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Sample records for mobility spectrometry faims

  1. 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.

  2. Enhancement of biological mass spectrometry by using separations based on changes in ion mobility (FAIMS and DMS).

    PubMed

    Purves, Randy W

    2013-01-01

    Analysis of complex biological samples for low-level analytes by liquid chromatography-tandem mass spectrometry (LC-MS/MS) often requires additional selectivity. Differential mobility techniques (FAIMS and DMS) have been shown to enhance LC-MS/MS analyses by separating ions in the gas-phase on a millisecond timescale by use of a mechanism that is complementary to both liquid chromatography and mass spectrometry. In this overview, a simplified description of the operation of these devices is given and an example presented that illustrates the utility of FAIMS (DMS) for solving a challenging analytical assay. Important recent advances in the field, including work with gas modifiers, are presented, along with an outlook for the technology.

  3. Separation of cis and trans Isomers of Polyproline by FAIMS Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Creese, Andrew J.; Cooper, Helen J.

    2016-10-01

    High field asymmetric waveform ion mobility spectrometry (FAIMS) is well-established as a tool for separating peptide isomers (sequence inversions and post-translationally modified localization variants). Here, we demonstrate the FAIMS is able to differentiate cis and trans isomers of polyproline. Polyproline assumes an all-cis conformation—the PPI helix—in 1-propanol, and an all-trans conformation—the PPII helix—in aqueous solutions. Differentiation of these conformers may be achieved both through use of a cylindrical FAIMS device and a miniaturized ultrahigh field planar FAIMS device.

  4. Precise determination of nonlinear function of ion mobility for explosives and drugs at high electric fields for microchip FAIMS.

    PubMed

    Guo, Dapeng; Wang, Yonghuan; Li, Lingfeng; Wang, Xiaozhi; Luo, Jikui

    2015-01-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) separates ions by utilizing the characteristics of nonlinear ion mobility at high and low electric fields. Accurate ion discrimination depends on the precise solution of nonlinear relationships and is essential for accurate identification of ion species for applications. So far, all the nonlinear relationships of ion mobility obtained are based at low electric fields (E/N <65 Td). Microchip FAIMS (μ-FAIMS) with small dimensions has high electric field up to E/N = 250 Td, making the approximation methods and conclusions for nonlinear relationships inappropriate for these systems. In this paper, we deduced nonlinear functions based on the first principle and a general model. Furthermore we considered the hydrodynamics of gas flow through microchannels. We then calculated the specific alpha coefficients for cocaine, morphine, HMX, TNT and RDX, respectively, based on their FAIMS spectra measured by μ-FAIMS system at ultra-high fields up to 250 Td. The results show that there is no difference in nonlinear alpha functions obtained by the approximation and new method at low field (<120 Td), but the error induced by using approximation method increases monotonically with the increase in field, and could be as much as 30% at a field of 250 Td.

  5. 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

  6. High-field asymmetric waveform ion mobility spectrometry for mass spectrometry-based proteomics.

    PubMed

    Swearingen, Kristian E; Moritz, Robert L

    2012-10-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that separates gas-phase ions by their behavior in strong and weak electric fields. FAIMS is easily interfaced with electrospray ionization and has been implemented as an additional separation mode between liquid chromatography (LC) and mass spectrometry (MS) in proteomic studies. FAIMS separation is orthogonal to both LC and MS and is used as a means of on-line fractionation to improve the detection of peptides in complex samples. FAIMS improves dynamic range and concomitantly the detection limits of ions by filtering out chemical noise. FAIMS can also be used to remove interfering ion species and to select peptide charge states optimal for identification by tandem MS. Here, the authors review recent developments in LC-FAIMS-MS and its application to MS-based proteomics. PMID:23194268

  7. Improving FAIMS sensitivity using a planar geometry with slit interfaces.

    PubMed

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

    2009-09-01

    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 can be more effectively interfaced to MS. 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 entrance 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 approximately 50 microL/min. The exit 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.

  8. Improving FAIMS Sensitivity using a Planar Geometry with Slit Interfaces

    SciTech Connect

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

    2009-09-01

    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 universal acceptance in 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. 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 is raised by over an order of magnitude without affecting the FAIMS resolution.

  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.

  10. 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.

  11. Distortion of Ion Structures by Field Asymmetric Waveform Ion Mobility Spectrometry

    SciTech Connect

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

    2007-02-15

    Field asymmetric waveform ion mobility spectrometry (FAIMS) is emerging as a major analytical tool, especially in conjunction with mass spectrometry (MS) and/or conventional ion mobility spectrometry (IMS). In particular, FAIMS is used to separate protein or peptide conformers prior to characterization by IMS, MS/MS, or H/D exchange. High electric fields in FAIMS induce ion heating, previously estimated at <10 0C on average and believed too weak to affect ion geometries. Here we use a FAIMS/IMS/MS system to compare the IMS spectra for ESI-generated ubiquitin ions that have and have not passed FAIMS, and find that some unfolding occurs for all charge states. The analysis of those data and their comparison with reported protein unfolding in a Paul trap indicate that at least some structural transitions observed in FAIMS, or previously in an ion trap, are not spontaneous. The observed unfolding is overall similar to that produced by heating of ~40 - 50 0C above room temperature, consistent with the calculated heating of ions at FAIMS waveform peaks. Hence the isomerization in FAIMS likely proceeds in steps during “hot” periods, especially right after ions entering the device. That process distorts ion geometries and causes ion losses by a “self-cleaning” mechanism, and thus should be suppressed as much as possible. We propose achieving that via cooling FAIMS by the amount of ion heating; in most relevant cases cooling by ~75 0C should suffice.

  12. On an aerodynamic mechanism to enhance ion transmission and sensitivity of FAIMS for nano-electrospray ionization-mass spectrometry.

    PubMed

    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).

  13. 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).

  14. 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

  15. 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.

  16. Nanospray FAIMS fractionation provides significant increases in proteome coverage of unfractionated complex protein digests.

    PubMed

    Swearingen, Kristian E; Hoopmann, Michael R; Johnson, Richard S; Saleem, Ramsey A; Aitchison, John D; Moritz, Robert L

    2012-04-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) is an atmospheric pressure ion mobility technique that can be used to reduce sample complexity and increase dynamic range in tandem mass spectrometry experiments. FAIMS fractionates ions in the gas-phase according to characteristic differences in mobilities in electric fields of different strengths. Undesired ion species such as solvated clusters and singly charged chemical background ions can be prevented from reaching the mass analyzer, thus decreasing chemical noise. To date, there has been limited success using the commercially available Thermo Fisher FAIMS device with both standard ESI and nanoLC-MS. We have modified a Thermo Fisher electrospray source to accommodate a fused silica pulled tip capillary column for nanospray ionization, which will enable standard laboratories access to FAIMS technology. Our modified source allows easily obtainable stable spray at flow rates of 300 nL/min when coupled with FAIMS. The modified electrospray source allows the use of sheath gas, which provides a fivefold increase in signal obtained when nanoLC is coupled to FAIMS. In this work, nanoLC-FAIMS-MS and nanoLC-MS were compared by analyzing a tryptic digest of a 1:1 mixture of SILAC-labeled haploid and diploid yeast to demonstrate the performance of nanoLC-FAIMS-MS, at different compensation voltages, for post-column fractionation of complex protein digests. The effective dynamic range more than doubled when FAIMS was used. In total, 10,377 unique stripped peptides and 1649 unique proteins with SILAC ratios were identified from the combined nanoLC-FAIMS-MS experiments, compared with 6908 unique stripped peptides and 1003 unique proteins with SILAC ratios identified from the combined nanoLC-MS experiments. This work demonstrates how a commercially available FAIMS device can be combined with nanoLC to improve proteome coverage in shotgun and targeted type proteomics experiments. PMID:22186714

  17. 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.

  18. 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

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

    PubMed

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

    2015-10-01

    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.

  20. Wide-field time-resolved fluorescence anisotropy imaging (TR-FAIM): Imaging the rotational mobility of a fluorophore

    NASA Astrophysics Data System (ADS)

    Siegel, J.; Suhling, K.; Lévêque-Fort, S.; Webb, S. E. D.; Davis, D. M.; Phillips, D.; Sabharwal, Y.; French, P. M. W.

    2003-01-01

    We report a picosecond time-gated fluorescence lifetime imaging (FLIM) system extended to perform time-resolved fluorescence anisotropy imaging (TR-FAIM). Upon excitation with linearly polarized laser pulses, the parallel and perpendicular components of the fluorescence emission from a sample are imaged simultaneously using a polarization-resolved imager. The imaging technique presented here quantitatively reports the rotational mobility of a fluorophore as it varies according to the local environment. In a single acquisition run it yields maps of both rotational correlation time and fluorescence lifetime as they vary across a sample. TR-FAIM has been applied to imaging standard multiwell plate samples of rhodamine 6G dissolved in methanol, ethylene glycol, trimethylene glycol, and glycerol. The observed rotational correlation times and fluorescence lifetimes, which report the local viscosity and refractive index of the local rhodamine 6G environment, respectively, are in good agreement with previously published single point measurements. By considering the linear dependence of the rotational correlation time on viscosity up to 20 cP, we are able to obtain a two-dimensional viscosity map. Wide-field maps of rotational correlation time, and therefore viscosity, have been obtained. This illustrates the potential to image the local viscosity and fluorescence lifetime distributions of fluorophore tagged proteins in cells.

  1. 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.

  2. 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.

  3. 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.

  4. Characterization of a temperature-controlled FAIMS system.

    PubMed

    Barnett, David A; Belford, Michael; Dunyach, Jean-Jacques; Purves, Randy W

    2007-09-01

    High-field asymmetric waveform ion mobility spectrometry (FAIMS) focuses and separates gas-phase analyte ions from chemical background, offering substantial improvements in the detection of targeted species in biological matrices. Ion separations have been typically performed at atmospheric pressure and ambient temperature, although routine small molecule quantitation by LC-MS (and thus LC-FAIMS-MS) is generally performed at liquid flow rates (e.g., in excess of 200 microL/min) in which atmospheric pressure ionization sources (e.g., APCI and ESI) need to be run at elevated temperatures to enhance ion desolvation. Heat from the ionization source and/or the mass spectrometer capillary interface is shown to have a significant impact on the performance of a conventional FAIMS electrode set. This study introduces a new FAIMS system that uses gas heating/cooling to quickly reach temperature equilibrium independent of the external temperature conditions. A series of equations and balance plots, which look at the effect of temperature and other variables, on the normalized field strength (E/N), are introduced and used to explain experimental observations. Examples where the ion behavior deviates from the predicted behavior are presented and explanations based on clusters or changes in ion-neutral interactions are given. Consequences of the use of temperature control, and in particular advantages of using different temperature settings on the inner and outer electrodes, for the purpose of manipulating ion separation are described. PMID:17662612

  5. 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.

  6. 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.

  7. 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.

  8. Enhanced analyte detection using in-source fragmentation of field asymmetric waveform ion mobility spectrometry-selected ions in combination with time-of-flight mass spectrometry.

    PubMed

    Brown, Lauren J; Smith, Robert W; Toutoungi, Danielle E; Reynolds, James C; Bristow, Anthony W T; Ray, Andrew; Sage, Ashley; Wilson, Ian D; Weston, Daniel J; Boyle, Billy; Creaser, Colin S

    2012-05-01

    Miniaturized ultra high field asymmetric waveform ion mobility spectrometry (FAIMS) is used for the selective transmission of differential mobility-selected ions prior to in-source collision-induced dissociation (CID) and time-of-flight mass spectrometry (TOFMS) analysis. The FAIMS-in-source collision induced dissociation-TOFMS (FISCID-MS) method requires only minor modification of the ion source region of the mass spectrometer and is shown to significantly enhance analyte detection in complex mixtures. Improved mass measurement accuracy and simplified product ion mass spectra were observed following FAIMS preselection and subsequent in-source CID of ions derived from pharmaceutical excipients, sufficiently close in m/z (17.7 ppm mass difference) that they could not be resolved by TOFMS alone. The FISCID-MS approach is also demonstrated for the qualitative and quantitative analysis of mixtures of peptides with FAIMS used to filter out unrelated precursor ions thereby simplifying the resulting product ion mass spectra. Liquid chromatography combined with FISCID-MS was applied to the analysis of coeluting model peptides and tryptic peptides derived from human plasma proteins, allowing precursor ion selection and CID to yield product ion data suitable for peptide identification via database searching. The potential of FISCID-MS for the quantitative determination of a model peptide spiked into human plasma in the range of 0.45-9.0 μg/mL is demonstrated, showing good reproducibility (%RSD < 14.6%) and linearity (R(2) > 0.99).

  9. Separation and identification of isomeric glycopeptides by high field asymmetric waveform ion mobility spectrometry.

    PubMed

    Creese, Andrew J; Cooper, Helen J

    2012-03-01

    The analysis of intact glycopeptides by mass spectrometry is challenging due to the numerous possibilities for isomerization, both within the attached glycan and the location of the modification on the peptide backbone. Here, we demonstrate that high field asymmetric wave ion mobility spectrometry (FAIMS), also known as differential ion mobility, is able to separate isomeric O-linked glycopeptides that have identical sequences but differing sites of glycosylation. Two glycopeptides from the glycoprotein mucin 5AC, GT(GalNAc)TPSPVPTTSTTSAP and GTTPSPVPTTST(GalNAc)TSAP (where GalNAc is O-linked N-acetylgalactosamine), were shown to coelute following reversed-phase liquid chromatography. However, FAIMS analysis of the glycopeptides revealed that the compensation voltage ranges in which the peptides were transmitted differed. Thus, it is possible at certain compensation voltages to completely separate the glycopeptides. Separation of the glycopeptides was confirmed by unique reporter ions produced by supplemental activation electron transfer dissociation mass spectrometry. These fragments also enable localization of the site of glycosylation. The results suggest that glycan position plays a key role in determining gas-phase glycopeptide structure and have implications for the application of FAIMS in glycoproteomics.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Identification of N-nitrosamines in treated drinking water using nanoelectrospray ionization high-field asymmetric waveform ion mobility spectrometry with quadrupole time-of-flight mass spectrometry.

    PubMed

    Zhao, Yuan Yuan; Liu, Xin; Boyd, Jessica M; Qin, Feng; Li, Jianjun; Li, Xing-Fang

    2009-01-01

    We report a nanoelectrospray ionization (nESI) with high-field asymmetric waveform ion mobility spectrometry (FAIMS) and tandem mass spectrometry (MS-MS) method for determination of small molecules of m/z 50 to 200 and its potential application in environmental analysis. Integration of nESI with FAIMS and MS-MS combines the advantages of these three techniques into one method. The nESI provides efficient sample introduction and ionization and allows for collection of multiple data from only microliters of samples. The FAIMS provides rapid separation, reduces or eliminates background interference, and improves the signal-to-noise ratio as much as 10-fold over nESI-MS-MS. The tandem quadrupole time-of-flight MS detection provides accurate mass and mass spectral measurements for structural identification. Characteristics of FAIMS compensation voltage (CV) spectra of seven nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosodi-n-butylamine (NDBA), N-nitrosopiperidine (NPip), and N-nitrosopyrrolidine (NPyr), were analyzed. The optimal CV of the nitrosamines (at DV -4000 V) were: -1.6 V, NDBA; 2.6 V, NDPA; 6.6 V, NPip; 8.8 V, NDEA; 13.2 V, NPyr; 14.4 V, NMEA; and 19.4 V, NDMA. Fragmentation patterns of the seven nitrosamines in the nESI-FAIMS-MS-MS were also obtained. The specific CV and MS-MS spectra resulted in positive identification of NPyr and NPip in a treated water sample, demonstrating the potential application of this technique in environmental analysis.

  17. 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.

  18. 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

  19. The architecture of FAIM-1

    SciTech Connect

    Anderson, J.M.; Coates, W.S.; Davis, A.L.; Hon, R.W.; Robinson, I.N.; Robison, S.V.; Stevens, K.S.

    1987-01-01

    This article describes a symbolic multiprocessing system called FAIM-1. FAIM-1 is a highly concurrent, general-purpose, symbolic accelerator for parallel AI symbolic computation. The paramount goal of the FAIM project is to produce an architecture that can be scaled to a configuration capable of performance improvements of two to three orders of magnitude over conventional architectures. In the design of FAIM-1, prime consideration was given to programmability, performance, extensibility, fault tolerance, and the cost-effective use of technology.

  20. High-field asymmetric waveform ion mobility spectrometry for determining the location of in-source collision-induced dissociation in electrospray ionization mass spectrometry.

    PubMed

    Xia, Yuan-Qing; Jemal, Mohammed

    2009-09-15

    The understanding and control of the in-source collision-induced dissociation (CID) of analytes is important for the accurate LC-MS/MS quantitation of drugs and metabolites in biological samples. Accordingly, it was of interest to us to establish whether such in-source CID takes place after and/or before the orifice of an electrospray ionization (ESI) mass spectrometer. A high-field asymmetric waveform ion mobility spectrometry (FAIMS) system that is physically located between the sprayer and the orifice of a mass spectrometer can serve as an ion filter to control ions entering the orifice of the mass spectrometer. In such a configuration, FAIMS could conceivably be used to determine if the in-source CID of an analyte occurs after and/or before the mass spectrometer orifice. We demonstrated this capability of FAIMS using ifetroban acylglucuronide metabolite as a model compound. Under the conditions used, the results showed that the in-source CID conversion of the acylglucuronide metabolite to its parent drug ifetroban occurred almost entirely after the orifice of the mass spectrometer, with the conversion upstream of the orifice accounting for only 5.6% of the conversion. Under the circumstance, the term "post-orifice CID" rather than "in-source CID" may be more appropriate in describing such a dissociation occurring in the front end of a mass spectrometer.

  1. 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.

  2. Trace level impurity method development with high-field asymmetric waveform ion mobility spectrometry: systematic study of factors affecting the performance.

    PubMed

    Champarnaud, Elodie; Laures, Alice M-F; Borman, Phil J; Chatfield, Marion J; Kapron, James T; Harrison, Mark; Wolff, Jean-Claude

    2009-01-01

    For the determination of trace level impurities, analytical chemists are confronted with complex mixtures and difficult separations. New technologies such as high-field asymmetric waveform ion mobility spectrometry (FAIMS) have been developed to make their work easier; however, efficient method development and troubleshooting can be quite challenging if little prior knowledge of the factors or their settings is available. We present the results of an investigation performed in order to obtain a better understanding of the FAIMS technology. The influence of eight factors (polarity of dispersion voltage, outer bias voltage, total gas flow rate, composition of the carrier gas (e.g. %He), outer electrode temperature, ratio between the temperatures of the inner and outer electrodes, flow rate and composition of the make-up mobile phase) was assessed. Five types of responses were monitored: value of the compensation voltage (CV), intensity, width and asymmetry of the compensation voltage peak, and resolution between two peaks. Three types of studies were performed using different test mixtures and various ionisation modes to assess whether the same conclusions could be drawn across these conditions for a number of different types of compounds. To extract the maximum information from as few experiments as possible, a Design of Experiment (DoE) approach was used. The results presented in this work provide detailed information on the factors affecting FAIMS separations and therefore should enable the user to troubleshoot more effectively and to develop efficient methods. PMID:19065601

  3. 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.

  4. Localization of Post-Translational Modifications in Peptide Mixtures via High-Resolution Differential Ion Mobility Separations Followed by Electron Transfer Dissociation

    NASA Astrophysics Data System (ADS)

    Baird, Matthew A.; Shvartsburg, Alexandre A.

    2016-09-01

    Precise localization of post-translational modifications (PTMs) on proteins and peptides is an outstanding challenge in proteomics. While electron transfer dissociation (ETD) has dramatically advanced PTM analyses, mixtures of localization variants that commonly coexist in cells often require prior separation. Although differential or field asymmetric waveform ion mobility spectrometry (FAIMS) achieves broad variant resolution, the need for standards to identify the features has limited the utility of approach. Here we demonstrate full a priori characterization of variant mixtures by high-resolution FAIMS coupled to ETD and the procedures to systematically extract the FAIMS spectra for all variants from such data.

  5. 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

  6. 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.

  7. A picosecond laser FAIMS analyzer for detecting ultralow quantities of explosives

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

    A method for detecting ultralow quantities of explosives in air and explosive traces using a state-of-the-art picosecond chip Nd3+:YAG laser has been elaborated. The method combines field asymmetric ion mobility spectrometry (FAIMS) with laser ionization of air samples and laser desorption of analyzed molecules from examined surfaces. Radiation of the fourth harmonic (λ = 266 nm, τpulse = 300 ps, Epulse = 20-150 μJ, ν = 20-300 Hz) was used. The ionization efficiencies for trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX), and glyceryl trinitrate (NG) were investigated. The dependences on frequency, pulse energy, peak intensity, and average power for TNT and RDX were determined. It was shown that the optimal peak intensity should be no less than 2•106 W/cm2; at lower peak intensities, the increase of the average laser power in the interval 5-15 mW enhanced the ion signal. The results of detection of TNT, RDX, and NG vapors under these conditions were compared with the results obtained using nanosecond laser excitation. The detected ion signals for all explosives were shown to be two- to threefold higher in the case of picosecond excitation. The FAIMS laser desorption regime was developed where a laser beam exiting the detector after removal of a special plug was used. The results of TNT and RDX detection are presented. The chip Nd3+:YAG laser has a small emitter and a consumed electric power of 25 W. The estimated detection threshold of the prototype picosecond laser FAIMS analyzer of explosives is (1-3)•10-15g/cm3 for TNT vapors.

  8. Differential mobility spectrometry-mass spectrometry for atomic analysis.

    PubMed

    Sinatra, Francy L; Wu, Tianpeng; Manolakos, Spiros; Wang, Jing; Evans-Nguyen, Theresa G

    2015-02-01

    Analysis and separation of atomic ions within a portable setting are studied in forensic applications of radiological debris analysis. Ion mobility spectrometry (IMS) may be used to show separation of atomic ions, while the related method of differential mobility spectrometry (DMS) has focused on fractionation of primarily molecular components. We set out to investigate DMS as a means for separating atomic ions. We initially derived the differential ion mobility parameter, alpha, from classic empirical IMS data of atomic ions, cesium and potassium, each showing its own distinct form of alpha. These alpha functions were applied to DMS simulations and supported by analytical treatment that suggested a means for a rapid disambiguation of atomic ions using DMS. We validated this hypothesis through the prototype cesium-potassium system investigated experimentally by DMS coupled to mass spectrometry (MS). Such a feature would be advantageous in a field portable instrument for rapid atomic analyses especially in the case of isobaric ions that cannot be distinguished by MS. Herein, we first report this novel method for the derivation of alpha from existing field dependent drift tube ion mobility data. Further, we translate experimental DMS data into alpha parameters by expanding upon existing methods. Refining the alpha parameter in this manner helps convey the interpretation of the alpha parameter particularly for those new to the DMS field.

  9. 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.

  10. 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

  11. Fundamentals of traveling wave ion mobility spectrometry.

    PubMed

    Shvartsburg, Alexandre A; Smith, Richard D

    2008-12-15

    Traveling wave ion mobility spectrometry (TW IMS) is a new IMS method implemented in the Synapt IMS/mass spectrometry system (Waters). Despite its wide adoption, the foundations of TW IMS were only qualitatively understood and factors governing the ion transit time (the separation parameter) and resolution remained murky. Here we develop the theory of TW IMS using derivations and ion dynamics simulations. The key parameter is the ratio (c) of ion drift velocity at the steepest wave slope to wave speed. At low c, the ion transit velocity is proportional to the squares of mobility (K) and electric field intensity (E), as opposed to linear scaling in drift tube (DT) IMS and differential mobility analyzers. At higher c, the scaling deviates from quadratic in a way controlled by the waveform profile, becoming more gradual with the ideal triangular profile but first steeper and then more gradual for realistic profiles with variable E. At highest c, the transit velocity asymptotically approaches the wave speed. Unlike with DT IMS, the resolving power of TW IMS depends on mobility, scaling as K(1/2) in the low-c limit and less at higher c. A nonlinear dependence of the transit time on mobility means that the true resolving power of TW IMS differs from that indicated by the spectrum. A near-optimum resolution is achievable over an approximately 300-400% range of mobilities. The major predicted trends are in agreement with TW IMS measurements for peptide ions as a function of mobility, wave amplitude, and gas pressure. The issues of proper TW IMS calibration and ion distortion by field heating are also discussed. The new quantitative understanding of TW IMS separations allows rational optimization of instrument design and operation and improved spectral calibration. PMID:18986171

  12. Biomolecule Analysis by Ion Mobility Spectrometry

    PubMed Central

    Bohrer, Brian C.; Merenbloom, Samuel I.; Koeniger, Stormy L.; Hilderbrand, Amy E.; Clemmer, David E.

    2013-01-01

    Although nonnative protein conformations, including intermediates along the folding pathway and kinetically trapped misfolded species that disfavor the native state, are rarely isolated in the solution phase, they are often stable in the gas phase, where macromolecular ions from electrospray ionization can exist in varying charge states. Differences in the structures of nonnative conformations in the gas phase are often large enough to allow different shapes and charge states to be separated because of differences in their mobilities through a gas. Moreover, gentle collisional activation can be used to induce structural transformations. These new structures often have different mobilities. Thus, there is the possibility of developing a multidimensional separation that takes advantage of structural differences of multiple stable states. This review discusses how nonnative states differ in the gas phase compared with solution and presents an overview of early attempts to utilize and manipulate structures in order to develop ion mobility spectrometry as a rapid and sensitive technique for separating complex mixtures of biomolecules prior to mass spectrometry. PMID:20636082

  13. 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.

  14. 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).

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Hybrid ion mobility and mass spectrometry as a separation tool.

    PubMed

    Ewing, Michael A; Glover, Matthew S; Clemmer, David E

    2016-03-25

    Ion mobility spectrometry (IMS) coupled to mass spectrometry (MS) has seen spectacular growth over the last two decades. Increasing IMS sensitivity and capacity with improvements in MS instrumentation have driven this growth. As a result, a diverse new set of techniques for separating ions by their mobility have arisen, each with characteristics that make them favorable for some experiments and some mass spectrometers. Ion mobility techniques can be broken down into dispersive and selective techniques based upon whether they pass through all mobilities for later analysis by mass spectrometry or select ions by mobility or a related characteristic. How ion mobility techniques fit within a more complicated separation including mass spectrometry and other techniques such as liquid chromatography is of fundamental interest to separations scientists. In this review we explore the multitude of ion mobility techniques hybridized to different mass spectrometers, detailing current challenges and opportunities for each ion mobility technique and for what experiments one technique might be chosen over another. The underlying principles of ion mobility separations, including: considerations regarding separation capabilities, ion transmission, signal intensity and sensitivity, and the impact that the separation has upon the ion structure (i.e., the possibility of configurational changes due to ion heating) are discussed.

  20. 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).

  1. 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

  2. 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

  3. Accelerated high-resolution differential ion mobility separations using hydrogen.

    PubMed

    Shvartsburg, Alexandre A; Smith, Richard D

    2011-12-01

    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 poorly compatible with online liquid-phase separations. Here, we report FAIMS employing hydrogen, specifically in mixtures with N(2) containing up to 90% H(2). 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 H(2) fractions above ~50%. Higher resolution can be exchanged for acceleration of the analyses by up to ~4 times. 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 H(2) should consistently improve resolution for all analytes.

  4. 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

  5. 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.

  6. 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.

  7. [Ion mobility spectrometry for the isomeric volatile organic compounds].

