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Sample records for fticr mass spectrometry

  1. Considerations for electron capture dissociation efficiency in FTICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Gorshkov, Michael V.; Masselon, Christophe D.; Nikolaev, Eugene N.; Udseth, Harold R.; Pasa-Tolic, Ljiljana; Smith, Richard D.

    2004-05-01

    An experimental approach for increasing the efficiency of Electron Capture Dissociation (ECD) with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is presented. The approach is based on manipulating the spatial distribution of an ion cloud inside an FTICR trap during electron irradiation, which is realized by using both on-resonance pre-excitation of the ions and sustained off-resonance irradiation (SORI). The achieved fragmentation efficiency is compared with the theoretical prediction. This method may be useful in biological applications of FTICR, such as identification of posttranslational modifications in proteins and de novo sequencing, where the ECD technique is most applicable.

  2. Absorption mode FTICR mass spectrometry imaging.

    PubMed

    Smith, Donald F; Kilgour, David P A; Konijnenburg, Marco; O'Connor, Peter B; Heeren, Ron M A

    2013-12-03

    Fourier transform ion cyclotron resonance mass spectrometry offers the highest mass resolving power for molecular imaging experiments. This high mass resolving power ensures that closely spaced peaks at the same nominal mass are resolved for proper image generation. Typically higher magnetic fields are used to increase mass resolving power. However, a gain in mass resolving power can also be realized by phase correction of the data for absorption mode display. In addition to mass resolving power, absorption mode offers higher mass accuracy and signal-to-noise ratio over the conventional magnitude mode. Here, we present the first use of absorption mode for Fourier transform ion cyclotron resonance mass spectrometry imaging. The Autophaser algorithm is used to phase correct each spectrum (pixel) in the image, and then, these parameters are used by the Chameleon work-flow based data processing software to generate absorption mode "Datacubes" for image and spectral viewing. Absorption mode reveals new mass and spatial features that are not resolved in magnitude mode and results in improved selected ion image contrast.

  3. Proteomics by FTICR Mass Spectrometry: Top Down and Bottom Up

    SciTech Connect

    Bogdanov, Bogdan; Smith, Richard D.

    2005-03-31

    This review offers a broad overview of recent FTICR applications and technological developments in the field of proteomics, directed to a variety of people with different expertise and interests. Both the ''bottom-up'' (peptide level) and ''top-down'' (intact protein level) approaches will be covered and various related aspects will be discussed and illustrated with examples that are among the best available references in the literature. ''Bottom-up topics include peptide fragmentation, the AMT approach and DREAMS technology, quantitative proteomics, post-translational modifications, and special FTICR software focused on peptide and protein identification. Topics in the ''top-down'' part include various aspects of high-mass measurements, protein tandem mass spectrometry, protein confirmations, protein-protein complexes, as well as some esoteric applications that may become more practical in the coming years. Finally, examples of integrating both approaches and medical proteomics applications using FTICR will be provided, closing with an outlook of what may be coming our way sooner than later.

  4. Tracking the Magnetron Motion in FT-ICR Mass Spectrometry.

    PubMed

    Jertz, Roland; Friedrich, Jochen; Kriete, Claudia; Nikolaev, Evgeny N; Baykut, Gökhan

    2015-08-01

    In Fourier transform ion cyclotron resonance spectrometry (FT-ICR MS) the ion magnetron motion is not usually directly measured, yet its contribution to the performance of the FT-ICR cell is important. Its presence is manifested primarily by the appearance of even-numbered harmonics in the spectra. In this work, the relationship between the ion magnetron motion in the ICR cell and the intensities of the second harmonic signal and its sideband peak in the FT-ICR spectrum is studied. Ion motion simulations show that during a cyclotron motion excitation of ions which are offset to the cell axis, a position-dependent radial drift of the cyclotron center takes place. This radial drift can be directed outwards if the ion is initially offset towards one of the detection electrodes, or it can be directed inwards if the ion is initially offset towards one of the excitation electrodes. Consequently, a magnetron orbit diameter can increase or decrease during a resonant cyclotron excitation. A method has been developed to study this behavior of the magnetron motion by acquiring a series of FT-ICR spectra using varied post-capture delay (PCD) time intervals. PCD is the delay time after the capture of the ions in the cell before the cyclotron excitation of the ion is started. Plotting the relative intensity of the second harmonic sideband peak versus the PCD in each mass spectrum leads to an oscillating "PCD curve". The position and height of minima and maxima of this curve can be used to interpret the size and the position of the magnetron orbit. Ion motion simulations show that an off-axis magnetron orbit generates even-numbered harmonic peaks with sidebands at a distance of one magnetron frequency and multiples of it. This magnetron offset is due to a radial offset of the electric field axis versus the geometric cell axis. In this work, we also show how this offset of the radial electric field center can be corrected by applying appropriate DC correction voltages to the

  5. Advanced Mass Calibration and Visualization for FT-ICR Mass Spectrometry Imaging

    SciTech Connect

    Smith, Donald F.; Kharchenko, Andriy; Konijnenburg, Marco; Klinkert, Ivo; Pasa-Tolic, Ljiljana; Heeren, Ronald M.

    2012-11-01

    Mass spectrometry imaging by Fourier transform ion cyclotron resonance (FT-ICR) yields hundreds of unique peaks, many of which cannot be resolved by lower performance mass spectrometers. The high mass accuracy and high mass resolving power allow confident identification of small molecules and lipids directly from biological tissue sections. Here, calibration strategies for FT-ICR MS imaging were investigated. Sub-parts-per-million mass accuracy is demonstrated over an entire tissue section. Ion abundance fluctuations are corrected by addition of total and relative ion abundances for a root-mean-square error of 0.158 ppm on 16,764 peaks. A new approach for visualization of FT-ICR MS imaging data at high resolution is presented. The "Mosaic Datacube" provides a flexible means to visualize the entire mass range at a mass spectral bin width of 0.001 Da. The high resolution Mosaic Datacube resolves spectral features not visible at lower bin widths, while retaining the high mass accuracy from the calibration methods discussed.

