMed

    Hagiwara, Kenta; Koike, Yuya; Aizawa, Mamoru; Nakamura, Toshihiro

    2015-11-01

    A rapid and simple method was developed for As determination in drinking water by solid-phase extraction (SPE)/mobile X-ray fluorescence (XRF) spectrometry. A 50 mL aqueous sample was adjusted to pH 3 with dilute hydrochloric acid, and then passed through a Ti and Zr-loaded carbon disk (TiZr-CD) to pre-concentrate the As. The SPE disk was adhered to an acrylic plate with cellophane tape, and then examined by mobile XRF spectrometry. The TiZr-CD adsorbed inorganic As (as As(III) and As(V)) and organic As (as methyl, phenyl and aromatic arsenic compounds) from water. The As calibration curve had good linearity over the range of 0.5-5 μg, and the limit of detection was 0.10 μg (2.0 μgL(-1) in As concentration). The concentrations of As in well water samples were determined using the proposed method were similar to results obtained from atomic absorption spectrometry. The proposed method did not require a power supply or a toxic solution and/or gas in any analytical step, therefore it is suitable for the on-site determination of As in drinking water. PMID:26452891

  18. A rapid and non-invasive method to determine toxic levels of alcohols and γ-hydroxybutyric acid in saliva samples by gas chromatography-differential mobility spectrometry.

    PubMed

    Criado-García, L; Ruszkiewicz, D M; Eiceman, G A; Thomas, C L P

    2016-03-01

    A polydimethylsiloxane oral sampler was used to extract methanol, ethanol, ethylene glycol, 1,3-propandiol and γ-hydroxybutyric acid from samples of human saliva obtained using a passive drool approach. The extracted compounds were recovered by thermal desorption, isolated by gas chromatography and detected with differential mobility spectrometry, operating with a programmed dispersion field. Complex signal behaviours were also observed that were consistent with hitherto unobserved fragmentation behaviours in differential mobility spectrometry. These yielded high-mobility fragments obscured within the envelope of the water-based reactant ion peak. Further, compensation field maxima shifts were also observed which were attributable to transport gas modification phenomena. Nevertheless, the responses obtained indicated that in vivo saliva sampling with thermal desorption gas chromatography may be used to provide a semi-quantitative diagnostic screen over the toxicity threshold concentration ranges of 100 mg dm(-3) to 3 g dm(-3). A candidate method suitable for use in low resource settings for the non-invasive screening of patients intoxicated by alcohols and volatile sedatives has been demonstrated. PMID:26744364

  19. From Planar to Cage in 15 Easy Steps: Resolving the C60H21F9(-) → C60(-) Transformation by Ion Mobility Mass Spectrometry.

    PubMed

    Greisch, Jean-François; Amsharov, Konstantin Yu; Weippert, Jürgen; Weis, Patrick; Böttcher, Artur; Kappes, Manfred M

    2016-09-01

    A combination of mass spectrometry, collision-induced dissociation, ion mobility mass spectrometry (IM-MS), and density functional theory (DFT) has been used to study the evolution of anionic species generated by laser-desorption of the near-planar, fluorinated polycyclic aromatic hydrocarbon (PAH), C60H21F9 (s). The dominant decay process for isolated, thermally activated C60H21F9(-) species comprises a sequence of multiple regioselective cyclodehydrofluorination and cyclodehydrogenation reactions (eliminating HF and H2, respectively, while forming additional pentagons and/or hexagons). The DFT calculations allow us to set narrow bounds on the structures of the resulting fragment ions by fitting structural models to experimentally determined collision cross sections. These show that the transformation of the precursor anion proceeds via a series of intermediate structures characterized by increasing curvature, ultimately leading to the closed-shell fullerene cage C60(-) as preprogrammed by the precursor structure. PMID:27501376

  20. Field detection and identification of a bioaerosol suite by pyrolysis-gas chromatography-ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Snyder, A. Peter; Tripathi, Ashish; Maswadeh, Waleed M.; Ho, Jim; Spence, Mel

    2002-06-01

    Improvements were made to a pyrolysis-gas chromatography-ion mobility spectrometry stand-alone biodetector to provide more pyrolyzate compound information to the IMS detector module. Air carrier gas flowing continuously through the pyrolysis tube, the rate of air flow, and pyrolysis rate were found to improve the relative quality and quantity of pyrolyzate compounds detected by the IMS detector compare to earlier work. These improvements allowed a greater degree of confidence in the correlation of biological aerosols obtain in outdoor testing scenarios to a standard GC-IMS biological aerosol dataset. The airflow improvement allowed more biomarker compounds to be observed in the GC-IMS data domain for aerosols of Gram-negative Erwinia herbicola (EH) and ovalbumin protein as compared to previous studies. Minimal differences were observed for Gram-positive spores of Bacillus subtilis var. globigii (BG) from that of earlier work. Prior outdoor aerosol challenges dealt with the detection of one organism, either EH or BG. Biological aerosols were disseminated in a Western Canadian prairie and the Py-GC-IMS was tested for its ability to detect the biological aerosols. The current series of outdoor trials consisted of three different biological aerosol challenges. Forty-two trials were conducted and a simple area calculation of the GC-IMS data domain biomarker peaks correlated with the correct bioaerosol challenge in 30 trials. In another 7 trials, the status of an aerosol was determined to be biological in origin. Two additional trials had no discernible, unambiguous GC-IMS biological response, because they were black water sprays. Reproducible limits of detection were at a concentration of less than 0.5 bacterial analyte-containing particles per liter of air (ACPLA). In order to realize this low concentration, an aerosol concentrator was used to concentrate 2000 liters of air in 2.2 minutes. Previous outdoor aerosol trials have shown the Py-GC-IMS device to be a credible

  1. Structural analysis of ruthenium-arene complexes using ion mobility mass spectrometry, collision-induced dissociation, and DFT.

    PubMed

    Czerwinska, Izabella; Far, Johann; Kune, Christopher; Larriba-Andaluz, Carlos; Delaude, Lionel; De Pauw, Edwin

    2016-04-21

    Ion mobility mass spectrometry (IM-MS) and collision-induced dissociation (CID) techniques were used to investigate the influence of the phosphine ligand on the physicochemical properties of [RuCl2(p-cymene)(PCy3)] (), [RuCl2(p-cymene)(PPh3)] (), and [RuCl2(p-cymene)(PTA)] () in the gas phase (PTA is 1,3,5-triaza-7-phosphaadamantane). Electrospray ionization of complexes and led to the corresponding [RuCl(p-cymene)(PR3)](+) ions via the dissociation of a chlorido ligand, whereas RAPTA-C () afforded two molecular ions by in-source oxidation ([Ru(III)Cl2(p-cymene)(PTA)](+)) or protonation ([RuCl2(p-cymene)(PTA+H)](+)). Control experiments showed that the balance between these two ionization paths was strongly influenced by the nature of the solvent used for infusion. Collision cross sections (CCSs) of the four molecular ions accurately reflected the variations of steric bulk inferred from the Tolman steric parameters (θ) of the phosphine ligands. Moreover, DFT calculations combined with a model based on the kinetic theory of gases (the trajectory method of the IMoS software) afforded reliable CCS predictions. The almost two times higher dipole moment of [RuCl2(p-cymene)(PTA+H)](+) (μ = 13.75 D) compared to [Ru(III)Cl2(p-cymene)(PTA)](+) (μ = 7.18 D) was held responsible for increased ion-induced dipole interactions with a polarizable drift gas such as N2. Further experiments with He and CO2 confirmed that increasing the polarizability of the buffer gas improved the separation between the two molecular ions derived from complex . The fragmentation patterns of complexes were determined by CID. The sequence of collision voltages at which 50% of a precursor ion dissociates (V50) recorded for the molecular ions derived from compounds was in good agreement with simple electronic considerations based on the donor strength of the phosphine ligand. Thus, the CCS and V50 parameters used to determine the shape and stability of ionic species in the gas phase are complementary

  2. Possible isomers in ligand protected Ag11 cluster ions identified by ion mobility mass spectrometry and fragmented by surface induced dissociation.

    PubMed

    Baksi, Ananya; Harvey, Sophie R; Natarajan, Ganapati; Wysocki, Vicki H; Pradeep, Thalappil

    2016-03-01

    This communication reports the identification of gas phase isomers in monolayer-protected silver clusters. Two different isomers of Ag11(SG)7(-) (SG-gulathione thiolate) with different drift times have been detected using combined electrospray ionization (ESI) and ion mobility (IM) mass spectrometry (MS). Surface induced dissociation (SID) of the 3(-) charge state of such clusters shows charge stripping to give the 1(-) charged ion with some sodium attachment, in addition to fragmentation. SID and collision induced dissociation (CID) for Ag11(SG)7(-) suggest different pathways being accessed with each method. SID was introduced for the first time for the study of monolayer-protected clusters. PMID:26864967

  3. Portable Solid Phase Micro-Extraction Coupled with Ion Mobility Spectrometry System for On-Site Analysis of Chemical Warfare Agents and Simulants in Water Samples

    PubMed Central

    Yang, Liu; Han, Qiang; Cao, Shuya; Yang, Jie; Yang, Junchao; Ding, Mingyu

    2014-01-01

    On-site analysis is an efficient approach to facilitate analysis at the location of the system under investigation as it can result in more accurate, more precise and quickly available analytical data. In our work, a novel self-made thermal desorption based interface was fabricated to couple solid-phase microextraction with ion mobility spectrometry for on-site water analysis. The portable interface can be connected with the front-end of an ion mobility spectrometer directly without other modifications. The analytical performance was evaluated via the extraction of chemical warfare agents and simulants in water samples. Several parameters including ionic strength and extraction time have been investigated in detail. The application of the developed method afforded satisfactory recoveries ranging from 72.9% to 114.4% when applied to the analysis of real water samples. PMID:25384006

  4. Gas chromatography with tandem differential mobility spectrometry of fatty acid alkyl esters and the selective detection of methyl linolenate in biodiesels by dual-stage ion filtering.

    PubMed

    Pasupuleti, D; Pierce, K; Eiceman, G A

    2015-11-20

    Alkyl esters of fatty acids (FAAEs) with carbon numbers from 8 to 20 formed protonated monomers and proton bound dimers through atmospheric pressure chemical ionization reactions and these gas ions were characterized for their field dependent mobility coefficients using differential mobility spectrometry (DMS). Separation of ion peaks with a vapor modifier was achieved for ions with masses of 317-1033 Da though the differences in these coefficients and the resolution of ion peaks decreased proportionally with increased ion mass. Differences in dispersion curves were sufficient to isolate ions from specific FAAEs in the effluent of a gas chromatograph by dual stage ion filtering using a tandem DMS detector. Methyl linolenate was isolated from nearby eluting methyl oleate, methyl stearate and methyl linoleate within analysis times of 10s without measureable complications from charge suppression in the ion source or leakage in filtering of ions with close proximity of dispersion behavior. PMID:26427321

  5. Portable solid phase micro-extraction coupled with ion mobility spectrometry system for on-site analysis of chemical warfare agents and simulants in water samples.

    PubMed

    Yang, Liu; Han, Qiang; Cao, Shuya; Yang, Jie; Yang, Junchao; Ding, Mingyu

    2014-01-01

    On-site analysis is an efficient approach to facilitate analysis at the location of the system under investigation as it can result in more accurate, more precise and quickly available analytical data. In our work, a novel self-made thermal desorption based interface was fabricated to couple solid-phase microextraction with ion mobility spectrometry for on-site water analysis. The portable interface can be connected with the front-end of an ion mobility spectrometer directly without other modifications. The analytical performance was evaluated via the extraction of chemical warfare agents and simulants in water samples. Several parameters including ionic strength and extraction time have been investigated in detail. The application of the developed method afforded satisfactory recoveries ranging from 72.9% to 114.4% when applied to the analysis of real water samples. PMID:25384006

  6. Hand-held gas chromatography-ion mobility spectrometry for on-site analysis of complex organic mixtures in air or vapors over waste sites

    SciTech Connect

    Bell, S.C. ); Eiceman, G.A. . Dept. of Chemistry)

    1991-01-01

    The strengths of Ion mobility spectrometry (IMS) are low detection limits, a wide range of application, and simplicity of design and operation. The gentle ionization processes used in IMS impart a measure of selectivity to its response. However, atmospheric pressure chemical ionization with compounds of comparable proton affinities leads to mobility spectra for which interpretive and predictive models do not exist. An alternative approach for the analysis of complex mixtures with IMS is the use of a separation device such as a gas chromatograph (GC) as an inlet. Results suggest that an IMS cell temperature of ca. 150{degrees} to 175{degrees}C provided mobility spectra with suitable spectral detail without the complications of ion-molecule clusters or fragmentation. Significant fluctuation in peak heights were observed over a 30 day test period. Neural network pattern identification techniques were applied to data obtained at room temperature and at 150{degrees}. Results showed that spectral variables within compound classes as insufficient to distinguish related compounds when mobility data was obtained using the commercial room temperature IMS cell. Similar but less severe difficulty was encountered using the 150{degrees} data. 5 refs., 3 figs., 2 tabs.

  7. Travelling-wave ion mobility time-of-flight mass spectrometry as an alternative strategy for screening of multi-class pesticides in fruits and vegetables.

    PubMed

    Goscinny, Séverine; Joly, Laure; De Pauw, Edwin; Hanot, Vincent; Eppe, Gauthier

    2015-07-31

    This paper reports a novel approach to screening multi-class pesticides by ion mobility time-of-flight mass spectrometry detection. Nitrogen was selected as mobility gas. After optimization of the different ion mobility parameters, determination of matrix effect on the drift times was conducted using different matrix extracts. The results showed that drift time values are not influenced by the matrix and also are independent of the concentration within the working range for 100 pesticides tested, making drift time a powerful additional identification tool. Based on statistics, 2% variation criteria provides a good fit for all the pesticides targeted, and could be considered as a maximum acceptable criteria associated with the drift time parameter for identification purpose. This 2% value is in agreement with already reported criteria, for instance, for GC or LC retention time in European documents. Finally, the well-known feature of mobility to separate complex mixtures was also tested to obtain purified extracted mass spectra of pesticides present in fruit extract. PMID:26100574

  8. On-site Rapid Detection of Trace Non-volatile Inorganic Explosives by Stand-alone Ion Mobility Spectrometry via Acid-enhanced Evaporization

    PubMed Central

    Peng, Liying; Hua, Lei; Wang, Weiguo; Zhou, Qinghua; Li, Haiyang

    2014-01-01

    New techniques for the field detection of inorganic improvised explosive devices (IEDs) are urgently developed. Although ion mobility spectrometry (IMS) has been proved to be the most effective method for screening organic explosives, it still faces a major challenge to detect inorganic explosives owing to their low volatilities. Herein, we proposed a strategy for detecting trace inorganic explosives by thermal desorption ion mobility spectrometry (TD-IMS) with sample-to-sample analysis time less than 5 s based on in-situ acidification on the sampling swabs. The responses for typical oxidizers in inorganic explosives, such as KNO3, KClO3 and KClO4 were at least enhanced by a factor of 3000 and their limits of detection were found to be subnanogram. The common organic explosives and their mixtures with inorganic oxidizers were detected, indicating that the acidification process did not affect the detection of organic explosives. Moreover, the typical inorganic explosives such as black powders, firecrackers and match head could be sensitively detected as well. These results demonstrated that this method could be easily employed in the current deployed IMS for on-site sensitive detection of either inorganic explosives or organic ones. PMID:25318960

  9. On-site rapid detection of trace non-volatile inorganic explosives by stand-alone ion mobility spectrometry via acid-enhanced evaporization.

    PubMed

    Peng, Liying; Hua, Lei; Wang, Weiguo; Zhou, Qinghua; Li, Haiyang

    2014-01-01

    New techniques for the field detection of inorganic improvised explosive devices (IEDs) are urgently developed. Although ion mobility spectrometry (IMS) has been proved to be the most effective method for screening organic explosives, it still faces a major challenge to detect inorganic explosives owing to their low volatilities. Herein, we proposed a strategy for detecting trace inorganic explosives by thermal desorption ion mobility spectrometry (TD-IMS) with sample-to-sample analysis time less than 5 s based on in-situ acidification on the sampling swabs. The responses for typical oxidizers in inorganic explosives, such as KNO3, KClO3 and KClO4 were at least enhanced by a factor of 3000 and their limits of detection were found to be subnanogram. The common organic explosives and their mixtures with inorganic oxidizers were detected, indicating that the acidification process did not affect the detection of organic explosives. Moreover, the typical inorganic explosives such as black powders, firecrackers and match head could be sensitively detected as well. These results demonstrated that this method could be easily employed in the current deployed IMS for on-site sensitive detection of either inorganic explosives or organic ones. PMID:25318960

  10. On-site Rapid Detection of Trace Non-volatile Inorganic Explosives by Stand-alone Ion Mobility Spectrometry via Acid-enhanced Evaporization

    NASA Astrophysics Data System (ADS)

    Peng, Liying; Hua, Lei; Wang, Weiguo; Zhou, Qinghua; Li, Haiyang

    2014-10-01

    New techniques for the field detection of inorganic improvised explosive devices (IEDs) are urgently developed. Although ion mobility spectrometry (IMS) has been proved to be the most effective method for screening organic explosives, it still faces a major challenge to detect inorganic explosives owing to their low volatilities. Herein, we proposed a strategy for detecting trace inorganic explosives by thermal desorption ion mobility spectrometry (TD-IMS) with sample-to-sample analysis time less than 5 s based on in-situ acidification on the sampling swabs. The responses for typical oxidizers in inorganic explosives, such as KNO3, KClO3 and KClO4 were at least enhanced by a factor of 3000 and their limits of detection were found to be subnanogram. The common organic explosives and their mixtures with inorganic oxidizers were detected, indicating that the acidification process did not affect the detection of organic explosives. Moreover, the typical inorganic explosives such as black powders, firecrackers and match head could be sensitively detected as well. These results demonstrated that this method could be easily employed in the current deployed IMS for on-site sensitive detection of either inorganic explosives or organic ones.