    PubMed

    Han, Hai-yan; Jia, Xian-de; Huang, Guo-dong; Wang, Hong-mei; Li, Jian-quan; Jin, Shun-ping; Jiang, Hai-he; Chu, Yan-nan; Zhou, Shi-kang

    2007-10-01

    Ion mobility spectrometry (IMS) is based on determining the drift velocities, which the ionized sample molecules attain in the weak electric field of a drift tube at atmospheric pressure. The drift behavior can be affected by structural differences of the analytes, so that ion mobility spectrometry has the ability to separated isomeric compounds. In the present article, an introduction to IMS is given, followed by a description of the instrument used for the experiments to differentiate isomeric compounds. Positive ion mobility spectras of three kinds of isomeric volatile organic compounds were studied in a homemade high-resolution IMS apparatus with a discharge ionization source. The study includes the differences in the structure of carbon chain, the style of function group, and the position of function group. The reduced mobility values were determined, which are in very good agreement with the previously reported theoretical values using neural network theory. The influence of the structural features of the substances and including the size and shape of the molecule has been investigated. The reduced mobility values increases in the order: alcohols < acetones < aromas, linears < branches < cycles, and para- < meta- < ortho-. The deviating ion mobility spectra of the constitutional isomers studied reflect the influence of structural features. In order to calibrate or determine the detection limits and the sensitivity of the ion mobility spectrometry, the exponential dilution flask (EDF) was used. Using this method, the detection limit of the analytes can reach the order of magnitude of ng x L(-1).

  8. 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.

  9. 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 ...

  10. 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.

  11. 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.

  12. Temperature effects in differential mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Krylov, Evgeny V.; Coy, Stephen L.; Nazarov, Erkinjon G.

    2009-01-01

    Drift gas temperature and pressure influence differential mobility spectrometer (DMS) performance, changing DMS peak positions, heights and widths. This study characterizes the effect of temperature on DMS peak positions. Positive ions of methyl salicylate, DMMP, and toluene, and negative ions of methyl salicylate and the reactant ion peaks were observed in purified nitrogen in the Sionex microDMx planar DMS. Measurements were made at ambient pressure (1 atm) at temperatures from 25 °C to 150 °C in a planar sensor with height 0.5 mm. Peak value of the separation voltage asymmetric waveform was scanned from 500 V to 1500 V. Compensation voltage (DMS peak position) showed a strong variation with temperature for all investigated ions. By generalizing the concept of effective ion temperature to include the effects of inelastic ion-molecular collisions, we have been able to condense peak position dependence on separation field and temperature to dependence on a redefined effective temperature including a smoothly varying inelasticity correction. It allows prediction and correction of the gas temperature effect on DMS peak positions.

  13. Secondary electrospray ionization ion mobility spectrometry/mass spectrometry of illicit drugs.

    PubMed

    Wu, C; Siems, W F; Hill, H H

    2000-01-15

    A secondary electrospray ionization (SESI) method was developed as a nonradioactive ionization source for ion mobility spectrometry (IMS). This SESI method relied on the gas-phase interaction between charged particles created by electrospray ionization (ESI) and neutral gaseous sample molecules. Mass spectrometry (MS) was used as the detection method after ion mobility separation for ion identification. Preliminary investigations focussed on understanding the ionization process of SESI. The performance of ESI-IMS and SESI-IMS for illicit drug detection was evaluated by determining the analytical figures of merit. In general, SESI had a higher ionization efficiency for small volatile molecules compared with the electrospray method. The potential of developing a universal interface for both GC- and LC-MS with an addition stage of mobility separation was demonstrated.

  14. 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.

  15. The role of ion mobility spectrometry-mass spectrometry in the analysis of protein reference standards.

    PubMed

    Pritchard, Caroline; O'Connor, Gavin; Ashcroft, Alison E

    2013-08-01

    To achieve comparability of measurement results of protein amount of substance content between clinical laboratories, suitable reference materials are required. The impact on measurement comparability of potential differences in the tertiary and quaternary structure of protein reference standards is as yet not well understood. With the use of human growth hormone as a model protein, the potential of ion mobility spectrometry-mass spectrometry as a tool to assess differences in the structure of protein reference materials and their interactions with antibodies has been investigated here.

  16. 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

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

    PubMed

    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.

  18. 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.

  19. 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

  20. Fast Screening of Polycyclic Aromatic Hydrocarbons using Trapped Ion Mobility Spectrometry - Mass Spectrometry

    PubMed Central

    Castellanos, A.; Benigni, P.; Hernandez, D. R.; DeBord, J. D.; Ridgeway, M. E.; Park, M. A.

    2014-01-01

    In the present paper, we showed the advantages of trapped ion mobility spectrometry coupled too mass spectrometry (TIMS-MS) combined with theoretical calculations for fast identification (millisecond timescale) of polycyclic aromatic hydrocarbons (PAH) compounds from complex mixtures. Accurate PAH collision cross sections (CCS, in nitrogen as a bath gas) are reported for the most commonly encountered PAH compounds and the ability to separate PAH geometric isomers is shown for three isobaric pairs with mobility resolution exceeding 150 (3–5 times higher than conventional IMS devices). Theoretical candidate structures (optimized at the DFT/B3LYP level) are proposed for the most commonly encountered PAH compounds showing good agreement with the experimental CCS values (<5%). The potential of TIMS-MS for the separation and identification of PAH compounds from complex mixtures without the need of lengthy pre-separation steps is illustrated for the case of a complex soil mixture. PMID:25558291

  1. 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.

  2. Ion Mobility Separation of Isomeric Phosphopeptides from a Protein with Variant Modification of Adjacent Residues

    SciTech Connect

    Shvartsburg, Alexandre A.; Singer, David; Smith, Richard D.; Hoffmann, Ralf

    2011-06-13

    Ion mobility spectrometry (IMS), and particularly differential IMS or field asymmetric waveform IMS (FAIMS), was recently shown capable of separating post-translationally modified peptides with variant PTM localization. However, that work was limited to a model peptide with serine phosphorylation on fairly distant alternative sites. Here, we demonstrate that FAIMS (coupled to ESI/MS) can broadly baseline-resolve variant phosphopeptides from a biologically modified human protein, including those involving phosphorylation of different residues and adjacent sites that existing MS/MS methods are most challenged to distinguish. Singly and doubly phosphorylated variants can be resolved equally well and identified without dissociation, based on accurate separation properties. The results are unchanged over a range of infusion solvent pH, hence present approach should work in conjunction with chromatographic separations using a mobile phase gradient.

  3. 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

  4. 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

  5. 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.

  6. Analysis of phthalate esters by ion mobility spectrometry

    SciTech Connect

    Giam, C.S.; Reed, G.E.; Holliday, T.L.

    1995-12-31

    Esters of phthalic acid can be detected by IMS (ion mobility spectrometry). The six phthalates in the EPA`s Priority Pollutant List can be detected in both modes--positive as well as negative mode. In the positive mode, a characteristic reduced mobility was obtained for each phthalate; thus the different esters can be distinguished, including the isomeric di-n-octyl- and di-2-ethylhexyl phthalate. Phthalates can be detected in the low nanogram range; detection sensitivity is comparable or better than those found by gas chromatography using different detectors, including by GC-ECD, GC-FID or GC-MS. Direct Monitoring of environmental phthalates by IMS possess several advantages, e.g., without the usual separation protocols for ubiquitous interferants, faster instrumental analysis time (minutes instead of hours), and lower cost. Thus, IMS of phthalates has a great potential as an environmental monitor.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

    2016-03-01

    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. 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

  13. 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.

  14. Tandem ion mobility spectrometry coupled to laser excitation.

    PubMed

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

    2015-09-01

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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).

  1. Ion Mobility Spectrometry-Mass Spectrometry of Intrinsically Unfolded Proteins: Trying to Put Order into Disorder

    PubMed Central

    Knapman, T. W; Valette, N. M; Warriner, S. L; Ashcroft, A. E

    2013-01-01

    Intrinsically disordered proteins do not adopt well-defined native structures and therefore present an intriguing challenge in terms of structural elucidation as they are relatively inaccessible to traditional approaches such as NMR and X-ray crystallography. Many members of this important group of proteins have a distinct biological function and frequently undergo a conformational change on binding to their physiological targets which can in turn modulate their function. Furthermore, many intrinsically unstructured proteins are associated with a wide range of major diseases including cancer and amyloid-related disorders. Here, electrospray ionisation-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) has been used to probe the conformational characteristics of two intrinsically disordered proteins: apo-cytochrome c and apo-osteocalcin. Both proteins are structured in their holo-states when bound to their respective substrates, but disordered in their apo-states. Here, the conformational properties of the holo- and the apo-protein forms for both species have been analysed and their mass spectral data and ion mobility spectrometry-derived collision cross-sectional areas, indicative of their physical size, compared to study the relationship between substrate binding and tertiary structure. In both cases, the intrinsically unstructured apo-states populated multiple conformations with larger cross-sectional areas than their holo-analogues, suggesting that intrinsic disorder in proteins does not preclude the formation of preferred conformations. Additionally, analysis of truncated analogues of osteocalcin has located the region of the protein responsible for the conformational changes detected upon metal cation binding. Together, the data illustrate the scope and utility of ESI-IMS-MS for studying the characteristics and properties of intrinsically disordered proteins whose analysis by other techniques is limited. PMID:23885220

  2. Quality issues in the use of ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Poziomek, Edward J.; Homstead, Juliana; Almeer, Saeed H.

    1998-12-01

    Ion mobility spectrometry (IMS) is often used in the detection of explosives and drugs in the laboratory and field scenarios. It is gaining popularity in the semiquantitative analysis of these and related compounds. We have successfully used IMS in studies with cocaine, 2,4,6 trinitrotoluene (TNT) and similar chemicals, and have developed a protocol to access and ensure the quality of our data. This protocol employs TNT as the reference standard in the IMS negative mode and cocaine hydrochloride as the reference standard in the IMS positive mode. A five-point calibration curve is normally generated for each reference compound in order to determine a concentration level suitable for quality control (QC) check solutions. We have established peak amplitudes and reduced mobility constants for the QC solutions that must be met each day before proceeding with analyses. Any deviation from these criteria requires assessment of the problem and appropriate corrective action. We have found this procedure helpful in maintaining data quality, and in providing an early indication of potential problems. The present paper focuses on the use of IMS with explosives though several examples are given with cocaine hydrochloride.

  3. Selection and generation of waveforms for differential mobility spectrometry

    SciTech Connect

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

    2010-02-15

    Devices based on differential mobility spectrometry (DMS) are used in a number of ways, including applications as ion prefilters for API-MS systems, as detectors or selectors in hybrid instruments (GC-DMS, DMS-IMS), and in standalone systems for chemical detection and identification. DMS ion separation is based on the relative difference between high field and low field ion mobility known as the alpha dependence, and requires the application of an intense asymmetric electric field known as the DMS separation field, typically in the megahertz frequency range. DMS performance depends on the waveform and on the magnitude of this separation field. In this paper, we analyze the relationship between separation waveform and DMS resolution and consider feasible separation field generators. We examine ideal and practical DMS separation field waveforms and discuss separation field generator circuit types and their implementations. To facilitate optimization of the generator designs, we present a set of relations that connect ion alpha dependence to DMS separation fields. Using these relationships we evaluate the DMS separation power of common generator types as a function of their waveform parameters. Optimal waveforms for the major types of DMS separation generators are determined for ions with various alpha dependences. These calculations are validated by comparison with experimental data.

  4. 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.

  5. 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

  6. 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.

  7. Determining the topology of virus assembly intermediates using ion mobility spectrometry-mass spectrometry.

    PubMed

    Knapman, Tom W; Morton, Victoria L; Stonehouse, Nicola J; Stockley, Peter G; Ashcroft, Alison E

    2010-10-30

    We have combined ion mobility spectrometry-mass spectrometry with tandem mass spectrometry to characterise large, non-covalently bound macromolecular complexes in terms of mass, shape (cross-sectional area) and stability (dissociation) in a single experiment. The results indicate that the quaternary architecture of a complex influences its residual shape following removal of a single subunit by collision-induced dissociation tandem mass spectrometry. Complexes whose subunits are bound to several neighbouring subunits to create a ring-like three-dimensional (3D) architecture undergo significant collapse upon dissociation. In contrast, subunits which have only a single neighbouring subunit within a complex retain much of their original shape upon complex dissociation. Specifically, we have determined the architecture of two transient, on-pathway intermediates observed during in vitro viral capsid assembly. Knowledge of the mass, stoichiometry and cross-sectional area of each viral assembly intermediate allowed us to model a range of potential structures based on the known X-ray structure of the coat protein building blocks. Comparing the cross-sectional areas of these potential architectures before and after dissociation provided tangible evidence for the assignment of the topologies of the complexes, which have been found to encompass both the 3-fold and the 5-fold symmetry axes of the final icosahedral viral shell. Such insights provide unique information about virus assembly pathways that could allow the design of anti-viral therapeutics directed at the assembly step. This methodology can be readily applied to the structural characterisation of many other non-covalently bound macromolecular complexes and their assembly pathways.

  8. Ion mobility spectrometry reveals duplex DNA dissociation intermediates.

    PubMed

    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.

  9. How hot are your ions in TWAVE ion mobility spectrometry?

    PubMed

    Merenbloom, Samuel I; Flick, Tawnya G; Williams, Evan R

    2012-03-01

    Effective temperatures of ions during traveling wave ion mobility spectrometry (TWIMS) analysis were measured using singly protonated leucine enkephalin dimer as a chemical thermometer by monitoring dissociation of the dimer into monomer, as well as the subsequent dissociation of monomer into a-, b-, and y-ions, as a function of instrumental parameters. At fixed helium cell and TWIMS cell gas flow rates, the extent of dissociation does not vary significantly with either the wave velocity or wave height, except at low (<500 m/s) wave velocities that are not commonly used. Increasing the flow rate of nitrogen gas into the TWIMS cell and decreasing the flow rate of helium gas into the helium cell resulted in greater dissociation. However, the mobility distributions of the fragment ions formed by dissociation of the dimer upon injection into the TWIMS cell are nearly indistinguishable from those of fragment ions formed in the collision cell prior to TWIMS analysis for all TWIMS experiments. These results indicate that heating and dissociation occur when ions are injected into the TWIMS cell, and that the effective temperature subsequently decreases to a point at which no further dissociation is observed during the TWIMS analysis. An upper limit to the effective ion temperature of 449 K during TWIMS analysis is obtained at a helium flow rate of 180 mL/min, TWIMS flow rate of 80 mL/min, and traveling wave height of 40 V, which is well below previously reported values. Effects of ion heating in TWIMS on gas-phase protein conformation are presented.

  10. Multiplexed Ion Mobility Spectrometry - Orthogonal Time-Of-Flight Mass Spectrometry

    SciTech Connect

    Belov, Mikhail E.; Buschbach, Michael A.; Prior, David C.; Tang, Keqi; Smith, Richard D.

    2007-03-15

    Ion mobility spectrometry (IMS) coupled to orthogonal time-of-flight mass spectrometry (TOF) has shown significant promise for the characterization of complex biological mixtures. The enormous complexity of biological samples (e.g. from proteomics) and the need for both biological and technical analysis replicates imposes major challenges for multidimensional separation platforms in regard to both sensitivity and sample throughput. A major potential attraction of the IMS-TOF MS platform is separation speeds exceeding that of conventional condensed-phase separations by orders of magnitude. Known limitations of the IMS-TOF MS platforms that presently mitigate this attraction include the need for extensive signal averaging due to factors that include significant ion losses in the IMS-TOF interface and an ion utilization efficiency of less than ~1% with continuous ion sources (e.g. ESI). We have developed a new multiplexed ESI-IMS-TOF mass spectrometer that enables lossless ion transmission through the IMS-TOF as well as a utilization efficiency of >50% for ions from the ESI source. Initial results with a mixture of peptides show a ~10-fold increase in signal-to-noise ratio with the multiplexed approach compared to a signal averaging approach, with no reduction in either IMS or TOF MS resolution.

  11. 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.

  12. 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.

  13. An online peak extraction algorithm for ion mobility spectrometry data.

    PubMed

    Kopczynski, Dominik; Rahmann, Sven

    2015-01-01

    Ion mobility (IM) spectrometry (IMS), coupled with multi-capillary columns (MCCs), has been gaining importance for biotechnological and medical applications because of its ability to detect and quantify volatile organic compounds (VOC) at low concentrations in the air or in exhaled breath at ambient pressure and temperature. Ongoing miniaturization of spectrometers creates the need for reliable data analysis on-the-fly in small embedded low-power devices. We present the first fully automated online peak extraction method for MCC/IMS measurements consisting of several thousand individual spectra. Each individual spectrum is processed as it arrives, removing the need to store the measurement before starting the analysis, as is currently the state of the art. Thus the analysis device can be an inexpensive low-power system such as the Raspberry Pi. The key idea is to extract one-dimensional peak models (with four parameters) from each spectrum and then merge these into peak chains and finally two-dimensional peak models. We describe the different algorithmic steps in detail and evaluate the online method against state-of-the-art peak extraction methods.

  14. 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.

  15. An online peak extraction algorithm for ion mobility spectrometry data.

    PubMed

    Kopczynski, Dominik; Rahmann, Sven

    2015-01-01

    Ion mobility (IM) spectrometry (IMS), coupled with multi-capillary columns (MCCs), has been gaining importance for biotechnological and medical applications because of its ability to detect and quantify volatile organic compounds (VOC) at low concentrations in the air or in exhaled breath at ambient pressure and temperature. Ongoing miniaturization of spectrometers creates the need for reliable data analysis on-the-fly in small embedded low-power devices. We present the first fully automated online peak extraction method for MCC/IMS measurements consisting of several thousand individual spectra. Each individual spectrum is processed as it arrives, removing the need to store the measurement before starting the analysis, as is currently the state of the art. Thus the analysis device can be an inexpensive low-power system such as the Raspberry Pi. The key idea is to extract one-dimensional peak models (with four parameters) from each spectrum and then merge these into peak chains and finally two-dimensional peak models. We describe the different algorithmic steps in detail and evaluate the online method against state-of-the-art peak extraction methods. PMID:26157473

  16. 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.

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

    PubMed

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

    2011-06-15

    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(2)V(-1)s(-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. PMID:21524145

  18. 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

  19. 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.

  20. An alternatively spliced long form of Fas apoptosis inhibitory molecule (FAIM) with tissue-specific expression in the brain.

    PubMed

    Zhong, X; Schneider, T J; Cabral, D S; Donohoe, T J; Rothstein, T L

    2001-01-01

    The gene encoding Fas apoptosis inhibitory molecule (FAIM) was cloned by differential display using RNA obtained from Fas-resistant and Fas-sensitive primary murine B lymphocytes. FAIM is highly evolutionarily conserved and broadly expressed, suggesting that its gene product plays a key role in cellular physiology. Here we report the identification of a new, longer form of FAIM (FAIM-L) and characterization of the genomic locus that clarifies its origin. The murine FAIM gene is located at chromosome 9f1, a region syntenic to the corresponding location of the human FAIM gene. The gene consists of six exons and contains putative translation initiation sites within exons II and III. The long form of FAIM is generated by all six exons, whereas the originally cloned form of FAIM, now termed FAIM-Short (FAIM-S) is generated from five exons by alternative splicing. FAIM-L is dominantly expressed in the brain whereas FAIM-S is widely expressed in many tissues.

  1. 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.

  2. 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.

  3. 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.

  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.

    2016-05-01

    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.

  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. 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.

  7. 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.

  8. FAIM-L regulation of XIAP degradation modulates Synaptic Long-Term Depression and Axon Degeneration

    PubMed Central

    Martínez-Mármol, Ramón; Barneda-Zahonero, Bruna; Soto, David; Andrés, Rosa Maria; Coccia, Elena; Gasull, Xavier; Planells-Ferrer, Laura; Moubarak, Rana S.; Soriano, Eduardo; Comella, Joan X.

    2016-01-01

    Caspases have recently emerged as key regulators of axonal pruning and degeneration and of long-term depression (LTD), a long-lasting form of synaptic plasticity. However, the mechanism underlying these functions remains unclear. In this context, XIAP has been shown to modulate these processes. The neuron-specific form of FAIM protein (FAIM-L) is a death receptor antagonist that stabilizes XIAP protein levels, thus preventing death receptor-induced neuronal apoptosis. Here we show that FAIM-L modulates synaptic transmission, prevents chemical-LTD induction in hippocampal neurons, and thwarts axon degeneration after nerve growth factor (NGF) withdrawal. Additionally, we demonstrate that the participation of FAIM-L in these two processes is dependent on its capacity to stabilize XIAP protein levels. Our data reveal FAIM-L as a regulator of axonal degeneration and synaptic plasticity. PMID:27767058

  9. Crystallization and preliminary X-ray crystallographic studies of human FAIM protein.

    PubMed

    Li, Guoming; Qu, Linglong; Meng, Geng; Bai, Xiaoyun; Dai, Kesheng; Zheng, Xiaofeng

    2010-08-01

    Fas apoptosis inhibitory molecule (FAIM), an antagonist of Fas-induced cell death, is highly conserved and is broadly expressed in many tissues. It has been found that FAIM can stimulate neurite outgrowth in PC12 cells and primary neurons. However, the molecular mechanisms of action of FAIM are not understood in detail. Here, full-length human FAIM and two truncation constructs have successfully been cloned, expressed and purified in Escherichia coli. FAIM (1-90) was crystallized and diffracted to a resolution of 2.5 A; the crystal belonged to space group P3(1), with unit-cell parameters a=b=58.02, c=71.11 A, alpha=beta=90, gamma=120 degrees. There were two molecules in the asymmetric unit.

  10. 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

  11. Treatise on the Measurement of Molecular Masses with Ion Mobility Spectrometry

    PubMed Central

    Valentine, Stephen J.; Clemmer, David E.

    2009-01-01

    The ability to separate isotopes by high-resolution ion mobility spectrometry techniques is considered as a direct means for determining mass at ambient pressures. Calculations of peak shapes from the transport equation show that it should be possible to separate isotopes for low mass ions (<200) by utilizing heavy collision gasses and high resolution ion mobility analyzers. The mass accuracy associated with this isotopic separation approach based on ion mobility separation is considered. Finally, we predict several isotopes that should be separable. PMID:19548697

  12. Treatise on the measurement of molecular masses with ion mobility spectrometry.

    PubMed

    Valentine, Stephen J; Clemmer, David E

    2009-07-15

    The ability to separate isotopes by high-resolution ion mobility spectrometry techniques is considered as a direct means for determining mass at ambient pressures. Calculations of peak shapes from the transport equation show that it should be possible to separate isotopes for low-mass ions (<200) by utilizing heavy collision gases and high-resolution ion mobility analyzers. The mass accuracy associated with this isotopic separation approach based on ion mobility separation is considered. Finally, we predict several isotopes that should be separable.

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

    PubMed

    Hall, Adam B; Coy, Stephen L; Nazarov, Erkinjon; Vouros, Paul

    2012-09-01

    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.

  14. Buffer Gas Modifiers Effect Resolution in Ion Mobility Spectrometry through Selective Ion-Molecule Clustering Reactions

    PubMed Central

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

    2013-01-01

    RATIONALE When polar molecules (modifiers) are introduced into the buffer gas of an ion mobility spectrometer, most ion mobilities decrease due to the formation of ion-modifier clusters. METHODS We used ethyl lactate, nitrobenzene, 2-butanol, and tetrahydrofuran-2-carbonitrile as buffer gas modifiers and electrospray ionization ion mobility spectrometry (IMS) coupled to quadrupole mass spectrometry. Ethyl lactate, nitrobenzene, and tetrahydrofuran-2-carbonitrile had not been tested as buffer gas modifiers and 2-butanol had not been used with basic amino acids. RESULTS The ion mobilities of several diamines (arginine, histidine, lysine, and atenolol) were not affected or only slightly reduced when these modifiers were introduced into the buffer gas (3.4% average reduction in an analyte's mobility for the three modifiers). Intramolecular bridges caused limited change in the ion mobilities of diamines when modifiers were added to the buffer gas; these bridges hindered the attachment of modifier molecules to the positive charge of ions and delocalized the charge, which deterred clustering. There was also a tendency towards large changes in ion mobility when the mass of the analyte decreased; ethanolamine, the smallest compound tested, had the largest reduction in ion mobility with the introduction of modifiers into the buffer gas (61%). These differences in mobilities, together with the lack of shift in bridge-forming ions, were used to separate ions that overlapped in IMS, such as isoleucine and lysine, and arginine and phenylalanine, and made possible the prediction of separation or not of overlapping ions. CONCLUSIONS The introduction of modifiers into the buffer gas in IMS can selectively alter the mobilities of analytes to aid in compound identification and/or enable the separation of overlapping analyte peaks. PMID:22956312

  15. Proton-bound cluster ions in ion mobility spectrometry.

    PubMed

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

    1999-10-28

    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.

  16. 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.

  17. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H]2- ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H]3- ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H]2- ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H]3- ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented.

  18. 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.

  19. Electron attachment rate constant measurement by photoemission electron attachment ion mobility spectrometry (PE-EA-IMS)

    NASA Astrophysics Data System (ADS)

    Su, Desheng; Niu, Wenqi; Liu, Sheng; Shen, Chengyin; Huang, Chaoqun; Wang, Hongmei; Jiang, Haihe; Chu, Yannan

    2012-12-01

    Photoemission electron attachment ion mobility spectrometry (PE-EA-IMS), with a source of photoelectrons induced by vacuum ultraviolet radiation on a metal surface, has been developed to study electron attachment reaction at atmospheric pressure using nitrogen as the buffer gas. Based on the negative ion mobility spectra, the rate constants for electron attachment to tetrachloromethane and chloroform were measured at ambient temperature as a function of the average electron energy in the range from 0.29 to 0.96 eV. The experimental results are in good agreement with the data reported in the literature.

  20. Analysis of model Titan atmospheric components using ion mobility spectrometry

    NASA Technical Reports Server (NTRS)

    Kojiro, D. R.; Cohen, M. J.; Wernlund, R. F.; Stimac, R. M.; Humphry, D. E.; Takeuchi, N.

    1991-01-01

    The Gas Chromatograph-Ion Mobility Spectrometer (GC-IMS) was proposed as an analytical technique for the analysis of Titan's atmosphere during the Cassini Mission. The IMS is an atmospheric pressure, chemical detector that produces an identifying spectrum of each chemical species measured. When the IMS is combined with a GC as a GC-IMS, the GC is used to separate the sample into its individual components, or perhaps small groups of components. The IMS is then used to detect, quantify, and identify each sample component. Conventional IMS detection and identification of sample components depends upon a source of energetic radiation, such as beta radiation, which ionizes the atmospheric pressure host gas. This primary ionization initiates a sequence of ion-molecule reactions leading to the formation of sufficiently energetic positive or negative ions, which in turn ionize most constituents in the sample. In conventional IMS, this reaction sequence is dominated by the water cluster ion. However, many of the light hydrocarbons expected in Titan's atmosphere cannot be analyzed by IMS using this mechanism at the concentrations expected. Research at NASA Ames and PCP Inc., has demonstrated IMS analysis of expected Titan atmospheric components, including saturated aliphatic hydrocarbons, using two alternate sample ionizations mechanisms. The sensitivity of the IMS to hydrocarbons such as propane and butane was increased by several orders of magnitude. Both ultra dry (waterless) IMS sample ionization and metastable ionization were successfully used to analyze a model Titan atmospheric gas mixture.

  1. 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

  2. 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.

  3. 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.

  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. Ion mobility spectrometry: Arriving on site and moving beyond a low profile

    SciTech Connect

    Baumbach, Joerg Ingo; Eiceman, Gary A.

    1999-09-01

    Since the inception of modern analytical ion mobility spectrometry in the early 1970s, developments in IMS have followed an unconventional pattern. During the 1990s, dramatic changes have occurred in the understanding of response, so that contemporary IMS is largely unrecognizable from any descriptions in the 1970s and 1980s. Some of these changes are documented in this article and the future of IMS is outlined. (c) American Institute of Physics (c) 2000 American Institute of Physics.

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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.

  7. Separation of a set of peptide sequence isomers using differential ion mobility spectrometry.

    PubMed

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

    2011-09-15

    Protein identification in bottom-up proteomics requires disentangling isomers of proteolytic peptides, a major class of which are sequence inversions. Their separation using ion mobility spectrometry (IMS) has been limited to isomeric pairs. Here we demonstrate baseline separation of all seven 8-mer tryptic peptide isomers using differential IMS. Evaluation of peak capacity implies that even larger libraries should be resolved for heavier peptides with higher charge states.