  6. Vacuum Ultraviolet Photodissociation and Fourier Transform–Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited

    SciTech Connect

    Shaw, Jared B.; Robinson, Errol W.; Pasa-Tolic, Ljiljana

    2016-02-16

    We revisited the implementation of UVPD within the ICR cell of a FT-ICR mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and small protein within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing relative to ion magnetron motion and the potential applied to an ion optical element that photons impinge on. It is shown that UVPD yields efficient and extensive fragmentation resulting in excellent sequence coverage for model peptide and protein cations.

  7. Fourier-Transform ion cyclotron mass spectrometry (FT-ICR MS)

    SciTech Connect

    Robinson, Errol W.

    2014-03-28

    FT-ICR MS achieves the highest resolution and best mass measurement accuracy of any mass spectrometry method. These remarkable achievements are due to several factors, including multi-channel detection, measurement of frequency, magnetic field stability, and dependence of cyclotron frequency on only the magnetic field and ion mass to charge ratio, not on ion kinetic energy and other factors. Significant advances in magnet technology, instrument design and construction continue to enhance the capabilities of FT-ICR MS. FT-ICR has been applied to a variety of analytical challenges and is particularly suited to the analysis of complex mixtures and in applications where high resolution and mass measurement accuracy are critical analytical parameters.

  8. Ultrahigh-resolution FT-ICR mass spectrometry characterization of a-pinene ozonolysis SOA

    EPA Science Inventory

    Secondary organic aerosol (SOA) of α-pinene ozonolysis with and without hydroxyl radical scavenging hexane was characterized by ultrahigh-resolution. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Molecular formulas for more than 900 negative ions were i...

  9. Ultrahigh-resolution FT-ICR mass spectrometry characterization of a-pinene ozonolysis SOA

    EPA Science Inventory

    Secondary organic aerosol (SOA) of α-pinene ozonolysis with and without hydroxyl radical scavenging hexane was characterized by ultrahigh-resolution. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Molecular formulas for more than 900 negative ions were i...

  10. Absorption Mode FT-ICR Mass Spectrometry Imaging

    SciTech Connect

    Smith, Donald F.; Kilgour, David P.; Konijnenburg, Marco; O'Connor, Peter B.; Heeren, Ronald M.

    2013-12-03

    Fourier transform ion cyclotron resonance mass spectrometry offers the highest mass resolving power for molecular imaging experiments. This high mass resolving power ensures that closely spaced peaks at the same nominal mass are resolved for proper image generation. Typically higher magnetic fields are used to increase mass resolving power. However, a gain in mass resolving power can also be realized by phase correction of the data for absorption mode display. In addition to mass resolving power, absorption mode offers higher mass accuracy and signal-to-noise ratio over the conventional magnitude mode. Here we present the first use of absorption mode for Fourier transform ion cyclotron resonance mass spectrometry imaging. The Autophaser algorithm is used to phase correct each spectrum (pixel) in the image and then these parameters are used by the Chameleon work-flow based data processing software to generate absorption mode ?Datacubes? for image and spectral viewing. Absorption mode reveals new mass and spatial features that are not resolved in magnitude mode and results in improved selected ion image contrast.

  11. Characterization of PCR products from bacilli using electrospray ionization FTICR mass spectrometry

    SciTech Connect

    Muddiman, D.C.; Liu, C.; Pasa-Tolic, L.; Anderson, G.A.; Smith, R.D.; Wunschel, D.S.; Fox, K.F.; Fox, A.

    1996-11-01

    A procedure for rapid purification of polymerase chain reaction (PCR) products allowing precise molecular weight determination using electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry is described. PCR amplification utilized the DNA polymerase from Pyrococcus furiosus (Pfu) which , unlike Taq, does not incorporate a nontemplated terminal deoxyadenosine phosphate. An 89-base pair nucleotide portion of the spacer region between the 16S and 23S ribosomal rRNA genes was amplified from the genome of three members of Bacillus cereus group and a 114 nucleotide region from the Bacillus subtilis. PCR involves polymerization of nucleotide precursors using two oligonucleotide primers and an amplification enzyme, as well as the presence of metal ions. The molecular weights of the PCR products determined by nucleotide sequence and MS analysis were in excellent agreement, and several PCR products were analyzed where mass differences corresponding to single base substitutions could be accurately assigned. These assignments were possible due to the high mass precision, accuracy, and resolution FTICR inherently affords. This constitutes the first report demonstrating the ionization and detection of PCR products by mass spectrometry with mass precision and accuracy for assignment of such modifications or substitutions. 45 refs., 5 figs., 1 tab.

  12. Detecting glycan cancer biomarkers in serum samples using MALDI FT-ICR mass spectrometry data.

    PubMed

    Barkauskas, Donald A; An, Hyun Joo; Kronewitter, Scott R; de Leoz, Maria Lorna; Chew, Helen K; de Vere White, Ralph W; Leiserowitz, Gary S; Miyamoto, Suzanne; Lebrilla, Carlito B; Rocke, David M

    2009-01-15

    The development of better tests to detect cancer in its earliest stages is one of the most sought-after goals in medicine. Especially important are minimally invasive tests that require only blood or urine samples. By profiling oligosaccharides cleaved from glycosylated proteins shed by tumor cells into the blood stream, we hope to determine glycan profiles that will help identify cancer patients using a simple blood test. The data in this article were generated using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI FT-ICR MS). We have developed novel methods for analyzing this type of mass spectrometry data and applied it to eight datasets from three different types of cancer (breast, ovarian and prostate). The techniques we have developed appear to be effective in the analysis of MALDI FT-ICR MS data. We found significant differences between control and cancer groups in all eight datasets, including two structurally related compounds that were found to be significantly different between control and cancer groups in all three types of cancer studied.