  11. Dopant-assisted negative photoionization Ion mobility spectrometry coupled with on-line cooling inlet for real-time monitoring H2S concentration in sewer gas.

    PubMed

    Peng, Liying; Jiang, Dandan; Wang, Zhenxin; Hua, Lei; Li, Haiyang

    2016-06-01

    Malodorous hydrogen sulfide (H2S) gas often exists in the sewer system and associates with the problems of releasing the dangerous odor to the atmosphere and causing sewer pipe to be corroded. A simple method is in demand for real-time measuring H2S level in the sewer gas. In this paper, an innovated method based on dopant-assisted negative photoionization ion mobility spectrometry (DANP-IMS) with on-line semiconductor cooling inlet was put forward and successfully applied for the real-time measurement of H2S in sewer gas. The influence of moisture was effectively reduced via an on-line cooling method and a non-equilibrium dilution with drift gas. The limits of quantitation for the H2S in ≥60% relative humidity air could be obtained at ≤79.0ng L(-1) with linear ranges of 129-2064ng L(-1). The H2S concentration in a sewer manhole was successfully determined while its product ions were identified by an ion-mobility time-of-fight mass spectrometry. Finally, the correlation between sewer H2S concentration and the daily routines and habits of residents was investigated through hourly or real-time monitoring the variation of sewer H2S in manholes, indicating the power of this DANP-IMS method in assessing the H2S concentration in sewer system. PMID:27130121

  12. A study of calibrant selection in measurement of carbohydrate and peptide ion-neutral collision cross sections by traveling wave ion mobility spectrometry.

    PubMed

    Gelb, Abby S; Jarratt, Rebecca E; Huang, Yuting; Dodds, Eric D

    2014-11-18

    While ion-neutral collision cross sections (CCSs) can be directly calculated from drift tube ion mobility spectrometry (DTIMS) data, measurements made using the more recently introduced traveling wave ion mobility spectrometry (TWIMS) technique are usually calibrated using standards with known CCS. Presently, there remains some question regarding how selection of calibrants influences TWIMS CCS measurements. This is of particular concern when calibrants of the same molecular class (e.g., carbohydrate versus peptide) or charge state as the unknowns are unavailable. This report presents a study of calibrant ion influence on CCS determination via TWIMS. Drift times from TWIMS were calibrated to CCSs using either carbohydrates or peptides as standards. These calibrations were then applied to other carbohydrates and peptides with known CCSs, and the errors of the measurements were assessed. In addition, calibrations with standards having charge states either matched or mismatched with those of the target analytes were applied and evaluated for accuracy. The use of carbohydrates to calibrate peptide CCSs and vice versa was found to introduce errors only modestly larger than the inherent uncertainties of the measurements (on average, 1.0%). Charge state mismatching while the same molecular class of calibrant and analyte was maintained yielded larger errors (on average, 3.5%). Mismatching of both calibrant molecular class and charge state resulted in the largest errors (on average, 4.7%). These results suggest that matching of both molecular class and charge state is recommended when possible, while matching at least the charge state is strongly advisable. PMID:25329513

  13. Differential Ion Mobility Separations in up to 100 % Helium Using Microchips

    PubMed Central

    Shvartsburg, Alexandre A.; Ibrahim, Yehia M.; Smith, Richard D.

    2014-01-01

    The performance of differential IMS (FAIMS) analyzers is much enhanced by gases comprising He, especially He/N2 mixtures. However, electrical breakdown has limited the He fraction to ~50 %–75 %, depending on the field strength. By the Paschen law, the threshold field for breakdown increases at shorter distances. This allows FAIMS using chips with microscopic channels to utilize much stronger field intensities (E) than “full-size” analyzers with wider gaps. Here we show that those chips can employ higher He fractions up to 100 %. Use of He-rich gases improves the resolution and resolution/sensitivity balance substantially, although less than for full-size analyzers. The optimum He fraction is ~80 %, in line with first-principles theory. Hence, one can now measure the dependences of ion mobility on E in pure He, where ion-molecule cross section calculations are much more tractable than in other gases that form deeper and more complex interaction potentials. This capability may facilitate quantitative modeling of high-field ion mobility behavior and, thus, FAIMS separation properties, which would enable a priori extraction of structural information about the ions. PMID:24402673

  14. Determination of human insulin and its analogues in human blood using liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS).

    PubMed

    Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2014-01-01

    The qualitative and quantitative determination of insulin from human blood samples is an emerging topic in doping controls as well as in other related disciplines (e.g. forensics). Beside the therapeutic use, insulin represents a prohibited, performance enhancing substance in sports drug testing. In both cases accurate, sensitive, specific, and unambiguous determination of the target peptide is of the utmost importance. The challenges concerning identifying insulins in blood by liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS) are detecting the basal concentrations of approximately 0.2 ng/mL and covering the hyperinsulinaemic clamps at > 3 ng/mL simultaneously using up to 200 μL of plasma or serum. This is achieved by immunoaffinity purification of the insulins with magnetic beads and subsequent separation by micro-scale liquid chromatography coupled to ion mobility / high resolution mass spectrometry. The method includes human insulin as well as the synthetic or animal analogues insulin aspart, glulisine, glargine, detemir, lispro, bovine, and porcine insulin. The method validation shows reliable results considering specificity, limit of detection (0.2 ng/mL except for detemir: 0.8 ng/mL), limit of quantification (0.5 ng/mL for human insulin), precision (CV < 20%), linearity (r > 0.99), recovery, accuracy (>90%), robustness (plasma/serum), and ion suppression. For quantification of human insulin a labelled internal standard ([[(2) H10 ]-Leu(B6,B11,B15,B17) ] - human Insulin) is introduced. By means of the additional ion mobility separation of the different analogues, the chromatographic run time is shortened to 8 min without losing specificity. As proof-of-concept, the procedure was successfully applied to different blood specimens from diabetic patients receiving recombinant synthetic analogues. PMID:25219675

  15. Ion mobility spectrometry-mass spectrometry examination of the structures, stabilities, and extents of hydration of dimethylamine-sulfuric acid clusters.

    PubMed

    Thomas, Jikku M; He, Siqin; Larriba-Andaluz, Carlos; DePalma, Joseph W; Johnston, Murray V; Hogan, Christopher J

    2016-08-17

    We applied an atmospheric pressure differential mobility analyzer (DMA) coupled to a time-of-flight mass spectrometer to examine the stability, mass-mobility relationship, and extent of hydration of dimethylamine-sulfuric acid cluster ions, which are of relevance to nucleation in ambient air. Cluster ions were generated by electrospray ionization and were of the form: [H((CH3)2NH)x(H2SO4)y](+) and [(HSO4)((CH3)2NH)x(H2SO4)y](-), where 4 ≤ x ≤ 8, and 5 ≤ y ≤ 12. Under dry conditions, we find that positively charged cluster ions dissociated via loss of both multiple dimethylamine and sulfuric acid molecules after mobility analysis but prior to mass analysis, and few parent ions were detected in the mass spectrometer. Dissociation also occurred for negative ions, but to a lesser extent than for positive ions for the same mass spectrometer inlet conditions. Under humidified conditions (relative humidities up to 30% in the DMA), positively charged cluster ion dissociation in the mass spectrometer inlet was mitigated and occurred primarily by H2SO4 loss from ions containing excess acid molecules. DMA measurements were used to infer collision cross sections (CCSs) for all identifiable cluster ions. Stokes-Millikan equation and diffuse/inelastic gas molecule scattering predicted CCSs overestimate measured CCSs by more than 15%, while elastic-specular collision model predictions are in good agreement with measurements. Finally, cluster ion hydration was examined by monitoring changes in CCSs with increasing relative humidity. All examined cluster ions showed a modest amount of water molecule adsorption, with percentage increases in CCS smaller than 10%. The extent of hydration correlates directly with cluster ion acidity for positive ions. PMID:27485283

  16. Negative corona discharge-ion mobility spectrometry as a detection system for low density extraction solvent-based dispersive liquid-liquid microextraction.

    PubMed

    Ebrahimi, Amir; Jafari, Mohammad T

    2015-03-01

    This paper deals with a method based on negative corona discharge ionization ion mobility spectrometry (NCD-IMS) for the analysis of ethion (as an organophosphorus pesticide). The negative ions such as O2(-) and NO(x)(-) were eliminated from the background spectrum to increase the instrument sensitivity. The method was used to specify the sample extracted via dispersive liquid-liquid microextraction (DLLME) based on low density extraction solvent. The ion mobility spectrum of ethion in the negative mode and the reduced mobility value for its ion peak are firstly reported and compared with those of the positive mode. In order to combine the low density solvent DLLME directly with NCD-IMS, cyclohexane was selected as the extraction solvent, helping us to have a direct injection up to 20 µL solution, without any signal interference. The method was exhaustively validated in terms of sensitivity, enrichment factor, relative recovery, and repeatability. The linear dynamic range of 0.2-100.0 µg L(-1), detection limit of 0.075 µg L(-1), and the relative standard deviation (RSD) of about 5% were obtained for the analysis of ethion through this method. The average recoveries were calculated about 68% and 92% for the grape juice and underground water, respectively. Finally, some real samples were analyzed and the feasibility of the proposed method was successfully verified by the efficient extraction of the analyte using DLLME before the analysis by NCD-IMS. PMID:25618728

  17. Comparison of reactant and analyte ions for ⁶³Nickel, corona discharge, and secondary electrospray ionization sources with ion mobility-mass spectrometry.

    PubMed

    Crawford, C L; Hill, H H

    2013-03-30

    (63)Nickel radioactive ionization ((63)Ni) is the most common and widely used ion source for ion mobility spectrometry (IMS). Regulatory, financial, and operational concerns with this source have promoted recent development of non-radioactive sources, such as corona discharge ionization (CD), for stand-alone IMS systems. However, there has been no comparison of the negative ion species produced by all three sources in the literature. This study compares the negative reactant and analyte ions produced by three sources on an ion mobility-mass spectrometer: conventional (63)Ni, CD, and secondary electrospray ionization (SESI). Results showed that (63)Ni and SESI produced the same reactant ion species while CD produced only the nitrate monomer and dimer ions. The analyte ions produced by each ion source were the same except for the CD source which produced a different ion species for the explosive RDX than either the (63)Ni or SESI source. Accurate and reproducible reduced mobility (K0) values, including several values reported here for the first time, were found for each explosive with each ion source. Overall, the SESI source most closely reproduced the reactant ion species and analyte ion species profiles for (63)Ni. This source may serve as a non-radioactive, robust, and flexible alternative for (63)Ni. PMID:23598216

  18. Structure of aldehyde cluster ions in the gas phase, according to data from ion mobility spectrometry and ab initio calculations

    NASA Astrophysics Data System (ADS)

    Lantsuzskaya (Krisilova), E. V.; Krisilov, A. V.; Levina, A. M.

    2015-09-01

    Ion-mobility spectra of a set of aliphatic linear aldehydes with the number of carbon atoms from 3 to 7 are obtained. Values of the mobility corresponding to two most intense peaks, considered to be those of a monomer and dimer, are determined according the spectra. Based on mobility, collision cross sections are calculated using the Mason-Schamp equation. The linear increase in the collision cross sections upon an increase in molecular weight is determined. According to the experimental results, the contribution to the cross section that has no dependence on molecular weight diminishes with the formation of dimers. It is established using quantum chemical calculations that this is associated with a reduction in the dipole moment upon the formation of dimers.

  19. Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS).

    PubMed

    Zhao, Yuejie; Singh, Arunima; Li, Lingyun; Linhardt, Robert J; Xu, Yongmei; Liu, Jian; Woods, Robert J; Amster, I Jonathan

    2015-10-21

    We validate the utility of ion mobility to measure protein conformational changes induced by the binding of glycosaminoglycan ligands, using the well characterized system of Antithrombin III (ATIII) and Arixtra, a pharmaceutical agent with heparin (Hp) activity. Heparin has been used as a therapeutic anticoagulant drug for several decades through its interaction with ATIII, a serine protease inhibitor that plays a central role in the blood coagulation cascade. This interaction induces conformational changes within ATIII that dramatically enhance the ATIII-mediated inhibition rate. Arixtra is the smallest synthetic Hp containing the specific pentasaccharide sequence required to bind with ATIII. Here we report the first travelling wave ion mobility mass spectrometry (TWIMS) investigation of the conformational changes in ATIII induced by its interaction with Arixtra. Native electrospray ionization mass spectrometry allowed the gentle transfer of the native topology of ATIII and ATIII-Arixtra complex. IM measurements of ATIII and ATIII-Arixtra complex showed a single structure, with well-defined collisional cross section (CCS) values. An average 3.6% increase in CCS of ATIII occurred as a result of its interaction with Arixtra, which agrees closely with the theoretical estimation of the change in CCS based on protein crystal structures. A comparison of the binding behavior of ATIII under both denaturing and non-denaturing conditions confirmed the significance of a folded tertiary structure of ATIII for its biological activity. A Hp oligosaccharide whose structure is similar to Arixtra but missing the 3-O sulfo group on the central glucosamine residue showed a dramatic decrease in binding affinity towards ATIII, but no change in the mobility behavior of the complex, consistent with prior studies that suggested that 3-O sulfation affects the equilibrium constant for binding to ATIII, but not the mode of interaction. In contrast, nonspecific binding by a Hp

  20. Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS)

    PubMed Central

    Zhao, Yuejie; Singh, Arunima; Li, Lingyun; Linhardt, Robert J.; Xu, Yongmei; Liu, Jian; Woods, Robert J.

    2015-01-01

    We validate the utility of ion mobility to measure protein conformational changes induced by the binding of glycosaminoglycan ligands, using the well characterized system of Antithrombin III (ATIII) and Arixtra, a pharmaceutical agent with heparin (Hp) activity. Heparin has been used as a therapeutic anticoagulant drug for several decades through its interaction with ATIII, a serine protease inhibitor that plays a central role in the blood coagulation cascade. This interaction induces conformational changes within ATIII that dramatically enhance the ATIII-mediated inhibition rate. Arixtra is the smallest synthetic Hp containing the specific pentasaccharide sequence required to bind with ATIII. Here we report the first travelling wave ion mobility mass spectrometry (TWIMS) investigation of the conformational changes in ATIII induced by its interaction with Arixtra. Native electrospray ionization mass spectrometry allowed the gentle transfer of the native topology of ATIII and ATIII–Arixtra complex. IM measurements of ATIII and ATIII–Arixtra complex showed a single structure, with well-defined collisional cross section (CCS) values. An average 3.6% increase in CCS of ATIII occurred as a result of its interaction with Arixtra, which agrees closely with the theoretical estimation of the change in CCS based on protein crystal structures. A comparison of the binding behavior of ATIII under both denaturing and non-denaturing conditions confirmed the significance of a folded tertiary structure of ATIII for its biological activity. A Hp oligosaccharide whose structure is similar to Arixtra but missing the 3-O sulfo group on the central glucosamine residue showed a dramatic decrease in binding affinity towards ATIII, but no change in the mobility behavior of the complex, consistent with prior studies that suggested that 3-O sulfation affects the equilibrium constant for binding to ATIII, but not the mode of interaction. In contrast, nonspecific binding by a Hp

  1. Application of Ion Mobility-Mass Spectrometry to the Study of Ionic Clusters: Investigation of Cluster Ions with Stable Sizes and Compositions

    PubMed Central

    Ohshimo, Keijiro; Komukai, Tatsuya; Takahashi, Tohru; Norimasa, Naoya; Wu, Jenna Wen Ju; Moriyama, Ryoichi; Koyasu, Kiichirou; Misaizu, Fuminori

    2014-01-01

    Stable cluster sizes and compositions have been investigated for cations and anions of ionic bond clusters such as alkali halides and transition metal oxides by ion mobility-mass spectrometry (IM-MS). Usually structural information of ions can be obtained from collision cross sections determined in IM-MS. In addition, we have found that stable ion sizes or compositions were predominantly produced in a total ion mass spectrum, which was constructed from the IM-MS measurement. These stable species were produced as a result of collision induced dissociations of the ions in a drift cell. We have confirmed this result in the sodium fluoride cluster ions, in which cuboid magic number cluster ions were predominantly observed. Next the stable compositions, which were obtained for the oxide systems of the first row transition metals, Ti, Fe, and Co, are characteristic for each of the metal oxide cluster ions. PMID:26819887

  2. Towards monitoring real-time cellular response using an integrated microfluidics-MALDI/nESI-ion mobility-mass spectrometry platform

    PubMed Central

    Enders, Jeffrey R.; Marasco, Christina C.; Kole, Ayeeshik; Nguyen, Bao; Sundarapandian, Sevugarajan; Seale, Kevin T.; Wikswo, John P.; McLean, John A.