  8. QconCAT standard for calibration of ion mobility-mass spectrometry systems.

    PubMed

    Chawner, Ross; McCullough, Bryan; Giles, Kevin; Barran, Perdita E; Gaskell, Simon J; Eyers, Claire E

    2012-11-01

    Ion mobility-mass spectrometry (IM-MS) is a useful technique for determining information about analyte ion conformation in addition to mass/charge ratio. The physical principles that govern the mobility of an ion through a gas in the presence of a uniform electric field are well understood, enabling rotationally averaged collision cross sections (Ω) to be directly calculated from measured drift times under well-defined experimental conditions. However, such "first principle" calculations are not straightforward for Traveling Wave (T-Wave) mobility separations due to the range of factors that influence ion motion through the mobility cell. If collision cross section information is required from T-Wave mobility separations, then calibration of the instruments using known standards is essential for each set of experimental conditions. To facilitate such calibration, we have designed and generated an artificial protein based on the QconCAT technology, QCAL-IM, which upon proteolysis can be used as a universal ion mobility calibration standard. This single unique standard enables empirical calculation of peptide ion collision cross sections from the drift time on a T-Wave mobility instrument.

  9. On-tissue protein identification and imaging by MALDI-ion mobility mass spectrometry.

    PubMed

    Stauber, Jonathan; MacAleese, Luke; Franck, Julien; Claude, Emmanuelle; Snel, Marten; Kaletas, Basak Kükrer; Wiel, Ingrid M V D; Wisztorski, Maxence; Fournier, Isabelle; Heeren, Ron M A

    2010-03-01

    MALDI imaging mass spectrometry (MALDI-IMS) has become a powerful tool for the detection and localization of drugs, proteins, and lipids on-tissue. Nevertheless, this approach can only perform identification of low mass molecules as lipids, pharmaceuticals, and peptides. In this article, a combination of approaches for the detection and imaging of proteins and their identification directly on-tissue is described after tryptic digestion. Enzymatic digestion protocols for different kinds of tissues--formalin fixed paraffin embedded (FFPE) and frozen tissues--are combined with MALDI-ion mobility mass spectrometry (IM-MS). This combination enables localization and identification of proteins via their related digested peptides. In a number of cases, ion mobility separates isobaric ions that cannot be identified by conventional MALDI time-of-flight (TOF) mass spectrometry. The amount of detected peaks per measurement increases (versus conventional MALDI-TOF), which enables mass and time selected ion images and the identification of separated ions. These experiments demonstrate the feasibility of direct proteins identification by ion-mobility-TOF IMS from tissue. The tissue digestion combined with MALDI-IM-TOF-IMS approach allows a proteomics "bottom-up" strategy with different kinds of tissue samples, especially FFPE tissues conserved for a long time in hospital sample banks. The combination of IM with IMS marks the development of IMS approaches as real proteomic tools, which brings new perspectives to biological studies.

  10. Ion mobility mass spectrometry enables the efficient detection and identification of halogenated natural products from cyanobacteria with minimal sample preparation.

    PubMed

    Esquenazi, Eduardo; Daly, Michael; Bahrainwala, Tasneem; Gerwick, William H; Dorrestein, Pieter C

    2011-11-15

    Direct observation of halogenated natural products produced by different strains of marine cyanobacteria was accomplished by electrospray ionization and matrix assisted laser desorption ionization and gas phase separation via ion mobility mass spectrometry of extracts as well as intact organisms.

  11. 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

  12. 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

  13. 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.

  14. Characterization of the explosive triacetone triperoxide and detection by ion mobility spectrometry.

    PubMed

    Buttigieg, Gavin A; Knight, Andrew K; Denson, Stephen; Pommier, Carolyn; Denton, M Bonner

    2003-07-29

    The improvised explosive triacetone triperoxide (TATP) was synthesized and characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, Raman and infrared (IR) spectroscopy. Triacetone triperoxide was subsequently analyzed by ion mobility spectrometry (IMS) in positive ion mode, and detected as a cluster of three peaks with a drift time of the most intense peak at 13.06 ms. Triacetone triperoxide was then analyzed after dissolution in toluene, where a dramatic increase in peak intensity was observed, at a flight time of 12.56 ms (K0=2.71 cm2V(-1)s(-1)). Triacetone triperoxide was subsequently analyzed by coupling the ion mobility spectrometer to a triple quadrupole mass spectrometer, where a single peak at m/z of 223 atomic mass units identified the species present in the ion mobility spectra as being triacetone triperoxide.

  15. Screening and classifying small-molecule inhibitors of amyloid formation using ion mobility spectrometry-mass spectrometry.

    PubMed

    Young, Lydia M; Saunders, Janet C; Mahood, Rachel A; Revill, Charlotte H; Foster, Richard J; Tu, Ling-Hsien; Raleigh, Daniel P; Radford, Sheena E; Ashcroft, Alison E

    2015-01-01

    The search for therapeutic agents that bind specifically to precursor protein conformations and inhibit amyloid assembly is an important challenge. Identifying such inhibitors is difficult because many protein precursors of aggregation are partially folded or intrinsically disordered, which rules out structure-based design. Furthermore, inhibitors can act by a variety of mechanisms, including specific or nonspecific binding, as well as colloidal inhibition. Here we report a high-throughput method based on ion mobility spectrometry-mass spectrometry (IMS-MS) that is capable of rapidly detecting small molecules that bind to amyloid precursors, identifying the interacting protein species and defining the mode of inhibition. Using this method we have classified a variety of small molecules that are potential inhibitors of human islet amyloid polypeptide (hIAPP) aggregation or amyloid-beta 1-40 aggregation as specific, nonspecific, colloidal or non-interacting. We also demonstrate the ability of IMS-MS to screen for inhibitory small molecules in a 96-well plate format and use this to discover a new inhibitor of hIAPP amyloid assembly.

  16. Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzmán by ion mobility spectrometry and gas chromatography-mass spectrometry.

    PubMed

    Keller, T; Schneider, A; Regenscheit, P; Dirnhofer, R; Rücker, T; Jaspers, J; Kisser, W

    1999-01-11

    A new method has been developed for the rapid analysis of psilocybin and/or psilocin in fungus material using ion mobility spectrometry. Quantitative analysis was performed by gas chromatography-mass spectrometry after a simple one-step extraction involving homogenization of the dried fruit bodies of fungi in chloroform and derivatization with MSTFA. The proposed methods resulted in rapid procedures useful in analyzing psychotropic fungi for psilocybin and psilocin.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Radio-Frequency (rf) Confinement in Ion Mobility Spectrometry: Apparent Mobilities and Effective Temperatures

    NASA Astrophysics Data System (ADS)

    Allen, Samuel J.; Bush, Matthew F.

    2016-08-01

    Ion mobility is a powerful tool for separating and characterizing the structures of ions. Here, a radio-frequency (rf) confining drift cell is used to evaluate the drift times of ions over a broad range of drift field strengths (E/P, V cm-1 Torr-1). The presence of rf potentials radially confines ions and results in excellent ion transmission at low E/P (less than 1 V cm-1 Torr-1), thereby reducing the dependence of ion transmission on the applied drift voltage. Non-linear responses between drift time and reciprocal drift voltages are observed for extremely low E/P and high rf amplitudes. Under these conditions, pseudopotential wells generated by the rf potentials dampen the mobility of ions. The effective potential approximation is used to characterize this mobility dampening behavior, which can be mitigated by adjusting rf amplitudes and electrode dimensions. Using SIMION trajectories and statistical arguments, the effective temperatures of ions in an rf-confining drift cell are evaluated. Results for the doubly charged peptide GRGDS suggest that applied rf potentials can result in a subtle increase (2 K) in effective temperature compared to an electrostatic drift tube. Additionally, simulations of native-like ions of the protein complex avidin suggest that rf potentials have a negligible effect on the effective temperature of these ions. In general, the results of this study suggest that applied rf potentials enable the measurement of drift times at extremely low E/P and that these potentials have negligible effects on ion effective temperature.

  4. 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.

  5. 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].

  6. Ion Mobility-Mass Spectrometry Differentiates Protein Quaternary Structures Formed in Solution and in Electrospray Droplets.

    PubMed

    Han, Linjie; Ruotolo, Brandon T

    2015-07-01

    Electrospray ionization coupled to mass spectrometry is a key technology for determining the stoichiometries of multiprotein complexes. Despite highly accurate results for many assemblies, challenging samples can generate signals for artifact protein-protein binding born of the crowding forces present within drying electrospray droplets. Here, for the first time, we study the formation of preferred protein quaternary structures within such rapidly evaporating nanodroplets. We use ion mobility and tandem mass spectrometry to investigate glutamate dehydrogenase dodecamers and serum amyloid P decamers as a function of protein concentration, along with control experiments using carefully chosen protein analogues, to both establish the formation of operative mechanisms and assign the bimodal conformer populations observed. Further, we identify an unprecedented symmetric collision-induced dissociation pathway that we link directly to the quaternary structures of the precursor ions selected.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

    2014-09-04

    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.

  15. Net-Faim: distributed computation of aerial images

    NASA Astrophysics Data System (ADS)

    Hollerbach, Uwe

    1998-06-01

    Simulation of aerial images is an important part of modern microchip manufacturing, but computation of the image of an entire mask is a challenging problem requiring a large amount of memory and CPU time. Fortunately, it is possible to decompose the large problem of computing the full image into many smaller, mostly independent, sub-problems. In this paper, one particular decomposition is described and implemented. The target platform is a heterogeneous group of networked workstations. The program, net-faim, was designed to be robust, to scale well with available resources, and to place modest demands on participating workstations. All of these design criteria have been realized. The overall performance of the distributed computation is linearly proportional to the sum of the performances of the individual processors, up to a rather high level of parallelism. Robustness is achieved by not relying on any one server to complete a given task; instead, if an idle server is available, the task is sent out to the idle server even if it has previously been sent to another server. The task is only retired when a server returns the completed answer. This 'paranoid' method of processing tasks has the pleasant side effect of doing automatic dynamic load balancing. The results of runs with several different configurations, both of participating workstations and of sub- domain sizes, are displayed.

  16. 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

  17. Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia.

    PubMed

    Reich, Arno; Spering, Christopher; Gertz, Karen; Harms, Christoph; Gerhardt, Ellen; Kronenberg, Golo; Nave, Klaus A; Schwab, Markus; Tauber, Simone C; Drinkut, Anja; Harms, Kristian; Beier, Chrstioph P; Voigt, Aaron; Göbbels, Sandra; Endres, Matthias; Schulz, Jörg B

    2011-01-01

    Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.

  18. A two-phase approach to Fourier transform ion mobility time-of-flight mass spectrometry.

    PubMed

    Clowers, Brian H; Siems, William F; Yu, Zhihao; Davis, Austen L

    2015-10-21

    It is well known that the duty cycle of common drift-tube ion mobility experiments is often below 1%. However, multiplexing approaches such as Fourier and Hadamard pulsing schemes have been shown to independently enhance the throughput of ion mobility spectrometry (IMS) experiments to levels that approach 50%. While challenges remain to their broad scale implementation we describe a new Fourier transform (FT) IMS experiment that is directly compatible with standard drift tube ion mobility mass spectrometers (DT-IMMS). Compared to previous FT-IMS experiments, our new approach requires only a single gate and circumvents the need for signal apodization by combining data from two frequency pulsing sequences 180° out of phase. Assessment of our initial results highlights an increase in signal-to-noise (SNR) relative to both previous implementations FT-IMS experiments and signal averaged (SA) experiments. For select tetraalkylammonium salts SNR improvements of more than one order of magnitude are routinely possible. To explore the performance metrics associated with the technique a number of experimental variables were systematically altered including frequency sweep range, sweep time, and data acquisition time. Using this experimental design we present the key aspects, considerations, and minimum resources necessary for other IMS researchers to incorporate this operational mode into their research. The two-phase FT-IMMS technique offers a tractable mechanism to enhance sensitivity for IMMS measurements and its broad-scale adoption by IMMS researchers promises to enhance the acquisition speed for mobility measurements using hybrid instrumentation.

  19. Differential mobility spectrometry of chlorocarbons with a micro-fabricated drift tube.

    PubMed

    Eiceman, G A; Krylov, E V; Tadjikov, B; Ewing, R G; Nazarov, E G; Miller, R A

    2004-04-01

    Chlorocarbons were ionized through gas phase chemistry at ambient pressure in air and resultant ions were characterized using a micro-fabricated drift tube with differential mobility spectrometry (DMS). Positive and negative product ions were characterized simultaneously in a single drift tube equipped with a 3 mCi (63)Ni ion source at 50 degrees C and drift gas of air with 1 ppm moisture. Scans of compensation voltage for most chlorocarbons produced differential mobility spectra with Cl(-) as the sole product ion and a few chlorocarbons produced adduct ions, M (.-) Cl(-). Detection limits were approximately 20-80 pg for gas chromatography-DMS measurements. Chlorocarbons also yielded positive ions through chemical ionization in air and differential mobility spectra showed peaks with characteristic compensation voltages for each substance. Field dependence of mobility was determined for positive and negative ions of each substance and confirmed characteristic behavior for each ion. A DMS analyzer with a membrane inlet was used to continuously monitor effluent from columns of bentonite or synthetic silica beads to determine breakthrough volumes of individual chlorocarbons. These findings suggest a potential of DMS for monitoring subsurface environments either on site or perhaps in situ.

  20. A novel gene coding for a Fas apoptosis inhibitory molecule (FAIM) isolated from inducibly Fas-resistant B lymphocytes.

    PubMed

    Schneider, T J; Fischer, G M; Donohoe, T J; Colarusso, T P; Rothstein, T L

    1999-03-15

    The sensitivity of primary splenic B cells to Fas-mediated apoptosis is modulated in a receptor-specific fashion. Here we used a differential display strategy to detect cDNAs present in B cells rendered Fas resistant but absent in those rendered Fas sensitive. This led to the cloning and characterization of a novel 1.2-kb gene that encodes a Fas apoptosis inhibitory molecule (FAIM). faim-transfected BAL-17 B lymphoma cells were less sensitive by half or more to Fas-mediated apoptosis than were vector-transfected controls, using Fas ligand-bearing T cells or a cytotoxic anti-Fas antibody to trigger Fas, and this was associated with inhibition of Fas- induced poly-ADP ribose polymerase (PARP) cleavage. In primary B cells, the time course of faim mRNA and FAIM protein expression correlated with the induction of Fas resistance by surface (s)Ig engagement. Thus, FAIM is an inducible effector molecule that mediates Fas resistance produced by sIg engagement in B cells. However, faim is broadly expressed in various tissues and the faim sequence is highly conserved evolutionarily, suggesting that its role extends beyond lymphocyte homeostasis. As FAIM has no significant regions of homology to other gene products that modulate Fas killing, it appears to represent a distinct, new class of antiapoptotic protein.

  1. Detection of explosive related nitroaromatic compounds (ERNC) by laser-based ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Laudien, Robert; Riebe, Daniel; Beitz, Toralf; Löhmannsröben, Hans-Gerd

    2008-10-01

    In this study two issues are addressed, namely laser ionisation of selected nitroaromatic compounds (NAC) and the characterisation of their anions by photodetachment (PD) spectroscopy. Laser ionisation of the NAC at λ = 226.75 nm is investigated by ion mobility (IM) spectrometry at atmospheric pressure. The main product after laser ionisation is the reactive NO+ ion formed in a sequence of photofragmentation and multiphoton ionisation processes. NO+ is trapped by specific ion molecule reactions (IMR). Alternatively, NO, added as laser dopant, can directly be ionised. The formed NO+ reacts with the NAC under complex formation. This allows fragmentless NAC detection. The combination of IM spectrometry and PD spectroscopy provides real-time characterisation of the anions in the IM spectrum. This is useful to differentiate between NAC and interfering substances and, thus, to reduce false-positive detections of NAC. The electrons detached by the PD laser at λ = 532 nm are detected in the same spectrum as the anions. The potential of PD-IM spectrometry in terms of cross section determination, analytical improvements, tomographic mapping, spatial hole burning etc., is outlined.

  2. Interfacing an ion mobility spectrometry based explosive trace detector to a triple quadrupole mass spectrometer.

    PubMed

    Kozole, Joseph; Stairs, Jason R; Cho, Inho; Harper, Jason D; Lukow, Stefan R; Lareau, Richard T; DeBono, Reno; Kuja, Frank

    2011-11-15

    Hardware from a commercial-off-the-shelf (COTS) ion mobility spectrometry (IMS) based explosive trace detector (ETD) has been interfaced to an AB/SCIEX API 2000 triple quadrupole mass spectrometer. To interface the COTS IMS based ETD to the API 2000, the faraday plate of the IMS instrument and the curtain plate of the mass spectrometer were removed from their respective systems and replaced by a custom faraday plate, which was fabricated with a hole for passing the ion beam to the mass spectrometer, and a custom interface flange, which was designed to attach the IMS instrument onto the mass spectrometer. Additionally, the mass spectrometer was modified to increase the electric field strength and decrease the pressure in the differentially pumped interface, causing a decrease in the effect of collisional focusing and permitting a mobility spectrum to be measured using the mass spectrometer. The utility of the COTS-ETD/API 2000 configuration for the characterization of the gas phase ion chemistry of COTS-ETD equipment was established by obtaining mass and tandem mass spectra in the continuous ion flow and selected mobility monitoring operating modes and by obtaining mass-selected ion mobility spectra for the explosive standard 2,4,6 trinitrotoluene (TNT). This analysis confirmed that the product ion for TNT is [TNT - H](-), the predominant collision-induced dissociation pathway for [TNT- H](-) is the loss of NO and NO(2), and the reduced mobility value for [TNT - H](-) is 1.54 cm(2)V(-1) s(-1). Moreover, this analysis was attained for sample amounts of 1 ng and with a resolving power of 37. The objective of the research is to advance the operational effectiveness of COTS IMS based ETD equipment by developing a platform that can facilitate the understanding of the ion chemistry intrinsic to the equipment.

  3. MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness

    PubMed Central

    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

  4. 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.

  5. Ion-molecule clustering in differential mobility spectrometry: lessons learned from tetraalkylammonium cations and their isomers.

    PubMed

    Campbell, J Larry; Zhu, Mabel; Hopkins, W Scott

    2014-09-01

    Differential mobility spectrometry (DMS) can distinguish ions based upon the differences in their high- and low-field ion mobilities as they experience the asymmetric waveform applied to the DMS cell. These mobilities are known to be influenced by the ions' structure, m/z, and charge distribution (i.e., resonance structures) within the ions themselves, as well as by the gas-phase environment of the DMS cell. While these associations have been developed over time through empirical observations, the exact role of ion structures or their interactions with clustering molecules remains generally unknown. In this study, that relationship is explored by observing the DMS behaviors of a series of tetraalkylammonium ions as a function of their structures and the gas-phase environment of the DMS cell. To support the DMS experiments, the basin-hopping search strategy was employed to identify candidate cluster structures for density functional theory treatment. More than a million cluster structures distributed across 72 different ion-molecule cluster systems were sampled to determine global minimum structures and cluster binding energies. This joint computational and experimental approach suggests that cluster geometry, in particular ion-molecule intermolecular separation, plays a critical role in DMS. PMID:25001379

  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. Ion-molecule clustering in differential mobility spectrometry: lessons learned from tetraalkylammonium cations and their isomers.

    PubMed

    Campbell, J Larry; Zhu, Mabel; Hopkins, W Scott

    2014-09-01

    Differential mobility spectrometry (DMS) can distinguish ions based upon the differences in their high- and low-field ion mobilities as they experience the asymmetric waveform applied to the DMS cell. These mobilities are known to be influenced by the ions' structure, m/z, and charge distribution (i.e., resonance structures) within the ions themselves, as well as by the gas-phase environment of the DMS cell. While these associations have been developed over time through empirical observations, the exact role of ion structures or their interactions with clustering molecules remains generally unknown. In this study, that relationship is explored by observing the DMS behaviors of a series of tetraalkylammonium ions as a function of their structures and the gas-phase environment of the DMS cell. To support the DMS experiments, the basin-hopping search strategy was employed to identify candidate cluster structures for density functional theory treatment. More than a million cluster structures distributed across 72 different ion-molecule cluster systems were sampled to determine global minimum structures and cluster binding energies. This joint computational and experimental approach suggests that cluster geometry, in particular ion-molecule intermolecular separation, plays a critical role in DMS.

  8. Qualitative screening for adulterants in weight-loss supplements by ion mobility spectrometry.

    PubMed

    Dunn, Jamie D; Gryniewicz-Ruzicka, Connie M; Mans, Daniel J; Mecker-Pogue, Laura C; Kauffman, John F; Westenberger, Benjamin J; Buhse, Lucinda F

    2012-12-01

    Ion mobility spectrometry (IMS) served as a rapid, qualitative screening tool for the analysis of adulterated weight-loss products. We have previously shown that sibutramine extracted into methanol from dietary supplements can be detected at low levels (2ng) using a portable IMS spectrometer, and have adapted a similar method for the analysis of additional weight-loss product adulterants. An FDA collaborative study helped to define the limits for fluoxetine with a limit of detection of 2ng. We also evaluated more readily available, less toxic extraction solvents and found isopropanol and water were comparable to methanol. Isopropanol was favored over water for two reasons: (1) water increases the analysis time and (2) aqueous solutions were more susceptible to pH change, which affected the detection of sibutramine. In addition to sibutamine and fluoxetine, we surveyed 11 weight-loss adulterants; bumetanide, fenfluramine, furosemide, orlistat, phenolphthalein, phentermine, phenytoin, rimonabant, sertraline and two sibutramine analogs, desmethylsibutramine and didesmethylsibutramine, using portable and benchtop ion mobility spectrometers. Out of these 13 active pharmaceutical ingredients (APIs), portable and benchtop ion mobility spectrometers were capable of screening products for 10 of these APIs. The developed procedure was applied to two weight-loss dietary supplements using both portable and benchtop instruments. One product contained didesmethylsibutramine while the other contained didesmethylsibutramine and phenolphthalein. PMID:22902504

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

    PubMed

    Fernández-Maestre, Roberto; Hill, Herbert H

    2009-08-01

    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.

  10. 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.

  11. Ion Mobility Mass Spectrometry of a Rotary ATPase Reveals ATP-induced Reduction in Conformational Flexibility

    PubMed Central

    Davies, Roberta; Liko, Idlir; Wu, Kuan-Jung; Stewart, Alastair G.; Stock, Daniela; Robinson, Carol V.

    2014-01-01

    Rotary ATPases play fundamental roles in energy conversion, their catalytic rotation being associated with inter-domain fluctuations and heterogeneity of conformational states. Using ion mobility mass spectrometry (IM-MS) we compare the conformational dynamics of the intact ATPase from Thermus thermophilus (TtATPase) with its membrane and soluble subcomplexes. Our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. To provide a structural context for our experimental data we performed molecular dynamics (MD) simulations and observed conformational changes of the peripheral stalks reflecting their intrinsic flexibility. By isolating complexes at different phases of cell growth and manipulating nucleotides, metal ions and pH during isolation, we reveal differences that can be related to conformational changes in the Vo complex, triggered by ATP binding. Together these results implicate nucleotides in modulating flexibility of the stator components and uncover mechanistic detail underlying operation and regulation in the context of the holo-enzyme. PMID:24557135

  12. 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.

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

    DOE PAGES

    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

  14. 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.

  15. 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.

  16. Unfolding of Hydrated Alkyl Diammonium Cations Revealed by Cryogenic Ion Mobility-Mass Spectrometry.

    PubMed

    Servage, Kelly A; Fort, Kyle L; Silveira, Joshua A; Shi, Liuqing; Clemmer, David E; Russell, David H

    2015-07-22

    Hydration of the ammonium ion plays a key role in determining the biomolecular structure as well as local structure of water in aqueous environments. Experimental data obtained by cryogenic ion mobility-mass spectrometry (cryo-IM-MS) show that dehydration of alkyl diammonium cations induces a distinct unfolding transition at a critical number of water molecules, n = 21 to 23, n = 24 to 26, and n = 27 to 29, for 1,7-diaminoheptane, 1,8-diaminooctane, and 1,10-diaminodecane, respectively. Results are also presented that reveal compelling evidence for unique structural transitions of hydrated ammonium ions associated with the development of the hydrogen-bond network around individual charged groups. The ability to track the evolution of structure upon stepwise dehydration provides direct insight into the intricate interplay between solvent-molecule interactions that are responsible for defining conformations. Such insights are potentially valuable in understanding how ammonium ion solvation influences conformation(s) of larger biomolecules.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Modulation of Hippocampal Neuroplasticity by Fas/CD95 Regulatory Protein 2 (Faim2) in the Course of Bacterial Meningitis

    PubMed Central

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

    2014-01-01

    Abstract 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

  5. 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.

  6. FAIM-L is an IAP-binding protein that inhibits XIAP ubiquitinylation and protects from Fas-induced apoptosis.

    PubMed

    Moubarak, Rana S; Planells-Ferrer, Laura; Urresti, Jorge; Reix, Stéphanie; Segura, Miguel F; Carriba, Paulina; Marqués-Fernàndez, Fernando; Sole, Carme; Llecha-Cano, Nuria; Lopez-Soriano, Joaquin; Sanchis, Daniel; Yuste, Victor J; Comella, Joan X

    2013-12-01

    The neuronal long isoform of Fas Apoptotic Inhibitory Molecule (FAIM-L) protects from death receptor (DR)-induced apoptosis, yet its mechanism of protection remains unknown. Here, we show that FAIM-L protects rat neuronal Type II cells from Fas-induced apoptosis. XIAP has previously emerged as a molecular discriminator that is upregulated in Type II and downregulated in Type I apoptotic signaling. We demonstrate that FAIM-L requires sustained endogenous levels of XIAP to protect Type II cells as well as murine cortical neurons from Fas-induced apoptosis. FAIM-L interacts with the BIR2 domain of XIAP through an IAP-binding motif, the mutation of which impairs the antiapoptotic function of FAIM-L. Finally, we report that FAIM-L inhibits XIAP auto-ubiquitinylation and maintains its stability, thus conferring protection from apoptosis. Our results bring new understanding of the regulation of endogenous XIAP by a DR antagonist, pointing out at FAIM-L as a promising therapeutic tool for protection from apoptosis in pathological situations where XIAP levels are decreased.

  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.

  8. Discrimination of large maltooligosaccharides from isobaric dextran and pullulan using ion mobility mass spectrometry

    PubMed Central

    Rashid, Abdul M; Saalbach, Gerhard; Bornemann, Stephen

    2013-01-01

    RATIONALE Ion mobility mass spectrometry (IMMS) has previously been shown to resolve small isobaric oligosaccharides, but larger alpha-oligoglucans are also abundant in biology and are of industrial importance. If conformational differences between such isomers are retained in the gas phase, IMMS could be used to address questions in biology and industry. METHODS Negative mode electrospray ionization (ESI) travelling-wave IMMS was used to resolve large isobaric α-glucan ions on the basis of their different gas-phase conformations. α,ω-Dicarboxy-terminated polystyrene was used to calibrate the instrument allowing the collision cross-sections (CCSs) of ions to be determined. RESULTS α-1,4-Linked maltooligosaccharides with a degree of polymerisation of up to 35 could be discriminated from α-1,6-linked dextran and α-1,4/1,6-linked pullulan using IMMS. Fragmentation spectra of ions separated by IMMS could also distinguish isomers. Two conformational isomers of maltohexaose were resolvable by IMMS, likely reflecting extended and V6 helical conformations. IMMS was also able to identify a product within a mixture of maltooligosaccharides treated with the potential anti-tuberculosis drug target Mycobacterium tuberculosis GlgB branching enzyme. CONCLUSIONS Biological samples of complex isobaric oligosaccharides can be analysed using IMMS in the negative mode providing facile analyses and high sensitivity without the need for either derivatisation or chromatographic separation. © 2013 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd. PMID:24338967

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Analysis of triacetone triperoxide complexes with alkali metal ions by electrospray and extractive electrospray ionisation combined with ion mobility spectrometry and mass spectrometry.