  13. High Mass Accuracy and High Mass Resolving Power FT-ICR Secondary Ion Mass Spectrometry for Biological Tissue Imaging

    SciTech Connect

    Smith, Donald F.; Kiss, Andras; Leach, Franklin E.; Robinson, Errol W.; Pasa-Tolic, Ljiljana; Heeren, Ronald M.

    2013-07-01

    Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for exact mass elemental formula assignment. We have recently reported a secondary ion mass spectrometer with the combination of a C60 primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 μm spatial resolution (75 μm primary ion spot size) with mass resolving power (m/Δm50%) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/Δm50% > 3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 μm. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging.

  14. The Chemical Exhaust Hazards of Dichlorosilane Deposits Determined with FT-ICR Mass Spectrometry

    SciTech Connect

    JAREK, RUSSELL L.; THORNBERG, STEVEN M.

    1999-10-01

    Flammable deposits have been analyzed from the exhaust systems of tools employing dichlorosilane (DCS) as a processing gas. Exact mass determinations with a high-resolution Fourier-transform ion-cyclotron resonance (FT-ICR) mass spectrometer allowed the identification of various polysiloxane species present in such an exhaust flow. Ion-molecule reactions indicate the preferred reaction pathway of siloxane formation is through HCl loss, leading to the highly reactive polysiloxane that was detected in the flammable deposits.

  15. Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry.

    PubMed

    Anderson, Lissa C; DeHart, Caroline J; Kaiser, Nathan K; Fellers, Ryan T; Smith, Donald F; Greer, Joseph B; LeDuc, Richard D; Blakney, Greg T; Thomas, Paul M; Kelleher, Neil L; Hendrickson, Christopher L

    2017-02-03

    Successful high-throughput characterization of intact proteins from complex biological samples by mass spectrometry requires instrumentation capable of high mass resolving power, mass accuracy, sensitivity, and spectral acquisition rate. These limitations often necessitate the performance of hundreds of LC-MS/MS experiments to obtain reasonable coverage of the targeted proteome, which is still typically limited to molecular weights below 30 kDa. The National High Magnetic Field Laboratory (NHMFL) recently installed a 21 T FT-ICR mass spectrometer, which is part of the NHMFL FT-ICR User Facility and available to all qualified users. Here we demonstrate top-down LC-21 T FT-ICR MS/MS of intact proteins derived from human colorectal cancer cell lysate. We identified a combined total of 684 unique protein entries observed as 3238 unique proteoforms at a 1% false discovery rate, based on rapid, data-dependent acquisition of collision-induced and electron-transfer dissociation tandem mass spectra from just 40 LC-MS/MS experiments. Our identifications included 372 proteoforms with molecular weights over 30 kDa detected at isotopic resolution, which substantially extends the accessible mass range for high-throughput top-down LC-MS/MS.

  16. Lung alveolar proteomics of bronchoalveolar lavage from a pulmonary alveolar proteinosis patient using high-resolution FTICR mass spectrometry.

    PubMed

    Bai, Yu; Galetskiy, Dmitry; Damoc, Eugen; Ripper, Jan; Woischnik, Markus; Griese, Matthias; Liu, Zhiqiang; Liu, Shuying; Przybylski, Michael

    2007-10-01

    High-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometry was developed and applied to the proteome analysis of bronchoalveolar lavage fluid (BALF) from a patient with pulmonary alveolar proteinosis. With use of 1-D and 2-D gel electrophoresis, surfactant protein A (SP-A) and other surfactant-related lung alveolar proteins were efficiently separated and identified by matrix-assisted laser desorption/ionization FTICR mass spectrometry . Low molecular mass BALF proteins were separated using a gradient 2-D gel. An efficient extraction/precipitation system was developed and used for the enrichment of surfactant proteins. The result of the BALF proteome analysis show the presence of several isoforms of SP-A, in which an N-non-glycosylierte form and several proline hydroxylations were identified. Furthermore, a number of protein spots were found to contain a mixture of proteins unresolved by 2-D gel electrophoresis, illustrating the feasibility of high-resolution mass spectrometry to provide identifications of proteins that remain unseparated in 2-D gels even upon extended pH gradients.

  17. Environmental Forensics: Molecular Insight into Oil Spill Weathering Helps Advance High Magnetic Field FT-ICR Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    McKenna, Amy

    2013-03-01

    The depletion of terrestrial global oil reserves has shifted oil exploration into offshore and ultra-deep water (> 5000 ft) oil reserves to meet global energy demands. Deep water reservoirs are currently in production in many parts of the world, including the Gulf of Mexico, but production is complicated by the water depth and thick salt caps that challenge reservoir characterization / production. The explosion aboard the Deepwater Horizon in April 2010 resulted in an estimated total release of ~5 million barrels (BP claims that they collected ~1M barrels, for a net release of 4 M) of light, sweet crude oil into the Gulf of Mexico and shifted attention toward the environmental risks associated with offshore oil production. The growing emphasis on deep water and ultra-deep water oil production poses a significant environmental threat, and increased regulations require that oil companies minimize environmental impact to prevent oil spills, and mitigate environmental damage when spills occur. Every oil spill is unique. The molecular transformations that occur to petroleum after contact with seawater depend on the physical and chemical properties of the spilled oil, environmental conditions, and deposition environment. Molecular-level knowledge of the composition, distribution, and total mass of released hydrocarbons is essential to disentangle photo- and bio-degradation, source identification, and long-term environmental impact of hydrocarbons released into the environment. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is unsurpassed in its ability to characterize complex mixtures at the level of elemental composition assignment. Only FT-ICR mass spectrometry can routinely achieve the required minimum resolving power necessary to elucidate molecular-level characterization of crude oil. Conversely, the spectral complexity of petroleum facilitates identification of systematic errors in the accumulation, transfer, excitation, and detection

  18. Identification of Two Reactive Cysteine Residues in the Tumor Suppressor Protein p53 Using Top-Down FTICR Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Scotcher, Jenna; Clarke, David J.; Weidt, Stefan K.; Mackay, C. Logan; Hupp, Ted R.; Sadler, Peter J.; Langridge-Smith, Pat R. R.