    2014-01-01

    The combination of microfluidic cell trapping devices with ion mobility-mass spectrometry offers the potential for elucidating in real time the dynamic responses of small populations of cells to paracrine signals, changes in metabolite levels, and delivery of drugs and toxins. Preliminary experiments examining peptides in methanol and recording the interactions of yeast and Jurkat cells with their superfusate have identified instrumental setup and control parameters and on-line desalting procedures. Numerous initial experiments demonstrate and validate this new instrumental platform. Future outlooks and potential applications are addressed, specifically how this instrumentation may be used for fully automated systems biology studies of the significantly interdependent, dynamic internal workings of cellular metabolic and signaling pathways. PMID:21073240

  3. Direct Infusion Electrospray Ionization - Ion Mobility - High Resolution Mass Spectrometry (DIESI-IM-HRMS) for Rapid Characterization of Potential Bioprocess Streams

    NASA Astrophysics Data System (ADS)

    Munisamy, Sharon M.; Chambliss, C. Kevin; Becker, Christopher

    2012-07-01

    Direct infusion electrospray ionization - ion mobility - high resolution mass spectrometry (DIESI-IM-HRMS) has been utilized as a rapid technique for the characterization of total molecular composition in "whole-sample" biomass hydrolysates and extracts. IM-HRMS data reveal a broad molecular weight distribution of sample components (up to 1100 m/z) and provide trendline isolation of feedstock components from those introduced "in process." Chemical formulas were obtained from HRMS exact mass measurements (with typical mass error less than 5 ppm) and were consistent with structural carbohydrates and other lignocellulosic degradation products. Analyte assignments are supported via IM-MS collision-cross-section measurements and trendline analysis (e.g., all carbohydrate oligomers identified in a corn stover hydrolysate were found to fall within 6 % of an average trendline). These data represent the first report of collision cross sections for several negatively charged carbohydrates and other acidic species occurring natively in biomass hydrolysates.

  4. Increasing conclusiveness of clinical breath analysis by improved baseline correction of multi capillary column - ion mobility spectrometry (MCC-IMS) data.

    PubMed

    Szymańska, Ewa; Tinnevelt, Gerjen H; Brodrick, Emma; Williams, Mark; Davies, Antony N; van Manen, Henk-Jan; Buydens, Lutgarde M C

    2016-08-01

    Current challenges of clinical breath analysis include large data size and non-clinically relevant variations observed in exhaled breath measurements, which should be urgently addressed with competent scientific data tools. In this study, three different baseline correction methods are evaluated within a previously developed data size reduction strategy for multi capillary column - ion mobility spectrometry (MCC-IMS) datasets. Introduced for the first time in breath data analysis, the Top-hat method is presented as the optimum baseline correction method. A refined data size reduction strategy is employed in the analysis of a large breathomic dataset on a healthy and respiratory disease population. New insights into MCC-IMS spectra differences associated with respiratory diseases are provided, demonstrating the additional value of the refined data analysis strategy in clinical breath analysis. PMID:26879424

  5. Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry

    SciTech Connect

    Webb, Ian K.; Garimella, Venkata BS; Tolmachev, Aleksey V.; Chen, Tsung-Chi; Zhang, Xinyu; Norheim, Randolph V.; Prost, Spencer A.; Lamarche, Brian L.; Anderson, Gordon A.; Ibrahim, Yehia M.; Smith, Richard D.

    2014-09-05

    We report on the performance of Structures for Lossless Ion Manipulation (SLIM) devices as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM device and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central ‘rung’ electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2-6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning the RF on the rung electrodes and DC on the guard electrodes; however, both resolving power and ion transmission showed a dependence on these voltages and the best conditions for both were > 300 Vp-p RF (685 kHz) and 7-11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R~58), showing that the negative “racetrack” effect from turning around a corner can be successfully avoided, as well as the capability for essentially lossless ion transmission.

  6. Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry

    PubMed Central

    2015-01-01

    We report on the performance of structures for lossless ion manipulation (SLIM) as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM, demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central “rung” electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2–6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a significant range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning RF on the rung electrodes and DC on the guard electrodes. However, both resolving power and ion transmission showed a dependence on these voltages, and the best conditions for both were >300 Vp-p RF (685 kHz) and 7–11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R ∼ 58), showing that degraded resolution from a “racetrack” effect from turning around a corner can be successfully avoided, and the capability also was maintained for essentially lossless ion transmission. PMID:25152066

  7. Structural characterization of synthetic polymers and copolymers using multidimensional mass spectrometry interfaced with thermal degradation, liquid chromatography and/or ion mobility separation

    NASA Astrophysics Data System (ADS)

    Alawani, Nadrah

    This dissertation focuses on coupling mass spectrometry (MS) and tandem mass spectrometry (MS/MS) to thermal degradation, liquid chromatography (LC) and/or ion mobility (IM) spectrometry for the characterization of complex mixtures. In chapter II, an introduction of the history and the principles of MS and LC are discussed. Chapter III illustrates the materials and instrumentation used to complete this dissertation. Polyethers have been characterized utilizing MS/MS, as presented in Chapter IV and Chapter VI. Diblock copolymers of polyethylene oxide and polycaprolactone, PEO-b-PCL, have been characterized by matrix-assisted laser desorption/ionization quadrupole/time-of-flight mass spectrometry (MALDI-Q/ToF) and LC-MS/MS (Chapter V). Thermoplastic elastomers have been characterized by thermal degradation using an atmospheric solids analysis probe (ASAP) and ion mobility mass spectrometry (IM-MS), as discussed in Chapter VII. Interfacing separation techniques with mass spectrometry permitted the detection of species present with low concentration in complex materials and improved the sensitivity of MS. In chapter IV, the fragmentation mechanisms in MS/MS experiments of cyclic and linear poly(ethylene oxide) macroinitiators are discussed. This study aimed at determining the influence of end groups on the fragmentation pathways. In the study reported in Chapter V, ultra high performance liquid chromatography (UHPLC) was interfaced with MS and MS/MS to achieve the separation and in-depth characterization and separation of amphiphilic diblock copolymers (PEO- b-PCL) in which the architecture of the PEO block is linear or cyclic. Applying UPLC-MS and UPLC-MS/MS provides fast accurate information about the number and type of the blocks in the copolymers. Chapter VI reports MS/MS and IM-MS analyses which were performed to elucidate the influence of molecular size and collision energy on the fragmentation pathways of polyethers subjected to collisionally activated

  8. Gas-Phase Structure of Amyloid-β (12 - 28) Peptide Investigated by Infrared Spectroscopy, Electron Capture Dissociation and Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Le, Thi Nga; Poully, Jean Christophe; Lecomte, Frédéric; Nieuwjaer, Nicolas; Manil, Bruno; Desfrançois, Charles; Chirot, Fabien; Lemoine, Jerome; Dugourd, Philippe; van der Rest, Guillaume; Grégoire, Gilles

    2013-12-01

    The gas-phase structures of doubly and triply protonated Amyloid-β12-28 peptides have been investigated through the combination of ion mobility (IM), electron capture dissociation (ECD) mass spectrometry, and infrared multi-photon dissociation (IRMPD) spectroscopy together with theoretical modeling. Replica-exchange molecular dynamics simulations were conducted to explore the conformational space of these protonated peptides, from which several classes of structures were found. Among the low-lying conformers, those with predicted diffusion cross-sections consistent with the ion mobility experiment were further selected and their IR spectra simulated using a hybrid quantum mechanical/semiempirical method at the ONIOM DFT/B3LYP/6-31 g(d)/AM1 level. In ECD mass spectrometry, the c/z product ion abundance (PIA) has been analyzed for the two charge states and revealed drastic differences. For the doubly protonated species, N - Cα bond cleavage occurs only on the N and C terminal parts, while a periodic distribution of PIA is clearly observed for the triply charged peptides. These PIA distributions have been rationalized by comparison with the inverse of the distances from the protonated sites to the carbonyl oxygens for the conformations suggested from IR and IM experiments. Structural assignment for the amyloid peptide is then made possible by the combination of these three experimental techniques that provide complementary information on the possible secondary structure adopted by peptides. Although globular conformations are favored for the doubly protonated peptide, incrementing the charge state leads to a conformational transition towards extended structures with 310- and α-helix motifs.

  9. Ultra Performance Liquid Chromatography Ion Mobility Time-of-Flight Mass Spectrometry Characterization of Naphthenic Acids Species from Oil Sands Process-Affected Water.

    PubMed

    Huang, Rongfu; McPhedran, Kerry N; Gamal El-Din, Mohamed

    2015-10-01

    Ultraperformance liquid chromatography ion mobility time-of-flight mass spectrometry (UPLC-IM-TOFMS), integrating traveling wave ion mobility spectrometry (TWIMS) with negative electrospray ionization (ESI) mode, was used to achieve two-dimensional (2D) separation (drift vs retention times) of naphthenic acids (NAs). Unprocessed and ozonated commercial NAs were used for method development. Only O2-NAs were found in unprocessed NAs with ozonation creating O3-NAs and O4-NAs. Unprocessed and ozonated oil sands process-affected waters (OSPW) were examined to validate the method for complex matrix NAs. Ozonation increased the x number for Ox-NAs (2 ≤ x ≤ 5) and also impacted the -Z number distribution. OSPW extracted using dichloromethane removed the potential for sample matrix impacts and was used for MS/MS NAs characterization. The Ox-NAs (2 ≤ x ≤ 6) were identified with O2-NAs separated into three clusters indicating isobaric and isomeric species. MS/MS was used to verify compounds, while also indicating the presence of CH3CH2S- NAs groups. This result may be useful for future studies of sulfur-NAs fate, toxicity, and treatment. Overall, the value-added information provided by UPLC-IM-TOFMS makes it a promising analytical technique for analysis of NAs in complex OSPW samples. Moreover, this methodology can be used for other matrices to investigate relative molecular sizes and to separate complex species (e.g., fatty acids, lipids), making it beneficial for environmental and bioanalytical applications. PMID:26322530

  10. Effects of drift gas on collision cross sections of a protein standard in linear drift tube and traveling wave ion mobility mass spectrometry.

    PubMed

    Jurneczko, Ewa; Kalapothakis, Jason; Campuzano, Iain D G; Morris, Michael; Barran, Perdita E

    2012-10-16

    There has been a significant increase in the use of ion mobility mass spectrometry (IM-MS) to investigate conformations of proteins and protein complexes following electrospray ionization. Investigations which employ traveling wave ion mobility mass spectrometry (TW IM-MS) instrumentation rely on the use of calibrants to convert the arrival times of ions to collision cross sections (CCS) providing "hard numbers" of use to structural biology. It is common to use nitrogen as the buffer gas in TW IM-MS instruments and to calibrate by extrapolating from CCS measured in helium via drift tube (DT) IM-MS. In this work, both DT and TW IM-MS instruments are used to investigate the effects of different drift gases (helium, neon, nitrogen, and argon) on the transport of multiply charged ions of the protein myoglobin, frequently used as a standard in TW IM-MS studies. Irrespective of the drift gas used, recorded mass spectra are found to be highly similar. In contrast, the recorded arrival time distributions and the derived CCS differ greatly. At low charge states (7 ≤ z ≤ 11) where the protein is compact, the CCS scale with the polarizability of the gas; this is also the case for higher charge states (12 ≤ z ≤ 22) where the protein is more unfolded for the heavy gases (neon, argon, and nitrogen) but not the case for helium. This is here interpreted as a different conformational landscape being sampled by the lighter gas and potentially attributable to increased field heating by helium. Under nanoelectrospray ionization (nESI) conditions, where myoglobin is sprayed from an aqueous solution buffered to pH 6.8 with 20 mM ammonium acetate, in the DT IM-MS instrument, each buffer gas can yield a different arrival time distribution (ATD) for any given charge state. PMID:22974196

  11. Final Technical Report for DE-FG02-06ER15835: Chemical Imaging with 100nm Spatial Resolution: Combining High Resolution Flurosecence Microscopy and Ion Mobility Mass Spectrometry

    SciTech Connect

    Buratto, Steven K.

    2013-09-03

    We have combined, in a single instrument, high spatial resolution optical microscopy with the chemical specificity and conformational selectivity of ion mobility mass spectrometry. We discuss the design and construction of this apparatus as well as our efforts in applying this technique to thin films of molecular semiconductor materials.

  12. Using differential mobility spectrometry to measure ion solvation: an examination of the roles of solvents and ionic structures in separating quinoline-based drugs.

    PubMed

    Liu, Chang; Le Blanc, J C Yves; Shields, Jefry; Janiszewski, John S; Ieritano, Christian; Ye, Gene F; Hawes, Gillian F; Hopkins, W Scott; Campbell, J Larry

    2015-10-21

    Understanding the mechanisms and energetics of ion solvation is critical in many scientific areas. Here, we present a methodlogy for studying ion solvation using differential mobility spectrometry (DMS) coupled to mass spectrometry. While in the DMS cell, ions experience electric fields established by a high frequency asymmetric waveform in the presence of a desired pressure of water vapor. By observing how a specific ion's behavior changes between the high- and low-field parts of the waveform, we gain knowledge about the aqueous microsolvation of that ion. In this study, we applied DMS to investigate the aqueous microsolvation of protonated quinoline-based drug candidates. Owing to their low binding energies with water, the clustering propensity of 8-substituted quinolinium ions was less than that of the 6- or 7-substituted analogues. We attribute these differences to the steric hinderance presented by subtituents in the 8-position. In addition, these experimental DMS results were complemented by extensive computational studies that determined cluster structures and relative thermodynamic stabilities. PMID:26165786

  13. Optimization of a liquid chromatography ion mobility-mass spectrometry method for untargeted metabolomics using experimental design and multivariate data analysis.

    PubMed

    Tebani, Abdellah; Schmitz-Afonso, Isabelle; Rutledge, Douglas N; Gonzalez, Bruno J; Bekri, Soumeya; Afonso, Carlos

    2016-03-24

    High-resolution mass spectrometry coupled with pattern recognition techniques is an established tool to perform comprehensive metabolite profiling of biological datasets. This paves the way for new, powerful and innovative diagnostic approaches in the post-genomic era and molecular medicine. However, interpreting untargeted metabolomic data requires robust, reproducible and reliable analytical methods to translate results into biologically relevant and actionable knowledge. The analyses of biological samples were developed based on ultra-high performance liquid chromatography (UHPLC) coupled to ion mobility - mass spectrometry (IM-MS). A strategy for optimizing the analytical conditions for untargeted UHPLC-IM-MS methods is proposed using an experimental design approach. Optimization experiments were conducted through a screening process designed to identify the factors that have significant effects on the selected responses (total number of peaks and number of reliable peaks). For this purpose, full and fractional factorial designs were used while partial least squares regression was used for experimental design modeling and optimization of parameter values. The total number of peaks yielded the best predictive model and is used for optimization of parameters setting. PMID:26944989

  14. Differentiation of Compact and Extended Conformations of Di-Ubiquitin Conjugates with Lysine-Specific Isopeptide Linkages by Ion Mobility-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Jung, Ji Eun; Pierson, Nicholas A.; Marquardt, Andreas; Scheffner, Martin; Przybylski, Michael; Clemmer, David E.

    2011-08-01

    Modification of ubiquitin, a key cellular regulatory polypeptide of 76 amino acids, to polyubiquitin conjugates by lysine-specific isopeptide linkage at one of its seven lysine residues has been recognized as a central pathway determining its biochemical properties and cellular functions. Structural details and differences of distinct lysine-isopeptidyl ubiquitin conjugates that reflect their different functions and reactivities, however, are only partially understood. Ion mobility spectrometry (IMS) combined with mass spectrometry (MS) has recently emerged as a powerful tool for probing conformations and topology involved in protein interactions by an electric field-driven separation of polypeptide ions through a drift gas. Here we report the conformational characterization and differentiation of Lys63- and Lys48-linked ubiquitin conjugates by IMS-MS. Lys63- and Lys48-linked di-ubiquitin conjugates were prepared by recombinant bacterial expression and by chemical synthesis using a specific chemical ligation strategy, and characterized by high-resolution Fourier transform ion cyclotron resonance mass spectrometry, circular dichroism spectroscopy, and molecular modeling. IMS-MS was found to be an effective tool for the identification of structural differences of ubiquitin complexes in the gas phase. The comparison of collision cross-sections of Lys63- and Lys48-linked di-ubiquitin conjugates showed a more elongated conformation of Lys63-linked di-ubiquitin. In contrast, the Lys48-linked di-ubiquitin conjugate showed a more compact conformation. The IMS-MS results are consistent with published structural data and a comparative molecular modeling study of the Lys63- and Lys48-linked conjugates. The results presented here suggest IMS techniques can provide information that complements MS measurements in differentiating higher-order polyubiquitins and other isomeric protein linkages.

  15. Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Fas apoptotic pathway has been implicated in type 2 diabetes and cardiovascular disease. Although a polymorphism (rs7138803; G'>'A) near the Fas apoptotic inhibitory molecule 2 (FAIM2) locus has been related to obesity, its association with other cardiovascular risk factors and disease remains u...

  16. An integrated electrophoretic mobility control device with split design for signal improvement in liquid chromatography-electrospray ionization mass spectrometry analysis of aminoglycosides using a heptafluorobutyric acid containing mobile phase.