    PubMed

    Hill, Alex R; Edgar, Mark; Chatzigeorgiou, Maria; Reynolds, James C; Kelly, Paul F; Creaser, Colin S

    2015-01-01

    The complexation of triacetone triperoxide (TATP) with a range of alkali metals has been studied by electrospray ionisation-mass spectrometry yield [M+Cat](+) ions for all of the alkali metals. The formation of [2TATP+Li+LiX](+) (X = Br, Cl) sandwich complexes was also observed. Collision cross- sections for the lithium-containing complexes of TATP were measured by travelling wave ion mobility spectrometry mass spectrometry, and compared well with computationally determined structures. Extractive electrospray ionisation (EESI) using a lithium doped electrospray is demonstrated for the detection of TATP vapours desorbed from a metal surface. The limit of detection for EESI was shown to be 20 ng using the [TATP+Li](+) ion. PMID:26307706

  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. 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

  17. The analysis of methamphetamine hydrochloride by thermal desorption ion mobility spectrometry and SIMPLISMA.

    PubMed

    Reese, E S; Harrington, P B

    1999-01-01

    Ion mobility spectrometry (IMS) has been successfully developed to yield an advanced portable instrument. Such instruments may detect trace quantities of regulated substances at the crime scene. The atmospheric ion chemistry that occurs within the instrument may hinder the determination of analytes in real-world samples. The use of temperature programming adds an extra dimension to the data that improves the selectivity of the IMS data when chemometric processing is applied. The SIMPLISMA (SIMPLe-to-use-Interactive Self-Modeling Mixture Analysis) method is demonstrated for modeling variances in IMS data that are introduced from the temperature program. Methamphetamine hydrochloride IMS peaks are obscured by chemical interferences that arise from cigarette smoke residue. Cigarette smoke residue is pervasive at crime scenes. The ability of SIMPLISMA to resolve the analyte peaks that correspond to methamphetamine hydrochloride from interfering cigarette smoke has been demonstrated. A reduced mobility of 1.62 cm2V-1s-1 was observed for a methamphetamine hydrochloride monomer. With the IMS drift tube at room temperature, a second peak was observed at 1.24 cm2V-1s-1, which is consistent with a dimer ion. This peak has not been previously reported.

  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.

  19. Comparison of pulse glow discharge-ion mobility spectrometry and liquid chromatography with tandem mass spectrometry based on multiplug filtration cleanup for the analysis of tricaine mesylate residues in fish and water.

    PubMed

    Zou, Nan; Chen, Ronghua; Qin, Yuhong; Song, Shuangyu; Tang, Xinglin; Pan, Canping

    2016-09-01

    Analytical methods based on multiplug filtration cleanup coupled with pulse glow discharge-ion mobility spectrometry and liquid chromatography tandem mass spectrometry were developed for the analysis of tricaine mesylate residue in fish and fish-raising water samples. A silica fiber holder and an appropriate new interface were designed to make the direct introduction of the fiber into the pulse glow discharge-ion mobility spectrometry introduction mechanism. The multiplug filtration cleanup method with adsorption mixtures was optimized for the determination of tricaine mesylate in fish samples. Good linear relationships were obtained by the two methods. For fish samples, limits of detection were 6 and 0.6 μg/kg by ion mobility spectrometry and liquid chromatography with tandem mass spectrometry, respectively. The matrix effect of the established liquid chromatography tandem mass spectrometry method was negligible for fish samples but that of the ion mobility spectrometry method was not. The two methods were compared. The ion mobility spectrometry system could be used a rapid screening tool on site with the advantage of rapidity, simplicity, and portability, and the liquid chromatography tandem mass spectrometry system could be used for validation in laboratory conditions with the advantage of lower limit of detection, stability, and precision. PMID:27440123

  20. 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.

  1. Dopant-assisted negative photoionization ion mobility spectrometry for sensitive detection of explosives.

    PubMed

    Cheng, Shasha; Dou, Jian; Wang, Weiguo; Chen, Chuang; Hua, Lei; Zhou, Qinghua; Hou, Keyong; Li, Jinghua; Li, Haiyang

    2013-01-01

    Ion mobility spectrometry (IMS) is a key trace detection technique for explosives and the development of a simple, stable, and efficient nonradioactive ionization source is highly demanded. A dopant-assisted negative photoionization (DANP) source has been developed for IMS, which uses a commercial VUV krypton lamp to ionize acetone as the source of electrons to produce negative reactant ions in air. With 20 ppm of acetone as the dopant, a stable current of reactant ions of 1.35 nA was achieved. The reactant ions were identified to be CO(3)(-)(H(2)O)(n) (K(0) = 2.44 cm(2) V(-1) s(-1)) by atmospheric pressure time-of-flight mass spectrometry, while the reactant ions in (63)Ni source were O(2)(-)(H(2)O)(n) (K(0) = 2.30 cm(2) V(-1) s(-1)). Finally, its capabilities for detection of common explosives including ammonium nitrate fuel oil (ANFO), 2,4,6-trinitrotoluene (TNT), N-nitrobis(2-hydroxyethyl)amine dinitrate (DINA), and pentaerythritol tetranitrate (PETN) were evaluated, and the limits of detection of 10 pg (ANFO), 80 pg (TNT), and 100 pg (DINA) with a linear range of 2 orders of magnitude were achieved. The time-of-flight mass spectra obtained with use of DANP source clearly indicated that PETN and DINA can be directly ionized by the ion-association reaction of CO(3)(-) to form PETN·CO(3)(-) and DINA·CO(3)(-) adduct ions, which result in good sensitivity for the DANP source. The excellent stability, good sensitivity, and especially the better separation between the reactant and product ion peaks make the DANP a potential nonradioactive ionization source for IMS.

  2. 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.

  3. Influence of lifestyle on the FAIM2 promoter methylation between obese and lean children: a cohort study

    PubMed Central

    Wu, Lijun; Zhao, Xiaoyuan; Shen, Yue; Huang, Guimin; Zhang, Meixian; Yan, Yinkun; Hou, Dongqing; Meng, Linghui; Liu, Junting; Cheng, Hong; Mi, Jie

    2015-01-01

    Objective An obesity-related gene, Fas apoptotic inhibitory molecule 2 (FAIM2), is regulated by nutritional state and the methylation levels of the FAIM2 promoter are significantly associated with obesity. Lifestyle factors, such as sedentary behaviour and physical activity, might modify epigenetic patterns that have been related to obesity. Whether the molecular mechanisms by which FAIM2 affects obesity are involved in lifestyle is unclear. This study investigates the potential differences of the FAIM2 promoter methylation with sedentary behaviour and physical activity in obese and lean children. Design Cohort study. Setting Institute of Pediatrics in China. Participants 59 obese cases and 39 lean controls aged 8–18 years recruited from a cross-sectional survey of children from Beijing in 2013. Primary and secondary outcome measures The FAIM2 promoter methylation was quantified using the Sequenom MassARRAY platform. Sedentary behaviour and physical activity were investigated using a questionnaire. The influences of different lifestyles on methylation variations in obese and lean children were examined by multiple linear regression. Results The methylation levels at seven CpG sites of the FAIM2 promoter were significantly associated with sedentary behaviour, especially the methylation levels at site −975, site −413, sites −362 and −360, and sites −353 and −349 (p=0.00004, 0.00009, 0.0006 and 0.00005, respectively). There were significant differences between the methylation levels at four CpG sites in obese and lean participants with high or moderate physical activity level <150 min/week. Conclusions This study provides the first evidence that there are significant differences in the associations of the FAIM2 promoter methylation with sedentary behaviour and physical activity between obese and lean children. Our results suggest that lifestyle may possibly be mediating the process of the FAIM2 involved in obesity. PMID:25922107

  4. Gas-phase metalloprotein complexes interrogated by ion mobility-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Faull, Peter A.; Korkeila, Karoliina E.; Kalapothakis, Jason M.; Gray, Andrew; McCullough, Bryan J.; Barran, Perdita E.

    2009-06-01

    Gas-phase biomolecular structure may be explored through a number of analytical techniques. Ion mobility-mass spectrometry (IM-MS) continues to prove itself as a sensitive and reliable bioanalytical tool for gas-phase structure determination due to intense study and development over the past 15 years. A vast amount of research interest, especially in protein and peptide conformational studies has generated a wealth of structural information for biological systems from small peptides to megadalton-sized biomolecules. In this work, linear low field IM-MS has been used to study gas-phase conformations and determine rotationally averaged collision cross-sections of three metalloproteins--cytochrome c, haemoglobin and calmodulin. Measurements have been performed on the MoQToF, a modified QToF 1 instrument (Micromass UK Ltd., Manchester, UK) modified in house. Gas-phase conformations and cross-sections of multimeric cytochrome c ions of the form [xM + nH+]n+ for x = 1-3 (monomer to trimer) have been successfully characterised and measured. We believe these to be the first reported collision cross-sections of higher order multimeric cytochrome c. Haemoglobin is investigated to obtain structural information on the associative mechanism of tetramer formation. Haemoglobin molecules, comprising apo- and holo-monomer chains, dimer and tetramer are transferred to the gas phase under a range of solution conditions. Structural information on the proposed critical intermediate, semi-haemoglobin, is reported. Cross-sections of the calcium binding protein calmodulin have been obtained under a range of calcium-bound conditions. Metalloprotein collision cross-sections from ion mobility measurements are compared with computationally derived values from published NMR and X-ray crystallography structural data. Finally we consider the change in the density of the experimentally measured rotationally averaged collision cross-section for compact geometries of the electrosprayed proteins.

  5. 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.

  6. 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

  7. 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

  8. Development of a short pulsed corona discharge ionization source for ion mobility spectrometry

    SciTech Connect

    An Yuan; Aliaga-Rossel, R.; Choi, Peter; Gilles, Jean-Paul

    2005-08-15

    The development of a pulsed corona discharge ionization source and its use in ion mobility spectrometry (IMS) is presented. In a point-plane electrode geometry, an electrical pulse up to 12 kV, 150 ns rise time and 500 ns pulse width was used to generate a corona discharge in air. A single positive high voltage pulse was able to generate about 1.6x10{sup 10} ions at energy consumption of 22 {mu}J. Since the temporal distribution of ions is in a pulsed form, the possibility of removal the ion gate has been investigated. By purposely arranging the interface between discharge field and drift field, nearly 10{sup 7} positive ions were drawn into the drift region with absence of the ion gate after every single discharge. The positive spectrum of acetone dimer (working at room temperature) was obtained with a resolving power of 20 by using this configuration. The advantages of this new scheme are the low power consumption compared with the dc method as well as the simplicity of the IMS cell structure.

  9. 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.

  10. 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.

  11. 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

  12. Determination of fuel ethers in water by membrane extraction ion mobility spectrometry.

    PubMed

    Holopainen, Sanna; Nousiainen, Marjaana; Sillanpää, Mika

    2013-03-15

    Fuel oxygenates are environmentally detrimental compounds due to their rapid migration to groundwater. Fuel oxygenates have been reported to cause taste and odour problems in drinking water, and they also have long-term health effects. Feasible analytical methods are required to observe the presence of fuel oxygenates in drinking and natural water. The authors studied ion mobility spectrometry (IMS) to determinate isomeric fuel ether oxygenates; ethyl tert-butyl ether (ETBE), diisopropyl ether (DIPE), and tert-amyl methyl ether (TAME), separated from aqueous matrices with a pervaporation membrane module. Methyl tert-butyl ether (MTBE) was also membrane extracted and detected with IMS. The authors demonstrated that fuel ethers (MTBE, ETBE, DIPE, and TAME) can be quantified at μg/L level with membrane extraction IMS. A membrane extraction module coupled to IMS is a time and cost effective analysis method because sampling can be performed in a single procedure and from different natural water matrices within a few minutes. Consequently, IMS combined with membrane extraction is suitable not only for waterworks and other online applications but also in the field monitoring the quality of drinking and natural water.

  13. Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5.

    PubMed

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

    2015-08-01

    Many proteins exhibit conformation flexibility as part of their biological function, whether through the presence of a series of well-defined states or by the existence of intrinsic disorder. Ion mobility spectrometry, in combination with MS (IM-MS), offers a rapid and sensitive means of probing ensembles of protein structures through measurement of gas-phase collisional cross sections. We have applied IM-MS analysis to the multidomain deubiquitinating enzyme ubiquitin specific protease 5 (USP5), which is believed to exhibit significant conformational flexibility. Native ESI-MS measurement of the 94-kDa USP5 revealed two distinct charge-state distributions: [M + 17H](+) to [M + 21H](+) and [M + 24H](+) to [M + 29H](+). The collisional cross sections of these ions revealed clear groupings of 52 ± 4 nm(2) for the lower charges and 66 ± 6 nm(2) for the higher charges. Molecular dynamics simulation of a compact form of USP5, based on a crystal structure, produced structures of 53-54 nm(2) following 2 ns in the gas phase, while simulation of an extended form (based on small-angle X-ray scattering data) led to structures of 64 nm(2). These data demonstrate that IM-MS is a valuable tool in studying proteins with different discrete conformational states.

  14. 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

  15. 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

  16. Ion mobility spectrometry: a comprehensive and versatile tool for occupational pharmaceutical exposure assessment.

    PubMed

    Armenta, S; Blanco, M

    2012-05-15

    The qualitative and quantitative capabilities of ion mobility spectrometry (IMS) as a comprehensive and powerful tool in workplace air monitoring have been demonstrated on the example of a Spanish pharmaceutical company. The developed IMS based procedure is capable of detecting and determining in air samples the active pharmaceutical ingredients (APIs) manipulated and/or produced in this pharmaceutical industry. Sensitivity, in the ng-pg range, selectivity, possibly to provide results in near real time, and reduction of analysis costs are the most important properties that ratify IMS as a serious alternative in occupational exposure assessment. The possibility of false positives by drift time interferences and false negatives by competitive ionization and also desorption process interferences has been deeply evaluated. Moreover, chemometric strategies based on self-modeling curve resolution (SMCR) have been applied to obtain qualitative and quantitative individual component information from overlapped peaks. The IMS procedure has been successfully applied to evaluate the concentration of APIs (nimesulide, dexketoprofen, deflazacort) handled by the pharmaceutical company employees in the making of tablets and granulates, and control measures have been suggested in accordance.

  17. Characterization and validation of ion mobility spectrometry in methamphetamine clandestine laboratory remediation.

    PubMed

    Moran, Jordan; McCall, Holly; Yeager, Brittany; Bell, Suzanne

    2012-10-15

    This project evaluated the efficacy of ion mobility spectrometry (IMS) as a tool for determining remediation success at clandestine methamphetamine laboratory sites. Specifically, limits of detection (LOD), limits of quantitation (LOQ), and matrix effects were investigated as relevant to typical remediation sites and situations. The recoveries of pseudoephedrine and methamphetamine from a range of various surfaces likely to be found in a clandestine laboratory were examined. Portable IMS instruments with thermal desorption were found to be a reliable tool for evaluating the degree of remediation if sufficient procedural and instrumental controls are put into place. In general, detection limits were in the same range as state guidelines as well as laboratory methods using GC/MS and LC/MS. Direct vapor sampling can be used to detect high levels of methamphetamine and potential interferences, but cannot approach the detection limits needed for evaluation of remediation efforts. IMS cannot be used alone to determine the efficacy of remediation efforts; final confirmation using laboratory instrumentation is essential. For the purpose of this study, typical field settings of the IMS were used and the conditions were not optimized.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Discrimination of Isomeric Carbohydrates as the Electron Transfer Products of Group II Cation Adducts by Ion Mobility Spectrometry and Tandem Mass Spectrometry.

    PubMed

    Huang, Yuting; Dodds, Eric D

    2015-06-01

    The rapid and unambiguous distinction of isomeric carbohydrate structures persists as a tremendous analytical challenge. This paper reports the first exploitation of carbohydrate/metal ion interactions in concert with gas-phase ion chemistry to improve discrimination of oligosaccharide isomers by both ion mobility spectrometry and tandem mass spectrometry. This is demonstrated for two isomeric pentasaccharides and two isomeric hexasaccharides, each studied in an underivatized form as their calcium ion adducts, barium ion adducts, and gas-phase electron transfer products thereof. With appropriate selection of the charge carrier, transfer of a single electron to the carbohydrate metal ion adducts resulted in isomer-distinguishing shifts in their ion/neutral collision cross sections and the appearance of unique features in their vibrational activation/dissociation spectra. These findings suggest novel and elegant gas-phase strategies for rapid differentiation of isomeric oligosaccharides.

  3. Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes.

    PubMed

    Huo, J; Xu, S; Guo, K; Zeng, Q; Lam, K-P

    2009-07-01

    Fas-apoptosis inhibitory molecule (FAIM) is inducibly expressed in B lymphocytes and had been shown to antagonize Fas-mediated killing of B-cell lines in vitro. However, its mechanism and role in vivo are unknown. We have generated faim(-/-) mice and found these mutants to be viable. In contrast to fas(-/-) mice, faim(-/-) mice have normal B- and T-cell populations. However, faim(-/-) B cells and thymocytes show increased sensitivity to Fas-triggered apoptosis in vitro, and faim(-/-) mice suffer greater mortality and exhibit exacerbated liver damage in response to Fas (CD95) engagement in vivo. The lack of FAIM results in greater activation of caspase-8 and -3 in Fas-stimulated thymocytes. Detailed biochemical analyses further reveal the decreased expression of c-FLIP(L) and c-FLIP(R) in faim(-/-) thymocytes and increased association of caspase-8 with Fas in Fas-activated mutant cells. Decreased levels of c-FLIP(L) and c-FLIP(R) are also evident in faim(-/-) liver. Thus, FAIM plays a novel role in modulating Fas-mediated apoptosis and acts through influencing the expression of c-FLIP and regulating the physical binding of caspase-8 to Fas.

  4. The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kapp B signaling.

    PubMed

    Sole, Carme; Dolcet, Xavier; Segura, Miguel F; Gutierrez, Humberto; Diaz-Meco, Maria-Teresa; Gozzelino, Raffaella; Sanchis, Daniel; Bayascas, Jose R; Gallego, Carme; Moscat, Jorge; Davies, Alun M; Comella, Joan X

    2004-11-01

    Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist of Fas-induced cell death. We show that FAIM overexpression fails to rescue neurons from trophic factor deprivation, but exerts a marked neurite growth-promoting action in different neuronal systems. Whereas FAIM overexpression greatly enhanced neurite outgrowth from PC12 cells and sympathetic neurons grown with nerve growth factor (NGF), reduction of endogenous FAIM levels by RNAi decreased neurite outgrowth in these cells. FAIM overexpression promoted NF-kappa B activation, and blocking this activation by using a super-repressor I kappa B alpha or by carrying out experiments using cortical neurons from mice that lack the p65 NF-kappa B subunit prevented FAIM-induced neurite outgrowth. The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras-ERK pathway. Finally, we show that FAIM interacts with both Trk and p75 neurotrophin receptor NGF receptors in a ligand-dependent manner. These results reveal a new function of FAIM in promoting neurite outgrowth by a mechanism involving activation of the Ras-ERK pathway and NF-kappa B.

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

    PubMed Central

    2015-01-01

    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 the efficient switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be efficiently directed 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 of, for example, the selection of specific mobilities for storage and accumulation, and the key component of modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations. PMID:25222548

  6. 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

  7. Transversal modulation ion mobility spectrometry (IMS) coupled with mass spectrometry (MS): exploring the IMS-IMS-MS possibilities of the instrument.

    PubMed

    Vidal-de-Miguel, G; Macía, M; Barrios, C; Cuevas, J

    2015-02-01

    A prototype is introduced based on the transversal modulation ion mobility spectrometry (TMIMS) technique, which provides a continuous output of mobility-selected ions, greatly easing the synchronization between different analyzing stages. In the new architecture, two stages of filtration are used to drastically reduce the background produced by one stage alone. Two-stages TMIMS was coupled with two different atmospheric pressure interface mass spectrometers (MS). The new system enables IMS-IMS-MS analysis and other modes of operation: IMS prefiltration, IMS-IMS, and full transmission mode. It provides a resolving power R > 60 in IMS mode, and R > 40 in each stage of IMS-IMS mode. 2-Propanol vapors were introduced in one of the stages to enhance the mobility variations, and their effect was studied on a set of tetraalkylammonium ions. We found that concentrations as low as 1% (in partial pressure) produce mobility variations as high as 20%, which suggest that IMS-IMS separation using dried N2 (in one stage) and a dopant (in the other stage), could be a very powerful way to enhance the separation capacity of the IMS-IMS prefiltration approach.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Characterization of Polylactides with Different Stereoregularity Using Electrospray Ionization Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kim, Kihyun; Lee, Jong Wha; Chang, Taihyun; Kim, Hugh I.

    2014-10-01

    We investigated the effect of stereoregularity on the gas-phase conformations of linear and cyclic polylactides (PLA) using electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) combined with molecular dynamics simulations. IM-MS analysis of PLA ions shows intriguing difference between the collision cross section (ΩD) value of poly-L-lactide (PLLA) and poly-LD-lactide (PLDLA) ions with respect to their chain architecture and stereoregularity. In the singly sodiated linear PLA ( l-PLA•Na+) case, both l-PLLA and l-PLDLA up to 11mer have very similar ΩD values, but the ΩD values of l-PLLA are greater than that of l-PLDLA ions for larger ions. In the case of cyclic PLA ( c-PLA), c-PLLA•Na+ is more compact than c-PLDLA•Na+ for short PLA ions. However, c-PLLA exhibits larger ΩD value than c-PLDLA for PLA ions longer than 13mer. The origin of difference in the ΩD values was investigated using theoretical investigation of PLAs in the gas phase. The gas-phase conformation of PLA ions is influenced by Na+-oxygen coordination and the weak intramolecular hydrogen bond interaction, which are more effectively formed in more flexible chains. Therefore, the less flexible PLLA has a larger ΩD value than PLDLA. However, for short c-PLA, concomitant maximization of both Na+-oxygen coordination and hydrogen bond interaction is difficult due to the constricted chain freedom, which makes the ΩD value of PLAs in this range show a different trend compared with other PLA ions. Our study facilitates the understanding of correlation between stereoregularity of PLAs and their structure, providing potential utility of IM-MS to characterize stereoisomers of polymers.

  13. 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.

  14. 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.

  15. Analysis of methanobactin from Methylosinus trichosporium OB3b via ion mobility mass spectrometry.

    PubMed

    Choi, DongWon; Sesham, Ramakrishna; Kim, Yuri; Angel, Laurence A

    2012-01-01

    Methanobactins (mbs) are Low molecular mass copper binding chromopeptides analogous to pyoverdin class iron-binding siderophores. Mb produced by Methylosinus trichosporium OB3b (mb-oB3b) has been used as a model molecuLe for methanobactin although the amino acid sequence of mb-OB3b differs significantly from other characterized mbs. In particular, there is the presence of a pair of cystine residues which are absent in other characterized mbs. The role of the Cys3-Cys6 in copper binding, Cu(ll) reduction and its role on the mb-OB3b structure remains in debate. Here, we use a single-step dithiothreitol treatment as an effective method in reducing the disulfide bond allowing in-depth ion mobility-mass spectrometry (IM-MS) analysis. The IM-MS results show mb-oB3b exists in the gas-phase as three different negatively-charged states and exists in multiple conformational states, when introduced via electrospray ionization from aqueous solution near physiological pH. The disulfide bond serves a structural role and is not involved in the Cu(I/ll) binding capability of mb-OB3b, with the binding of a second Cu(I/ll) related to a further deprotonation of mb-OB3b. Overall, these findings are in good correlation with expected solution-phase behavior of mb-OB3b. The results suggest IM-MS is an effective tool for better understanding the complex nature of this intriguing peptide. PMID:23654196

  16. Understanding gas phase modifier interactions in rapid analysis by differential mobility-tandem mass spectrometry.

    PubMed

    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 10(6) 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.

  17. 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

  18. Comprehensive analysis of fatty alcohol ethoxylates by ultra high pressure hydrophilic interaction chromatography coupled with ion mobility spectrometry mass spectrometry using a custom-designed sub-2 μm column.

    PubMed

    Ma, Qiang; Ma, Wei; Chen, Xi; Wang, Ziming; Bai, Hua; Zhang, Lanwei; Li, Wentao; Wang, Chao; Li, Xinshi

    2015-06-01

    Comprehensive analysis of fatty alcohol ethoxylates has been conducted by coupling ultra high pressure hydrophilic interaction chromatography and ion mobility spectrometry mass spectrometry. A custom-designed sub-2 μm column was used for the chromatographic separation of fatty alcohol ethoxylates by hydrophilic interaction chromatography. Ion mobility spectrometry provided a post-ionization resolution during a very short period of 6.4 ms. Distinguishable families of singly, doubly, and triply charged fatty alcohol ethoxylates were clearly observed. By virtue of the combination of hydrophilic interaction chromatography and ion mobility spectrometry, comprehensive resolution based on both hydrophobicity difference and mobility disparity has been achieved for fatty alcohol ethoxylates. The orthogonality of the developed separation and analysis system was evaluated with the correlation coefficient and peak spreading angle of 0.0224 and 88.72°, respectively. The actual peak capacity obtained was individually 40 and 193 times than those when hydrophilic interaction chromatography and ion mobility spectrometry were used alone. The collision cross-sections of fatty alcohol ethoxylates were calculated by calibrating the traveling wave ion mobility device with polyalanine.

  19. 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

  20. Ion mobility spectrometry-mass spectrometry studies of ion processes in air at atmospheric pressure and their application to thermal desorption of 2,4,6-trinitrotoluene

    NASA Astrophysics Data System (ADS)

    Sabo, Martin; Malásková, Michaela; Matejčík, Štefan

    2014-02-01

    In this study we have investigated the negative reactant ion formation in a negative corona discharge (CD) using the corona discharge ion mobility spectrometry orthogonal acceleration time-of-flight (CD-IMS-oaTOF) technique. The reactant ions were formed in the CD operating in the reverse gas flow mode at an elevated temperature of 363.5 K in synthetic and ambient air. Under these conditions mainly O_{2}^{-} and their clusters were formed. We have also studied the influence of CCl4 admixture to air (dopant gas) on the composition of the reactant ions, which resulted in the formation of Cl- and its clusters with a reduced ion mobility of 3.05 cm2 V-1 s-1 as a major reactant ion peak. Additional IMS peaks with reduced ion mobilities of 2.49, 2.25 and 2.03 cm2 V-1 s-1 were detected, and Cl- · (NO2) and Cl- · (NO)n(n = 2, 3) anions were identified. The negative reactant ions were used to detect 2,4,6 trinitrotoluene (TNT) using the thermal desorption (TD) technique using a CD-IMS instrument. Using TD sampling and a negative CD ion source doped by CCl4 we have achieved a limit of detection of 350 pg for direct surface analysis of TNT.

  1. Fast vaporization solid phase microextraction and ion mobility spectrometry: A new approach for determination of creatinine in biological fluids.

    PubMed

    Jafari, Mostafa; Ebrahimzadeh, Homeira; Banitaba, Mohamma Hossein

    2015-11-01

    In this work a rapid and simple method for creatinine determination in urine and plasma samples based on aqueous derivatization of creatinine and complete vaporization of sample (as low as 10 µL), followed by ion mobility spectrometry analysis has been proposed. The effect of four important parameters (extraction temperature, total volume of solution, desorption temperature and extraction time) on ion mobility signal has been studied. Under the optimized conditions, the quantitative response of ion mobility spectrometry for creatinine was linear in the range of 0-500 mg L(-1) with a detection limit of 0.6 mg L(-1) in urine and 0-250 mg L(-1) with a detection limit of 2.6 mg L(-1) in plasma sample. The limit of quantitation of creatinine was 2.1 mg L(-1) and 8.7 mg L(-1) in urine and plasma samples, respectively. The relative standard deviation of the method was found to be 13%. The method was successfully applied to the analysis of creatinine in biological samples, showing recoveries from 92% to 104% in urine and 101-110% in plasma samples. PMID:26452850

  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.

  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. Determination of cross sections by overtone mobility spectrometry: evidence for loss of unstable structures at higher overtones.