    2011-05-01

    The tumor suppressor p53 is a redox-regulated transcription factor involved in cell cycle arrest, apoptosis and senescence in response to multiple forms of stress, as well as many other cellular processes such as DNA repair, glycolysis, autophagy, oxidative stress and differentiation. The discovery of cysteine-targeting compounds that cause re-activation of mutant p53 and the death of tumor cells in vivo has emphasized the functional importance of p53 thiols. Using a combination of top-down and middle-down FTICR mass spectrometry, we show that of the 10 Cys residues in the core domain of wild-type p53, Cys182 and Cys277 exhibit a remarkable preference for modification by the alkylating reagent N-ethylmaleimide. The assignment of Cys182 and Cys277 as the two reactive Cys residues was confirmed by site-directed mutagenesis. Further alkylation of p53 beyond Cys182 and Cys277 was found to trigger co-operative modification of the remaining seven Cys residues and protein unfolding. This study highlights the power of top-down FTICR mass spectrometry for analysis of the cysteine reactivity and redox chemistry in multiple cysteine-containing proteins.

  19. Gas Chromatography Coupled to Atmospheric Pressure Chemical Ionization FT-ICR Mass Spectrometry for Improvement of Data Reliability.

    PubMed

    Schwemer, Theo; Rüger, Christopher P; Sklorz, Martin; Zimmermann, Ralf

    2015-12-15

    Atmospheric pressure chemical ionization (APCI) offers the advantage of molecular ion information with low fragmentation. Hyphenating APCI to gas chromatography (GC) and ultrahigh resolution mass spectrometry (FT-ICR MS) enables an improved characterization of complex mixtures. Data amounts acquired by this system are very huge, and existing peak picking algorithms are usually extremely time-consuming, if both gas chromatographic and ultrahigh resolution mass spectrometric data are concerned. Therefore, automatic routines are developed that are capable of handling these data sets and further allow the identification and removal of known ionization artifacts (e.g., water- and oxygen-adducts, demethylation, dehydrogenation, and decarboxylation). Furthermore, the data quality is enhanced by the prediction of an estimated retention index, which is calculated simply from exact mass data combined with a double bond equivalent correction. This retention index is used to identify mismatched elemental compositions. The approach was successfully tested for analysis of semivolatile components in heavy fuel oil and diesel fuel as well as primary combustion particles emitted by a ship diesel research engine. As a result, 10-28% of the detected compounds, mainly low abundant species, classically assigned by using only the mass spectrometric information, were identified as not valid and removed. Although GC separation is limited by the slow acquisition rate of the FT-ICR MS (<1 Hz), a database driven retention time comparison, as commonly used for low resolution GC/MS, can be applied for revealing isomeric information.

  20. Mechanisms of humic acids degradation by white rot fungi explored using 1H NMR spectroscopy and FTICR mass spectrometry.

    PubMed

    Grinhut, Tzafrir; Hertkorn, Norbert; Schmitt-Kopplin, Philippe; Hadar, Yitzhak; Chen, Yona

    2011-04-01

    Enzymatic activities involved in decay processes of natural aromatic macromolecules, such as humic acids (HA) and lignin by white rot fungi, have been widely investigated. However, the physical and chemical analysis of degradation products of these materials has not been intensively explored. Fourier transform cyclotron resonance mass spectrometry (FTICR MS) and 1H NMR as well as CHNOS and size exclusion chromatography were employed to study the mechanisms of HA degradation by Trametes sp. M23 and Phanerochaete sp. Y6. Size exclusion chromatography analyses demonstrate and provide evidence for HA breakdown into low MW compounds. The 1H NMR analysis revealed oxidation, a decrease in the aromatic content, and an indication of demethylation of the HA during biodegradation. Evidence for oxidation was also obtained using CHNOS. Analysis of FTICR MS results using a new software program developed by our group (David Mass Sort) revealed consecutive series of masses suggesting biochemical degradation trends such as oxidation, aromatic cleavage, and demethylation. These results are in agreement with the 1H NMR analysis and with the suggested role of the ligninolytic system leading to HA degradation.

  1. Cello-, malto- and xylooligosaccharide fragmentation by collision-induced dissociation using QIT and FT-ICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pasanen, Salla; Jänis, Janne; Vainiotalo, Pirjo

    2007-05-01

    In order to study the effects of the precursor ion type and the carbohydrate structure on the fragmentation of neutral unsubstituted oligosaccharides in collision-induced dissociation (CID), a systematic study of deprotonated, protonated, ammoniated and alkali metal cationized cello-, malto- and xylooligosaccharides was carried out using a quadrupole ion trap (QIT) and Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. The fragmentation pathway was highly dependent on the choice of the precursor ion type. Deprotonated precursors gave rise to both glycosidic and cross-ring fragmentation, with clear differences among the three oligosaccharides, therefore being the most prominent for structural analysis. The fragmentation behavior of the xylooligosaccharides differed from that of the cello- and maltooligosaccharides for all the precursor ions studied, most remarkably with the deprotonated and ammoniated precursors. Stereochemical differentiation of cello- and maltooligosaccharides was possible with the use of deprotonated, lithiated and sodiated precursors. In general, as the size of the alkali metal cation increased the amount of structurally informative cross-ring fragmentation increased, but the probability for metal ion loss from the precursor ion also increased. The CID spectra of xylooligosaccharides measured with the QIT and FT-ICR were surprisingly similar.