    PubMed

    Hung, Sih-Hua; Yu, Meng-Ju; Wang, Nan-Hsuan; Hsu, Ren-Yu; Wei, Guor-Jien; Her, Guor-Rong

    2016-08-24

    Electrophoretic mobility control (EMC) was used to alleviate the adverse effect of the ion-pairing agent heptafluorobutyric acid (HFBA) in the liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis of aminoglycosides. Aminoglycosides separated by LC were directed to a connecting column before their detection via ESI. Applying an electric field across the connecting column caused the positively charged aminoglycosides to migrate toward the mass spectrometer whereas the HFBA anions remained in the junction reservoir, thus alleviating the ion suppression caused by HFBA. To accommodate the flow rate of a narrow-bore column, minimize the effect of electrophoretic mobility on separation, and facilitate the operation, an integrated EMC device with a split design was fabricated. With the proposed EMC device, the signals of aminoglycosides were enhanced by a factor of 5-85 without affecting the separation efficiency or elution order. For the analysis of aminoglycosides in bovine milk, the proposed approach demonstrates a sensitivity that is at least 10 times below the maximum residue limits set by most countries. PMID:27497008

  17. Characterizing the gas phase ion chemistry of an ion trap mobility spectrometry based explosive trace detector using a tandem mass spectrometer.

    PubMed

    Kozole, Joseph; Tomlinson-Phillips, Jill; Stairs, Jason R; Harper, Jason D; Lukow, Stefan R; Lareau, Richard T; Boudries, Hacene; Lai, Hanh; Brauer, Carolyn S

    2012-09-15

    A commercial-off-the-shelf (COTS) ion trap mobility spectrometry (ITMS) based explosive trace detector (ETD) has been interfaced to a triple quadrupole mass spectrometer (MS/MS) for the purpose of characterizing the gas phase ion chemistry intrinsic to the ITMS instrument. The overall objective of the research is to develop a fundamental understanding of the gas phase ionization processes in the ITMS based ETD to facilitate the advancement of its operational effectiveness as well as guide the development of next generation ETDs. Product ion masses, daughter ion masses, and reduced mobility values measured by the ITMS/MS/MS configuration for a suite of nitro, nitrate, and peroxide containing explosives are reported. Molecular formulas, molecular structures, and ionization pathways for the various product ions are inferred using the mass and mobility data in conjunction with density functional theory. The predominant product ions are identified as follows: [TNT-H](-) for trinitrotoluene (TNT), [RDX+Cl](-) for cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), [NO(3)](-) for ethylene glycol dinitrate (EGDN), [NG+NO(3)](-) for nitroglycerine (NG), [PETN+NO(3)](-) for pentaerythritol tetranitrate (PETN), [HNO(3)+NO(3)](-) for ammonium nitrate (NH(4)NO(3)), [HMTD-NC(3)H(6)O(3)+H+Cl](-) for hexamethylene triperoxide diamine (HMTD), and [(CH(3))(2)CNH(2)](+) for triacetone triperoxide (TATP). The predominant ionization pathways for the formation of the various product ions are determined to include proton abstraction, ion-molecule attachment, autoionization, first-order and multi-order thermolysis, and nucleophilic substitution. The ion trapping scheme in the reaction region of the ITMS instrument is shown to increase predominant ion intensities relative to the secondary ion intensities when compared to non-ion trap operation. PMID:22967626

  18. Quantitative analysis of dendron-conjugated cisplatin-complexed gold nanoparticles using scanning particle mobility mass spectrometry

    NASA Astrophysics Data System (ADS)

    Tsai, De-Hao; Cho, Tae Joon; Elzey, Sherrie R.; Gigault, Julien C.; Hackley, Vincent A.

    2013-05-01

    We report a high-resolution and traceable method to quantify the drug loading on nanoparticle-based cancer therapeutics, and demonstrate this method using a model cisplatin functionalized dendron-gold nanoparticle (AuNP) conjugate. Electrospray differential mobility analysis (ES-DMA) provides upstream size classification based on the electrical mobility of AuNP conjugates in aerosol form following electrospray conversion from the aqueous suspension. A condensation particle counter (CPC) and inductively coupled plasma mass spectrometer (ICP-MS) provide the principal downstream quantification. CPC and ICP-MS yield complementary number-based and elemental mass-based particle size distributions, respectively. Conjugation using three different dendron formulations was differentiated based on changes in the mean mobility particle size. The subsequent cisplatin complexation to the dendron conjugates was quantified by coupling ES-DMA with ICP-MS. Discrete AuNP clusters (e.g., dimers, trimers) could be resolved from the relative quantity of atoms (i.e., Au and Pt) per particle after separation by ES-DMA. Surface density of cisplatin on Au was shown to be proportional to the density of carboxylic groups present and was independent of the state of AuNP clustering. Additionally, we found that colloidal stability of the conjugate is inversely proportional to the surface loading of cisplatin. This study demonstrates a prototype methodology to provide traceable quantification and to determine other important formulation factors relevant to therapeutic performance.We report a high-resolution and traceable method to quantify the drug loading on nanoparticle-based cancer therapeutics, and demonstrate this method using a model cisplatin functionalized dendron-gold nanoparticle (AuNP) conjugate. Electrospray differential mobility analysis (ES-DMA) provides upstream size classification based on the electrical mobility of AuNP conjugates in aerosol form following electrospray conversion

  19. Global structural changes of an ion channel during its gating are followed by ion mobility mass spectrometry

    PubMed Central

    Konijnenberg, Albert; Yilmaz, Duygu; Ingólfsson, Helgi I.; Dimitrova, Anna; Marrink, Siewert J.; Li, Zhuolun; Vénien-Bryan, Catherine; Sobott, Frank; Koçer, Armağan

    2014-01-01

    Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase using native ion mobility–mass spectrometry (IM-MS). By using IM-MS, we could detect the native mass of MscL from Escherichia coli, determine various global structural changes during its gating by measuring the rotationally averaged collision cross-sections, and show that it can function in the absence of a lipid bilayer. We could detect global conformational changes during MscL gating as small as 3%. Our findings will allow studying native structure of many other membrane proteins. PMID:25404294

  20. Electrospray Quadrupole Travelling Wave Ion Mobility Time-of-Flight Mass Spectrometry for the Detection of Plasma Metabolome Changes Caused by Xanthohumol in Obese Zucker (fa/fa) Rats

    PubMed Central

    Wickramasekara, Samanthi I.; Zandkarimi, Fereshteh; Morré, Jeff; Kirkwood, Jay; Legette, LeeCole; Jiang, Yuan; Gombart, Adrian F.; Stevens, Jan F.; Maier, Claudia S.

    2013-01-01

    This study reports on the use of traveling wave ion mobility quadrupole time-of-flight (ToF) mass spectrometry for plasma metabolomics. Plasma metabolite profiles of obese Zucker fa/fa rats were obtained after the administration of different oral doses of Xanthohumol; a hop-derived dietary supplement. Liquid chromatography coupled data independent tandem mass spectrometry (LC-MSE) and LC-ion mobility spectrometry (IMS)-MSE acquisitions were conducted in both positive and negative modes using a Synapt G2 High Definition Mass Spectrometry (HDMS) instrument. This method provides identification of metabolite classes in rat plasma using parallel alternating low energy and high energy collision spectral acquisition modes. Data sets were analyzed using pattern recognition methods. Statistically significant (p < 0.05 and fold change (FC) threshold > 1.5) features were selected to identify the up-/down-regulated metabolite classes. Ion mobility data visualized using drift scope software provided a graphical read-out of differences in metabolite classes. PMID:24958146

  1. Analysis of psychoactive cathinones and tryptamines by electrospray ionization atmospheric pressure ion mobility time-of-flight mass spectrometry.

    PubMed

    Kanu, A Bakarr; Brandt, Simon D; Williams, Mike D; Zhang, Nancy; Hill, Herbert H

    2013-09-17

    The ability to use positive ion monitoring mode with an atmospheric pressure ion mobility time-of-flight mass spectrometer (APIM(tof)MS) to detect psychoactive cathinones and tryptamines from aqueous phase samples was evaluated. The study used a traditional electrospray ionization (ESI) source for sample introduction and ionization. A total of four cathinones (mephedrone, butylone, 4-Me-PPP, and 4-MEC) and five tryptamines (5-EtO-DPT, 5-EtO-DALT, 5-EtO-MIPT, 5-EtO-ALCHT, and 5-EtO-2MALET) were investigated, and we report on parent ions, collision induced dissociation (CID) fragment ions, reduced mobility (Ko), mass flight times, and detection limits obtained from a single instrument run for the psychoactive substances. Detection limits reported ranged from 3 to 11 μM concentration for the compounds studied. This detection limit range corresponded to 1-5 ng of material needed for improved detection on the instrument. This article demonstrates that it was possible to use a single instrument platform for the separation, detection, and identification of cathinones and tryptamines in less than 1 min. The application holds great promise for detecting and identifying a new class of drugs often referred to as "bath salts" or "legal highs" distributed over the Internet. PMID:23875808

  2. Elucidation of conformer preferences for a hydrophobic antimicrobial peptide by vesicle capture-freeze-drying: a preparatory method coupled to ion mobility-mass spectrometry.

    PubMed

    Patrick, John W; Gamez, Roberto C; Russell, David H

    2015-01-01

    A novel sample preparation method to probe the solution phase structure of dimerized Gramicidin A (GA) inserted into lipid vesicle bilayers is described. This method, termed vesicle capture-freeze-drying (VCFD), when coupled with electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS), successfully demonstrates the first evidence for the preservation of membrane-bound structure in the analysis of solution phase conformers retained into the gas phase. The extremely hydrophobic character of GA ensures that only membrane-bound conformations are captured and subsequently monitored when samples are prepared using VCFD, removing a barrier that has prevented previous attempts at direct analysis using mass spectrometry. Solution-phase physicochemical interactions of GA influenced by lipid acyl chain length and extent of acyl chain unsaturation can now be probed by monitoring the conformer preferences using IM-MS. Increasing the acyl chain length from 12 to 22 carbons yields [2GA + 2Na](2+) IM-MS profiles with reduced conformer microheterogeneity. POPC (16:0, 18:1 PC), a lipid possessing a single acyl chain unsaturation point, yields the highest abundance of the single stranded head to head (SSHH) conformer. Conformer preferences adopted in the lipid bilayer are maintained as GA dimers travel from the solution phase to fully desolvated gas-phase ions demonstrating that distributions observed using ESI-IM-MS unambiguously reflect the ensemble of conformers observed in the solution phase. VCFD-ESI-IM-MS yields novel biophysical insight into the influence of lipid bilayer membranes on conformer preferences and conformer heterogeneity of an important channel-forming membrane peptide. PMID:25522119

  3. Fragmentation, auto-modification and post ionisation proton bound dimer ion formation: the differential mobility spectrometry of low molecular weight alcohols.

    PubMed

    Ruszkiewicz, D M; Thomas, C L P; Eiceman, G A

    2016-08-01

    Differential mobility spectrometry (DMS) is currently being used for environmental monitoring of space craft atmospheres and has been proposed for the rapid assessment of patients at accident and emergency receptions. Three studies investigated hitherto undescribed complexity in the DMS spectra of methanol, ethanol, propan-1-ol and butan-1-ol product ions formed from a (63)Ni ionisation source. 54 000 DMS spectra obtained over a concentration range of 0.01 mg m(-3)(g) to 1.80 g m(-3)(g) revealed the phenomenon of auto-modification of the product ions. This occurred when the neutral vapour concentration exceeded the level required to induce a neutral-ion collision during the low field portion of the dispersion field waveform. Further, post-ionisation cluster-ion formation or protonated monomer/proton bound dimer inter-conversion within the ion-filter was indicated by apparent shifts in the values of the protonated monomer compensation field maximum; indicative of post-ionisation conversion of the protonated monomer to a proton-bound dimer. APCI-DMS-quadrupole mass spectrometry studies enabled the ion dissociation products from dispersion-field heating to be monitored and product ion fragmentation relationships to be proposed. Methanol was not observed to dissociate, while propan-1-ol and butan-1-ol underwent dissociation reactions consistent with dehydration processes that led ultimately to the generation of what is tentatively assigned as a cyclo-C3H3(+) ion (m/z 39) and hydrated protons. Studies of the interaction of ion filter temperature with dispersion-field heating of product ions isolated dissociation/fragmentation product ions that have not been previously described in DMS. The implications of these combined findings with regard to data sharing and data interpretation were highlighted. PMID:27227997

  4. Alignment of retention time obtained from multicapillary column gas chromatography used for VOC analysis with ion mobility spectrometry

    PubMed Central

    Bödeker, Bertram; Jünger, Melanie; Nolte, Jürgen; Vautz, Wolfgang

    2010-01-01

    Multicapillary column (MCC) ion mobility spectrometers (IMS) are increasingly in demand for medical diagnosis, biological applications and process control. In a MCC-IMS, volatile compounds are differentiated by specific retention time and ion mobility when rapid preseparation techniques are applied, e.g. for the analysis of complex and humid samples. Therefore, high accuracy in the determination of both parameters is required for reliable identification of the signals. The retention time in the MCC is the subject of the present investigation because, for such columns, small deviations in temperature and flow velocity may cause significant changes in retention time. Therefore, a universal correction procedure would be a helpful tool to increase the accuracy of the data obtained from a gas-chromatographic preseparation. Although the effect of the carrier gas flow velocity and temperature on retention time is not linear, it could be demonstrated that a linear alignment can compensate for the changes in retention time due to common minor deviations of both the carrier gas flow velocity and the column temperature around the MCC-IMS standard operation conditions. Therefore, an effective linear alignment procedure for the correction of those deviations has been developed from the analyses of defined gas mixtures under various experimental conditions. This procedure was then applied to data sets generated from real breath analyses obtained in clinical studies using different instruments at different measuring sites for validation. The variation in the retention time of known signals, especially for compounds with higher retention times, was significantly improved. The alignment of the retention time—an indispensable procedure to achieve a more precise identification of analytes—using the proposed method reduces the random error caused by small accidental deviations in column temperature and flow velocity significantly. PMID:20512565

  5. Determination of artificial sweeteners in beverages with green mobile phases and high temperature liquid chromatography-tandem mass spectrometry.

    PubMed

    Ordoñez, Edgar Y; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2015-02-15

    A new analytical procedure involving the use of water and a low percentage of ethanol combined to high temperature liquid chromatography-tandem mass spectrometry has been developed for the determination of nine high-intensity sweeteners in a variety of drink samples. The method permitted the analysis in 23min (including column reequilibration) and consuming only 0.85mL of a green organic solvent (ethanol). This methodology provided limits of detection (after 50-fold dilution) in the 0.05-10mg/L range, with recoveries (obtained from five different types of beverages) being in the 86-110% range and relative standard deviation values lower than 12%. Finally, the method was applied to 25 different samples purchased in Spain, where acesulfame and sucralose were the most frequently detected analytes (>50% of the samples) and cyclamate was found over the legislation limit set by the European Union in a sample and at the regulation boundary in three others. PMID:25236212

  6. Enhanced capabilities for imaging gangliosides in murine brain with matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry coupled to ion mobility separation.

    PubMed

    Škrášková, Karolina; Claude, Emmanuelle; Jones, Emrys A; Towers, Mark; Ellis, Shane R; Heeren, Ron M A

    2016-07-15

    The increased interest in lipidomics calls for improved yet simplified methods of lipid analysis. Over the past two decades, mass spectrometry imaging (MSI) has been established as a powerful technique for the analysis of molecular distribution of a variety of compounds across tissue surfaces. Matrix-assisted laser desorption/ionization (MALDI) MSI is widely used to study the spatial distribution of common lipids. However, a thorough sample preparation and necessity of vacuum for efficient ionization might hamper its use for high-throughput lipid analysis. Desorption electrospray ionization (DESI) is a relatively young MS technique. In DESI, ionization of molecules occurs under ambient conditions, which alleviates sample preparation. Moreover, DESI does not require the application of an external matrix, making the detection of low mass species more feasible due to the lack of chemical matrix background. However, irrespective of the ionization method, the final information obtained during an MSI experiment is very complex and its analysis becomes challenging. It was shown that coupling MSI to ion mobility separation (IMS) simplifies imaging data interpretation. Here we employed DESI and MALDI MSI for a lipidomic analysis of the murine brain using the same IMS-enabled instrument. We report for the first time on the DESI IMS-MSI of multiply sialylated ganglioside species, as well as their acetylated versions, which we detected directly from the murine brain tissue. We show that poly-sialylated gangliosides can be imaged as multiply charged ions using DESI, while they are clearly separated from the rest of the lipid classes based on their charge state using ion mobility. This represents a major improvement in MSI of intact fragile lipid species. We additionally show that complementary lipid information is reached under particular conditions when DESI is compared to MALDI MSI. PMID:26922843

  7. Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections.