    PubMed

    Lee, Sunyoung; Ewing, Michael A; Nachtigall, Fabiane M; Kurulugama, Ruwan T; Valentine, Stephen J; Clemmer, David E

    2010-09-30

    Overtone mobility spectrometry (OMS) is examined as a means of determining the collision cross sections for multiply charged ubiquitin and substance P ions, as well as for singly charged rafinose and melezitose ions. Overall, values of collision cross section measured by OMS for stable ion conformations are found to be in agreement with values determined by conventional ion mobility spectrometry (IMS) measurements to within ∼1% relative uncertainty. The OMS spectra for ubiquitin ions appear to favor different conformations at higher overtones. We propose that the changes in the distributions as a function of the overtone region in which they are measured arise from the elimination of ions that undergo structural transitions in the drift regions. Kinetics simulations suggest that structural transitions occurring on the order of a few ms and resulting in an ∼4% change in ion collision cross sections are detected by OMS measurements. The unique method of distinguishing ion mobilities with OMS reveals these structural transitions which are not readily apparent from traditional IMS measurements.

  5. 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.

  6. Triacylglycerol mobilization is suppressed by brefeldin A in Chlamydomonas reinhardtii.

    PubMed

    Kato, Naohiro; Dong, Trung; Bailey, Michael; Lum, Tony; Ingram, Drury

    2013-10-01

    Brefeldin A suppresses vesicle trafficking by inhibiting exchange of GDP for GTP in ADP-ribosylation factor. We report that brefeldin A suppresses mobilization of triacylglycerols in Chlamydomonas reinhardtii, a model organism of green microalgae. Analyses revealed that brefeldin A causes Chlamydomonas to form lipid droplets in which triacylglycerols accumulate in a dose-dependent manner. Pulse labeling experiment using fluorescent fatty acids suggested that brefeldin A inhibits the cells from degrading fatty acids. The experiment also revealed that the cells transiently form novel compartments that accumulate exogenously added fatty acids in the cytoplasm, designated fatty acid-induced microbodies (FAIMs). Brefeldin A up-regulates the formation of FAIMs, whereas nitrogen deprivation that up-regulates triacylglycerol synthesis in Chlamydomonas does not cause the cells to form FAIMs. These results underscore the role of the vesicle trafficking machinery in triacylglycerol metabolism in green microalgae.

  7. 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.

  8. A kinetic study on decomposition of proton-bound dimer using data obtained by ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Jazan, Elham; Ghazali Khoob, Abdolhosein S.

    2014-08-01

    In this study, an equation for measuring the rate constant of the proton-bound dimer decomposition reaction was derived using the data obtained by ion mobility spectrometry (IMS) technique. The ion mobility spectra of cyclohexanone (as the test compound) were obtained at various temperatures and different electric fields. The applied electric field for each temperature was varied between 375 and 500 V cm-1 and the rate constant values of 188.24, 180.54, 280.64, 288.34 and 379.60 s-1 were obtained at different temperatures of 463, 468, 473, 478 and 483 K, respectively. Subsequently, the activation energy and pre-exponential factor were calculated to be 69.5 kJ mol-1 and 1.2 × 1010 s-1, respectively. In addition, the standard enthalpy changes were calculated for the dimer decomposition reaction of cyclohexanone at the above-mentioned temperatures.

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

    PubMed

    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. Graphical Abstract ᅟ.

  10. Rapid analysis of tile industry gaseous emissions by ion mobility spectrometry and comparison with solid phase micro-extraction/gas chromatography/mass spectrometry.

    PubMed

    Pozzi, R; Bocchini, P; Pinelli, F; Galletti, G C

    2006-12-01

    The present paper reports on a rapid method for the analysis of gaseous emissions from ceramic industry, based on ion mobility spectrometry (IMS) as a means for on-site monitoring of volatile organic compounds (VOCs) produced during tile baking. IMS was calibrated with a set of reference compounds (i.e. ethyl acetate, ethanol, ethylene glycol, diethylene glycol, acetaldehyde, formaldehyde, 2-methyl-1,3-dioxolane, 2,2-dimethyl-1,3-dioxolane, 1,3-dioxolane, 1,4-dioxane, benzene, toluene, cyclohexane, acetone, acetic acid) via air-flow permeation. The technique was tested on a laboratory-scale kiln and tiles prepared with selected glycol- and resin-based additives. Finally, the analytical method was applied to emissions from two industries in the Modena (Italy) ceramic area. The results of all experimental phases were compared to those obtained by solid phase micro-extraction/gas chromatography/mass spectrometry (SPME/GC/MS). IMS showed potential as a real-time monitoring device for quality assessment in ceramic industry emissions. IMS spectra, SPME/GC/MS data, relationship between additives/baking conditions and produced VOCs and advantages and limitations of both techniques will be discussed.

  11. 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

    2016-10-01

    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.

  12. 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.

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

    PubMed

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

    2016-10-01

    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. Graphical Abstract ᅟ. PMID:27392730

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

    PubMed

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

    2016-10-01

    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. Graphical Abstract ᅟ.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Simultaneous determination of nitrite and nitrate in potato and water samples using negative electrospray ionization ion mobility spectrometry.

    PubMed

    Jafari, M T; Torki, F; Saraji, M

    2012-01-01

    Nowadays, nitrite and nitrate ions are analyzed in biological samples using laborious and expensive methods; such as HPLC, CE, MS-MS. In this work, the simultaneous analysis of nitrite and nitrate ions was conducted by electrospray ionization-ion mobility spectrometry (ESI-IMS), without using any complicated or laborious derivitization step. Ion mobility spectrometry with low cost, inexpensive maintenance and very fast analysis makes an attractive technique for the simultaneous determination of these ions in foodstuff and drinking water samples. The analyte interference was systematically investigated for binary mixture analysis. The obtained results provided detection limits of 3.8 and 4.7 µg/L for nitrite and nitrate, respectively. A linear dynamic range of about 2 orders of magnitude, and relative standard deviations below 5% were obtained by the proposed method for the analysis of both ions. Also, the proposed method was used to analyze various real samples of potato and drinking water samples, and the obtained results confirmed the capability of negative ESI-IMS for the simultaneous detection of nitrite and nitrate.

  20. 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

  1. 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.

  2. A new method based on electrospray ionisation ion mobility spectrometry (ESI-IMS) for simultaneous determination of caffeine and theophylline.

    PubMed

    Jafari, M T; Rezaei, B; Javaheri, M

    2011-06-15

    In this work for the first time, simultaneous analysis of caffeine and theophylline was done by ion mobility spectrometry (IMS) only, without a powerful separation technique (e.g., HPLC). Ion mobility spectrometry with low cost, inexpensive maintenance and very fast analysis makes an attractive technique for the simultaneous determination of the caffeine and theophylline in foodstuff samples and biological matrices. In this study, the extraction protocol using molecular imprinted polymer-solid phase extraction (MIP-SPE) was successfully used to directly extract caffeine and theophylline from real samples. The results obtained provided the detection limits of 0.2 and 0.3μgmL(-1) for caffeine and theophylline, respectively. The linear dynamic range of about two orders of magnitude was obtained for these compounds. Also, the proposed method was used to analyse various real samples of green tea and spiked human plasma, and the obtained results confirmed the capability of ESI-IMS for simultaneous detection of caffeine and theophylline.

  3. External Second Gate, Fourier Transform Ion Mobility Spectrometry: Parametric Optimization for Detection of Weapons of Mass Destruction

    PubMed Central

    Tarver, Edward E.

    2004-01-01

    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 efforts have mandated that equal importance be placed on the time required to obtain results as well as the quality of the analytical data. [1] In this regard IMS is virtually unrivaled when both speed of response and sensitivity have to be considered. [2] 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. 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 (scan time and sampling rate) to increase the spectral resolution to reduce false alarms and improve the sensitivity for early warning and contamination avoidance. In addition, with FT-IMS the entrance gate operates with a 50% duty cycle and so affords a seven-fold increase in sensitivity. Recent data on high explosives are presented to demonstrate the parametric optimization in sensitivity and resolution of our system.

  4. 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.

  5. 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.

  6. Ion mobility-mass spectrometry with a radial opposed migration ion and aerosol classifier (ROMIAC).

    PubMed

    Mui, Wilton; Thomas, Daniel A; Downard, Andrew J; Beauchamp, Jesse L; Seinfeld, John H; Flagan, Richard C

    2013-07-01

    The first application of a novel differential mobility analyzer, the radial opposed migration ion and aerosol classifier (ROMIAC), is demonstrated. The ROMIAC uses antiparallel forces from an electric field and a cross-flow gas to both scan ion mobilities and continuously transmit target mobility ions with 100% duty cycle. In the ROMIAC, diffusive losses are minimized, and resolution of ions, with collisional cross-sections of 200-2000 Å(2), is achieved near the nondispersive resolution of ~20. Higher resolution is theoretically possible with greater cross-flow rates. The ROMIAC was coupled to a linear trap quadrupole mass spectrometer and used to classify electrosprayed C2-C12 tetra-alkyl ammonium ions, bradykinin, angiotensin I, angiotensin II, bovine ubiquitin, and two pairs of model peptide isomers. Instrument and mobility calibrations of the ROMIAC show that it exhibits linear responses to changes in electrode potential, making the ROMIAC suitable for mobility and cross-section measurements. The high resolution of the ROMIAC facilitates separation of isobaric isomeric peptides. Monitoring distinct dissociation pathways associated with peptide isomers fully resolves overlapping peaks in the ion mobility data. The ability of the ROMIAC to operate at atmospheric pressure and serve as a front-end analyzer to continuously transmit ions with a particular mobility facilitates extensive studies of target molecules using a variety of mass spectrometric methods. PMID:23730869

  7. Evaluation of ion mobility-mass spectrometry for determining the isomeric heterogeneity of oligosaccharide-alditols derived from bovine submaxillary mucin.

    PubMed

    Li, Hongli; Bendiak, Brad; Kaplan, Kimberly; Davis, Eric; Siems, William F; Hill, Herbert H

    2013-10-15

    Rapid separation and independent analysis of isomeric species are needed for the structural characterization of carbohydrates in glycomics research. Ion mobility-mass spectrometry techniques were used to examine a series of isomeric neutral oligosaccharide-alditols derived from bovine submaxillary mucin. Several analytical techniques were employed: (1) off line separation of the oligosaccharide-alditol mixture by HPLC; (2) direct and rapid evaluation of isomeric heterogeneity of oligosaccharides by electrospray ionization-ion mobility-time of flight mass spectrometry; and (3) mobility-selected MS(2) and MS(3) to evaluate isomeric mobility peaks by dual gate ion mobility-tandem mass spectrometry. Multiple isomeric ion mobility peaks were observed for the majority of oligosaccharide-alditols, which was achieved on the millisecond time scale after LC separation. Fragmentation spectra obtained from the collision-induced dissociation of isomeric precursor ions could be essentially identical, or dramatically different for a given precursor m/z using the dual-gate ion mobility quadrupole ion trap mass spectrometer. This further confirmed the need for rapid physical resolution of isomeric precursor species prior to their tandem mass spectral analysis.

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

    DOE PAGES

    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

  9. ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death.

    PubMed

    Besirli, Cagri G; Zheng, Qiong-Duon; Reed, David M; Zacks, David N

    2012-01-01

    In this study, we examined the role of Fas apoptotic inhibitory molecule 2 (Faim2), an inhibitor of the Fas signaling pathway, and its regulation by stress kinase signaling during Fas-mediated apoptosis of 661W cells, an immortalized photoreceptor-like cell line Treatment of 661W cells with a Fas-activating antibody led to increased levels of Faim2. Both ERK and JNK stress kinase pathways were activated in Fas-treated 661W cells, but only the inhibition of the ERK pathway reduced the levels of Faim2. Blocking the ERK pathway using a pharmacological inhibitor increased the susceptibility of 661W cells to Fas-induced caspase activation and apoptosis. When the levels of Faim2 were reduced in 661W cells by siRNA knockdown, Fas activating antibody treatment resulted in earlier and more robust caspase activation, and increased cell death. These results demonstrate that Faim2 acts as a neuroprotectant during Fas-mediated apoptosis of 661W cells. The expression of Faim2 is triggered, at least in part, by Fas-receptor activation and subsequent ERK signaling. Our findings identify a novel protective pathway that auto-regulates Fas-induced photoreceptor apoptosis in vitro. Modulation of this pathway to increase Faim2 expression may be a potential therapeutic option to prevent photoreceptor death.

  10. ERK-Mediated Activation of Fas Apoptotic Inhibitory Molecule 2 (Faim2) Prevents Apoptosis of 661W Cells in a Model of Detachment-Induced Photoreceptor Cell Death

    PubMed Central

    Besirli, Cagri G.; Zheng, Qiong-Duon; Reed, David M.; Zacks, David N.

    2012-01-01

    In this study, we examined the role of Fas apoptotic inhibitory molecule 2 (Faim2), an inhibitor of the Fas signaling pathway, and its regulation by stress kinase signaling during Fas-mediated apoptosis of 661W cells, an immortalized photoreceptor-like cell line Treatment of 661W cells with a Fas-activating antibody led to increased levels of Faim2. Both ERK and JNK stress kinase pathways were activated in Fas-treated 661W cells, but only the inhibition of the ERK pathway reduced the levels of Faim2. Blocking the ERK pathway using a pharmacological inhibitor increased the susceptibility of 661W cells to Fas-induced caspase activation and apoptosis. When the levels of Faim2 were reduced in 661W cells by siRNA knockdown, Fas activating antibody treatment resulted in earlier and more robust caspase activation, and increased cell death. These results demonstrate that Faim2 acts as a neuroprotectant during Fas-mediated apoptosis of 661W cells. The expression of Faim2 is triggered, at least in part, by Fas-receptor activation and subsequent ERK signaling. Our findings identify a novel protective pathway that auto-regulates Fas-induced photoreceptor apoptosis in vitro. Modulation of this pathway to increase Faim2 expression may be a potential therapeutic option to prevent photoreceptor death. PMID:23029562

  11. The Influence of Drift Gas Composition on the Separation Mechanism in Traveling Wave Ion Mobility Spectrometry: Insight from Electrodynamic Simulations.

    PubMed

    May, Jody C; McLean, John A

    2003-06-01

    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.

  12. 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.

  13. [Rapid detection of residual cyclohexanone in disposable medical devices by ultraviolet photoionization ion mobility spectrometry (UV-IMS)].

    PubMed

    Li, Hu; Han, Hai-yan; Niu, Wen-qi; Wang, Hong-mei; Huang, Chao-qun; Jiang, Hai-he; Chu, Yan-nan

    2012-01-01

    In the manufacture of disposable PVC medical devices, cyclohexanone is frequently used as an adhesive reagent, which can be released into the tube airspace or stored solution and thus may cause some adverse effects on patients in therapy. In this paper, an ultraviolet photoionization ion mobility spectrometry (UV-IMS) technique has been developed to detect cyclohexanone through monitoring the gas composition within a package of infusion sets. The concentrations of cyclohexanone were prepared by means of exponential dilution method, and the experiments show that the UV-IMS has a limit of detection at 15 ppb and its measurable linear dynamics range is over three orders of magnitude. The concentrations of cyclohexanone in three brands of infusion sets packages were determined to be 16.78, 17.59 and 46.69 ppm respectively. The UV-IMS is proposed as a tool for the quality control of medical devices to monitor illegal uses of chemical solvents like cyclohexanone.

  14. 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.

  15. Ion mobility-mass spectrometry of a rotary ATPase reveals ATP-induced reduction in conformational flexibility

    NASA Astrophysics Data System (ADS)

    Zhou, Min; Politis, Argyris; Davies, Roberta B.; Liko, Idlir; Wu, Kuan-Jung; Stewart, Alastair G.; Stock, Daniela; Robinson, Carol V.

    2014-03-01

    Rotary ATPases play fundamental roles in energy conversion as their catalytic rotation is associated with interdomain fluctuations and heterogeneity of conformational states. Using ion mobility mass spectrometry we compared the conformational dynamics of the intact ATPase from Thermus thermophilus with those of its membrane and soluble subcomplexes. Our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. To provide a structural context for our experimental data we performed molecular dynamics simulations and observed conformational changes of the peripheral stalks that reflect their intrinsic flexibility. By isolating complexes at different phases of cell growth and manipulating nucleotides, metal ions and pH during isolation, we reveal differences that can be related to conformational changes in the Vo complex triggered by ATP binding. Together these results implicate nucleotides in modulating flexibility of the stator components and uncover mechanistic detail that underlies operation and regulation in the context of the holoenzyme.

  16. 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

  17. 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.

  18. Ion mobility-mass spectrometry of a rotary ATPase reveals ATP-induced reduction in conformational flexibility.

    PubMed

    Zhou, Min; Politis, Argyris; Davies, Roberta B; Liko, Idlir; Wu, Kuan-Jung; Stewart, Alastair G; Stock, Daniela; Robinson, Carol V

    2014-03-01

    Rotary ATPases play fundamental roles in energy conversion as their catalytic rotation is associated with interdomain fluctuations and heterogeneity of conformational states. Using ion mobility mass spectrometry we compared the conformational dynamics of the intact ATPase from Thermus thermophilus with those of its membrane and soluble subcomplexes. Our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. To provide a structural context for our experimental data we performed molecular dynamics simulations and observed conformational changes of the peripheral stalks that reflect their intrinsic flexibility. By isolating complexes at different phases of cell growth and manipulating nucleotides, metal ions and pH during isolation, we reveal differences that can be related to conformational changes in the Vo complex triggered by ATP binding. Together these results implicate nucleotides in modulating flexibility of the stator components and uncover mechanistic detail that underlies operation and regulation in the context of the holoenzyme.

  19. Ion mobility mass spectrometry as a potential tool to assign disulfide bonds arrangements in peptides with multiple disulfide bridges.

    PubMed

    Echterbille, Julien; Quinton, Loïc; Gilles, Nicolas; De Pauw, Edwin

    2013-05-01

    Disulfide bridges play a major role in defining the structural properties of peptides and proteins. However, the determination of the cysteine pairing is still challenging. Peptide sequences are usually achieved using tandem mass spectrometry (MS/MS) spectra of the totally reduced unfolded species, but the cysteine pairing information is lost. On the other hand, MS/MS experiments performed on native folded species show complex spectra composed of nonclassical ions. MS/MS alone does not allow either the cysteine pairing or the full sequence of an unknown peptide to be determined. The major goal of this work is to set up a strategy for the full structural characterization of peptides including disulfide bridges annotation in the sequence. This strategy was developed by combining ion mobility spectrometry (IMS) and collision-induced dissociation (CID). It is assumed that the opening of one S-S bridge in a peptide leads to a structural evolution which results in a modification of IMS drift time. In the presence of multiple S-S bridges, the shift in arrival time will depend on which disulfide(s) has (have) been reduced and on the shape adopted by the generated species. Due to specific fragmentations observed for each species, CID experiments performed after the mobility separation could provide not only information on peptide sequence but also on the localization of the disulfide bridges. To achieve this goal, synthetic peptides containing two disulfides were studied. The openings of the bridges were carried out following different experimental conditions such as reduction, reduction/alkylation, or oxidation. Due to disulfide scrambling highlighted with the reduction approaches, oxidation of S-S bonds into cysteic acids appeared to be the best strategy. Cysteine connectivity was then unambiguously determined for the two peptides, without any disulfide scrambling interference.

  20. 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.

  1. Combining Ion Mobility Spectrometry with Hydrogen-Deuterium Exchange and Top-Down MS for Peptide Ion Structure Analysis

    NASA Astrophysics Data System (ADS)

    Khakinejad, Mahdiar; Kondalaji, Samaneh Ghassabi; Maleki, Hossein; Arndt, James R.; Donohoe, Gregory C.; Valentine, Stephen J.

    2014-12-01

    The gas-phase conformations of electrosprayed ions of the model peptide KKDDDDIIKIIK have been examined by ion mobility spectrometry (IMS) and hydrogen deuterium exchange (HDX)-tandem mass spectrometry (MS/MS) techniques. [M+4H]4+ ions exhibit two conformers with collision cross sections of 418 Å2 and 471 Å2. [M+3H]3+ ions exhibit a predominant conformer with a collision cross section of 340 Å2 as well as an unresolved conformer (shoulder) with a collision cross section of ~367 Å2. Maximum HDX levels for the more compact [M+4H]4+ ions and the compact and partially-folded [M+3H]3+ ions are ~12.9, ~15.5, and ~14.9, respectively. Ion structures obtained from molecular dynamics simulations (MDS) suggest that this ordering of HDX level results from increased charge-site/exchange-site density for the more compact ions of lower charge. Additionally, a new model that includes two distance calculations (charge site to carbonyl group and carbonyl group to exchange site) for the computer-generated structures is shown to better correlate to the experimentally determined per-residue deuterium uptake. Future comparisons of IMS-HDX-MS data with structures obtained from MDS are discussed with respect to novel experiments that will reveal the HDX rates of individual residues.

  2. Effects of Fe(II)/H2O2 Oxidation on Ubiquitin Conformers Measured by Ion Mobility-Mass Spectrometry

    PubMed Central

    Shi, Huilin; Gu, Liqing; Clemmer, David E.; Robinson, Renã A. S.

    2013-01-01

    Oxidative modifications can have significant effects on protein structure in solution. Here, the structures and stabilities of oxidized ubiquitin ions electrosprayed from an aqueous solution (pH 2) are studied by ion mobility spectrometry-mass spectrometry (IMS-MS). IMS-MS has proven to be a valuable technique to assess gas-phase and in many cases, solution structures. Herein, in vitro oxidation is performed by Fenton chemistry with Fe(II)/hydrogen peroxide. Most molecules in solution remain unmodified whereas ~20% of the population belongs to an M+16 Da oxidized species. Ions of low charge states (+7 and +8) show substantial variance in collision cross section distributions between unmodified and oxidized species. Novel and previously reported Gaussian conformers are used to model cross section distributions for +7 and +8 oxidized ubiquitin ions, respectively, in order to correlate variances in observed gas-phase distributions to changes in populations of solution states. Based on Gaussian modeling, oxidized ions of charge state +7 have an A-state conformation which is more populated for oxidized relative to unmodified ions. Oxidized ubiquitin ions of charge state +8 have a distribution of conformers arising from native-state ubiquitin and higher intensities of A- and U-state conformers relative to unmodified ions. This work provides evidence that incorporation of a single oxygen atom to ubiquitin leads to destabilization of the native state in an acidic solution (pH ~2) and to unfolding of gas-phase compact structures. PMID:23211023

  3. Gas-phase microsolvation of ubiquitin: investigation of crown ether complexation sites using ion mobility-mass spectrometry.

    PubMed

    Göth, Melanie; Lermyte, Frederik; Schmitt, Xiao Jakob; Warnke, Stephan; von Helden, Gert; Sobott, Frank; Pagel, Kevin

    2016-10-01

    In this study the gas-phase structure of ubiquitin and its lysine-to-arginine mutants was investigated using ion mobility-mass spectrometry (IM-MS) and electron transfer dissociation-mass spectrometry (ETD-MS). Crown ether molecules were attached to positive charge sites of the proteins and the resulting non-covalent complexes were analysed. Collision induced dissociation (CID) experiments revealed relative energy differences between the wild type and the mutant crown-ether complexes. ETD-MS experiments were performed to identify the crown ether binding sites. Although not all of the binding sites could be revealed, the data confirm that the first crown ether is able to bind to the N-terminus. IM-MS experiments show a more compact structure for specific charge states of wild type ubiquitin when crown ethers are attached. However, data on ubiquitin mutants reveal that only specific lysine residues contribute to the effect of charge microsolvation. A compaction is only observed for one of the investigated mutants, in which the lysine has no proximate interaction partner. On the other hand when the lysine residues are involved in salt bridges, attachment of crown ethers has little effect on the structure. PMID:27494002

  4. Investigation of isomeric flavanol structures in black tea thearubigins using ultraperformance liquid chromatography coupled to hybrid quadrupole/ion mobility/time of flight mass spectrometry.

    PubMed

    Yassin, Ghada H; Grun, Christian; Koek, Jean H; Assaf, Khaleel I; Kuhnert, Nikolai

    2014-11-01

    Ultra performance liquid chromatography (UPLC) when coupled to ion mobility (IMS)/orthogonal acceleration time of flight mass spectrometry is a suitable technique for analyzing complex mixtures such as the black tea thearubigins. With the aid of this advanced instrumental analysis, we were able to separate and identify different isomeric components in the complex mixture which could previously not be differentiated by a conventional high performance liquid chromatography/tandem mass spectrometry. In this study, the difference between isomeric structures theasinensins, proanthocyanidins B-type and rutin (quercetin-3O-rutinoside) were studied, and these are present abundantly in many botanical sources. The differentiation between these structures was accomplished according to their acquired mobility drift times differing from the traditional investigations in mass spectrometry, where calculation of theoretical collisional cross sections allowed assignment of the individual isomeric structures. The present work demonstrates UPLC-IMS-MS as an efficient technology for isolating and separating isobaric and isomeric structures existing in complex mixtures discriminating between them according to their characteristic fragment ions and mobility drift times. Therefore, a rational assignment of isomeric structures in many phenolic secondary metabolites based on the ion mobility data might be useful in mass spectrometry-based structure analysis in the future.

  5. 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.

  6. 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.

  7. 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.

  8. Analysis of ecstasy in oral fluid by ion mobility spectrometry and infrared spectroscopy after liquid-liquid extraction.

    PubMed

    Armenta, Sergio; Garrigues, Salvador; de la Guardia, Miguel; Brassier, Judit; Alcalà, Manel; Blanco, Marcelo

    2015-03-01

    We developed and evaluated two different strategies for determining abuse drugs based on (i) the analysis of saliva by ion mobility spectrometry (IMS) after thermal desorption and (ii) the joint use of IMS and infrared (IR) spectroscopy after liquid-liquid microextraction (LLME) to enable the sensitivity-enhanced detection and double confirmation of ecstasy (MDMA) abuse. Both strategies proved effective for the intended purpose. Analysing saliva by IMS after thermal desorption, which provides a limit of detection (LOD) of 160μgL(-1), requires adding 0.2M acetic acid to the sample and using the truncated negative second derivative of the ion mobility spectrum. The joint use of IMS and IR spectroscopy after LLME provides an LOD of 11μgL(-1) with the former technique and 800μgL(-1) with the latter, in addition to a limit of confirmation (LOC) of 1.5mgL(-1). Using IMS after thermal desorption simplifies the operational procedure, and using it jointly with IR spectroscopy after LLME allows double confirmation of MDMA abuse with two techniques based on different principles (viz., IMS drift times and IR spectra). Also, it affords on-site analyses, albeit at a lower throughput.

  9. 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

  10. 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

  11. 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.

  12. Desorption electrospray ionization (DESI) with atmospheric pressure ion mobility spectrometry for drug detection.

    PubMed

    Roscioli, Kristyn M; Tufariello, Jessica A; Zhang, Xing; Li, Shelly X; Goetz, Gilles H; Cheng, Guilong; Siems, William F; Hill, Herbert H

    2014-04-01

    Desorption electrospray ionization (DESI) was coupled to an ambient pressure drift tube ion mobility time-of-flight mass spectrometer (IM-TOFMS) for the direct analysis of active ingredients in pharmaceutical samples. The DESI source was also coupled with a standalone IMS demonstrating potential of portable and inexpensive drug-quality testing platforms. The DESI-IMS required no sample pretreatment as ions were generated directly from tablets and cream formulations. The analysis of a range of over-the-counter and prescription tablet formations was demonstrated for amphetamine (methylphenidate), antidepressant (venlafaxine), barbiturate (Barbituric acid), depressant (alprazolam), narcotic (3-methylmorphine) and sympatholytic (propranolol) drugs. Active ingredients from soft and liquid formulations, such as Icy Hot cream (methyl salicylate) and Nyquil cold medicine (acetaminophen, dextromethorphan, doxylamine) were also detected. Increased sensitivity for selective drug responses was demonstrated through the formation of sodiated adduct ions by introducing small quantities of NaCl into the DESI solvent. Of the drugs and pharmaceuticals tested in this study, 68% (22 total samples) provided a clear ion mobility response at characteristic mobilities either as (M + H)(+), (M - H)(-), or (M + Na)(+) ions.