  2. Atmospheric organic matter in clouds: exact masses and molecular formula identification using ultrahigh resolution FT-ICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Zhao, Y.; Hallar, A. G.; Mazzoleni, L. R.

    2013-08-01

    cyclotron resonance (FT-ICR) mass spectrometry provides an unambiguous identification of the cloud water organic composition in the Rocky Mountain area which could help to improve the understanding of aqueous phase processes.

  3. Next-generation technologies for spatial proteomics: Integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis

    PubMed Central

    Spraggins, Jeffrey M.; Rizzo, David G.; Moore, Jessica L.; Noto, Michael J.; Skaar, Eric P.; Caprioli, Richard M.

    2016-01-01

    MALDI imaging mass spectrometry is a powerful analytical tool enabling the visualization of biomolecules in tissue. However, there are unique challenges associated with protein imaging experiments including the need for higher spatial resolution capabilities, improved image acquisition rates, and better molecular specificity. Here we demonstrate the capabilities of ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR IMS platforms as they relate to these challenges. High spatial resolution MALDI-TOF protein images of rat brain tissue and cystic fibrosis lung tissue were acquired at image acquisition rates >25 pixels/s. Structures as small as 50 μm were spatially resolved and proteins associated with host immune response were observed in cystic fibrosis lung tissue. Ultra-high speed MALDI-TOF enables unique applications including megapixel molecular imaging as demonstrated for lipid analysis of cystic fibrosis lung tissue. Additionally, imaging experiments using MALDI FTICR IMS were shown to produce data with high mass accuracy (<5 ppm) and resolving power (∼75 000 at m/z 5000) for proteins up to ∼20 kDa. Analysis of clear cell renal cell carcinoma using MALDI FTICR IMS identified specific proteins localized to healthy tissue regions, within the tumor, and also in areas of increased vascularization around the tumor. PMID:27060368

  4. Next-generation technologies for spatial proteomics: Integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis.

    PubMed

    Spraggins, Jeffrey M; Rizzo, David G; Moore, Jessica L; Noto, Michael J; Skaar, Eric P; Caprioli, Richard M

    2016-06-01

    MALDI imaging mass spectrometry is a powerful analytical tool enabling the visualization of biomolecules in tissue. However, there are unique challenges associated with protein imaging experiments including the need for higher spatial resolution capabilities, improved image acquisition rates, and better molecular specificity. Here we demonstrate the capabilities of ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR IMS platforms as they relate to these challenges. High spatial resolution MALDI-TOF protein images of rat brain tissue and cystic fibrosis lung tissue were acquired at image acquisition rates >25 pixels/s. Structures as small as 50 μm were spatially resolved and proteins associated with host immune response were observed in cystic fibrosis lung tissue. Ultra-high speed MALDI-TOF enables unique applications including megapixel molecular imaging as demonstrated for lipid analysis of cystic fibrosis lung tissue. Additionally, imaging experiments using MALDI FTICR IMS were shown to produce data with high mass accuracy (<5 ppm) and resolving power (∼75 000 at m/z 5000) for proteins up to ∼20 kDa. Analysis of clear cell renal cell carcinoma using MALDI FTICR IMS identified specific proteins localized to healthy tissue regions, within the tumor, and also in areas of increased vascularization around the tumor. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Atmospheric organic matter in clouds: exact masses and molecular formula identification using ultrahigh-resolution FT-ICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Zhao, Y.; Hallar, A. G.; Mazzoleni, L. R.

    2013-12-01

    cyclotron resonance (FT-ICR) mass spectrometry provides an unambiguous identification of the cloud water organic anion composition in the Rocky Mountain area that could help to improve the understanding of aqueous-phase processes.

  6. Analysis of MALDI FT-ICR Mass Spectrometry Data: a Time Series Approach

    PubMed Central

    Kronewitter, Scott R.; Lebrilla, Carlito B.; Rocke, David M.

    2009-01-01

    Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry is a technique for high mass-resolution analysis of substances that is rapidly gaining popularity as an analytic tool. Extracting signal from the background noise, however, poses significant challenges. In this article, we model the noise part of a spectrum as an autoregressive, moving average (ARMA) time series with innovations given by a generalized gamma distribution with varying scale parameter but constant shape parameter and exponent. This enables us to classify peaks found in actual spectra as either noise or signal using a reasonable criterion that outperforms a standard threshold criterion. PMID:19646586

  7. Analysis of MALDI FT-ICR mass spectrometry data: a time series approach.

    PubMed

    Barkauskas, Donald A; Kronewitter, Scott R; Lebrilla, Carlito B; Rocke, David M

    2009-08-26

    Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry is a technique for high mass-resolution analysis of substances that is rapidly gaining popularity as an analytic tool. Extracting signal from the background noise, however, poses significant challenges. In this article, we model the noise part of a spectrum as an autoregressive, moving average (ARMA) time series with innovations given by a generalized gamma distribution with varying scale parameter but constant shape parameter and exponent. This enables us to classify peaks found in actual spectra as either noise or signal using a reasonable criterion that outperforms a standard threshold criterion.

  8. Oligomers, organosulfates, and nitroxy organosulfates in rainwater identified by ultra-high resolution electrospray ionization FT-ICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Altieri, K. E.; Turpin, B. J.; Seitzinger, S. P.