    PubMed

    Campuzano, Iain; Bush, Matthew F; Robinson, Carol V; Beaumont, Claire; Richardson, Keith; Kim, Hyungjun; Kim, Hugh I

    2012-01-17

    We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (Ω(N(2))) range of 124.5-254.3 Å(2) and the helium collision cross-section (Ω(He)) range of 63.0-178.8 Å(2). Absolute Ω(N(2)) and Ω(He) values for the drug-like calibrants and two diastereomers were measured using a drift-tube instrument with radio frequency (RF) ion confinement. T-wave drift-times for the protonated diastereomers betamethasone and dexamethasone are reproducibly different. Calibration of these drift-times yields T-wave Ω(N(2)) values of 189.4 and 190.4 Å(2), respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in Ω(N(2)) value by only 1 Å(2), even though the resolution of these IM experiments were ∼40 (Ω/ΔΩ). Demonstrated through density functional theory optimized geometries and ionic electrostatic surface potential analysis, the small but measurable mobility difference between the two diastereomers is mainly due to short-range van der Waals interactions with the neutral buffer gas and not long-range charge-induced dipole interactions. The experimental RF-confining drift-tube and T-wave Ω(N(2)) values were also evaluated using a nitrogen based trajectory method, optimized for T-wave operating temperature and pressures, incorporating additional scaling factors to the Lennard-Jones potentials. Experimental Ω(He) values were also compared to the original and optimized helium based trajectory methods. PMID:22141445

  8. Analysis of a Common Cold Virus and Its Subviral Particles by Gas-Phase Electrophoretic Mobility Molecular Analysis and Native Mass Spectrometry

    PubMed Central

    2015-01-01

    Gas-phase electrophoretic mobility molecular analysis (GEMMA) separates nanometer-sized, single-charged particles according to their electrophoretic mobility (EM) diameter after transition to the gas-phase via a nano electrospray process. Electrospraying as a soft desorption/ionization technique preserves noncovalent biospecific interactions. GEMMA is therefore well suited for the analysis of intact viruses and subviral particles targeting questions related to particle size, bioaffinity, and purity of preparations. By correlating the EM diameter to the molecular mass (Mr) of standards, the Mr of analytes can be determined. Here, we demonstrate (i) the use of GEMMA in purity assessment of a preparation of a common cold virus (human rhinovirus serotype 2, HRV-A2) and (ii) the analysis of subviral HRV-A2 particles derived from such a preparation. (iii) Likewise, native mass spectrometry was employed to obtain spectra of intact HRV-A2 virions and empty viral capsids (B-particles). Charge state resolution for the latter allowed its Mr determination. (iv) Cumulatively, the data measured and published earlier were used to establish a correlation between the Mr and EM diameter for a range of globular proteins and the intact virions. Although a good correlation resulted from this analysis, we noticed a discrepancy especially for the empty and subviral particles. This demonstrates the influence of genome encapsulation (preventing analytes from shrinking upon transition into the gas-phase) on the measured analyte EM diameter. To conclude, GEMMA is useful for the determination of the Mr of intact viruses but needs to be employed with caution when subviral particles or even empty viral capsids are targeted. The latter could be analyzed by native MS. PMID:26221912

  9. Compositions and Structures of Vanadium Oxide Cluster Ions VmOn(±) (m = 2-20) Investigated by Ion Mobility Mass Spectrometry.

    PubMed

    Wu, Jenna W J; Moriyama, Ryoichi; Tahara, Hiroshi; Ohshimo, Keijiro; Misaizu, Fuminori

    2016-06-01

    Stable compositions and geometrical structures of vanadium oxide cluster ions, VmOn(±), were investigated by ion mobility mass spectrometry (IM-MS). The most stable compositions of vanadium oxide cluster cations were (V2O4)(V2O5)(m-2)/2(+) and (VO2)(V2O5)(m-1)/2(+), depending on the clusters with even and odd numbers of vanadium atoms. Compositions one-oxygen richer than the cations, such as (V2O5)m/2(-) and (VO3)(V2O5)(m-1)/2(-), were predominantly observed for cluster anions. Assignments of these stable cluster ion compositions, which were determined as a result of collision-induced dissociations in IM-MS, can partly be explained with consideration of spin density distribution. By comparing the experimental collision cross sections (CCSs) obtained from ion mobility measurement with CCSs of the theoretically calculated structures, we confirmed the patterned growth of geometrical structures partially discussed in previous theoretical and spectroscopic studies. We showed that even sized (V2O5)m/2(±) where m = 6-12 had right polygonal prism structures except for the anionic V12O30(-), and for the clusters of odd numbers of vanadium m, cations and anions can either have bridged or pyramid structures. Both of the odd sized structures proposed were derivatives from the even sized right polygonal prism structures. The exception, V12O30(-), which had a CCS almost equal to that of the neighboring smaller V11O28(-), should have a structure of higher density than the right hexagonal prism, in which it was proposed to be a captured pyramid structure, derived from V11O28(-). PMID:27172006

  10. Analysis of amantadine in biological fluids using hollow fiber-based liquid-liquid-liquid microextraction followed by corona discharge ion mobility spectrometry.

    PubMed

    Saraji, Mohammad; Khayamian, Taghi; Mirmahdieh, Shiva; Bidgoli, Ali Akbar Hajialiakbari

    2011-10-15

    A method based on liquid-liquid-liquid microextraction combined with corona discharge ion mobility spectrometry was developed for the analysis of amantadine in human urine and plasma samples. Amantadine was extracted from alkaline aqueous sample as donor phase through a thin phase of organic solvent (n-dodecane) filling the pores of the hollow fiber wall and then back extracted into the organic acceptor phase (methanol) located in the lumen of the hollow fiber. All variables affecting the extraction of analyte including acceptor organic solvent type, concentration of NaOH in donor phase, ionic strength of the sample and extraction time were studied. The linear range was 20-1000 and 5-250 ng/mL for plasma and urine, respectively (r(2)≥0.990). The limits of detection were calculated to be 7.2 and 1.6 ng/mL for plasma and urine, respectively. The relative standard deviation was lower than 8.2% for both urine and plasma samples. The enrichment factors were between 45 and 54. The method was successfully applied for the analysis of amantadine in urine and plasma samples. PMID:21956021

  11. Comparison of two methods for selegiline determination: A flow-injection chemiluminescence method using cadmium sulfide quantum dots and corona discharge ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Khataee, Alireza; Lotfi, Roya; Hasanzadeh, Aliyeh; Iranifam, Mortaza; Zarei, Mahmoud; Joo, Sang Woo

    2016-01-01

    Two analytical approaches including chemiluminescence (CL) and corona discharge ionization ion mobility spectrometry (CD-IMS) were developed for sensitive determination of selegiline (SG). We found that the CL intensity of the KMnO4-Na2S2O3 CL system was significantly enhanced in the presence of L-cysteine capped CdS quantum dots (QDs). A possible CL mechanism for this CL reaction is proposed. In the presence of SG, the enhanced CL system was inhibited. Based on this inhibition, a simple and sensitive flow-injection CL method was proposed for the determination of SG. Under optimum experimental conditions, the decreased CL intensity was proportional to SG concentration in the range of 0.01 to 30.0 mg L- 1. The detection limit (3σ) was 0.004 mg L- 1. Also, SG was determined using CD-IMS, and under optimum conditions of CD-IMS, calibration curves were linear in the range of 0.15 to 42.0 mg L- 1, with a detection limit (3σ) of 0.03 mg L- 1. The precision of the two methods was calculated by analyzing samples containing 5.0 mg L- 1 of SG (n = 11). The relative standard deviations (RSDs%) of the flow-injection CL and CD-IMS methods are 2.17% and 3.83%, respectively. The proposed CL system exhibits a higher sensitivity and precision than the CD-IMS method for the determination of SG.

  12. Detection of piperonal emitted from polymer controlled odor mimic permeation systems utilizing Canis familiaris and solid phase microextraction-ion mobility spectrometry.

    PubMed

    Macias, Michael S; Guerra-Diaz, Patricia; Almirall, José R; Furton, Kenneth G

    2010-02-25

    Currently, in the field of odor detection, there is generally a wider variation in limit of detections (LODs) for canines than instruments. The study presented in this paper introduces an improved protocol for the creation of controlled odor mimic permeation system (COMPS) devices for use as standards in canine training and discusses the canine detection thresholds of piperonal, a starting material for the illicit drug 3,4-methylenedioxymethamphetamine (MDMA), when exposed to these devices. Additionally, this paper describes the first-ever reported direct comparison of solid phase microextraction-ion mobility spectrometry (SPME-IMS) to canine detection for the MDMA odorant, piperonal. The research presented shows the reliability of COMPS devices as low cost field calibrants providing a wide range of odorant concentrations for biological and instrumental detectors. The canine LOD of piperonal emanating from the 100 ng s(-1) COMPS was found to be 1 ng as compared to the SPME-IMS LOD of piperonal in a static, closed system at 2 ng, with a linear dynamic range from 2 ng to 11 ng. The utilization of the COMPS devices would allow for training that will reduce the detection variability between canines and maintain improved consistency for training purposes. Since both SPME and IMS are field portable technologies, it is expected that this coupled method will be useful as a complement to canine detection for the field detection of MDMA. PMID:20044224

  13. Simplifying and expanding the screening for peptides <2 kDa by direct urine injection, liquid chromatography, and ion mobility mass spectrometry.

    PubMed

    Thomas, Andreas; Görgens, Christian; Guddat, Sven; Thieme, Detlef; Dellanna, Frank; Schänzer, Wilhelm; Thevis, Mario

    2016-01-01

    The analysis of low-molecular-mass peptides in doping controls has become a mandatory aspect in sports drug testing and, thus, the number of samples that has to be tested for these analytes has been steadily increasing. Several peptides <2 kDa with performance-enhancing properties are covered by the list of prohibited substances of the World Anti-Doping Agency including Desmopressin, LH-RH, Buserelin, Triptorelin, Leuprolide, GHRP-1, GHRP-2, GHRP-3, GHRP-4, GHRP-5,GHRP-6, Alexamorelin, Ipamorelin, Hexarelin, ARA-290, AOD-9604, TB-500 and Anamorelin. With the presented method employing direct urine injection into a liquid chromatograph followed by ion-mobility time-of-flight mass spectrometry, a facile, specific and sensitive assay for the aforementioned peptidic compounds is provided. The accomplished sensitivity allows for limits of detection between 50 and 500 pg/mL and thus covers the minimum required performance level of 2 ng/mL accordingly. The method is precise (imprecision <20%) and linear in the estimated working range between 0 and 10 ng/mL. The stability of the peptides in urine was tested, and -20°C was found to be the appropriate storage temperature for sports drug testing. Finally, proof-of-concept was shown by analysing elimination study urine samples collected from individuals having administered GHRP-6, GHRP-2, or LHRH. PMID:26578461

  14. Diagnostic filtering to screen polycyclic polyprenylated acylphloroglucinols from Garcinia oblongifolia by ultrahigh performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry.

    PubMed

    Zhang, Hong; Zheng, Dan; Li, Hao-Hao; Wang, Hui; Tan, Hong-Sheng; Xu, Hong-Xi

    2016-03-17

    A novel multistage MS approach, insource collision-induced dissociation (CID) combined with Time Aligned Parallel (TAP) fragmentation, was established to study the fragmentation behavior of polycyclic polyprenylated acylphloroglucinols (PPAPs), which could provide a more reliable fragmentation relationship between precursor and daughter ions. The diagnostic ions for different subtypes of PPAPs and their fragmentation behaviors have been summarized. Moreover, a new and reliable multidimensional analytical workflow that combines ultrahigh performance liquid chromatography (UHPLC), data-independent mass spectrometry (MS(E)), and tandem MS with ion mobility (IM) has been optimized and established for the analysis of PPAPs in the plant Garcinia oblongifolia by diagnostic filtering. Diagnostic fragment ions were used to selectively screen PPAPs from extracts, whereas IM coupled to MS was used to maximize the peak capacity. Under the optimized UHPLC-IM-MS(E) and UHPLC-IM-MS/MS method, 140 PPAPs were detected from the crude extract of G. oblongifolia, and 10 of them were unambiguously identified by comparing them to the reference compounds. Among those PPAPs, 7 pairs of coeluting isobaric PPAPs that were indistinguishable by conventional UHPLC-HRMS alone, were further resolved using UHPLC-IM-MS. It is anticipated that the proposed method will be extended to the rapid screening and characterization of the other targeted or untargeted compounds, especially these coeluting isomers in complex samples. PMID:26920776

  15. Ion Mobility-Mass Spectrometry Reveals Highly-Compact Intermediates in the Collision Induced Dissociation of Charge-Reduced Protein Complexes

    NASA Astrophysics Data System (ADS)

    Bornschein, Russell E.; Niu, Shuai; Eschweiler, Joseph; Ruotolo, Brandon T.

    2016-01-01

    Protocols that aim to construct complete models of multiprotein complexes based on ion mobility and mass spectrometry data are becoming an important element of integrative structural biology efforts. However, the usefulness of such data is predicated, in part, on an ability to measure individual subunits removed from the complex while maintaining a compact/folded state. Gas-phase dissociation of intact complexes using collision induced dissociation is a potentially promising pathway for acquiring such protein monomer size information, but most product ions produced are possessed of high charge states and elongated/string-like conformations that are not useful in protein complex modeling. It has previously been demonstrated that the collision induced dissociation of charge-reduced protein complexes can produce compact subunit product ions; however, their formation mechanism is not well understood. Here, we present new experimental evidence for the avidin (64 kDa) and aldolase (157 kDa) tetramers that demonstrates significant complex remodeling during the dissociation of charge-reduced assemblies. Detailed analysis and modeling indicates that highly compact intermediates are accessed during the dissociation process by both complexes. Here, we present putative pathways that describe the formation of such ions, as well as discuss the broader significance of such data for structural biology applications moving forward.

  16. A novel method for the determination of three volatile organic compounds in exhaled breath by solid-phase microextraction-ion mobility spectrometry.

    PubMed

    Allafchian, Ali Reza; Majidian, Zahra; Ielbeigi, Vahideh; Tabrizchi, Mahmoud

    2016-01-01

    A method was carried out for the quantitative determination of the concentrations of volatile organic compounds (VOCs) using solid-phase microextraction and ion mobility spectrometry (SPME-IMS). This method was optimized and evaluated. The best results were obtained at sorption temperature 70 °C, desorption temperature 200 °C, and extraction time 15 min. Under the optimized conditions, the linear dynamic range was found to be 0.01-4.0 ppb (R(2) > 0.995), 2.3-400 ppm (R(2) > 0.994), and 2.5-76 ppb (R(2) > 0.998) for acetone, acetaldehyde, and acetonitrile, respectively. The detection limits for acetone, acetaldehyde, and acetonitrile were 0.001 ppb, 0.18 ppm, and 0.22 ppb, respectively. As a practical application, the method was applied for the determination of acetone, acetaldehyde, and acetonitrile in human breath matrix. Therefore, the proposed method was found to be effective and simple enough to be strongly recommended for real sample analysis. PMID:26558761

  17. Polypyrrole nanowire as an excellent solid phase microextraction fiber for bisphenol A analysis in food samples followed by ion mobility spectrometry.

    PubMed

    Kamalabadi, Mahdie; Mohammadi, Abdorreza; Alizadeh, Naader

    2016-08-15

    A polypyrrole nanowire coated fiber was prepared and used in head-space solid phase microextraction coupled with ion mobility spectrometry (HS-SPME-IMS) to the analysis of bisphenol A (BPA) in canned food samples, for the first time. This fiber was synthesized by electrochemical oxidation of the monomer in aqueous solution. The fiber characterization by scanning electron microscopy (SEM) revealed that the new fiber exhibited two-dimensional structures with a nanowire morphology. The effects of important extraction parameters on the efficiency of HS-SPME were investigated and optimized. Under the optimum conditions, the linearity of 10-150ngg(-1) and limit of detection (based on S/N=3) of 1ngg(-1) were obtained in BPA analysis. The repeatability (n=5) expressed as the relative standard deviation (RSD%) was 5.8%. At the end, the proposed method was successfully applied to determine BPA in various canned food samples (peas, corns, beans). Relative recoveries were obtained 93-96%. Method validation was conducted by comparing our results with those obtained through HPLC with fluorescence detection (FLD). Compatible results indicate that the proposed method can be successfully used in BPA analysis. This method is simple and cheaper than chromatographic methods, with no need of extra organic solvent consumption and derivatization prior to sample introduction. PMID:27260447

  18. Identification of ion series using ion mobility mass spectrometry: the example of alkyl-benzothiophene and alkyl-dibenzothiophene ions in diesel fuels.

    PubMed

    Maire, Florian; Neeson, Kieran; Denny, Richard; McCullagh, Michael; Lange, Catherine; Afonso, Carlos; Giusti, Pierre

    2013-06-01

    Ion mobility-mass spectrometry (IMMS) has been presented as a promising method for analysis of highly complex mixtures. This coupling adds an additional postionization separation dimension to MS. The IM separation of ions is obtained in the millisecond time scale and can be particularly helpful when chromatographic separation is not possible. For obtaining relevant information about the samples, data processing is usually the bottleneck because of the high amount of data generated with IMMS. In the current work, we present a new workflow using specific comparison software dedicated to IMMS data, which allows one to compare m/z-drift time plots to highlight differences between samples. Two diesel fuels have been compared, i.e., the feed and the product of hydrodesulfurization (HDS) process, and this approach allowed us to clearly highlight the variation of intensity of several ions distributed along the plots of both samples. Accurate mass measurements and post IM collision induced dissociation experiments allowed us to identify two series of polycyclic aromatic sulfur-containing heterocycle (PASH) compounds among the matrix ions. PMID:23638962

  19. Thermal degradation of β-carotene studied by ion mobility atmospheric solid analysis probe mass spectrometry: full product pattern and selective ionization enhancement.