  13. Traveling wave ion mobility mass spectrometry and ab initio calculations of phosphoric acid clusters.

    PubMed

    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.

  14. FAIM2, as a novel diagnostic maker and a potential therapeutic target for small-cell lung cancer and atypical carcinoid

    PubMed Central

    Kang, Hio Chung; Kim, Jong In; Chang, Hee Kyung; Woodard, Gavitt; Choi, Young Sik; Ku, Ja-Lok; Jablons, David M.; Kim, Il-Jin

    2016-01-01

    Lung neuroendocrine (NE) tumors are a heterogeneous group of tumors arising from neuroendocrine cells that includes typical carcinoid, atypical carcinoid, small cell lung cancer (SCLC), and large cell NE cancer. The subtyping of NE tumors is based on the number of mitoses per high powered field and the presences of necrosis. However, the best diagnostic criteria to differentiate various subtypes of lung NE tumors remains controversial and few diagnostic markers distinguish typical and atypical carcinoid. In this study, we show that FAIM2, an inhibitory molecule in the Fas-apoptosis pathway, is significantly overexpressed in SCLC compared to non-small cell lung cancer. In addition, FAIM2 expression is significantly higher in atypical carcinoid than typical carcinoid. As atypical carcinoid has been shown to have worse clinical outcomes than typical carcinoid, our data suggests that FAIM2 may be a useful diagnostic marker for atypical carcinoid. Knockdown of FAIM2 expression increases Fas-induced apoptotic cell death in SCLC cells. Etoposide treatment combined with FAIM2 inhibition also shows modest but significant reduction of viable SCLC cells. Taken together, our results suggest that FAIM2 is a potential NE tumor marker with higher expression in atypical carcinoid and SCLC, and could be a new therapeutic target for SCLC. PMID:27677402

  15. 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.

  16. Lineage-specific duplications of Muroidea Faim and Spag6 genes and atypical accelerated evolution of the parental Spag6 gene.

    PubMed

    Qiu, Huan; Gołas, Aniela; Grzmil, Paweł; Wojnowski, Leszek

    2013-09-01

    Gene duplications restricted to single lineage combined with an asymmetric evolution of the resulting genes may play particularly important roles in this lineage's biology. We searched and identified asymmetrical evolution in nine gene families that duplicated exclusively in rodents and are present as single-copies in human, dog, cow, elephant, opossum, chicken, lizard, and Western clawed frog. Among those nine gene families are Fas apoptosis inhibitory molecule (Faim), implicated in apoptosis, and Sperm antigen 6 (Spag6), implicated in sperm mobility. Both genes were duplicated in or before the Muroidea ancestor. Due to the highly asymmetric evolution of the resulting paralogs, the existence of these duplications had been previously overlooked. Interestingly, Spag6, previously regarded and characterized as a single-copy ortholog of human Spag6, turns out to be a Muroidea-specific paralog. Conversely, the newly identified, highly divergent Spag6-BC061194 is in fact the parental gene. In consequence, this gene represents a rare exception from the general rule of rapid evolution of derived rather than parental genes following gene duplication. Unusual genes such as murine Spag6 may help to understand which mechanisms are responsible for this rule.

  17. 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.

  18. 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

  19. Small-molecule inhibition of c-MYC:MAX leucine zipper formation is revealed by ion mobility mass spectrometry.

    PubMed

    Harvey, Sophie R; Porrini, Massimiliano; Stachl, Christiane; MacMillan, Derek; Zinzalla, Giovanna; Barran, Perdita E

    2012-11-28

    The leucine zipper interaction between MAX and c-MYC has been studied using mass spectrometry and drift time ion mobility mass spectrometry (DT IM-MS) in addition to circular dichroism spectroscopy. Peptides comprising the leucine zipper sequence with (c-MYC-Zip residues 402-434) and without a postulated small-molecule binding region (c-MYC-ZipΔDT residues 406-434) have been synthesized, along with the corresponding MAX leucine zipper (MAX-Zip residues 74-102). c-MYC-Zip:MAX-Zip complexes are observed both in the absence and in the presence of the reported small-molecule inhibitor 10058-F4 for both forms of c-MYC-Zip. DT IM-MS, in combination with molecular dynamics (MD), shows that the c-MYC-Zip:MAX-Zip complex [M+5H](5+) exists in two conformations, one extended with a collision cross section (CCS) of 1164 ± 9.3 Å(2) and one compact with a CCS of 982 ± 6.6 Å(2); similar values are observed for the two forms of c-MYC-ZipΔDT:MAX-Zip. Candidate geometries for the complexes have been evaluated with MD simulations. The helical leucine zipper structure previously determined from NMR measurements (Lavigne, P.; et al. J. Mol. Biol. 1998, 281, 165), altered to include the DT region and subjected to a gas-phase minimization, yields a CCS of 1247 Å(2), which agrees with the extended conformation we observe experimentally. More extensive MD simulations provide compact complexes which are found to be highly disordered, with CCSs that correspond to the compact form from experiment. In the presence of the ligand, the leucine zipper conformation is completely inhibited and only the more disordered species is observed, providing a novel method to study the effect of interactions of disordered systems and subsequent inhibition of the formation of an ordered helical complex.

  20. Characterization of an Ion Mobility-Multiplexed Collision Induced Dissociation- Tandem Time-of-Flight Mass Spectrometry Approach

    SciTech Connect

    Ibrahim, Yehia M.; Prior, David C.; Baker, Erin Shammel; Smith, Richard D.; Belov, Mikhail E.

    2010-06-01

    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 a novel approach for collision-induced dissociation (CID) with an 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 the matching drift time profiles and by effectively utilizing high mass measurement accuracy of the TOFMS. In a single IMS separation with a tryptic digest of bovine serum albumin (BSA), we have reliably identified 20 unique peptides using 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%.

  1. 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

  2. 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.

  3. Ion mobility spectrometry: A personal view of its development at UCSB.

    PubMed

    Bowers, Michael T

    2014-09-15

    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.

  4. Explosive ordnance detection in land and water environments with solid phase extraction/ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Chambers, William B.; Phelan, James M.; Rodacy, Philip J.; Reber, Steven; Woodfin, Ronald L.

    1999-08-01

    The qualitative and quantitative determination of nitroaromatic compounds such as trinitrotoluene (TNT) and dinitrotoluene (DNT) in water and soil has applications to environmental remediation and the detection of buried military ordnance. Recent results of laboratory and field test have shown that trace level concentrations of these compounds can be detected in water, soil, and solid gas samples taken from the vicinity of submerged or buried ordnance using specialized sampling and signal enhancement techniques. Solid phase micro-extraction methods have been combined with Ion Mobility Spectroscopy to provide rapid, sub-parts-per-billion analysis of these compounds. In this paper, we will describe the gas. These sampling systems, when combined with field-portable IMS, are being developed as a means of classifying buried or submerged objects as explosive ordnance.

  5. Control of dopants/modifiers in differential mobility spectrometry using a piezoelectric injector.

    PubMed

    Moll, Victor; Bocoş-Binţinţan, Victor; Raţiu, Ileana-Andreea; Ruszkiewicz, Dorota; Thomas, C L Paul

    2012-03-21

    A piezoelectric injector has been interfaced to a differential mobility spectrometer to enable fast and reversible control of dopant/transport-gas modifier levels within the reaction region of the instrument. Operating at 1 Hz with optimised bipolar waveforms for the piezoelectric injector and gas flows within the injector, steady-state 2-butanol mass fluxes of 21 to 1230 ng min(-1) and 1-bromohexane mass fluxes of 149 to 2644 ng min(-1) were delivered to the differential mobility cell. Control of split-flow and transport-gas flow rates enabled rapid and flexible control of the dopant concentrations. The system was consistently reproducible with a relative standard deviation (RSD) of 7.9% at every mass- flux level studied. Stable responses were achieved between 3 to 5 s following a change in the control levels and no significant hysteresis effects were observed. In the positive mode it was possible to control the extent of formation protonated monomer and proton bound cluster ions, tentatively assigned to{C(4)H(9)OH(H(2)O)(n)H}(+) and {(C(4)H(9)OH)(2)(H(2)O)(n)H}(+) and similar control was possible in the negative mode where the concentration relationship for the formation of bromide clusters indicated the presence of multiple ionisation mechanisms. A dopant formulation for the simultaneous control of ions in both the positive and negative modes was demonstrated by the injection of a 50%/50% v/v solution of 2-butanol/1-bromohexane with mass fluxes of 2-butanol in the mixture of between 11 and 1161 ng min(-1) and between 13 and 1325 ng min(-1) for 1-bromohexane.

  6. 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.

  7. 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

  8. Quantitative detection of benzene in toluene- and xylene-rich atmospheres using high-kinetic-energy ion mobility spectrometry (IMS).

    PubMed

    Langejuergen, Jens; Allers, Maria; Oermann, Jens; Kirk, Ansgar; Zimmermann, Stefan

    2014-12-01

    One major drawback of ion mobility spectrometry (IMS) is the dependence of the response to a certain analyte on the concentration of water or the presence of other compounds in the sample gas. Especially for low proton affine analytes, e.g., benzene, which often exists in mixtures with other volatile organic compounds, such as toluene and xylene (BTX), a time-consuming preseparation is necessary. In this work, we investigate BTX mixtures using a compact IMS operated at decreased pressure (20 mbar) and high kinetic ion energies (HiKE-IMS). The reduced electric field in both the reaction tube and the drift tube can be independently increased up to 120 Td. Under these conditions, the water cluster distribution of reactant ions is shifted toward smaller clusters independent of the water content in the sample gas. Thus, benzene can be ionized via proton transfer from H3O(+) reactant ions. Also, a formation of benzene ions via charge transfer from NO(+) is possible. Furthermore, the time for interaction between ions and neutrals of different analytes is limited to such an extent that a simultaneous quantification of benzene, toluene, and xylene is possible from low ppbv up to several ppmv concentrations. The mobility resolution of the presented HiKE-IMS varies from R = 65 at high field (90 Td) to R = 73 at lower field (40 Td) in the drift tube, which is sufficient to separate the analyzed compounds. The detection limit for benzene is 29 ppbv (2 s of averaging) with 3700 ppmv water, 12.4 ppmv toluene, and 9 ppmv xylene present in the sample gas. Furthermore, a less-moisture-dependent benzene measurement with a detection limit of 32 ppbv with ca. 21 000 ppmv (90% relative humidity (RH) at 20 °C) water present in the sample gas is possible evaluating the signal from benzene ions formed via charge transfer.

  9. Determining the isomeric heterogeneity of neutral oligosaccharide-alditols of bovine submaxillary mucin using negative ion traveling wave ion mobility mass spectrometry.

    PubMed

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

    2015-02-17

    Negative ions produced by electrospray ionization were used to evaluate the isomeric heterogeneity of neutral oligosaccharide-alditols isolated from bovine submaxillary mucin (BSM). The oligosaccharide-alditol mixture was preseparated on an off-line high-performance liquid chromatography (HPLC) column, and the structural homogeneity of individual LC fractions was investigated using a Synapt G2 traveling wave ion mobility spectrometer coupled between quadupole and time-of-flight mass spectrometers. Mixtures of isomers separated by both chromatography and ion mobility spectrometry were studied. Tandem mass spectrometry (MS/MS) of multiple mobility peaks having the same mass-to-charge ratio (m/z) demonstrated the presence of different structural isomers and not differences in ion conformations due to charge site location. Although the oligosaccharide-alditol mixture was originally separated by HPLC, multiple ion mobility peaks due to structural isomers were observed for a number of oligosaccharide-alditols from single LC fractions. The collision-induced dissociation cells located in front of and after the ion mobility separation device enabled oligosaccharide precursor or product ions to be separated by ion mobility and independent fragmentation spectra to be acquired for isomeric carbohydrate precursor or product ions. MS/MS spectra so obtained for independent mobility peaks at a single m/z demonstrated the presence of structural variants or stereochemical isomers having the same molecular formula. This was observed both for oligosaccharide precursor and product ions. In addition, mobilities of both [M - H](-) and [M + Cl](-) ions, formed by adding NH4OH or NH4Cl to the electrospray solvent, were examined and compared for selected oligosaccharide-alditols. Better separation among structural isomers appeared to be achieved for some [M + Cl](-) anions.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry and molecular dynamics simulations.

    PubMed

    Borysik, Antoni J

    2015-09-01

    The structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry (IMS) and vacuum molecular dynamics (MD) simulations is reported. Direct evidence is provided for the ability of the surfactant dodecyl-β-D-maltoside (DDM) to prevent charge-induced unfolding of the membrane protein (PagP) in the gas-phase. Restraints obtained by IMS are used to map the surfactant positions onto the protein surface. Surfactants occupying more exposed positions at the apexes of the β-barrel structure are most in-line with the experimental observations. MD simulations provide additional evidence for this assembly organization through surfactant inversion and migration on the protein structure in the absence of solvent. Surfactant migration entails a net shift from apolar membrane spanning regions to more polar regions of the protein structure with the DDM molecule remaining attached to the protein via headgroup interactions. These data provide evidence for the role of protein-DDM headgroup interactions in stabilizing membrane protein structure from gas-phase unfolding.

  16. 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

  17. Detection of cocaine and its metabolites in urine using solid phase extraction-ion mobility spectrometry with alternating least squares.

    PubMed

    Lu, Yao; O'Donnell, Ryan M; Harrington, Peter B

    2009-08-10

    A reliable, alternative screening method for detection of cocaine and its metabolites, benzoylecgonine and cocaethylene in urine is demonstrated using solid phase extraction (SPE) coupled with ion mobility spectrometry (IMS). Data analysis with alternating least squares (ALS) is used to model IMS spectral datasets and separate the reactant ion peak from the product ion peaks. IMS has been used as a screening device for drug and explosive detection for many years. It has the advantages of atmospheric pressure operation, simple sample preparation, portability, fast analysis, and high sensitivity when compared to similar methods. Coupling SPE with IMS decreases the detection limits of drug metabolites in urine while removing salts and other polar compounds that suppress ionization during the measurement. The IMS analysis time in this experiment is 20s, much shorter than traditional chromatographic analysis. The application of ALS further increases the sensitivity and selectivity of this method. The detection limits of benzoylecgonine and cocaethylene are 10 ng/mL and 4 ng/mL, respectively. Commercial adulteration of urine specimens does not influence the ability to detect cocaine metabolites after sampling the urine with SPE. This method provides forensic chemists a viable approach for fast and simple drug screening. PMID:19457629

  18. 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

    2016-10-01

    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.

  19. 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.

  20. 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.

  1. Detection of malignant pleural mesothelioma in exhaled breath by multicapillary column/ion mobility spectrometry (MCC/IMS).

    PubMed

    Lamote, Kevin; Vynck, Matthijs; Van Cleemput, Joris; Thas, Olivier; Nackaerts, Kristiaan; van Meerbeeck, Jan P

    2016-01-01

    Malignant pleural mesothelioma (MPM) is predominantly caused by previous asbestos exposure. Diagnosis often happens in advanced stages restricting any therapeutic perspectives. Early stage detection via breath analysis was explored using multicapillary column/ion mobility spectrometry (MCC/IMS) to detect volatile organic compounds (VOCs) in the exhaled breath of MPM patients in comparison to former occupational asbestos-exposed and non-exposed controls. Breath and background samples of 23 MPM patients, 22 asymptomatic former asbestos (AEx) workers and 21 healthy non-asbestos exposed persons were taken for analysis. After background correction, we performed a logistic least absolute shrinkage and selection operator (lasso) regression to select the most important VOCs, followed by receiver operating characteristic (ROC) analysis. MPM patients were discriminated from both controls with 87% sensitivity, 70% specificity and respective positive and negative predictive values of 61% and 91%. The overall accuracy was 76% and the area under the ROC-curve was 0.81. AEx individuals could be discriminated from MPM patients with 87% sensitivity, 86% specificity and respective positive and negative predictive values of 87% and 86%. The overall accuracy was 87% with an area under the ROC-curve of 0.86. Breath analysis by MCC/IMS allows MPM patients to be discriminated from controls and holds promise for further investigation as a screening tool for former asbestos-exposed persons at risk of developing MPM. PMID:27669062

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Fast detection of methyl tert-butyl ether from water using solid phase microextraction and ion mobility spectrometry.

    PubMed

    Nousiainen, Marjaana; Holopainen, Sanna; Puton, Jaroslaw; Sillanpää, Mika

    2011-05-15

    Methyl tert-butyl ether (MTBE) is commonly used as chemical additive to increase oxygen content and octane rating of reformulated gasoline. Despite its impact on enhancing cleaner combustion of gasoline, MTBE poses a threat to surface and ground water when gasoline is released into the environment. Methods for onsite analysis of MTBE in water samples are also needed. A less common technique for MTBE detection from water is ion mobility spectrometry (IMS). We describe a method for fast sampling and screening of MTBE from water by solid phase microextraction (SPME) and IMS. MTBE is adsorbed from the head space of a sample to the coating of SPME fiber. The interface containing a heated sample chamber, which couples SPME and IMS, was constructed and the SPME fiber was introduced into the sample chamber for thermal desorption and IMS detection of MTBE vapors. The demonstrated SPME-IMS method proved to be a straightforward method for the detection of trace quantities of MTBE from waters including surface and ground water. We determined the relative standard deviation of 8.3% and detection limit of 5 mg L(-1) for MTBE. Because of short sampling, desorption, and detection times, the described configuration of combined SPME and IMS is a feasible method for the detection of hazardous substances from environmental matrices.

  8. 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.

  9. 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 5-20 ppm and for air humidity in a range 0-12 g/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 1 ppm for each: benzene, toluene and xylene. We also successfully determined water vapor content in air. The error achieved was 0.2 g/kg. The obtained results are very promising regarding further development of DMS technique as well as its application.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Arrival time distributions of product ions reveal isomeric ratio of deprotonated molecules in ion mobility-mass spectrometry of hyaluronan-derived oligosaccharides.

    PubMed

    Hermannová, Martina; Iordache, Andreea-Maria; Slováková, Kristína; Havlíček, Vladimír; Pelantová, Helena; Lemr, Karel

    2015-06-01

    Hyaluronic acid is a naturally occurring linear polysaccharide with substantial medical potential. In this work, discrimination of tyramine-based hyaluronan derivatives was accessed by ion mobility-mass spectrometry of deprotonated molecules and nuclear magnetic resonance spectroscopy. As the product ion mass spectra did not allow for direct isomer discrimination in mixture, the reductive labeling of oligosaccharides as well as stable isotope labeling was performed. The ion mobility separation of parent ions together with the characteristic fragmentation for reduced isomers providing unique product ions allowed us to identify isomers present in a mixture and determine their mutual isomeric ratio. The determination used simple recalculation of arrival time distribution areas of unique ions to areas of deprotonated molecules. Mass spectrometry data were confirmed by nuclear magnetic resonance spectroscopy.

  15. 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.

  16. Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death

    PubMed Central

    Carriba, P; Jimenez, S; Navarro, V; Moreno-Gonzalez, I; Barneda-Zahonero, B; Moubarak, R S; Lopez-Soriano, J; Gutierrez, A; Vitorica, J; Comella, J X

    2015-01-01

    The brains of patients with Alzheimer's disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1M146LxAPP751sl) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells. PMID:25675299

  17. Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death.

    PubMed

    Carriba, P; Jimenez, S; Navarro, V; Moreno-Gonzalez, I; Barneda-Zahonero, B; Moubarak, R S; Lopez-Soriano, J; Gutierrez, A; Vitorica, J; Comella, J X

    2015-02-12

    The brains of patients with Alzheimer's disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1(M146L)xAPP(751sl)) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells.

  18. 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

  19. 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.

  20. 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.

  1. Evaluation and application of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry for complex sample analysis.

    PubMed

    Denawaka, Chamila J; Fowlis, Ian A; Dean, John R

    2014-04-18

    An evaluation of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS) has been undertaken to assess its applicability for the determination of 32 volatile compounds (VCs). The key experimental variables of sample incubation time and temperature have been evaluated alongside the MCC-GC variables of column polarity, syringe temperature, injection temperature, injection volume, column temperature and carrier gas flow rate coupled with the IMS variables of temperature and drift gas flow rate. This evaluation resulted in six sets of experimental variables being required to separate the 32 VCs. The optimum experimental variables for SHS-MCC-GC-IMS, the retention time and drift time operating parameters were determined; to normalise the operating parameters, the relative drift time and normalised reduced ion mobility for each VC were determined. In addition, a full theoretical explanation is provided on the formation of the monomer, dimer and trimer of a VC. The optimum operating condition for each VC calibration data was obtained alongside limit of detection (LOD) and limit of quantitation (LOQ) values. Typical detection limits ranged from 0.1ng bis(methylthio)methane, ethylbutanoate and (E)-2-nonenal to 472ng isovaleric acid with correlation coefficient (R(2)) data ranging from 0.9793 (for the dimer of octanal) through to 0.9990 (for isobutyric acid). Finally, the developed protocols were applied to the analysis of malodour in sock samples. Initial work involved spiking an inert matrix and sock samples with appropriate concentrations of eight VCs. The average recovery from the inert matrix was 101±18% (n=8), while recoveries from the sock samples were lower, that is, 54±30% (n=8) for sock type 1 and 78±24% (n=6) for sock type 2. Finally, SHS-MCC-GC-IMS was applied to sock malodour in a field trial based on 11 volunteers (mixed gender) over a 3-week period. By applying the SHS-MCC-GC-IMS database, four VCs were

  2. Comparison of enzyme kinetics of warfarin analyzed by LC-MS/MS QTrap and differential mobility spectrometry.

    PubMed

    Shaik, Abdul Naveed; Grater, Richard; Lulla, Mukesh; Williams, David A; Gan, Lawrence L; Bohnert, Tonika; LeDuc, Barbara W

    2016-01-01

    Warfarin is an anticoagulant used in the treatment of thrombosis and thromboembolism. It is given as a racemic mixture of R and S enantiomers. These two enantiomers show differences in metabolism by CYPs: S-warfarin undergoes 7 hydroxylation by CYP2C9 and R-warfarin by CYP3A4 to form 10 hydroxy warfarin. In addition, warfarin is acted upon by different CYPs to form the minor metabolites 3'-hydroxy, 4'-hydroxy, 6-hydroxy, and 8-hydroxy warfarin. For analysis, separation of these metabolites is necessary since all have the same m/z ratio and similar fragmentation pattern. Enzyme kinetics for the formation of all of the six hydroxylated metabolites of warfarin from human liver microsomes were determined using an LC-MS/MS QTrap and LC-MS/MS with a differential mobility spectrometry (DMS) (SelexION™) interface to compare the kinetic parameters. These two methods were chosen to compare their selectivity and sensitivity. Substrate curves for 3'-OH, 4'-OH, 6-OH, 7-OH, 8-OH and 10-OH warfarin formation were generated to determine the kinetic parameters (Km and Vmax) in human liver microsomal preparations. The limit of quantitation (LOQ) for all the six hydroxylated metabolites of warfarin were in the range of 1-3nM using an LC-MS/MS QTrap method which had a run time of 22min. In contrast, the LOQ for all the six hydroxylated metabolites using DMS interface technology was 100nM with a run time of 2.8min. We compare these two MS methods and discuss the kinetics of metabolite formation for the metabolites generated from racemic warfarin. In addition, we show inhibition of major metabolic pathways of warfarin by sulfaphenazole and ketoconazole which are known specific inhibitors of CYP2C9 and CYP3A4 respectively. PMID:26655108

  3. 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

  4. 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.

  5. Determination of ion mobility collision cross sections for unresolved isomeric mixtures using tandem mass spectrometry and chemometric deconvolution.

    PubMed

    Harper, Brett; Neumann, Elizabeth K; Stow, Sarah M; May, Jody C; McLean, John A; Solouki, Touradj

    2016-10-01

    Ion mobility (IM) is an important analytical technique for determining ion collision cross section (CCS) values in the gas-phase and gaining insight into molecular structures and conformations. However, limited instrument resolving powers for IM may restrict adequate characterization of conformationally similar ions, such as structural isomers, and reduce the accuracy of IM-based CCS calculations. Recently, we introduced an automated technique for extracting "pure" IM and collision-induced dissociation (CID) mass spectra of IM overlapping species using chemometric deconvolution of post-IM/CID mass spectrometry (MS) data [J. Am. Soc. Mass Spectrom., 2014, 25, 1810-1819]. Here we extend those capabilities to demonstrate how extracted IM profiles can be used to calculate accurate CCS values of peptide isomer ions which are not fully resolved by IM. We show that CCS values obtained from deconvoluted IM spectra match with CCS values measured from the individually analyzed corresponding peptides on uniform field IM instrumentation. We introduce an approach that utilizes experimentally determined IM arrival time (AT) "shift factors" to compensate for ion acceleration variations during post-IM/CID and significantly improve the accuracy of the calculated CCS values. Also, we discuss details of this IM deconvolution approach and compare empirical CCS values from traveling wave (TW)IM-MS and drift tube (DT)IM-MS with theoretically calculated CCS values using the projected superposition approximation (PSA). For example, experimentally measured deconvoluted TWIM-MS mean CCS values for doubly-protonated RYGGFM, RMFGYG, MFRYGG, and FRMYGG peptide isomers were 288.8 Å(2), 295.1 Å(2), 296.8 Å(2), and 300.1 Å(2); all four of these CCS values were within 1.5% of independently measured DTIM-MS values.

  6. 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

  7. Ion mobility-mass spectrometry reveals the influence of subunit packing and charge on the dissociation of multiprotein complexes.

    PubMed

    Boeri Erba, Elisabetta; Ruotolo, Brandon T; Barsky, Daniel; Robinson, Carol V

    2010-12-01

    The composition, stoichiometry, and organization of protein complexes can be determined by collision-induced dissociation (CID) coupled to tandem mass spectrometry (MS/MS). The increased use of this approach in structural biology prompts a better understanding of the dissociation mechanism(s). Here we report a detailed investigation of the CID of two dodecameric, heat-stable and toroidally shaped complexes: heat shock protein 16.9 (HSP16.9) and stable protein 1 (SP-1). While HSP16.9 dissociates by sequential loss of unfolded monomers, SP-1 ejects not only monomers, but also its building blocks (dimers), and multiples thereof (tetramers and hexamers). Unexpectedly, the dissociation of SP-1 is strongly charge-dependent: loss of the building blocks increases with higher charge states of this complex. By combining MS/MS with ion mobility (IM-MS/MS), we have monitored the unfolding and dissociation events for these complexes in the gas phase. For HSP16.9 unfolding occurs at lower energies than the ejection of subunits, whereas for SP-1 unfolding and dissociation take place simultaneously. We consider these results in the light of the structural organization of HSP16.9 and SP-1 and hypothesize that SP-1 is unable to unfold extensively due to its particular quaternary structure and unusually high charge density. This investigation increases our understanding of the factors governing the CID of protein complexes and moves us closer to the goal of obtaining structural information on subunit interactions and packing from gas-phase experiments. PMID:21053918

  8. Determination of ion mobility collision cross sections for unresolved isomeric mixtures using tandem mass spectrometry and chemometric deconvolution.