    2008-09-01

    Wet deposition is an important removal mechanism for atmospheric organic matter, and a potentially important input for receiving ecosystems, yet less than 50% of rainwater organic matter is considered chemically characterized. Precipitation samples collected in New Jersey, USA, were analyzed by negative ion ultra-high resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Elemental compositions of 552 unique molecular species were determined in the mass range 50 500 Da in the rainwater. Three main groups of organic compounds were identified: compounds containing carbon, hydrogen, and oxygen (CHO) only, sulfur (S) containing CHOS compounds, and S- and nitrogen containing CHONS compounds. Organic acids commonly identified in precipitation were detected, as well as linear alkylbenzene sulfonates, which are persistent pollutants commonly measured in river water, seawater, and sediments, but to our knowledge, not previously documented in atmospheric samples. Within the three main groups of compounds detected in the rainwater, oligomers, organosulfates, and nitroxy-organosulfates were identified. The majority of the compounds identified are products of atmospheric reactions and are known contributors to secondary organic aerosol (SOA) formed from gas phase, aerosol phase, and in-cloud reactions in the atmosphere. It is suggested that the large uncharacterized component of SOA is the main contributor to the large uncharacterized component of rainwater organic matter.

  9. The study of large biopolymer complexes in solution and the gas phase using electrospray ionization-FTICR mass spectrometry

    SciTech Connect

    Smith, R.D.; Lei, Q.P.; Wu, Qinyuan; Hofstadler, A.

    1997-12-31

    Electrospray ionization (ESI) can transfer large biopolymers and many noncovalently bound complexes into the gas phase and to preserve specific noncovalent biomolecular associations for subsequent mass spectrometric analysis. Although a number of details of the ESI process remain a subject of debate, it is now incontestable that many weak associations can survive transfer to the gas phase and are stable for periods of at least seconds. In this presentation, the application of ESI-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry methods for the study of large biopolymers and their noncovalent complexes will be described. It will also be shown that competitive binding studies can be used to quickly establish relative binding affinities in solution, allowing combinatorial libraries to be rapidly screened. After measurements of the intact complex, dissociation studies can be conducted to probe the structure of the individual constituents of complexes. Studies comparing the relative stabilities of protein-ligand complexes in solution and desolvated in the gas phase will also be presented, and discussed from both fundamental and analytical perspectives.

  10. Composition of dissolved organic nitrogen in continental precipitation investigated by ultra-high resolution FT-ICR mass spectrometry.

    PubMed

    Altieri, Katye E; Turpin, Barbara J; Seitzinger, Sybil P

    2009-09-15

    The atmospheric transport of fixed nitrogen (N) is a critical component of the global N cycle that has been heavily impacted by human activities. It has been shown that organic N is an important contributor to atmospheric N, but its sources and composition are largely unknown. Rainwater samples collected in New Jersey were analyzed by negative and positive ion ultrahigh-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Elemental compositions of 402 N-containing compounds were determined and five main groups of compound classes were identified: compounds containing carbon, hydrogen, oxygen, and N detected as positive ions (CHON+), compounds containing CHON detected as negative ions (CHON-), compounds containing CHN detected as positive ions (CHN+), and CHON compounds that contain sulfur (S) detected as both positive and negative ions (CHONS+, CHONS-, respectively). The CHON+ compound class has the largest number of compounds detected (i.e., 281), with the majority, i.e., 207, containing only one N atom. The elemental ratios of these compounds and their detection in the positive ion mode suggest that they are compounds with reduced N functionality. Known contributors to secondary organic aerosol with anthropogenic sources were also identified including organonitrate compounds and nitrooxy organosulfates.

  11. Characterization of bio-oil from hydrothermal liquefaction of organic waste by NMR spectroscopy and FTICR mass spectrometry.

    PubMed

    Leonardis, Irene; Chiaberge, Stefano; Fiorani, Tiziana; Spera, Silvia; Battistel, Ezio; Bosetti, Aldo; Cesti, Pietro; Reale, Samantha; De Angelis, Francesco

    2013-01-01

    Solid wastes of organic origins are potential feedstocks for the production of liquid biofuels, which could be suitable alternatives to fossil fuels for the transport and heating sectors, as well as for industrial use. By hydrothermal liquefaction, the wet biomass is partially transformed into a water-immiscible, oil-like organic matter called bio-oil. In this study, an integrated NMR spectroscopy/mass spectrometry approach has been developed for the characterization of the hydrothermal liquefaction of bio-oil at the molecular level. (1)H and (13)C NMR spectroscopy were used for the identification of functional groups and gauging the aromatic carbon content in the mixture. GC-MS analysis revealed that the volatile fraction was rich in fatty acids, as well as in amides and esters. High-resolution Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) has been applied in a systematic way to fully categorize the bio-oil in terms of different classes of components, according to their molecular formulas. Most importantly, for the first time, by using this technique, and for the liquefaction bio-oil characterization in particular, FT-MS data have been used to develop a methodology for the determination of the aromatic versus aliphatic carbon and nitrogen content. It is well known that, because they resist hydrogenation and represent sources of polluting species, both aromatic molecules and nitrogen-containing species raise concerns for subsequent upgrading of bio-oil into a diesel-like fuel. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Characterization of the mouse bronchoalveolar lavage proteome by micro-capillary LC–FTICR mass spectrometry

    SciTech Connect

    Pounds, Joel G.; Flora, Jason W.; Adkins, Joshua N.; Lee, Kyeonghee M.; Rana, Gaurav S.J.B.; Sengupta, Tapas; Smith, Richard D.; McKinney, Willie J.