    PubMed

    Xiao, Xiaoyin; Miller, Lance L; Bernstein, Robert; Hochrein, James M

    2016-04-01

    Atmospheric solid analysis probe mass spectrometry has the capability of capturing full product patterns simultaneously including both volatile and semi-volatile compounds produced at elevated temperatures. Real-time low-energy collision-induced fragmentation combined with ion mobility separations enables rapid identification of the chemical structures of products. We present here for the first time the recognition of full product patterns resulting from the thermal degradation of β-carotene at temperatures up to 600 °C. Solvent vapor-induced ionization enhancement is observed, which reveals parallel thermal dissociation processes that lead to even- and odd-numbered mass products. The drift-time distributions of high mass products, along with β-carotene, were monitored with temperature, showing multiple conformations that are associated with the presence of two β-rings. Products of masses 346/347, however, show a single conformation distribution, which indicates the separation of two β-rings resulting from the direct bond scission at the polyene hydrocarbon chain. The thermal degradation pathways are evaluated and discussed. PMID:27041662

  20. Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).

    PubMed

    Pont, Laura; Benavente, Fernando; Vilaseca, Marta; Giménez, Estela; Sanz-Nebot, Victoria

    2015-11-01

    Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I. PMID:26452950

  1. Determination of furfural and hydroxymethylfurfural from baby formula using headspace solid phase microextraction based on nanostructured polypyrrole fiber coupled with ion mobility spectrometry.

    PubMed

    Kamalabadi, Mahdie; Ghaemi, Elham; Mohammadi, Abdorreza; Alizadeh, Naader

    2015-08-15

    Furfural (Fu) and hydroxymethylfurfural (HMFu) are extracted using a dodecylbenzenesulfonate-doped polypyrrole coating as a fiber for headspace solid phase microextraction (HS-SPME) method in baby formula samples and detected using ion mobility spectrometry (IMS). Sample pH, salt effect, extraction time and temperature were investigated and optimized as effective parameters in HS-SPME. The calibration curves were linear in the range of 20-300 ng g(-1) (R(2)>0.99). Limits of detection for Fu and HMFu were 6 ng g(-1) and 5 ng g(-1), respectively. The RSD% of Fu and HMFu for five analyses was 4.4 and 4.9, respectively. The proposed method was successfully applied to determine of Fu and HMFu in the different baby formula samples with satisfactory result. The results were in agreement with those obtained using HPLC analysis. The HS-SPME-IMS is precise, selective and sensitive analytical method for determination of Fu and HMFu in baby formula samples, without any derivatization process. PMID:25794723

  2. Ion mobility spectrometry versus classical physico-chemical analysis for assessing the shelf life of extra virgin olive oil according to container type and storage conditions.

    PubMed

    Garrido-Delgado, Rocío; Dobao-Prieto, M Mar; Arce, Lourdes; Aguilar, Joaquín; Cumplido, José L; Valcárcel, Miguel

    2015-03-01

    An experimental study was conducted to assess the stability of a single-variety (Arbequina) extra virgin olive oil (EVOO) as a function of container type and storage conditions over a period of 11 months. EVOO quality was assessed by using ion mobility spectrometry (IMS), which provides increased simplicity, expeditiousness, and relative economy. The results were compared with the ones obtained by using the official method based on classical physico-chemical analysis. Bag-in-box, metal, dark glass, clear glass, and polyethylene terephthalate containers holding EVOO were opened on a periodic basis for sampling to simulate domestic use; in parallel, other containers were kept closed until analysis to simulate the storage conditions on market shelves. The results of the physico-chemical and instrumental analyses led to similar conclusions. Thus, samples packaged in bag-in-box containers preserved oil quality for 11 months, better than other container types. The HS-GC-IMS results confirm that 2-heptenal and 1-penten-3-one are two accurate markers of EVOO quality. PMID:25645180

  3. Multi-Component Ion Modifiers and Arcing Suppressants to Enhance Differential Mobility Spectrometry for Separation of Peptides and Drug Molecules

    NASA Astrophysics Data System (ADS)

    Blagojevic, Voislav; Koyanagi, Gregory K.; Bohme, Diethard K.

    2014-03-01

    The optimization of ion/molecule chemistry in a differential mobility spectrometer (DMS) is shown to result in improved peak capacity, separation, and sensitivity. We have experimented with a modifier composed of multiple components, where each component accomplishes a specific task on mixtures of peptides and small drug molecules. Use of a higher proton affinity modifier (hexanol) provides increased peak capacity and separation. Analyte ion/modifier proton transfer is suppressed by adding a large excess of low proton affinity modifier (water or methanol), significantly increasing signal intensity and sensitivity for low proton affinity analytes. Finally, addition of an electrical arcing suppressant (chloroform) allows the device to operate reliably at higher separation fields, improving peak capacity and separation. We demonstrate a 20 % increase in the device peak capacity without any loss of sensitivity and estimate that further optimization of the modifier composition can increase this to 50 %. Use of 3-, 4-, or even 5-component modifiers offers the opportunity for the user to fine-tune the modifier performance to maximize the device performance, something not possible with a single component modifier.

  4. Express analysis of explosives, chemical warfare agents and drugs with multicapillary column gas chromatography and ion mobility increment spectrometry.

    PubMed

    Buryakov, Igor A

    2004-02-01

    Description of a gas chromatograph designed for express analysis of explosives (2,4-dinitrotoluene, 2,4,6-trinitrotoluene, pentaerythritol tetranitrate), chemical warfare agents (mustard gas, lewisite, sarin) and drugs (heroin, cocaine hydrochloride, crack) is given. The devices comprises a multicapillary chromatographic column and an ion mobility increment spectrometer (MCC-IMIS). The main analytical characteristics of an IMIS (estimated detection limit (DL), linear dynamic range (LDR), speed of response) and a chromatographic column (separation power, degree of separation, a number of possible peaks at a chromatogram section, divided by analysis time) are determined. The maximum value of DL equal to 5 pg/ml was registered for cis-alpha-LW, and the lowest one of 0.001 pg/ml was for cocaine. The maximum value of LDR equal to 1000 was registered for sarin and the lowest one of 150 was for the ions of lewisite. Speed of response of one compound detection with the IMIS was 0.7 s. PMID:14698239

  5. Direct analysis in real time coupled to multiplexed drift tube ion mobility spectrometry for detecting toxic chemicals.

    PubMed

    Harris, Glenn A; Kwasnik, Mark; Fernández, Facundo M

    2011-03-15

    Current and future chemical threats to homeland security motivate the need for new chemical detection systems to provide border, transportation, and workplace security. We present the first successful coupling of a commercial direct analysis in real time (DART) ion source to a resistive glass monolithic drift tube ion mobility spectrometer (DTIMS) as the basis for a low maintenance, versatile, and robust chemical monitoring system. in situ ionization within the electric field gradient of the instrument enhances sensitivity and provides a safe sampling strategy. The instrument uses nitrogen as both the DART discharge and DTIMS drift gases, allowing for a high electric field to be used for ion separation while keeping cost-of-use low. With the use of a traditional signal averaging acquisition mode, the 95% probability of detection (POD) for analytes sampled from melting point capillary tubes was 11.81% v/v for DMMP, 1.13% v/v for 2-CEES, and 10.61 mM for methamidophos. Sensitivity was improved via a prototype transmission-mode geometry interface, resulting in an almost 2 orders of magnitude decrease in the POD level for DMMP (0.28% v/v). As an alternative to transmission mode operation, digital multiplexing of the DTIMS ion injection step was also implemented, finding a 3-fold improvement in signal-to-noise ratios for 200 μs gate injections and a 4.5-fold for 400 μs gate injections. PMID:21319810

  6. Ion mobility spectrometry nuisance alarm threshold analysis for illicit narcotics based on environmental background and a ROC-curve approach.

    PubMed

    Forbes, Thomas P; Najarro, Marcela

    2016-07-21

    The discriminative potential of an ion mobility spectrometer (IMS) for trace detection of illicit narcotics relative to environmental background was investigated with a receiver operating characteristic (ROC) curve framework. The IMS response of cocaine, heroin, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and Δ(9)-tetrahydro-cannabinol (THC) was evaluated against environmental background levels derived from the screening of incoming delivery vehicles at a federal facility. Over 20 000 samples were collected over a multiyear period under two distinct sets of instrument operating conditions, a baseline mode and an increased desorption/drift tube temperature and sampling time mode. ROC curves provided a quantifiable representation of the interplay between sensitivity (true positive rate, TPR) and specificity (1 - false positive rate, FPR). A TPR of 90% and minimized FPR were targeted as the detection limits of IMS for the selected narcotics. MDMA, THC, and cocaine demonstrated single nanogram sensitivity at 90% TPR and <10% FPR, with improvements to both MDMA and cocaine in the elevated temperature/increased sampling mode. Detection limits in the tens of nanograms with poor specificity (FPR ≈ 20%) were observed for methamphetamine and heroin under baseline conditions. However, elevating the temperature reduced the background in the methamphetamine window, drastically improving its response (90% TPR and 3.8% FPR at 1 ng). On the contrary, the altered mode conditions increased the level of background for THC and heroin, partially offsetting observed enhancements to desorption. The presented framework demonstrated the significant effect environmental background distributions have on sensitivity and specificity. PMID:27206280

  7. Analysis of heterogeneous water vapor uptake by metal iodide cluster ions via differential mobility analysis-mass spectrometry

    SciTech Connect

    Oberreit, Derek; Rawat, Vivek K.; Larriba-Andaluz, Carlos; Ouyang, Hui; McMurry, Peter H.; Hogan, Christopher J.

    2015-09-14

    The sorption of vapor molecules onto pre-existing nanometer sized clusters is of importance in understanding particle formation and growth in gas phase environments and devising gas phase separation schemes. Here, we apply a differential mobility analyzer-mass spectrometer based approach to observe directly the sorption of vapor molecules onto iodide cluster ions of the form (MI){sub x}M{sup +} (x = 1-13, M = Na, K, Rb, or Cs) in air at 300 K and with water saturation ratios in the 0.01-0.64 range. The extent of vapor sorption is quantified in measurements by the shift in collision cross section (CCS) for each ion. We find that CCS measurements are sensitive enough to detect the transient binding of several vapor molecules to clusters, which shift CCSs by only several percent. At the same time, for the highest saturation ratios examined, we observed CCS shifts of up to 45%. For x < 4, cesium, rubidium, and potassium iodide cluster ions are found to uptake water to a similar extent, while sodium iodide clusters uptake less water. For x ≥ 4, sodium iodide cluster ions uptake proportionally more water vapor than rubidium and potassium iodide cluster ions, while cesium iodide ions exhibit less uptake. Measured CCS shifts are compared to predictions based upon a Kelvin-Thomson-Raoult (KTR) model as well as a Langmuir adsorption model. We find that the Langmuir adsorption model can be fit well to measurements. Meanwhile, KTR predictions deviate from measurements, which suggests that the earliest stages of vapor uptake by nanometer scale species are not well described by the KTR model.

  8. Analysis of heterogeneous water vapor uptake by metal iodide cluster ions via differential mobility analysis-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Oberreit, Derek; Rawat, Vivek K.; Larriba-Andaluz, Carlos; Ouyang, Hui; McMurry, Peter H.; Hogan, Christopher J.

    2015-09-01

    The sorption of vapor molecules onto pre-existing nanometer sized clusters is of importance in understanding particle formation and growth in gas phase environments and devising gas phase separation schemes. Here, we apply a differential mobility analyzer-mass spectrometer based approach to observe directly the sorption of vapor molecules onto iodide cluster ions of the form (MI)xM+ (x = 1-13, M = Na, K, Rb, or Cs) in air at 300 K and with water saturation ratios in the 0.01-0.64 range. The extent of vapor sorption is quantified in measurements by the shift in collision cross section (CCS) for each ion. We find that CCS measurements are sensitive enough to detect the transient binding of several vapor molecules to clusters, which shift CCSs by only several percent. At the same time, for the highest saturation ratios examined, we observed CCS shifts of up to 45%. For x < 4, cesium, rubidium, and potassium iodide cluster ions are found to uptake water to a similar extent, while sodium iodide clusters uptake less water. For x ≥ 4, sodium iodide cluster ions uptake proportionally more water vapor than rubidium and potassium iodide cluster ions, while cesium iodide ions exhibit less uptake. Measured CCS shifts are compared to predictions based upon a Kelvin-Thomson-Raoult (KTR) model as well as a Langmuir adsorption model. We find that the Langmuir adsorption model can be fit well to measurements. Meanwhile, KTR predictions deviate from measurements, which suggests that the earliest stages of vapor uptake by nanometer scale species are not well described by the KTR model.

  9. Analysis of heterogeneous water vapor uptake by metal iodide cluster ions via differential mobility analysis-mass spectrometry.

    PubMed

    Oberreit, Derek; Rawat, Vivek K; Larriba-Andaluz, Carlos; Ouyang, Hui; McMurry, Peter H; Hogan, Christopher J

    2015-09-14

    The sorption of vapor molecules onto pre-existing nanometer sized clusters is of importance in understanding particle formation and growth in gas phase environments and devising gas phase separation schemes. Here, we apply a differential mobility analyzer-mass spectrometer based approach to observe directly the sorption of vapor molecules onto iodide cluster ions of the form (MI)xM(+) (x = 1-13, M = Na, K, Rb, or Cs) in air at 300 K and with water saturation ratios in the 0.01-0.64 range. The extent of vapor sorption is quantified in measurements by the shift in collision cross section (CCS) for each ion. We find that CCS measurements are sensitive enough to detect the transient binding of several vapor molecules to clusters, which shift CCSs by only several percent. At the same time, for the highest saturation ratios examined, we observed CCS shifts of up to 45%. For x < 4, cesium, rubidium, and potassium iodide cluster ions are found to uptake water to a similar extent, while sodium iodide clusters uptake less water. For x ≥ 4, sodium iodide cluster ions uptake proportionally more water vapor than rubidium and potassium iodide cluster ions, while cesium iodide ions exhibit less uptake. Measured CCS shifts are compared to predictions based upon a Kelvin-Thomson-Raoult (KTR) model as well as a Langmuir adsorption model. We find that the Langmuir adsorption model can be fit well to measurements. Meanwhile, KTR predictions deviate from measurements, which suggests that the earliest stages of vapor uptake by nanometer scale species are not well described by the KTR model. PMID:26374028

  10. Device for two-dimensional gas-phase separation and characterization of ion mixtures

    DOEpatents

    Tang, Keqi; Shvartsburg, Alexandre A.; Smith, Richard D.

    2006-12-12

    The present invention relates to a device for separation and characterization of gas-phase ions. The device incorporates an ion source, a field asymmetric waveform ion mobility spectrometry (FAIMS) analyzer, an ion mobility spectrometry (IMS) drift tube, and an ion detector. In one aspect of the invention, FAIMS operating voltages are electrically floated on top of the IMS drift voltage. In the other aspect, the FAIMS/IMS interface is implemented employing an electrodynamic ion funnel, including in particular an hourglass ion funnel. The present invention improves the efficiency (peak capacity) and sensitivity of gas-phase separations; the online FAIMS/IMS coupling creates a fundamentally novel two-dimensional gas-phase separation technology with high peak capacity, specificity, and exceptional throughput.

  11. Development and Evaluation of a DMS-based Method for the Detection of Insecticides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differential mobility spectrometry (DMS), also commonly referred to as high-field asymmetric waveform ion mobility spectrometry (FAIMS), is a rapidly advancing technology for gas-phase separation. DMS has the potential to emerge as a major stand-alone separation technique such as LC or GC. To date,...

  12. Ion Mobility-Mass Spectrometry Study of Folded Ubiquitin Conformers Induced By Treatment with cis-[Pd(en)(H2O)2]2+

    NASA Astrophysics Data System (ADS)

    Giganti, Virginia G.; Kundoor, Sriramu; Best, W. Alex; Angel, Laurence A.

    2011-02-01

    Ion mobility-mass spectrometry is used to study the new conformers of bovine ubiquitin (Ub) and the palladium(II) binding sites after the incubation with cis-[Pd(en)(H2O)2]2+ where en = ethylenediamine. Palladium(II) complexes are potentially useful proteomic reagents because they selectively bind to the side groups of methionine and histidine and hydrolytically cleave the peptide bond. Incubating 1.0 mM solution of Ub with 10.0 molar excess of cis-[Pd(en)(H2O)2]2+ results with one to four Pd2+ or Pd(en)2+ being attached to intact Ub and two conformer families at each of the 4+ to 11+ charge states. The 4+ and 5+ species exhibit a compact form, which is also observed in untreated Ub, and a new highly folded conformer. The 6+ to 10+ exhibit an elongated form, also observed in Ub, and a new partially folded conformer. The new conformers are shown to be more stable if they contain at least one Pd2+, rather than all Pd(en)2+. IM-MS/MS of [UbPd2en+5H]9+ shows that both the partially folded and elongated conformers first lose the en ligand, followed by dissociating into product ions that indicate that Met1, Glu51/Asp52, His68, and Glu16 are binding sites for Pd2+. These results suggest that Pd2+ is simultaneously binding to multiple side groups across different regions of Ub. This type of sequestering of Pd2+ probably reduces the efficiency of Pd2+ ions to selectively cleave Ub because it prevents Pd2+ anchoring to only Met or His and to an adjacent backbone amide nitrogen and forming the "activated complex" necessary for specific peptide bond cleavage.