    PubMed

    Harper, Brett; Neumann, Elizabeth K; Stow, Sarah M; May, Jody C; McLean, John A; Solouki, Touradj

    2016-10-01

    Ion mobility (IM) is an important analytical technique for determining ion collision cross section (CCS) values in the gas-phase and gaining insight into molecular structures and conformations. However, limited instrument resolving powers for IM may restrict adequate characterization of conformationally similar ions, such as structural isomers, and reduce the accuracy of IM-based CCS calculations. Recently, we introduced an automated technique for extracting "pure" IM and collision-induced dissociation (CID) mass spectra of IM overlapping species using chemometric deconvolution of post-IM/CID mass spectrometry (MS) data [J. Am. Soc. Mass Spectrom., 2014, 25, 1810-1819]. Here we extend those capabilities to demonstrate how extracted IM profiles can be used to calculate accurate CCS values of peptide isomer ions which are not fully resolved by IM. We show that CCS values obtained from deconvoluted IM spectra match with CCS values measured from the individually analyzed corresponding peptides on uniform field IM instrumentation. We introduce an approach that utilizes experimentally determined IM arrival time (AT) "shift factors" to compensate for ion acceleration variations during post-IM/CID and significantly improve the accuracy of the calculated CCS values. Also, we discuss details of this IM deconvolution approach and compare empirical CCS values from traveling wave (TW)IM-MS and drift tube (DT)IM-MS with theoretically calculated CCS values using the projected superposition approximation (PSA). For example, experimentally measured deconvoluted TWIM-MS mean CCS values for doubly-protonated RYGGFM, RMFGYG, MFRYGG, and FRMYGG peptide isomers were 288.8 Å(2), 295.1 Å(2), 296.8 Å(2), and 300.1 Å(2); all four of these CCS values were within 1.5% of independently measured DTIM-MS values. PMID:27639144

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Field detection of bacillus spore aerosols with stand-alone pyrolysis-gas chromatography and ion mobility spectrometry

    NASA Astrophysics Data System (ADS)

    Snyder, A.; Maswadeh, Waleed M.; Parsons, John A.; Tripathi, Ashish; Meuzelaar, Henk L. C.; Dworzanski, Jacek P.; Kim, Man-Goo

    1999-12-01

    A commercially available, hand-held chemical vapor detector was modified to detect Gram-positive Bacillus subtilis var. globigii spores (BG) in outdoor field scenarios. An Airborne Vapor Monitor (AVM) ion mobility spectrometry (IMS) vapor detector was interfaced to a biological sample processing and transfer introduction system. The biological sample processing was accomplished by quartz tube pyrolysis (Py), and the resultant vapor was transferred by gas chromatography (GC) to the IMS detector. The Py-GC/IMS system can be described as a hyphenated device where two analytical dimensions, in series, allow the separation and isolation of individual components from the pyrolytic decomposition of biological analytes. Gram positive spores such as BG contain 5 - 15% by weight of dipicolinic acid (DPA), and picolinic acid is a pyrolysis product of DPA. Picolinic acid has a high proton affinity, and it is detected in a sensitive fashion by the atmospheric pressure-based IMS device. Picolinic acid occupies a unique region in the GC/IMS data domain with respect to other bacterial pyrolysis products. A 1000 to 1, air-to-air, aerosol concentrator was interfaced to the Py-GC/IMS instrument, and the system was placed in an open-air, Western United States desert environment. The system was tested with BG spore aerosol releases, and the instrument was remotely operated during a trial. A Met-One aerosol particle counter was placed next to the Py-GC/IMS so as to obtain a real-time record of the ambient and bacterial aerosol challenges. The presence/absence of an aerosol event, determined by an aerosol particle counter and a slit sampler-agar plate system, was compared to the presence/absence of a picolinic acid response in a GC/IMS data window at selected times in a trial with respect to a BG challenge. In the 21 BG trials, the Py-GC/IMS instrument experienced two true negatives, no false positives, and the instrument developed a software failure in one trial. The remaining 18 trials

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Comparison of ionospheric data from Soviet and Chinese stations with the IRI-86 and the faim models

    NASA Astrophysics Data System (ADS)

    Kartal, S.; Radicella, S. M.

    1994-12-01

    Median values of ionospheric data from Moscow(55.5° N, 37.3° E), Tashkent (41.3° N, 69.6° E), Beijing (40.0° N, 116.3° E) and Guangzhou (23.1° N, 113.3° E) for different years at LT: 00.00, 06.00, 12.00 and 18.00 were used to produce vertical profiles of electron density with the analytic procedure introduced by Giovanni and Radicella. These profiles were compared with the IRI-86 model profiles adjusted to the F2 experimental peak values and with those obtained with the Fully Analytic Ionospheric Model (FAIM). The main differences with the IRI model are related to the shape of the topside profile under certain conditions and to the presence of the F1 layer in the median values used. The differences with the FAIM model appears to be more marked. The results are discussed.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Ion Mobility Measurements of Nondenatured 12-150 kDa Proteins and Protein Multimers by Tandem Differential Mobility Analysis-Mass Spectrometry (DMA-MS)

    NASA Astrophysics Data System (ADS)

    Hogan, Christopher J.; de la Mora, Juan Fernández

    2011-01-01

    The mobilities of electrosprayed proteins and protein multimers with molecular weights ranging from 12.4 kDa (cytochrome C monomers) to 154 kDa (nonspecific concanavalin A hexamers) were measured in dry air by a planar differential mobility analyzer (DMA) coupled to a time-of-flight mass spectrometer (TOF-MS). The DMA determines true mobility at atmospheric pressure, without perturbing ion structure from that delivered by the electrospray. A nondenaturing aqueous 20 mM triethylammonium formate buffer yields compact ions with low charge states, moderating polarization effects on ion mobility. Conversion of mobilities into cross-sections involves a reduction factor ξ for the actual mobility relative to that associated with elastic specular collisions with smooth surfaces. ξ is known to be 1.36 in air from Millikan's oil drop experiments. A similar enhancement effect ascribed to atomic-scale surface roughness has been found in numerical simulations. Adopting Millikan's value ξ = 1.36 and assuming a spherical geometry yields a gas-phase protein density ρ p = 0.949 ± 0.053 g cm-3 for all our protein data. This is substantially higher than the 0.67 g cm-3 found in recent low-resolution DMA measurements of singly charged proteins. DMA-MS can distinguish nonspecific protein aggregates formed during the electrospray process from those formed preferentially in solution. The observed charge versus diameter relation is compatible with a protein charge reduction mechanism based on the evaporation of triethylammonium ions from electrosprayed drops.

  8. 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

  9. 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.

  10. Mid-Ocean Ridge Mantle Processes Constrained by the FAIM Seismic Refraction Experiment

    NASA Astrophysics Data System (ADS)

    Collins, J. A.; Lizarralde, D.; Gaherty, J. B.; Hirth, G.; Kim, S.

    2003-12-01

    The seismic structure (e.g. velocity, velocity gradients, anisotropy) of the shallow upper mantle of oceanic lithosphere constrains the degree of melt extraction at mid-ocean ridges and the shear deformation of the lithosphere. The variation of fine-scale structure with depth is difficult to resolve with teleseismic data but, with some notable exceptions, seismic refraction techniques - which have excellent depth resolution - have not been used to elucidate oceanic upper mantle structure. Here we report further results from the FAIM (Far-offset Active-source Imaging of the Mantle) seismic refraction experiment conducted along an 800-km-long flow-line transect and a 150-km-long ridge-parallel transect in the western north Atlantic. Sixteen short-period, vertical-component ocean-bottom seismometers (OBS) were deployed along the spreading-parallel transect in 3-km-separated pairs spaced 80-120 km apart, and 3 OBS were deployed orthogonal to the primary transect to a maximum distance of 350 km. Shot spacing was 1 km. Coherent P-wave arrivals were observed to 350-km distance, and the amplitude of this phase and its increasing and fast apparent-velocity suggest that energy is propagating to ˜24 km depth below the Moho. Two-dimensional travel-time analyses predict velocities of ˜8.25-8.55 km/s over the uppermost 24 km of the mantle on the flow-line-parallel transect and velocities of ˜8.05-8.25 km/s over the uppermost 10 km of the mantle on the ridge-parallel transect. At face value, these values indicate P-wave anisotropy is at least ˜3.0% throughout the upper 10 km of the mantle. However, velocities in only two orthogonal directions cannot constrain the precise direction and magnitude of anisotropy. To improve this estimate we analyzed the travel times of P-waves with good signal to noise from shots at ranges of 75-250 km, with an azimuth range spanning ˜100\\deg. When plotted as a function of propagation azimuth, these travel times display a strong variation, with

  11. Ion mobility-mass spectrometry of phosphorylase B ions generated with supercharging reagents but in charge-reducing buffer.

    PubMed

    Hogan, Christopher J; Ogorzalek Loo, Rachel R; Loo, Joseph A; de la Mora, Juan Fernandez

    2010-11-01

    We investigate whether "supercharging" reagents able to shift the charge state distributions (CSDs) of electrosprayed protein ions upward also influence gas-phase protein structure. A differential mobility analyzer and a mass spectrometer are combined in series (DMA-MS) to measure the mass and mobility of monomer and multimeric phosphorylase B ions (monomer molecular weight ∼97 kDa) in atmospheric pressure air. Proteins are electrosprayed from charge-reducing triethylammonium formate in water (pH = 6.8) with and without the addition of the supercharging reagent tetramethylene sulfone (sulfolane). Because the DMA measures ion mobility prior to collisional heating or declustering, it probes the structure of supercharged protein ions immediately following solvent (water) evaporation. As in prior studies, the addition of sulfolane is found to drastically increase both the mean and maximum charge state of phosphorylase B ions. Ions from all protein n-mers were found to yield mobilities that, for a given charge state, were ∼6-10% higher in the absence of sulfolane. We find that the mobility decrease which arises with sulfolane is substantially smaller than that typically observed for folded-to-unfolded transitions in protein ions (where a ∼60% decrease in mobility is typical), suggesting that supercharging reagents do not cause structural protein modifications in solution as large as noted recently by Williams and colleagues [E. R. Williams et al., J. Am. Soc. Mass Spectrom., 2010, 21, 1762-1774]. In fact, the measurements described here indicate that the modest mobility decrease observed can be partly attributed to sulfolane trapping within the protein ions during DMA measurements, and probably also in solution. As the most abundant peaks in measured mass-mobility spectra for ions produced with and without sulfolane correspond to non-covalently bound phosphorylase B dimers, we find that in spite of a change in mobility/cross section, sulfolane addition does not

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Electron capture dissociation and drift tube ion mobility-mass spectrometry coupled with site directed mutations provide insights into the conformational diversity of a metamorphic protein.

    PubMed

    Harvey, Sophie R; Porrini, Massimiliano; Tyler, Robert C; MacPhee, Cait E; Volkman, Brian F; Barran, Perdita E

    2015-04-28

    Ion mobility mass spectrometry can be combined with data from top-down sequencing to discern adopted conformations of proteins in the absence of solvent. This multi-technique approach has particular applicability for conformationally dynamic systems. Previously, we demonstrated the use of drift tube ion mobility-mass spectrometry (DT IM-MS) and electron capture dissociation (ECD) to study the metamorphic protein lymphotactin (Ltn). Ltn exists in equilibrium between distinct monomeric (Ltn10) and dimeric (Ltn40) folds, both of which can be preserved and probed in the gas-phase. Here, we further test this mass spectrometric framework, by examining two site directed mutants of Ltn, designed to stabilise either distinct fold in solution, in addition to a truncated form consisting of a minimum model of structure for Ltn10. The truncated mutant has similar collision cross sections to the wild type (WT), for low charge states, and is resistant to ECD fragmentation. The monomer mutant (CC3) presents in similar conformational families as observed previously for the WT Ltn monomer. As with the WT, the CC3 mutant is resistant to ECD fragmentation at low charge states. The dimer mutant W55D is found here to exist as both a monomer and dimer. As a monomer W55D exhibits similar behaviour to the WT, but as a dimer presents a much larger charge state and collision cross section range than the WT dimer, suggesting a smaller interaction interface. In addition, ECD on the W55D mutant yields greater fragmentation than for the WT, suggesting a less stable β-sheet core. The results highlight the power of MS to provide insight into dynamic proteins, providing further information on each distinct fold of Ltn. In addition we observe differences in the fold stability following single or double point mutations. This approach, therefore, has potential to be a useful tool to screen for the structural effects of mutagenesis, even when sample is limited.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Differentiation of compact and extended conformations of di-ubiquitin conjugates with lysine-specific isopeptide linkages by ion mobility-mass spectrometry.

    PubMed

    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.

  5. Evaluation of atmospheric solid analysis probe ionization coupled to ion mobility mass spectrometry for characterization of poly(ether ether ketone) polymers.

    PubMed

    Cossoul, Emilie; Hubert-Roux, Marie; Sebban, Muriel; Churlaud, Florence; Oulyadi, Hassan; Afonso, Carlos

    2015-01-26

    Recently, the interest of the coupling between atmospheric solid analysis probe (ASAP) and ion mobility-mass spectrometry has been revealed in the field of polymers. This method associates a direct ionization technique with a bi-dimensional separation method. Poly(ether ether ketones) (PEEK) belong to the family of the poly(aryl ether ketones) (PAEK) which are high performance aromatic polymers usually used in aerospace, electronics and nuclear industries. PEEK are important commercial thermoplastics with excellent chemical resistance and good mechanical properties. Because of their low solubility, few structural characterization studies of PEEK have been reported. In mass spectrometry, only MALDI-TOF analyses for polymer synthesis monitoring have been described with the use of strong acids such as sulfuric acid. This work demonstrates that ASAP is particularly efficient for analysis of PEEK in a solvent free approach with the production of intact small oligomers (n≤2). Five types of PEEK oligomers with different end-groups were evidenced. With MALDI-TOF, the same end-groups with almost the same relative abundance were obtained which support the hypothesis that the oligomers detected in ASAP are intact small oligomers and not fragments or pyrolysis products. This is particularly interesting as generally the ASAP analysis of polymers yields pyrolysis products with the loss of end-group information. The end-groups assignments have been confirmed by tandem mass spectrometry (MS/MS) experiments on the M(+) molecular ions, which allowed highlighting some specific neutral or radical losses as well as two diagnostic product ions. Thus, ASAP-IM/MS/MS proves to be a fast and efficient alternative way to characterize low solubility polymers such as PEEK. PMID:25542357

  6. Headspace-multicapillary column-ion mobility spectrometry for the direct analysis of 2,4,6-trichloroanisole in wine and cork samples.

    PubMed

    Márquez-Sillero, Isabel; Cárdenas, Soledad; Valcárcel, Miguel

    2012-11-23

    Headspace-multicapillary column-ion mobility spectrometry coupling has been evaluated for the direct analysis of wine and cork stopper samples for the determination of 2,4,6-trichloroanisole (2,4,6-TCA). The instrumental configuration permits the sample to be introduced in headspace vials which are placed into the autosampler oven in order to facilitate the transference of the volatile compounds from the sample to its headspace. Further, an aliquot of 200 μL of the homogenized gaseous phase is injected into the multicapillary column in order to separate the target compounds from potential interferents. The detection of 2,4,6-TCA was carried out in an ion mobility spectrometer with a radioactive source and working under negative mode. All the system was computer controlled, including data acquisition and treatment. The limits of detection achieved were 0.012 ng L(-1) for wine and 0.28 ng g(-1) for the cork stopper. The procedure was applied to the analysis of commercial wine samples in different packages and 2,4,6-TCA was found in all of those closed with a cork stopper. The excellent recovery values obtained testify for the goodness of the method as no interference from the sample matrix exits.

  7. Mobile selected ion flow tube mass spectrometry (SIFT-MS) devices and their use for pollution exposure monitoring in breath and ambient air-pilot study.

    PubMed

    Storer, Malina; Salmond, Jennifer; Dirks, Kim N; Kingham, Simon; Epton, Michael

    2014-09-01

    Studies of health effects of air pollution exposure are limited by inability to accurately determine dose and exposure of air pollution in field trials. We explored the feasibility of using a mobile selected ion flow tube mass spectrometry (SIFT-MS) device, housed in a van, to determine ambient air and breath levels of benzene, xylene and toluene following exercise in areas of high motor vehicle traffic. The breath toluene, xylene and benzene concentration of healthy subjects were measured before and after exercising close to a busy road. The concentration of the volatile organic compounds (VOCs), in ambient air were also analysed in real time. Exercise close to traffic pollution is associated with a two-fold increase in breath VOCs (benzene, xylene and toluene) with levels returning to baseline within 20 min. This effect is not seen when exercising away from traffic pollution sources. Situating the testing device 50 m from the road reduced any confounding due to VOCs in the inspired air prior to the breath testing manoeuvre itself. Real-time field testing for air pollution exposure is possible using a mobile SIFT-MS device. This device is suitable for exploring exposure and dose relationships in a number of large scale field test scenarios.

  8. Relative quantification of multi-components in Panax notoginseng (Sanqi) by high-performance liquid chromatography with mass spectrometry using mobile phase compensation.

    PubMed

    Lai, Chang-jiang-sheng; Tan, Ting; Zeng, Su-ling; Dong, Xin; Liu, E-Hu; Li, Ping

    2015-01-01

    Relative quantification of multi-components in complex mixture is significantly affected by the ionization variance caused by mobile phase composition in high-performance liquid chromatography with electrospray ionization mass spectrometry (HPLC-ESI-MS) analyses. The normalization methods for eliminating the variance are still less investigated. Herein, the mobile-phase compensation (MPC) method was applied to overcome the above problem. The developed method was firstly used for convenient evaluation of the coeluent interference and subsequently applied for relative quantification of the identified multi-components in Panax notoginseng (Sanqi) samples. The good linearity, precision and low limit of quantification of targeted analytes confirmed that the MPC-HPLC-ESI-MS method in gradient elution could achieve the isocratic test results compared with classical HPLC-ESI-MS. The established method was used for relative quantification of the minor Sanqi saponins by their detected peak areas divided by that of ginsenoside Rd. The results demonstrated the potential of the newly developed method for obtaining the normalized data shared in different laboratories.

  9. 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

  10. High-performance ion mobility spectrometry with direct electrospray ionization (ESI-HPIMS) for the detection of additives and contaminants in food.

    PubMed

    Midey, Anthony J; Camacho, Amanda; Sampathkumaran, Jayanthi; Krueger, Clinton A; Osgood, Mark A; Wu, Ching

    2013-12-01

    High-performance ion mobility spectrometry (HPIMS) with an electrospray ionization (ESI) source detected a series of food contaminants and additive compounds identified as critical to monitoring the safety of food samples. These compounds included twelve phthalate plasticizers, legal and illegal food and cosmetic dyes, and artificial sweeteners that were all denoted as detection priorities. HPIMS separated and detected the range of compounds with a resolving power better than 60 in both positive and negative ion modes, comparable to the commonly used high-performance liquid chromatography (HPLC) methods, but with most acquisition times under a minute. The reduced mobilities, K0, have been determined, as have the linear response ranges for ESI-HPIMS, which are 1.5-2 orders of magnitude for concentrations down to sub-ng μL(-1) levels. At least one unique mobility peak was seen for two subsets of the phthalates grouped by the country where they were banned. Furthermore, ESI-HPIMS successfully detected low nanogram levels of a phthalate at up to 30 times lower concentration than international detection levels in both a cola matrix and a soy-based bubble tea beverage using only a simplified sample treatment. A newly developed direct ESI source (Directspray) was combined with HPIMS to detect food-grade dyes and industrial dye adulterants, as well as the sweeteners sodium saccharin and sodium cyclamate, with the same good performance as with the phthalates. However, the Directspray method eliminated sources of carryover and decreased the time between sample runs. Limits-of-detection (LOD) for the analyte standards were estimated to be sub-ng μL(-1) levels without extensive sample handling or preparation. PMID:24267082

  11. 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

  12. 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

  13. Differential ion mobility separations in up to 100% helium using microchips.

    PubMed

    Shvartsburg, Alexandre A; Ibrahim, Yehia M; Smith, Richard D

    2014-03-01

    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.

  14. Rapid analysis of pesticide residues in drinking water samples by dispersive solid-phase extraction based on multiwalled carbon nanotubes and pulse glow discharge ion source ion mobility spectrometry.

    PubMed

    Zou, Nan; Gu, Kejia; Liu, Shaowen; Hou, Yanbing; Zhang, Jialei; Xu, Xiang; Li, Xuesheng; Pan, Canping

    2016-03-01

    An analytical method based on dispersive solid-phase extraction with a multiwalled carbon nanotubes sorbent coupled with positive pulse glow discharge ion mobility spectrometry was developed for analysis of 30 pesticide residues in drinking water samples. Reduced ion mobilities and the mass-mobility correlation of 30 pesticides were measured. The pesticides were divided into five groups to verify the separation capability of pulse glow discharge in mobility spectrometry. The extraction conditions such as desorption solvent, ionic strength, conditions of adsorption and desorption, the amounts of multiwalled carbon nanotubes, and solution pH were optimized. The enrichment factors of pesticides were 5.4- to 48.7-fold (theoretical enrichment factor was 50-fold). The detection limits of pesticides were 0.01∼0.77 μg/kg. The linear range was 0.005-0.2 mg/L for pesticide standard solutions, with determination coefficients from 0.9616 to 0.9999. The method was applied for the analysis of practical and spiked drinking water samples. All results were confirmed by high-performance liquid chromatography with tandem mass spectrometry. The proposed method was proven to be a commendably rapid screening qualitative and semiquantitative technique for the analysis of pesticide residues in drinking water samples on site. PMID:27027594

  15. Rapid analysis of pesticide residues in drinking water samples by dispersive solid-phase extraction based on multiwalled carbon nanotubes and pulse glow discharge ion source ion mobility spectrometry.

    PubMed

    Zou, Nan; Gu, Kejia; Liu, Shaowen; Hou, Yanbing; Zhang, Jialei; Xu, Xiang; Li, Xuesheng; Pan, Canping

    2016-03-01

    An analytical method based on dispersive solid-phase extraction with a multiwalled carbon nanotubes sorbent coupled with positive pulse glow discharge ion mobility spectrometry was developed for analysis of 30 pesticide residues in drinking water samples. Reduced ion mobilities and the mass-mobility correlation of 30 pesticides were measured. The pesticides were divided into five groups to verify the separation capability of pulse glow discharge in mobility spectrometry. The extraction conditions such as desorption solvent, ionic strength, conditions of adsorption and desorption, the amounts of multiwalled carbon nanotubes, and solution pH were optimized. The enrichment factors of pesticides were 5.4- to 48.7-fold (theoretical enrichment factor was 50-fold). The detection limits of pesticides were 0.01∼0.77 μg/kg. The linear range was 0.005-0.2 mg/L for pesticide standard solutions, with determination coefficients from 0.9616 to 0.9999. The method was applied for the analysis of practical and spiked drinking water samples. All results were confirmed by high-performance liquid chromatography with tandem mass spectrometry. The proposed method was proven to be a commendably rapid screening qualitative and semiquantitative technique for the analysis of pesticide residues in drinking water samples on site.

  16. Receptor-based high-throughput screening and identification of estrogens in dietary supplements using bioaffinity liquid-chromatography ion mobility mass spectrometry.

    PubMed

    Aqai, Payam; Blesa, Natalia Gómez; Major, Hilary; Pedotti, Mattia; Varani, Luca; Ferrero, Valentina E V; Haasnoot, Willem; Nielen, Michel W F

    2013-11-01

    A high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of recombinant human estrogen receptor α (ERα) ligands in dietary supplements. For screening, a semi-automated mass spectrometric ligand binding assay was developed applying (13)C2, (15) N-tamoxifen as non-radioactive label and fast ultra-high-performance-liquid chromatography-electrospray ionisation-triple-quadrupole-MS (UPLC-QqQ-MS), operated in the single reaction monitoring mode, as a readout system. Binding of the label to ERα-coated paramagnetic microbeads was inhibited by competing estrogens in the sample extract yielding decreased levels of the label in UPLC-QqQ-MS. The label showed high ionisation efficiency in positive electrospray ionisation (ESI) mode, so the developed BioMS approach is able to screen for estrogens in dietary supplements despite their poor ionisation efficiency in both positive and negative ESI modes. The assay was performed in a 96-well plate, and all these wells could be measured within 3 h. Estrogens in suspect extracts were identified by full-scan accurate mass and collision-cross section (CCS) values from a UPLC-ion mobility-Q-time-of-flight-MS (UPLC-IM-Q-ToF-MS) equipped with a novel atmospheric pressure ionisation source. Thanks to the novel ion source, this instrument provided picogram sensitivity for estrogens in the negative ion mode and an additional identification point (experimental CCS values) next to retention time, accurate mass and tandem mass spectrometry data. The developed combination of bioaffinity screening with UPLC-QqQ-MS and identification with UPLC-IM-Q-ToF-MS provides an extremely powerful analytical tool for early warning of ERα bioactive compounds in dietary supplements as demonstrated by analysis of selected dietary supplements in which different estrogens were identified.

  17. 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

  18. 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.

  19. Characterization of TATP gas phase product ion chemistry via isotope labeling experiments using ion mobility spectrometry interfaced with a triple quadrupole mass spectrometer.

    PubMed

    Tomlinson-Phillips, Jill; Wooten, Alfred; Kozole, Joseph; Deline, James; Beresford, Pamela; Stairs, Jason

    2014-09-01

    Identification of the fragment ion species associated with the ion reaction mechanism of triacetone triperoxide (TATP), a homemade peroxide-based explosive, is presented. Ion mobility spectrometry (IMS) has proven to be a key analytical technique in the detection of trace explosive material. Unfortunately, IMS alone does not provide chemical identification of the ions detected; therefore, it is unknown what ion species are actually formed and separated by the IMS. In IMS, ions are primarily characterized by their drift time, which is dependent on the ion׳s mass and molecular cross-section; thus, IMS as a standalone technique does not provide structural signatures, which is in sharp contrast to the chemical and molecular information that is generally obtained from other customary analytical techniques, such as NMR, Raman and IR spectroscopy and mass spectrometry. To help study the ion chemistry that gives rise to the peaks observed in IMS, the hardware of two different commercial IMS instruments has been directly coupled to triple quadrupole (QQQ) mass spectrometers, in order to ascertain each ion׳s corresponding mass/charge (m/z) ratios with different dopants at two temperatures. Isotope labeling was then used to help identify and confirm the molecular identity of the explosive fragment and adduct ions of TATP. The m/z values and isotope labeling experiments were used to help propose probable molecular formulas for the ion fragments. In this report, the fragment and adduct ions m/z 58 and 240 of TATP have been confirmed to be [C3H6NH·H](+) and [TATP·NH4](+), respectively; while the fragment ions m/z 73 and 89 of TATP are identified as having the molecular formulas [C4H9NH2](+) and [C4H9O2](+), respectively. It is anticipated that the work in this area will not only help to facilitate improvements in mobility-based detection (IMS and MS), but also aid in the development and optimization of MS-based detection algorithms for TATP.

  20. Characterization of TATP gas phase product ion chemistry via isotope labeling experiments using ion mobility spectrometry interfaced with a triple quadrupole mass spectrometer.

    PubMed

    Tomlinson-Phillips, Jill; Wooten, Alfred; Kozole, Joseph; Deline, James; Beresford, Pamela; Stairs, Jason

    2014-09-01

    Identification of the fragment ion species associated with the ion reaction mechanism of triacetone triperoxide (TATP), a homemade peroxide-based explosive, is presented. Ion mobility spectrometry (IMS) has proven to be a key analytical technique in the detection of trace explosive material. Unfortunately, IMS alone does not provide chemical identification of the ions detected; therefore, it is unknown what ion species are actually formed and separated by the IMS. In IMS, ions are primarily characterized by their drift time, which is dependent on the ion׳s mass and molecular cross-section; thus, IMS as a standalone technique does not provide structural signatures, which is in sharp contrast to the chemical and molecular information that is generally obtained from other customary analytical techniques, such as NMR, Raman and IR spectroscopy and mass spectrometry. To help study the ion chemistry that gives rise to the peaks observed in IMS, the hardware of two different commercial IMS instruments has been directly coupled to triple quadrupole (QQQ) mass spectrometers, in order to ascertain each ion׳s corresponding mass/charge (m/z) ratios with different dopants at two temperatures. Isotope labeling was then used to help identify and confirm the molecular identity of the explosive fragment and adduct ions of TATP. The m/z values and isotope labeling experiments were used to help propose probable molecular formulas for the ion fragments. In this report, the fragment and adduct ions m/z 58 and 240 of TATP have been confirmed to be [C3H6NH·H](+) and [TATP·NH4](+), respectively; while the fragment ions m/z 73 and 89 of TATP are identified as having the molecular formulas [C4H9NH2](+) and [C4H9O2](+), respectively. It is anticipated that the work in this area will not only help to facilitate improvements in mobility-based detection (IMS and MS), but also aid in the development and optimization of MS-based detection algorithms for TATP. PMID:24913870

  1. Detection of tetrahydrocannabinol residues on hands by ion-mobility spectrometry (IMS). Correlation of IMS data with saliva analysis.