    2008-03-15

    Bronchoalveolar lavage fluid (BALF) contains proteins derived from various pulmonary cell types, secretions and blood. As the characterization of the BALF proteome will be instrumental in establishing potential biomarkers of pathophysiology in the lungs, the objective of this study was to contribute to the comprehensive collection of Mus musculus BALF proteins using high resolution and highly sensitive micro-capillary liquid chromatography (microLC) combined with state-of-the-art high resolution mass spectrometry (MS). BALF was collected from ICR and C57BL/6 male mice exposed to nose-only inhalation to either air or cigarette smoke. The tandem mass spectra were analyzed by SEQUEST for peptide identifications with the subsequent application of accurate mass and time tags resulting in the identification of 1797 peptides with high confidence by high resolution MS. These peptides covered 959 individual proteins constituting the largest collection of BALF proteins to date. High throughput monitoring profiles of this extensive collection of BALF proteins will facilitate the discovery and validation of biomarkers that would elucidate pathogenic or adaptive responses of the lungs upon toxic insults.

  13. Fragmentation analysis of water-soluble atmospheric organic matter using ultrahigh-resolution FT-ICR mass spectrometry.

    PubMed

    Leclair, Jeffrey P; Collett, Jeffrey L; Mazzoleni, Lynn R

    2012-04-17

    Isolated water-soluble atmospheric organic matter (AOM) analytes extracted from radiation fogwater samples were analyzed using collision induced dissociation with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Tandem mass analysis was performed on several mass ranges between 100 and 400 Da to characterize the functional groups of AOM species. Compounds containing nitrogen and/or sulfur were targeted because of the high number of oxygen atoms contained in their molecular formulas. Due to the large number of isobaric ions in the precursor isolation ranges, large numbers of product ions resulted from collision induced dissociation. Common neutral losses were assigned by matching the molecular formulas of the expected product ions with the detected product ions within the appropriate mass spectra. Since polar functional groups are expected to affect the hygroscopic properties of aerosols, the losses of H(2)O, CO(2), CH(3)OH, HNO(3), CH(3)NO(3), SO(3), SO(4) and combinations of these were specifically targeted. Among the 421 compounds studied, the most frequently observed neutral losses were CO(2) (54%), H(2)O (43%) and CH(3)OH (40%). HNO(3) losses were observed for 63% of the studied nitrogen containing compounds and 33% of the studied compounds containing both nitrogen and sulfur. SO(3) losses were observed for 85% of the studied sulfur containing compounds and 42% of studied compounds containing both nitrogen and sulfur. A number of molecular formulas matching those of monoterpene ozonolysis SOA were observed; they include organonitrates, organosulfates, and nitroxy-organosulfates. Overall, the results of fragmentation analysis of 400+ individual molecular precursors elucidate the complexity and multifunctional nature of the isolated water-soluble AOM.

  14. Chemical characterization of synthetic cannabinoids by electrospray ionization FT-ICR mass spectrometry.

    PubMed

    Kill, Jade B; Oliveira, Izabela F; Tose, Lilian V; Costa, Helber B; Kuster, Ricardo M; Machado, Leandro F; Correia, Radigya M; Rodrigues, Rayza R T; Vasconcellos, Géssica A; Vaz, Boniek G; Romão, Wanderson

    2016-09-01

    The synthetic cannabinoids (SCs) represent the most recent advent of the new psychotropic substances (NPS) and has become popularly known to mitigate the effects of the Δ(9)-THC. The SCs are dissolved in organic solvents and sprayed in a dry herbal blend. However, little information is reported on active ingredients of SCs as well as the excipients or diluents added to the herbal blend. In this work, the direct infusion electrospray ionization Fourier transform ion cyclotron mass spectrometry technique (ESI-FT-ICR MS) was applied to explore the chemical composition of nine samples of herbal extract blends, where a total of 11 SCs (UR-144, JWH-073, XLR-11, JWH-250, JWH-122, AM-2201, AKB48, JWH-210, JWH-081, MAM-2201 and 5F-AKB48) were identified in the positive ionization mode, ESI(+), and other 44 chemical species (saturated and unsaturated fatty acids, sugars, flavonoids, etc.) were detected in the negative ionization mode, ESI(-). Additionally, CID experiments were performed, and fragmentation pathways were proposed to identify the connectivity of SCs. Thus, the direct infusion ESI-FT-ICR MS technique is a powerful tool in forensic chemistry that enables the rapid and unequivocal way for the determination of molecular formula, the degree of unsaturation (DBE-double bond equivalent) and exact mass (<1ppm) of a total of 55 chemical species without the prior separation step. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. High molecular weight SOA formation during limonene ozonolysis: insights from ultrahigh-resolution FT-ICR mass spectrometry characterization

    NASA Astrophysics Data System (ADS)

    Kundu, S.; Fisseha, R.; Putman, A. L.; Rahn, T. A.; Mazzoleni, L. R.

    2012-06-01

    The detailed molecular composition of laboratory generated limonene ozonolysis secondary organic aerosol (SOA) was studied using ultrahigh-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Approximately 1200 molecular formulas were identified in the SOA over the mass range of 140 to 850 Da. Four characteristic groups of high relative abundance species were observed; they indicate an array of accretion products that retain a large fraction of the limonene skeleton. The identified molecular formulas of each of the groups are related to one another by CH2, O and CH2O homologous series. The CH2 and O homologous series of the low molecular weight (MW) SOA (m/z < 300) are explained with a combination of functionalization and fragmentation of radical intermediates and reactive uptake of gas-phase carbonyls. They include isomerization and elimination reactions of Criegee radicals, reactions between alkyl peroxy radicals, and scission of alkoxy radicals resulting from the Criegee radicals. The presence of compounds with 10-15 carbon atoms in the first group (e.g. C11H18O6) provides evidence for SOA formation by the reactive uptake of gas-phase carbonyls during limonene ozonolysis. The high MW compounds (m/z > 300) were found to constitute a significant number fraction of the identified SOA components. The formation of high MW compounds was evaluated by molecular formula trends, fragmentation analysis of select high MW compounds and a comprehensive reaction matrix including the identified low MW SOA, hydroperoxides and Criegee radicals as building blocks. Although the formation of high MW SOA may occur via a variety of radical and non-radical reaction channels, the combined approach indicates a greater importance of the non-condensation reactions over aldol and ester condensation reaction channels. Among these hemi-acetal reactions appear to be most dominant followed by hydroperoxide and Criegee reaction channels.