  13. Localization of Fatty Acyl and Double Bond Positions in Phosphatidylcholines Using a Dual Stage CID Fragmentation Coupled with Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Castro-Perez, Jose; Roddy, Thomas P.; Nibbering, Nico M. M.; Shah, Vinit; McLaren, David G.; Previs, Stephen; Attygalle, Athula B.; Herath, Kithsiri; Chen, Zhu; Wang, Sheng-Ping; Mitnaul, Lyndon; Hubbard, Brian K.; Vreeken, Rob J.; Johns, Douglas G.; Hankemeier, Thomas

    2011-09-01

    A high content molecular fragmentation for the analysis of phosphatidylcholines (PC) was achieved utilizing a two-stage [trap (first generation fragmentation) and transfer (second generation fragmentation)] collision-induced dissociation (CID) in combination with travelling-wave ion mobility spectrometry (TWIMS). The novel aspects of this work reside in the fact that a TWIMS arrangement was used to obtain a high level structural information including location of fatty acyl substituents and double bonds for PCs in plasma, and the presence of alkali metal adduct ions such as [M + Li]+ was not required to obtain double bond positions. Elemental compositions for fragment ions were confirmed by accurate mass measurements. A very specific first generation fragment ion m/z 577 (M-phosphoryl choline) from the PC [16:0/18:1 (9Z)] was produced, which by further CID generated acylium ions containing either the fatty acyl 16:0 (C15H31CO+, m/z 239) or 18:1 (9Z) (C17H33CO+, m/z 265) substituent. Subsequent water loss from these acylium ions was key in producing hydrocarbon fragment ions mainly from the α-proximal position of the carbonyl group such as the hydrocarbon ion m/z 67 (+H2C-HC = CH-CH = CH2). Formation of these ions was of important significance for determining double bonds in the fatty acyl chains. In addition to this, and with the aid of 13C labeled lyso-phosphatidylcholine (LPC) 18:1 (9Z) in the ω-position (methyl) TAP fragmentation produced the ion at m/z 57. And was proven to be derived from the α-proximal (carboxylate) or distant ω-position (methyl) in the LPC.

  14. Simultaneous determination of benzene and phenol in heat transfer fluid by head-space gas chromatography hyphenated with ion mobility spectrometry.

    PubMed

    Criado-García, L; Garrido-Delgado, R; Arce, L; López, F; Peón, R; Valcárcel, M

    2015-11-01

    The quantitative determination of some compounds such as benzene and phenol in a complex matrix by ion mobility spectrometry (IMS) can be a difficult task, due to the influence of other components present in the matrix and the chemical properties of both compounds, such as their high volatility and low proton affinity. Monitoring of these compounds in a heat transfer fluid (HTF) is essential to check the correct working of a thermosolar plant and for safety and environmental reasons. Benzene and phenol, among other compounds, are produced when HTF is exposed to high temperatures in continuous cycles and their presence can decrease the efficiency of HTF. For the first time, a headspace module coupled to a gas chromatography column in combination with an IMS (with a tritium ionization source) has been optimized and fully validated to simultaneously quantify benzene and phenol in HTF. The limit of detection (LOD) and limit of quantification (LOQ) achieved with the method proposed were 0.011 and 0.038 g L(-1) and 0.004 and 0.014 g L(-1) for benzene and phenol respectively. The precision of the method was evaluated in terms of repeatability and reproducibility with all values lower than 9.2% and 13.3%, respectively. Results demonstrated that benzene and phenol were generated in the HTF heating process, and its concentration increased with heating time (approximately 483 h). The average concentration values for benzene and phenol in degraded HTF samples were not significantly different to values obtained using a gas chromatography-flame ionization detector instrument. Therefore, IMS is a promising technique for in-field quality control of HTF in a thermosolar plant due to its speed, versatility, sensitivity and selectivity to quantify these degradation compounds. PMID:26452912

  15. Comparison of two methods for selegiline determination: A flow-injection chemiluminescence method using cadmium sulfide quantum dots and corona discharge ion mobility spectrometry.

    PubMed

    Khataee, Alireza; Lotfi, Roya; Hasanzadeh, Aliyeh; Iranifam, Mortaza; Zarei, Mahmoud; Joo, Sang Woo

    2016-01-15

    Two analytical approaches including chemiluminescence (CL) and corona discharge ionization ion mobility spectrometry (CD-IMS) were developed for sensitive determination of selegiline (SG). We found that the CL intensity of the KMnO4-Na2S2O3 CL system was significantly enhanced in the presence of L-cysteine capped CdS quantum dots (QDs). A possible CL mechanism for this CL reaction is proposed. In the presence of SG, the enhanced CL system was inhibited. Based on this inhibition, a simple and sensitive flow-injection CL method was proposed for the determination of SG. Under optimum experimental conditions, the decreased CL intensity was proportional to SG concentration in the range of 0.01 to 30.0 mg L(-1). The detection limit (3σ) was 0.004 mg L(-1). Also, SG was determined using CD-IMS, and under optimum conditions of CD-IMS, calibration curves were linear in the range of 0.15 to 42.0 mg L(-1), with a detection limit (3σ) of 0.03 mg L(-1). The precision of the two methods was calculated by analyzing samples containing 5.0 mg L(-1) of SG (n=11). The relative standard deviations (RSDs%) of the flow-injection CL and CD-IMS methods are 2.17% and 3.83%, respectively. The proposed CL system exhibits a higher sensitivity and precision than the CD-IMS method for the determination of SG. PMID:26318702

  16. Comparative direct infusion ion mobility mass spectrometry profiling of Thermus thermophilus wild-type and mutant ∆cruC carotenoid extracts.

    PubMed

    Stark, Timo D; Angelov, Angel; Hofmann, Mathias; Liebl, Wolfgang; Hofmann, Thomas

    2013-12-01

    The major carotenoid species isolated from the thermophilic bacterium Thermus thermophilus HB27 have been identified as zeaxanthin-glucoside-fatty acid esters (thermozeaxanthins and thermobiszeaxanthins). Most of the genes of the proposed T. thermophilus carotenoid pathway could be found in the genome, but there is less clarity about the genes which encode the enzymes performing the final carotenoid glycosylation and acylation steps. To get a further insight into the biosynthesis of thermo(bis)zeaxanthins in T. thermophilus, we deleted the megaplasmid open reading frame TT_P0062 (termed cruC) by both exchanging it with a kanamycin resistance cassette (ΔcruC:kat) and by generating a markerless gene deletion strain (ΔcruC). A fast and efficient electrospray ionization-ion mobility-time-of-flight mass spectrometry method via direct infusion was developed to compare the carotenoid profiles of wild type and mutant T. thermophilus cell culture extracts. These comparisons revealed significant alterations in the carotenoid composition of the ΔcruC mutant, which was found to accumulate zeaxanthin. This is the first experimental evidence that the ORF encodes the glycosyltransferase enzyme necessary for the glycosylation of zeaxanthin in the final modification steps of the thermozeaxanthin biosynthesis in T. thermophilus HB27. Also, the proposed method for direct determination of carotenoid amounts and species in crude acetone extracts represents an improvement over existing methods in terms of speed and sensitivity and may be applicable in high-throughput analyses of other terpenoids as well as other important bacterial metabolites like fatty acids and their derivatives. PMID:24213964

  17. Characterisation of an intrinsically disordered protein complex of Swi5-Sfr1 by ion mobility mass spectrometry and small-angle X-ray scattering.

    PubMed

    Saikusa, Kazumi; Kuwabara, Naoyuki; Kokabu, Yuichi; Inoue, Yu; Sato, Mamoru; Iwasaki, Hiroshi; Shimizu, Toshiyuki; Ikeguchi, Mitsunori; Akashi, Satoko

    2013-03-01

    It is now recognized that intrinsically disordered proteins (IDPs) play important roles as hubs in intracellular networks, and their structural characterisation is of significance. However, due to their highly dynamic features, it is challenging to investigate the structures of IDPs solely by conventional methods. In the present study, we demonstrate a novel method to characterise protein complexes using electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) in combination with small-angle X-ray scattering (SAXS). This method enables structural characterisation even of proteins that have difficulties in crystallisation. With this method, we have characterised the Schizosaccharomyces pombe Swi5-Sfr1 complex, which is expected to have a long disordered region at the N-terminal portion of Sfr1. ESI-IM-MS analysis of the Swi5-Sfr1 complex revealed that its experimental collision cross-section (CCS) had a wide distribution, and the CCS values of the most dominant ions were ∼56% of the theoretically calculated value based on the SAXS low-resolution model, suggesting a significant size reduction in the gas phase. The present study demonstrates that the newly developed method for calculation of the theoretical CCSs of the SAXS low-resolution models of proteins allows accurate evaluation of the experimental CCS values of IDPs provided by ESI-IM-MS by comparing with the low-resolution solution structures. Furthermore, it was revealed that the combination of ESI-IM-MS and SAXS is a promising method for structural characterisation of protein complexes that are unable to crystallise. PMID:23324799

  18. Rapid assessment of human amylin aggregation and its inhibition by copper(II) ions by laser ablation electrospray ionization mass spectrometry with ion mobility separation.

    PubMed

    Li, Hang; Ha, Emmeline; Donaldson, Robert P; Jeremic, Aleksandar M; Vertes, Akos

    2015-10-01

    Native electrospray ionization (ESI) mass spectrometry (MS) is often used to monitor noncovalent complex formation between peptides and ligands. The relatively low throughput of this technique, however, is not compatible with extensive screening. Laser ablation electrospray ionization (LAESI) MS combined with ion mobility separation (IMS) can analyze complex formation and provide conformation information within a matter of seconds. Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in pancreatic beta-cells through proteolytic cleavage of its prohormone. Both amylin and its precursor can aggregate and produce toxic oligomers and fibrils leading to cell death in the pancreas that can eventually contribute to the development of type 2 diabetes mellitus. The inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but details of the interaction remain unknown. Finding other more physiologically tolerated approaches requires large scale screening of potential inhibitors. Here, we demonstrate that LAESI-IMS-MS can reveal the binding stoichiometry, copper oxidation state, and the dissociation constant of human amylin-copper(II) complex. The conformations of hIAPP in the presence of copper(II) ions were also analyzed by IMS, and preferential association between the β-hairpin amylin monomer and the metal ion was found. The copper(II) ion exhibited strong association with the -HSSNN- residues of the amylin. In the absence of copper(II), amylin dimers were detected with collision cross sections consistent with monomers of β-hairpin conformation. When copper(II) was present in the solution, no dimers were detected. Thus, the copper(II) ions disrupt the association pathway to the formation of β-sheet rich amylin fibrils. Using LAESI-IMS-MS for the assessment of amylin-copper(II) interactions demonstrates the utility of this technique for the high-throughput screening of potential inhibitors of amylin

  19. Mobile membrane introduction tandem mass spectrometry for on-the-fly measurements and adaptive sampling of VOCs around oil and gas projects in Alberta, Canada

    NASA Astrophysics Data System (ADS)

    Krogh, E.; Gill, C.; Bell, R.; Davey, N.; Martinsen, M.; Thompson, A.; Simpson, I. J.; Blake, D. R.

    2012-12-01

    The release of hydrocarbons into the environment can have significant environmental and economic consequences. The evolution of smaller, more portable mass spectrometers to the field can provide spatially and temporally resolved information for rapid detection, adaptive sampling and decision support. We have deployed a mobile platform membrane introduction mass spectrometer (MIMS) for the in-field simultaneous measurement of volatile and semi-volatile organic compounds. In this work, we report instrument and data handling advances that produce geographically referenced data in real-time and preliminary data where these improvements have been combined with high precision ultra-trace VOCs analysis to adaptively sample air plumes near oil and gas operations in Alberta, Canada. We have modified a commercially available ion-trap mass spectrometer (Griffin ICX 400) with an in-house temperature controlled capillary hollow fibre polydimethylsiloxane (PDMS) polymer membrane interface and in-line permeation tube flow cell for a continuously infused internal standard. The system is powered by 24 VDC for remote operations in a moving vehicle. Software modifications include the ability to run continuous, interlaced tandem mass spectrometry (MS/MS) experiments for multiple contaminants/internal standards. All data are time and location stamped with on-board GPS and meteorological data to facilitate spatial and temporal data mapping. Tandem MS/MS scans were employed to simultaneously monitor ten volatile and semi-volatile analytes, including benzene, toluene, ethylbenzene and xylene (BTEX), reduced sulfur compounds, halogenated organics and naphthalene. Quantification was achieved by calibrating against a continuously infused deuterated internal standard (toluene-d8). Time referenced MS/MS data were correlated with positional data and processed using Labview and Matlab to produce calibrated, geographical Google Earth data-visualizations that enable adaptive sampling protocols

  20. Differential Mobility Spectrometry Coupled with Multiple Ion Monitoring in Regulated LC-MS/MS Bioanalysis of a Therapeutic Cyclic Peptide in Human Plasma.

    PubMed

    Fu, Yunlin; Xia, Yuan-Qing; Flarakos, Jimmy; Tse, Francis L S; Miller, Jeffrey D; Jones, Elliott B; Li, Wenkui

    2016-04-01

    A differential mobility spectrometry (DMS) in combination with a multiple ion monitoring (MIM) method was developed and validated for quantitative LC-MS/MS bioanalysis of pasireotide (SOM230) in human plasma. Pasireotide, a therapeutic cyclic peptide, exhibits poor collision-induced dissociation (CID) efficiency for multiple reaction monitoring (MRM) detection. Therefore, in an effort to increase the overall sensitivity of the assay, a DMS-MIM approach was explored. By selecting the most abundant doubly charged precursor ion in both the Q1 and Q3 of the mass analyzer in MIM and combining the DMS capability to significantly reduce the high matrix/chemical background noise, this new LC-DMS-MIM method overcomes the sensitivity challenge in the typical MRM method due to poor CID fragmentation of the analyte. Human plasma was spiked with pasireotide with concentrations in the range 0.01-50 ng/mL. Weak cation-exchange solid-phase extraction was employed for sample preparation. The sample extracts were analyzed with a SCIEX QTRAP 6500 system equipped with an ESI source and DMS device. The separation voltage and compensation voltage of the DMS and other parameters of the MS system were optimized to maximize signal responses. The performance of the LC-DMS-MIM assay for quantitative analysis of pasireotide in human plasma was evaluated and compared to those obtained via LC-MRM and LC-MIM without DMS. Overall, the assay sensitivity with DMS-MIM was approximately 5-fold better than that observed in MRM or MIM without DMS. The assay was validated with accuracy (% bias) and precision (% CV) of the QC results at eight concentration levels (0.01, 0.02, 0.05, 0.15, 0.3, 1.5, 15, and 37.5 ng/mL) evaluated ranging from -4.8 to 5.0% bias and 0.7 to 8.6% CV for the intraday and interday runs. The current LC-DMS-MIM workflow can be expanded to quantitative analysis of other molecules that have poor fragmentation efficiency in CID. PMID:26937555

  1. Rapid Assessment of Human Amylin Aggregation and Its Inhibition by Copper(II) Ions by Laser Ablation Electrospray Ionization Mass Spectrometry with Ion Mobility Separation

    PubMed Central

    Donaldson, Robert P.; Jeremic, Aleksandar M.; Vertes, Akos

    2015-01-01

    Native electrospray ionization (ESI) mass spectrometry (MS) is often used to monitor noncovalent complex formation between peptides and ligands. The relatively low throughput of this technique, however, is not compatible with extensive screening. Laser ablation electrospray ionization (LAESI) MS combined with ion mobility separation (IMS) can analyze complex formation and provide conformation information within a matter of seconds. Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in pancreatic beta-cells through proteolytic cleavage of its prohormone. Both amylin and its precursor can aggregate and produce toxic oligomers and fibrils leading to cell death in the pancreas that can eventually contribute to the development of type 2 diabetes mellitus. The inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but details of the interaction remain unknown. Finding other more physiologically tolerated approaches requires large scale screening of potential inhibitors. Here, we demonstrate that LAESI-IMS-MS can reveal the binding stoichiometry, copper oxidation state, and the dissociation constant of human amylin–copper(II) complex. The conformations of hIAPP in the presence of copper(II) ions were also analyzed by IMS, and preferential association between the β-hairpin amylin monomer and the metal ion was found. The copper(II) ion exhibited strong association with the –HSSNN– residues of the amylin. In the absence of copper(II), amylin dimers were detected with collision cross sections consistent with monomers of β-hairpin conformation. When copper(II) was present in the solution, no dimers were detected. Thus, the copper(II) ions disrupt the association pathway to the formation of β-sheet rich amylin fibrils. Using LAESI-IMS-MS for the assessment of amylin–copper(II) interactions demonstrates the utility of this technique for the high-throughput screening of potential inhibitors of

  2. Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial

    PubMed Central

    2014-01-01

    Background The Fas apoptotic pathway has been implicated in type 2 diabetes and cardiovascular disease. Although a polymorphism (rs7138803; G > A) near the Fas apoptotic inhibitory molecule 2 (FAIM2) locus has been related to obesity, its association with other cardiovascular risk factors and disease remains uncertain. Methods We analyzed the association between the FAIM2-rs7138803 polymorphism and obesity, blood pressure and heart rate in 7,161 participants (48.3% with type 2 diabetes) in the PREDIMED study at baseline. We also explored gene-diet interactions with adherence to the Mediterranean diet (MedDiet) and examined the effects of the polymorphism on cardiovascular disease incidence per diabetes status after a median 4.8-year dietary intervention (MedDiet versus control group) follow-up. Results We replicated the association between the FAIM2-rs7138803 polymorphism and greater obesity risk (OR: 1.08; 95% CI: 1.01-1.16; P = 0.011; per-A allele). Moreover, we detected novel associations of this polymorphism with higher diastolic blood pressure (DBP) and heart rate at baseline (B = 1.07; 95% CI: 0.97-1.28 bmp in AA vs G-carriers for the whole population), that remained statistically significant even after adjustment for body mass index (P = 0.012) and correction for multiple comparisons. This association was greater and statistically significant in type-2 diabetic subjects (B = 1.44: 95% CI: 0.23-2.56 bmp; P = 0.010 for AA versus G-carriers). Likewise, these findings were also observed longitudinally over 5-year follow-up. Nevertheless, we found no statistically significant gene-diet interactions with MedDiet for this trait. On analyzing myocardial infarction risk, we detected a nominally significant (P = 0.041) association in type-2 diabetic subjects (HR: 1.86; 95% CI:1.03-3.37 for AA versus G-carriers), although this association did not remain statistically significant following correction for multiple comparisons. Conclusions We

  3. Effect of adduct formation with molecular nitrogen on the measured collisional cross sections of transition metal-1,10-phenanthroline complexes in traveling wave ion-mobility spectrometry: N2 is not always an "inert" buffer gas.