    PubMed

    Sonnberg, Saskia; Armenta, Sergio; Garrigues, Salvador; de la Guardia, Miguel

    2015-08-01

    Ion-mobility spectroscopy (IMS) was evaluated as a high-throughput, cheap, and efficient analytical tool for detecting residues of tetrahydrocannabinol (THC) on hands. Regarding the usefulness of hand residues as potential samples for determining THC handling and abuse, we studied the correlation between data obtained from cannabis consumers who were classified as positive after saliva analysis and from those who were classified as positive on the basis of the information from hand-residue analysis. Sampling consisted of wiping the hands with borosilicate glass microfiber filters and introducing these directly into the IMS after thermal desorption. The possibility of false positive responses, resulting from the presence of other compounds with a similar drift time to THC, was evaluated and minimised by applying the truncated negative second-derivative algorithm. The possibility of false negative responses, mainly caused by competitive ionisation resulting from nicotine, was also studied. Graphical abstract THC residues: from hands to analytical signals. PMID:26072207

  2. Detection of tetrahydrocannabinol residues on hands by ion-mobility spectrometry (IMS). Correlation of IMS data with saliva analysis.

    PubMed

    Sonnberg, Saskia; Armenta, Sergio; Garrigues, Salvador; de la Guardia, Miguel

    2015-08-01

    Ion-mobility spectroscopy (IMS) was evaluated as a high-throughput, cheap, and efficient analytical tool for detecting residues of tetrahydrocannabinol (THC) on hands. Regarding the usefulness of hand residues as potential samples for determining THC handling and abuse, we studied the correlation between data obtained from cannabis consumers who were classified as positive after saliva analysis and from those who were classified as positive on the basis of the information from hand-residue analysis. Sampling consisted of wiping the hands with borosilicate glass microfiber filters and introducing these directly into the IMS after thermal desorption. The possibility of false positive responses, resulting from the presence of other compounds with a similar drift time to THC, was evaluated and minimised by applying the truncated negative second-derivative algorithm. The possibility of false negative responses, mainly caused by competitive ionisation resulting from nicotine, was also studied. Graphical abstract THC residues: from hands to analytical signals.

  3. Nutritional state affects the expression of the obesity-associated genes Etv5, Faim2, Fto, and Negr1.

    PubMed

    Boender, Arjen J; van Rozen, Andrea J; Adan, Roger A H

    2012-12-01

    Obesity is a risk factor for type II diabetes, atherosclerosis, and some forms of cancer. Variation in common measures of obesity (e.g., BMI, waist/hip ratio) is largely explained by heritability. The advent of genome-wide association studies (GWAS) has made it possible to identify several genetic variants that associate with measures of obesity, but how exactly these genetic variants contribute to overweight has remained largely unresolved. One first hint is given by the fact that many of the associated variants reside in or near genes that act in the central nervous system, which implicates neuronal signaling in the etiology of obesity. Although the brain controls both energy intake and expenditure, it has more capacity to regulate energy intake rather than energy expenditure. In environments where food is abundant, this renders the body prone to weight increases. To gain more insight into the neurobiological mechanisms involved, we set out to investigate the effect of dietary exposure on the expression levels of obesity-associated genes in the ventro-medial hypothalamus (VMH)/arcuate nucleus (ARC) and the substantia nigra (SN)/ventral tegmental area (VTA), two brain regions that are implicated in feeding behavior. We show that the expression of Etv5, Faim2, Fto, Negr1 but not Sh2b1 is affected by nutritional state in these two areas, thereby providing insight into the relationship between nutritional state and expression levels of obesity-associated genes in two brain areas relevant to feeding.

  4. 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(-).

  5. Gas-Phase Analysis of the Complex of Fibroblast GrowthFactor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study

    NASA Astrophysics Data System (ADS)

    Zhao, Yuejie; Singh, Arunima; Xu, Yongmei; Zong, Chengli; Zhang, Fuming; Boons, Geert-Jan; Liu, Jian; Linhardt, Robert J.; Woods, Robert J.; Amster, I. Jonathan

    2016-09-01

    Fibroblast growth factors (FGFs) regulate several cellular developmental processes by interacting with cell surface heparan proteoglycans and transmembrane cell surface receptors (FGFR). The interaction of FGF with heparan sulfate (HS) is known to induce protein oligomerization, increase the affinity of FGF towards its receptor FGFR, promoting the formation of the HS-FGF-FGFR signaling complex. Although the role of HS in the signaling pathways is well recognized, the details of FGF oligomerization and formation of the ternary signaling complex are still not clear, with several conflicting models proposed in literature. Here, we examine the effect of size and sulfation pattern of HS upon FGF1 oligomerization, binding stoichiometry and conformational stability, through a combination of ion mobility (IM) and theoretical modeling approaches. Ion mobility-mass spectrometry (IMMS) of FGF1 in the presence of several HS fragments ranging from tetrasaccharide (dp4) to dodecasaccharide (dp12) in length was performed. A comparison of the binding stoichiometry of variably sulfated dp4 HS to FGF1 confirmed the significance of the previously known high-affinity binding motif in FGF1 dimerization, and demonstrated that certain tetrasaccharide-length fragments are also capable of inducing dimerization of FGF1. The degree of oligomerization was found to increase in the presence of dp12 HS, and a general lack of specificity for longer HS was observed. Additionally, collision cross-sections (CCSs) of several FGF1-HS complexes were calculated, and were found to be in close agreement with experimental results. Based on the (CCSs) a number of plausible binding modes of 2:1 and 3:1 FGF1-HS are proposed.

  6. Analysis of a common cold virus and its subviral particles by gas-phase electrophoretic mobility molecular analysis and native mass spectrometry.

    PubMed

    Weiss, Victor U; Bereszcazk, Jessica Z; Havlik, Marlene; Kallinger, Peter; Gösler, Irene; Kumar, Mohit; Blaas, Dieter; Marchetti-Deschmann, Martina; Heck, Albert J R; Szymanski, Wladyslaw W; Allmaier, Günter

    2015-09-01

    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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Ion mobility-mass spectrometry of charge-reduced protein complexes reveals general trends in the collisional ejection of compact subunits.

    PubMed

    Bornschein, Russell E; Ruotolo, Brandon T

    2015-10-21

    Multiprotein complexes have been shown to play critical roles across a wide range of cellular functions, but most probes of protein quaternary structure are limited in their ability to analyze complex mixtures and polydisperse structures using small amounts of total protein. Ion mobility-mass spectrometry offers a solution to many of these challenges, but relies upon gas-phase measurements of intact multiprotein complexes, subcomplexes, and subunits that correlate well with solution structures. The greatest bottleneck in such workflows is the generation of representative subcomplexes and subunits. Collisional activation of complexes can act to produce product ions reflective of protein complex composition, but such product ions are typically challenging to interpret in terms of their relationship to solution structure due to their typically string-like conformations following activation and subsequent dissociation. Here, we used ion-ion chemistry to perform a broad survey of the gas-phase dissociation of charge-reduced protein complex ions, revealing general trends associated with the collisional ejection of compact, rather than unfolded, protein subunits. Furthermore, we also discover peptide and co-factor dissociation channels that dominate the product ion populations generated for such charge reduced complexes. We assess both sets of observations and discuss general principles that can be extended to the analysis of protein complex ions having unknown structures.

  17. 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.

  18. 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.

  19. Sizing up large protein complexes by electrospray ionisation-based electrophoretic mobility and native mass spectrometry: morphology selective binding of Fabs to hepatitis B virus capsids.

    PubMed

    Bereszczak, Jessica Z; Havlik, Marlene; Weiss, Victor U; Marchetti-Deschmann, Martina; van Duijn, Esther; Watts, Norman R; Wingfield, Paul T; Allmaier, Guenter; Steven, Alasdair C; Heck, Albert J R

    2014-02-01

    The capsid of hepatitis B virus (HBV) is a major viral antigen and important diagnostic indicator. HBV capsids have prominent protrusions ('spikes') on their surface and are unique in having either T = 3 or T = 4 icosahedral symmetry. Mouse monoclonal and also human polyclonal antibodies bind either near the spike apices (historically the 'α-determinant') or in the 'floor' regions between them (the 'β-determinant'). Native mass spectrometry (MS) and gas-phase electrophoretic mobility molecular analysis (GEMMA) were used to monitor the titration of HBV capsids with the antigen-binding domain (Fab) of mAb 3120, which has long defined the β-determinant. Both methods readily distinguished Fab binding to the two capsid morphologies and could provide accurate masses and dimensions for these large immune complexes, which range up to ~8 MDa. As such, native MS and GEMMA provide valuable alternatives to a more time-consuming cryo-electron microscopy analysis for preliminary characterisation of virus-antibody complexes.

  20. 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

  1. Determining urea levels in dialysis human serum by means of headspace solid phase microextraction coupled with ion mobility spectrometry and on the basis of nanostructured polypyrrole film.

    PubMed

    Kalhor, Hamideh; Alizadeh, Naader

    2013-06-01

    A simple and sensitive headspace (HS) solid phase microextraction (SPME) coupled with ion mobility spectrometry (IMS) method is presented for analysis of urea in dialysis human serum samples. A dodecylbenzenesulfonate-doped polypyrrole coating was used as a fiber for SPME. The HS-SPME-IMS method exhibits good repeatability (relative standard deviation of 3% or less), simplicity, and good sensitivity. The influence of various analytical parameters such as pH, ionic strength, extraction time and temperature was investigated and the parameters were optimized. The calibration graph was linear in the range from 5 to 50 μg mL(-1), and the detection limit was 2 μg mL(-1). The method was applied successfully for determination of urea in human serum and with acceptable recovery (more than 98%). Finally, a standard addition calibration method was applied to the HS-SPME-IMS method for the analysis of human serum samples before and at the end of dialysis. The proposed method appears to be suitable for the analysis of urea in serum samples as it is not time-consuming and requires only small quantities of the sample without any derivatization process.

  2. Uncovering the stoichiometry of Pyrococcus furiosus RNase P, a multi-subunit catalytic ribonucleoprotein complex, by surface-induced dissociation and ion mobility mass spectrometry.

    PubMed

    Ma, Xin; Lai, Lien B; Lai, Stella M; Tanimoto, Akiko; Foster, Mark P; Wysocki, Vicki H; Gopalan, Venkat

    2014-10-20

    We demonstrate that surface-induced dissociation (SID) coupled with ion mobility mass spectrometry (IM-MS) is a powerful tool for determining the stoichiometry of a multi-subunit ribonucleoprotein (RNP) complex assembled in a solution containing Mg(2+). We investigated Pyrococcus furiosus (Pfu) RNase P, an archaeal RNP that catalyzes tRNA 5' maturation. Previous step-wise, Mg(2+)-dependent reconstitutions of Pfu RNase P with its catalytic RNA subunit and two interacting protein cofactor pairs (RPP21⋅RPP29 and POP5⋅RPP30) revealed functional RNP intermediates en route to the RNase P enzyme, but provided no information on subunit stoichiometry. Our native MS studies with the proteins showed RPP21⋅RPP29 and (POP5⋅RPP30)2 complexes, but indicated a 1:1 composition for all subunits when either one or both protein complexes bind the cognate RNA. These results highlight the utility of SID and IM-MS in resolving conformational heterogeneity and yielding insights on RNP assembly.

  3. Extraction of toxic compounds from saliva by magnetic-stirring-assisted micro-solid-phase extraction step followed by headspace-gas chromatography-ion mobility spectrometry.

    PubMed

    Criado-García, Laura; Arce, Lourdes

    2016-09-01

    A new sample extraction procedure based on micro-solid-phase extraction (μSPE) using a mixture of sorbents of different polarities (polymeric reversed-phase sorbent HLB, silica-based sorbent C18, and multiwalled carbon nanotubes) was applied to extract benzene, toluene, butyraldehyde, benzaldehyde, and tolualdehyde present in saliva to avoid interference from moisture and matrix components and enhance sensitivity and selectivity of the ion mobility spectrometry (IMS) methodology proposed. The extraction of target analytes from saliva samples by using μSPE were followed by the desorption step carried out in the headspace vials placed in the autosampler of the IMS device. Then, 200 μL of headspace was injected into the GC column coupled to the IMS for its analysis. The method was fully validated in terms of sensitivity, precision, and recovery. The LODs and LOQs obtained, when analytes were dissolved in saliva samples to consider the matrix effect, were within the range of 0.38-0.49 and 1.26-1.66 μg mL(-1), respectively. The relative standard deviations were <3.5 % for retention time and drift time values, which indicate that the method proposed can be applied to determine toxic compounds in saliva samples. Graphical abstract Summary of steps followed in the experimental set up of this work. PMID:27481168

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Simultaneous analysis of non-steroidal anti-inflammatory drugs using electrochemically controlled solid-phase microextraction based on nanostructure molecularly imprinted polypyrrole film coupled to ion mobility spectrometry.

    PubMed

    Ameli, Akram; Kalhor, Hamideh; Alizadeh, Naader

    2013-06-01

    A simple, rapid, and highly sensitive method for simultaneous analysis of anti-inflammatory drugs (naproxen, ibuprofen, and mefenamic acid) in diluted human serum was developed using the electrochemically controlled solid-phase microextraction coupled to ion mobility spectrometry. A conducting molecularly imprinted polymer film based on polypyrrole was synthesized for the selective uptake and release of drugs. The film was prepared by incorporation of a template molecule (naproxen) during the electropolymerization of pyrrole onto a platinum electrode using cyclic voltammetry method. The measured ion mobility spectrometry intensity was related to the concentration of analytes taken up into the films. The calibration graphs (naproxen, ibuprofen, and mefenamic acid) were linear in the range of 0.1-30 ng/mL and detection limits were 0.07-0.37 ng/mL and relative standard deviation was lower than 6%. On the basis of the results obtained in this work, the conducting molecularly imprinted polymer films as absorbent have been applied in the electrochemically controlled solid-phase microextraction and ion mobility spectrometry system for the selective clean-up and quantification of trace amounts of anti-inflammatory drugs in human serum samples. Scanning electron microscopy has confirmed the nano-structure morphology of the polypyrrole film.

  9. 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.

  10. Structural elucidation of specific noncovalent association of folic acid with native cyclodextrins using an ion mobility mass spectrometry and theoretical approach.

    PubMed

    Zimnicka, Magdalena; Troć, Anna; Ceborska, Magdalena; Jakubczak, Michał; Koliński, Michał; Danikiewicz, Witold

    2014-05-01

    The combination of ion mobility mass spectrometry studies and theoretical calculations including docking studies permitted a detailed structural description of noncovalent complexes of folic acid (FA) and native cyclodextrins (α-CD, β-CD, and γ-CD). The mode of noncovalent association depended on the cavity size of the cyclodextrin. The structure of FA/α-CD represented the exclusion complex in which the aminobenzoic moiety and the aromatic pteridine ring of folic acid remain outside the cyclodextrin cavity, while the glutamate residue is anchored in the interior of the α-cyclodextrin. A rotaxane-type structure was proposed for the FA/β-CD complex with the aminobenzoic part of FA being trapped in the central cavity of β-CD. The glutamate residue and the aromatic pteridine ring interact with the primary and secondary rim hydroxyl residues, respectively, enhancing complex stability. Two possible structures of FA/γ-CD were suggested, the first one being analogous to the FA/β-CD complex and the second one being more stable-in which the aromatic pteridine ring penetrates into the CD cavity while the glutamate residue with the aminobenzoic part of FA is exposed to the cone exterior of CD at its wider edge. Further insight into the association behavior of the folic acid toward cyclodextrins evaluated by thermodynamic calculations indicates that the process is highly exothermic. The complex stability increased in the order FA/α-CD < FA/β-CD < FA/γ-CD. This order is consistent with the previously determined relative gas-phase stability established based on the dissociation efficiency curves of the FA/CD complexes.

  11. 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

  12. Rapid screening of methamphetamines in human serum by headspace solid-phase microextraction using a dodecylsulfate-doped polypyrrole film coupled to ion mobility spectrometry.

    PubMed

    Alizadeh, Naader; Mohammadi, Abdorreza; Tabrizchi, Mahmoud

    2008-03-01

    A simple, rapid and highly sensitive method for simultaneous analysis of methamphetamine (MA) and 3,4-methylenedioxy methamphetamine (MDMA) in human serum was developed using the solid-phase microextraction (SPME) combined with ion mobility spectrometry (IMS). A dodecylsulfate-doped polypyrrole (PPy-DS) was applied as a new fiber for SPME. Electrochemically polymerized PPy is formed on the surface of a platinum wire and will contain charge-compensating anion (dodecylsulfate) incorporated during synthesis using cyclic voltammetry (CV) technique. The extraction properties of the fiber to MA and MDMA were examined, using a headspace-SPME (HS-SPME) device and thermal desorption in injection port of IMS. The results show that PPy-DS as a SPME fiber coating is suitable for the successful extraction of these compounds. This method is suitable for the identification and determination of MAs, is not time-consuming, requires small quantities of sample and does not require any derivatization. Parameters like pH, extraction time, ionic strength, and temperature of the sample were studied and optimized to obtain the best extraction results. The HS-SPME-IMS method provided good repeatability (RSDs<7.8 %) for spiked serum samples. The calibration graphs were linear in the range of 20-4000 ng ml(-1) (R(2)>0.99) and detection limits for MDMA and MA were 5 and 8 ng ml(-1), respectively. HS-SPME-IMS of non-spiked serum sample provided a spectrum without any peak from the matrix, supporting an effective sample clean-up. Finally, the proposed method was applied for analysis one of the ecstasy tablet.

  13. Localization of fatty acyl and double bond positions in phosphatidylcholines using a dual stage CID fragmentation coupled with ion mobility mass spectrometry.

    PubMed

    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 (C(15)H(31)CO(+), m/z 239) or 18:1 (9Z) (C(17)H(33)CO(+), 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 (+H(2)C-HC = CH-CH = CH(2)). 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 (13)C 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. 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

  15. The use of ion mobility mass spectrometry to probe modulation of the structure of p53 and of MDM2 by small molecule inhibitors

    PubMed Central

    Dickinson, Eleanor R.; Jurneczko, Ewa; Nicholson, Judith; Hupp, Ted R.; Zawacka-Pankau, Joanna; Selivanova, Galina; Barran, Perdita E.

    2015-01-01

    Developing drug-like molecules to inhibit the interactions formed by disordered proteins is desirable due to the high correlation of disorder with protein implicated in disease, but is challenging due in part to the lack of atomistically resolved and resolvable structures from conformationally dynamic systems. Ion mobility mass spectrometry (IM-MS) is well-positioned to assess protein ligand interactions along with the effect of a given inhibitor on conformation. Here we demonstrate the use of IM-MS to characterize the effect of two inhibitors RITA and Nutlin-3 on their respective binding partners: p53 and MDM2. RITA binds N-terminal transactivation domain of p53 (Np53) weakly, preventing direct observation of the complex in the gas phase. Nonetheless, upon incubation with RITA, we observe an alteration in the charge state distribution and in the conformational distributions adopted by Np53 in the gas phase. This finding supports the hypothesis that RITAs mode of action proceeds via a conformational change in p53. Circular dichroism corroborates our gas phase findings, showing a slight increase in secondary structure content on ligand incubation, and HDX-MS experiments also highlight the dynamic properties of this protein. Using the same approach we present data to show the effect of Nutlin-3 binding to the N-terminal domain of MDM2 (N-MDM2), N-MDM2 presents as at least two conformational families in the absence of Nutlin-3. Upon Nutlin-3 binding, the protein undergoes a compaction event similar to that exhibited by RITA on Np53. This multi-technique approach highlights the inherent disorder in these systems; and in particular exemplifies the power of IM-MS as a technique to study transient interactions between small molecule inhibitors and intrinsically disordered proteins. PMID:26217671

  16. 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...

  17. 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

  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 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

  19. Field-Domain Ion Spectrometry

    NASA Technical Reports Server (NTRS)

    Bowers, W. D.; Chuan, R. L.

    1992-01-01

    Field-domain ion spectrometry (FDIS) is variant of established technique known as ion-mobility spectrometry. Operates at atmospheric pressure and only requires small pump to draw air sample into instrument. Strength of retarding electric field varied to distinguish among ions of different mobilities. New concept offers potential for development of small, (hand-held), low-power, portable devices detecting airborne chemical substances in real-time at concentrations at parts-per-billion level.

  20. 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,...

  1. 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.

  2. Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population.

    PubMed

    Hotta, Kikuko; Nakamura, Michihiro; Nakamura, Takahiro; Matsuo, Tomoaki; Nakata, Yoshio; Kamohara, Seika; Miyatake, Nobuyuki; Kotani, Kazuaki; Komatsu, Ryoya; Itoh, Naoto; Mineo, Ikuo; Wada, Jun; Masuzaki, Hiroaki; Yoneda, Masato; Nakajima, Atsushi; Funahashi, Tohru; Miyazaki, Shigeru; Tokunaga, Katsuto; Kawamoto, Manabu; Ueno, Takato; Hamaguchi, Kazuyuki; Tanaka, Kiyoji; Yamada, Kentaro; Hanafusa, Toshiaki; Oikawa, Shinichi; Yoshimatsu, Hironobu; Nakao, Kazuwa; Sakata, Toshiie; Matsuzawa, Yuji; Kamatani, Naoyuki; Nakamura, Yusuke

    2009-12-01

    There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.

  3. Native tandem and ion mobility mass spectrometry highlight structural and modular similarities in clustered-regularly-interspaced shot-palindromic-repeats (CRISPR)-associated protein complexes from Escherichia coli and Pseudomonas aeruginosa.

    PubMed

    van Duijn, Esther; Barbu, Ioana M; Barendregt, Arjan; Jore, Matthijs M; Wiedenheft, Blake; Lundgren, Magnus; Westra, Edze R; Brouns, Stan J J; Doudna, Jennifer A; van der Oost, John; Heck, Albert J R

    2012-11-01

    The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) immune system of bacteria and archaea provides acquired resistance against viruses and plasmids, by a strategy analogous to RNA-interference. Key components of the defense system are ribonucleoprotein complexes, the composition of which appears highly variable in different CRISPR/Cas subtypes. Previous studies combined mass spectrometry, electron microscopy, and small angle x-ray scattering to demonstrate that the E. coli Cascade complex (405 kDa) and the P. aeruginosa Csy-complex (350 kDa) are similar in that they share a central spiral-shaped hexameric structure, flanked by associating proteins and one CRISPR RNA. Recently, a cryo-electron microscopy structure of Cascade revealed that the CRISPR RNA molecule resides in a groove of the hexameric backbone. For both complexes we here describe the use of native mass spectrometry in combination with ion mobility mass spectrometry to assign a stable core surrounded by more loosely associated modules. Via computational modeling subcomplex structures were proposed that relate to the experimental IMMS data. Despite the absence of obvious sequence homology between several subunits, detailed analysis of sub-complexes strongly suggests analogy between subunits of the two complexes. Probing the specific association of E. coli Cascade/crRNA to its complementary DNA target reveals a conformational change. All together these findings provide relevant new information about the potential assembly process of the two CRISPR-associated complexes.

  4. 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

  5. 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.

  6. Separation and characterization of phenolic compounds and triterpenoid saponins in licorice (Glycyrrhiza uralensis) using mobile phase-dependent reversed-phase×reversed-phase comprehensive two-dimensional liquid chromatography coupled with mass spectrometry.

    PubMed

    Qiao, Xue; Song, Wei; Ji, Shuai; Wang, Qi; Guo, De-an; Ye, Min

    2015-07-10

    Licorice is one of the most popular herbal medicines worldwide. It contains a big array of phenolic compounds (flavonoids, coumarins, and diphenylethanones). Due to high structural diversity, low abundance, and co-elution with licorice saponins, these phenolic compounds are difficult to be separated by conventional chromatography. In this study, a mobile phase-dependent reversed-phase×reversed phase comprehensive two-dimensional liquid chromatography (RP×RP 2DLC) method was established to separate phenolic compounds in licorice (the roots of Glycyrrhiza uralensis). Organic solvents in the mobile phase were optimized to improve orthogonality of the first and second dimensions, and a synchronized gradient mode was used to improve chromatographic resolution. Finally, licorice extracts were eluted with methanol/water/formic acid in the first dimension (Acquity CSH C18 column), and acetonitrile/water/formic acid in the second dimension (Poroshell Phenyl-Hexyl column). By using this 2DLC system, a total of 311 compounds were detected within 40min. The practical and effective peak capacity was 1329 and 524, respectively, and the orthogonality was 79.8%. The structures of 21 selected unknown compounds were tentatively characterized by mass spectrometry, and 8 of them were discovered from G. uralensis for the first time. The mobile phase-dependent 2DLC/MS system could benefit the separation and characterization of natural products in complicated herbal extracts.

  7. Studies of peptide a- and b-type fragment ions using stable isotope labeling and integrated ion mobility/tandem mass spectrometry.

    PubMed

    Riba Garcia, Isabel; Giles, Kevin; Bateman, Robert H; Gaskell, Simon J

    2008-12-01

    The structures of peptide a- and b-type fragment ions were studied using synthetic peptides including a set of isomeric peptides, differing in the sequence location of an alanine residue labeled with (15)N and uniformly with (13)C. The pattern of isotope labeling of second-generation fragment ions derived via a(n) and b(n) ions (where n = 4 or 5) suggested that these intermediates existed in part as macrocyclic structures, where alternative sites of ring opening gave rise to different linear forms whose simple cleavage might give rise to the observed final products. Similar conclusions were derived from combined ion mobility/tandem MS analyses where different fragmentation patterns were observed for isomeric a- or b-type ions that display different ion mobilities. These analyses were facilitated by a new approach to the processing of ion mobility/tandem MS data, from which distinct and separate product ion spectra are derived from ions that are incompletely separated by ion mobility. Finally, an example is provided of evidence for a macrocyclic structure for b(n) ions where n = 8 or 9.

  8. 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

  9. Effects of liquid chromatography mobile phases and buffer salts on phosphorus inductively coupled plasma atomic emission and mass spectrometries utilizing ultrasonic nebulization and membrane desolvation.

    PubMed

    Carr, John E; Kwok, Kaho; Webster, Gregory K; Carnahan, Jon W

    2006-01-23

    Atomic spectrometry, specifically inductively coupled plasma atomic emission spectrometry (ICP-AES) and mass spectrometry (ICP-MS) show promise for heteroatom-based detection of pharmaceutical compounds. The combination of ultrasonic nebulization (USN) with membrane desolvation (MD) greatly enhances detection limits with these approaches. Because pharmaceutical analyses often incorporate liquid chromatography, the study herein was performed to examine the effects of solvent composition on the analytical behaviors of these approaches. The target analyte was phosphorus, introduced as phosphomycin. AES response was examined at the 253.7 nm atom line and mass 31 ions were monitored for the MS experiments. With pure aqueous solutions, detection limits of 5 ppb (0.5 ng in 0.1 mL injection volumes) were obtained with ICP-MS. The ICP-AES detection limit was 150 ppb. Solvent compositions were varied from 0 to 80% organic (acetonitrile and methanol) with nine buffers at concentrations typically used in liquid chromatography. In general, solvents and buffers had statistically significant, albeit small, effects on ICP-AES sensitivities. A few exceptions occurred in cases where typical liquid chromatography buffer concentrations produced higher mass loadings on the plasma. Indications are that isocratic separations can be reliably performed. Within reasonable accuracy tolerances, it appears that gradient chromatography can be performed without the need for signal response normalization. Organic solvent and buffer effects were more significant with ICP-MS. Sensitivities varied significantly with different buffers and organic solvent content. In these cases, gradient chromatography will require careful analytical calibration as solvent and buffer content is varied. However, for most buffer and solvent combinations, signal and detection limits are only moderately affected. Isocratic separations and detection are feasible.

  10. 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