    PubMed

    Rijs, Nicole J; Weiske, Thomas; Schlangen, Maria; Schwarz, Helmut

    2015-10-01

    The number of separations and analyses of molecular species using traveling wave ion-mobility spectrometry-mass spectrometry (TWIMS-MS) is increasing, including those extending the technique to analytes containing metal atoms. A critical aspect of such applications of TWIMS-MS is the validity of the collisional cross sections (CCSs) measured and whether they can be accurately calibrated against other ion-mobility spectrometry (IMS) techniques. Many metal containing species have potential reactivity toward molecular nitrogen, which is present in high concentration in the typical Synapt-G2 TWIMS cell. Here, we analyze the effect of nitrogen on the drift time of a series of cationic 1,10-phenanthroline complexes of the late transition metals, [(phen)M](+), (M = Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, and Hg) in order to understand potential deviations from expected drift time behaviors. These metal complexes were chosen for their metal open-coordination site and lack of rotameric species. The target species were generated via electrospray ionization (ESI), analyzed using TWIMS in N2 drift gas, and the observed drift time trends compared. Theoretically derived CCSs for all species (via both the projection approximation and trajectory method) were also compared. The results show that, indeed, for metal containing species in this size regime, reaction with molecular nitrogen has a dramatic effect on measured drift times and must not be ignored when comparing and interpreting TWIMS arrival time distributions. Density-functional theory (DFT) calculations are employed to analyze the periodic differences due to the metal's interaction with nitrogen (and background water) in detail. PMID:26378338

  4. Ion Mobility Mass Spectrometry for Extracting Spectra of N-Glycans Directly from Incubation Mixtures Following Glycan Release: Application to Glycans from Engineered Glycoforms of Intact, Folded HIV gp120

    NASA Astrophysics Data System (ADS)

    Harvey, David J.; Sobott, Frank; Crispin, Max; Wrobel, Antoni; Bonomelli, Camille; Vasiljevic, Snezana; Scanlan, Christopher N.; Scarff, Charlotte A.; Thalassinos, Konstantinos; Scrivens, James H.

    2011-03-01

    The analysis of glycosylation from native biological sources is often frustrated by the low abundances of available material. Here, ion mobility combined with electrospray ionization mass spectrometry have been used to extract the spectra of N-glycans released with PNGase F from a serial titration of recombinantly expressed envelope glycoprotein, gp120, from the human immunodeficiency virus (HIV). Analysis was also performed on gp120 expressed in the α-mannosidase inhibitor, and in a matched mammalian cell line deficient in GlcNAc transferase I. Without ion mobility separation, ESI spectra frequently contained no observable ions from the glycans whereas ions from other compounds such as detergents and residual buffer salts were abundant. After ion mobility separation on a Waters T-wave ion mobility mass spectrometer, the N-glycans fell into a unique region of the ion mobility/ m/z plot allowing their profiles to be extracted with good signal:noise ratios. This method allowed N-glycan profiles to be extracted from crude incubation mixtures with no clean-up even in the presence of surfactants such as NP40. Furthermore, this technique allowed clear profiles to be obtained from sub-microgram amounts of glycoprotein. Glycan profiles were similar to those generated by MALDI-TOF MS although they were more susceptible to double charging and fragmentation. Structural analysis could be accomplished by MS/MS experiments in either positive or negative ion mode but negative ion mode gave the most informative spectra and provided a reliable approach to the analysis of glycans from small amounts of glycoprotein.

  5. Development and evoluation of a DMS-based method for the detection of insecticides.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differential mobility spectrometry (DMS), also referred to as high-field asymmetric waveform ion mobility spectromety (FAIMS), is a reapidly advancing technology for gas-phase separation. DMS has the potential to emerge as a major stand-alone separation technique such as LC or GC. To date, several...

  6. Enhanced Detection of Low-Abundance Host Cell Protein Impurities in High-Purity Monoclonal Antibodies Down to 1 ppm Using Ion Mobility Mass Spectrometry Coupled with Multidimensional Liquid Chromatography.

    PubMed

    Doneanu, Catalin E; Anderson, Malcolm; Williams, Brad J; Lauber, Matthew A; Chakraborty, Asish; Chen, Weibin

    2015-10-20

    The enormous dynamic range of proteinaceous species present in protein biotherapeutics poses a significant challenge for current mass spectrometry (MS)-based methods to detect low-abundance HCP impurities. Previously, an HCP assay based on two-dimensional chromatographic separation (high pH/low pH) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry and developed in the author's laboratory has been shown to achieve a detection limit of about 50 ppm (parts per milion) for the identification and quantification of HCPs present in monoclonal antibodies following Protein A purification.1 To improve the HCP detection limit we have explored the utility of several new analytical techniques for HCP analysis and thereby developed an improved liquid chromatography-mass spectrometry (LC-MS) methodology for enhanced detection of HCPs. The new method includes (1) the use of a new charge-surface-modified (CSH) C18 stationary phase to mitigate the challenges of column saturation, peak tailing, and distortion that are commonly observed in the HCP analysis; (2) the incorporation of traveling-wave ion mobility (TWIM) separation of coeluting peptide precursors, and (3) the improvement of fragmentation efficiency of low-abundance HCP peptides by correlating the collision energy used for precursor fragmentation with their mobility drift time. As a result of these improvements, the detection limit of the new methodology was greatly improved, and HCPs present at a concentration as low as 1 ppm (1 ng HCP/mg mAb) were successfully identified and quantified. The newly developed method was applied to analyze two high-purity mAbs (NIST mAb and Infliximab) expressed in a murine cell line. For both samples, low-abundance HCPs (down to 1 ppm) were confidently identified, and the identities of the HCPs were further confirmed by targeted MS/MS experiments. In addition, the performance of the assay was evaluated by an interlaboratory study in which three independent

  7. Combination of corona discharge ion mobility spectrometry with a novel reagent gas and two immiscible organic solvent liquid-liquid-liquid microextraction for analysis of clomipramine in biological samples.

    PubMed

    Saraji, Mohammad; Bidgoli, Ali Akbar Hajialiakbari; Khayamian, Taghi; Moradmand, Ali

    2011-12-01

    A novel and sensitive method based on combination of two immiscible organic solvents hollow fiber-based liquid-liquid-liquid microextraction and corona discharge ion mobility spectrometry (HF-LLLME-CD-IMS) was employed for the analysis of clomipramine in human urine and plasma. The effect of formic, acetic and propionic acid as the reagent gas (dopant) on the corona discharge ion mobility signal was investigated. The influence of dopant amount was also studied. Optimum mass flow rates of the dopants were 3.7, 1.1 and 1.0 μmol min(-1) for formic, acetic and propionic acid, respectively. Experimental parameters influencing the extraction efficiency of HF-LLLME, such as NaOH concentration as donor solution, ionic strength of the sample, stirring rate, and extraction time were investigated and optimized. Under the optimum conditions, analytical parameters such as linearity, precision and limit of detection were also evaluated. The linear dynamic range was from 1 to 100 μg L(-1) (r(2)=0.9980) and the limit of detection was 0.35 μg L(-1). Intra- and inter-day precisions were satisfactory with a relative standard deviation (RSD) of 5.9 and 6.7%, respectively. The proposed method was satisfactorily applied for the determination of clomipramine in human plasma and urine. PMID:22041141

  8. Ion Mobility Mass Spectrometry for Ion Recovery and Clean-Up of MS and MS/MS Spectra Obtained from Low Abundance Viral Samples

    NASA Astrophysics Data System (ADS)

    Harvey, David J.; Crispin, Max; Bonomelli, Camille; Scrivens, Jim H.

    2015-07-01

    Many samples of complex mixtures of N-glycans released from small amounts of material, such as glycoproteins from viruses, present problems for mass spectrometric analysis because of the presence of contaminating material that is difficult to remove by conventional methods without involving sample loss. This study describes the use of ion mobility for extraction of glycan profiles from such samples and for obtaining clean CID spectra when targeted m/z values capture additional ions from those of the target compound. N-glycans were released enzymatically from within SDS-PAGE gels, from the representative recombinant glycoprotein, gp120 of the human immunodeficiency virus, and examined by direct infusion electrospray in negative mode followed by ion mobility with a Waters Synapt G2 mass spectrometer (Waters MS-Technologies, Manchester, UK). Clean profiles of singly, doubly, and triply charged N-glycans were obtained from samples in cases where the raw electrospray spectra displayed only a few glycan ions as the result of low sample concentration or the presence of contamination. Ion mobility also enabled uncontaminated CID spectra to be obtained from glycans when their molecular ions displayed coincidence with ions from fragments or multiply charged ions with similar m/z values. This technique proved to be invaluable for removing extraneous ions from many CID spectra. The presence of such ions often produces spectra that are difficult to interpret. Most CID spectra, even those from abundant glycan constituents, benefited from such clean-up, showing that the extra dimension provided by ion mobility was invaluable for studies of this type.

  9. Classification of biodiesel and fuel blends using gas chromatography - differential mobility spectrometry with cluster analysis and isolation of C18:3 me by dual ion filtering.

    PubMed

    Pasupuleti, Dedeepya; Eiceman, Gary A; Pierce, Karisa M

    2016-08-01

    Fatty acid alkyl esters (FAAEs) were determined at 10-100mg/L in biodiesel and blends with petrodiesel without sample pre-treatment using gas chromatography with a tandem differential mobility detector. Selectivity was provided through chromatographic separations and atmospheric pressure chemical ionization reactions in the detector with mobility characterization of gas ions. Limits of detection were ~0.5ng with an average of 2.98% RSD for peak area precision, ≤1.3% RSD for retention time precision, and ≤9.2% RSD for compensation voltage precision. Biodiesel blends were classified using principal component analysis (PCA) and hierarchical cluster analysis (HCA). Unsupervised cluster analysis captured 52.72% of variance in a single PC while supervised analysis captured 71.64% of variance using Fisher ratio feature selection. Test set predictions showed successful clustering according to source or feedstock when regressed onto the training set model. Detection of the regulated substance methyl linolenate (C18:3 me) was achieved in 6-10s with a 1m long capillary column using dual ion filtering in the tandem differential mobility detector. PMID:27216685

  10. Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. I: Investigation of mobile phase and MS conditions.

    PubMed

    Nováková, Lucie; Grand-Guillaume Perrenoud, Alexandre; Nicoli, Raul; Saugy, Martial; Veuthey, Jean-Luc; Guillarme, Davy

    2015-01-01

    The conditions for the analysis of selected doping substances by UHPSFC-MS/MS were optimized to ensure suitable peak shapes and maximized MS responses. A representative mixture of 31 acidic and basic doping agents was analyzed, in both ESI+ and ESI- modes. The best compromise for all compounds in terms of MS sensitivity and chromatographic performance was obtained when adding 2% water and 10mM ammonium formate in the CO2/MeOH mobile phase. Beside mobile phase, the nature of the make-up solvent added for interfacing UHPSFC with MS was also evaluated. Ethanol was found to be the best candidate as it was able to compensate for the negative effect of 2% water addition in ESI- mode and provided a suitable MS response for all doping agents. Sensitivity of the optimized UHPSFC-MS/MS method was finally assessed and compared to the results obtained in conventional UHPLC-MS/MS. Sensitivity was improved by 5-100-fold in UHPSFC-MS/MS vs. UHPLC-MS/MS for 56% of compounds, while only one compound (bumetanide) offered a significantly higher MS response (4-fold) under UHPLC-MS/MS conditions. In the second paper of this series, the optimal conditions for UHPSFC-MS/MS analysis will be employed to screen >100 doping agents in urine matrix and results will be compared to those obtained by conventional UHPLC-MS/MS. PMID:25467513

  11. Influence of sample and mobile phase composition on peptide retention behaviour and sensitivity in reversed-phase liquid chromatography/mass spectrometry.

    PubMed

    Houbart, V; Rozet, E; Matagne, A; Crommen, J; Servais, A-C; Fillet, M

    2013-11-01

    Because the chromatographic behaviour of peptides is totally different from that of small molecules, a good understanding of the mechanisms that occur from injection to detection in reversed-phase LC-MS is strongly recommended to successfully develop not only qualitative but also quantitative methods. In this study, design of experiments was used in order to investigate the influence of the experimental parameters, i.e. sample and mobile phase composition, on a peptide mixture covering a wide range of molecular weights, isoelectric points and hydropathies. First, a screening design was developed to identify the significant factors concerning mobile phase (ion-pairing reagent nature and concentration) and sample composition (organic modifier proportion and ion-pairing reagent nature) on retention and response intensity (sensitivity). Then, after having selected the experimental domain and the significant factors, a full factorial design was used to further investigate the role of the considered factors and their interactions. Interestingly, ion-pairing reagent nature present in the sample had a tremendous effect on retention and response intensity. Optimal conditions leading to good sensitivity and adequate peptide retention without band splitting were selected and could be used as starting point for rapid method development using classical solvents and ion-pairing reagents. PMID:24070623

  12. Mass spectrometry.

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Johanson, G. A.

    1972-01-01

    Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

  13. Evaluation of mobile phase composition for enhancing sensitivity of targeted quantification of oligonucleotides using ultra-high performance liquid chromatography and mass spectrometry: application to phosphorothioate deoxyribonucleic acid.

    PubMed

    Chen, Buyun; Bartlett, Michael G

    2013-05-01

    LC-MS based assays are a promising approach for the bioanalysis of oligonucleotide therapeutics due to their selectivity and structure identification capabilities. However, the lack of sensitivity and complicated sample preparation procedures remain a barrier for application of LC-MS based assays to preclinical and clinical studies. Numerous studies have shown that the mobile phase composition, especially organic solvent type, has a significant impact on the MS sensitivity of oligonucleotides. In this study, we systematically investigated the type of organic solvents and concentration of organic modifiers for their effect on electrospray desorption efficiency, chromatographic separation and LC-MS signal intensity and provide mechanisms for these effects. 25mM HFIP, 15mM DIEA and the use of ethanol as an organic solvent were observed to achieve a two order of magnitude increase in LC-MS signal intensity when compared to the most commonly used LC-MS mobile phase composition. Phenol-chloroform LLE in combination with ethanol precipitation was demonstrated to be effective for quantitative bioanalysis of therapeutic oligonucleotides. Various conditions for ethanol precipitation were evaluated and >75% absolute recovery was achieved using an optimized extraction procedure. No increase in column pressure or deterioration of separation was observed for >500 injections of biological samples. The method run time was 5min and the LOQ was 2.5ng/ml. The accuracy (% error) and precision (%RSD) are <5.09% and <10.56%, respectively, over a dynamic range of 2.5-1000ng/ml. The assay was applied to a proof of concept animal study and similar PK parameters to previous studies were obtained. PMID:23528868

  14. Adsorption mechanism of acids and bases in reversed-phase liquid chromatography in weak buffered mobile phases designed for liquid chromatography/mass spectrometry

    SciTech Connect

    Gritti, Fabrice; Guiochon, Georges A

    2009-01-01

    The overloaded band profiles of five acido-basic compounds were measured, using weakly buffered mobile phases. Low buffer concentrations were selected to provide a better understanding of the band profiles recorded in LC/MS analyses, which are often carried out at low buffer concentrations. In this work, 10 {micro}L samples of a 50 mM probe solution were injected into C{sub 18}-bonded columns using a series of five buffered mobile phases at {sub W}{sup S}pH between 2 and 12. The retention times and the shapes of the bands were analyzed based on thermodynamic arguments. A new adsorption model that takes into account the simultaneous adsorption of the acidic and the basic species onto the endcapped adsorbent, predicts accurately the complex experimental profiles recorded. The adsorption mechanism of acido-basic compounds onto RPLC phases seems to be consistent with the following microscopic model. No matter whether the acid or the base is the neutral or the basic species, the neutral species adsorbs onto a large number of weak adsorption sites (their saturation capacity is several tens g/L and their equilibrium constant of the order of 0.1 L/g). In contrast, the ionic species adsorbs strongly onto fewer active sites (their saturation capacity is about 1 g/L and their equilibrium constant of the order of a few L/g). From a microscopic point of