  16. High molecular weight SOA formation during limonene ozonolysis: insights from ultrahigh-resolution FT-ICR mass spectrometry characterization

    NASA Astrophysics Data System (ADS)

    Kundu, S.; Fisseha, R.; Putman, A. L.; Rahn, T. A.; Mazzoleni, L. R.

    2012-01-01

    The detailed molecular composition of secondary organic aerosols (SOA) from limonene ozonolysis was studied using ultrahigh-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. High molecular weight (MW) compounds (m/z > 300) were found to constitute a significant number fraction of the identified SOA components. Double bond equivalents (DBE = the number of rings plus the number of double bonds) increased with MW. The O:C ratios and relative abundances of compounds decreased with increasing MW. The mass spectra of limonene contain 4 distinct clusters of negative ions: Group I (140 < m/z < 300), Group II (300 < m/z < 500), Group III (500 < m/z < 700) and Group IV (700 < m/z < 850). A number of CH2 and O homologous series of low MW SOA (Group 1) with carbon number 7-15 and oxygen number 3-9 were observed. Their occurrence can be explained with isomerization and elimination reactions of Criegee radicals, reactions between alkyl peroxy radicals, and scission of alkoxy radicals resulting from the Criegee radicals. Additionally, fragmentation analysis and observations of formaldehyde homologous series provide evidence for aerosol growth by the reactive uptake of generated gas-phase carbonyls in limonene ozonolysis. The decreasing O:C ratios between group of compounds indicated the importance of condensation (aldol and esterification) reaction pathways for high MW compound formation. However, the prominent DBE changes of 2 between the groups of compounds and selected fragmentation (MS/MS) analysis of Group II and Group III ions indicated a predominance of non-condensation (hydroperoxide, Criegee and hemi-acetal) reaction pathways. A reaction matrix created with the combination of low MW SOA, hydroperoxides, and Criegee radicals indicated higher frequencies for the hemi-acetal and condensation reaction pathways. Overall, the combined approach confirms the importance of non-condensation reaction pathways over condensation reaction pathways. Among

  17. Enhanced Digestion Efficiency, Peptide Ionization Efficiency, and Sequence Resolution for Protein Hydrogen/Deuterium Exchange Monitored by FT-ICR Mass Spectrometry

    PubMed Central

    Zhang, Hui-Min; Kazazic, Saša; Schaub, Tanner M.; Tipton, Jeremiah D.; Emmett, Mark R.; Marshall, Alan G.

    2009-01-01

    Solution-phase hydrogen/deuterium exchange (HDX) monitored by high-resolution FT-ICR mass spectrometry offers a rapid method to study protein conformations and protein-protein interactions. Pepsin is usually used to digest proteins in HDX and is known as lack of cleavage specificity. To improve digestion efficiency and specificity, we have optimized digestion conditions and cleavage preferences for pepsin and protease type XIII from Aspergillus saitoi. A dilution series of the proteases was used to determine the digestion efficiency for several test proteins. Protease type XIII prefers to cleave on the C-terminal end of basic amino acids and produced the highest number of fragments and the best sequence coverage compared to pepsin or protease type XVIII from Rhizhopus. Furthermore, protease type XIII exhibited much less self-digestion than pepsin, and thus is superior for HDX experiments. Many highly overlapped segments from protease type XIII and pepsin digestion, combined with high-resolution FT-ICR mass spectrometry, provide high sequence resolution (to as few as one or two amino acids) for the assignment of amide hydrogen exchange rate. Our H/D exchange results correlate well with the secondary and tertiary structure of myoglobin. Such assignments of highly overlapped fragments promise to greatly enhance the accuracy and sequence resolution for determining conformational differences resulting from ligand binding or protein-protein interactions. PMID:19551977

  18. Mass recalibration of FT-ICR mass spectrometry imaging data using the average frequency shift of ambient ions

    PubMed Central

    Barry, Jeremy A.; Robichaud, Guillaume; Muddiman, David C.

    2013-01-01

    Achieving and maintaining high mass measurement accuracy (MMA) throughout a mass spectrometry imaging (MSI) experiment is vital to the identification of the observed ions. However, when using FTMS instruments, fluctuations in the total ion abundance at each pixel due to inherent biological variation in the tissue section can introduce space charge effects that systematically shift the observed mass. Herein we apply a recalibration based on the observed cyclotron frequency shift of ions found in the ambient laboratory environment, polydimethylcyclosiloxanes (PDMS). This calibration method is capable of achieving part per billion (ppb) mass accuracy with relatively high precision for an infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI dataset. Comparisons with previously published mass calibration approaches are also presented. PMID:23715870

  19. Size distributions and geometries of alkali halide nanoclusters probed using ESI FT-ICR mass spectrometry and quantum chemistry

    NASA Astrophysics Data System (ADS)

    Lemke, K.; Sadjadi, S.; Seward, T.

    2010-12-01

    The structures and energetic properties of ionic alkali metal halide clusters play a significant role in our understanding of aqueous geochemical processes such as salt dissolution, precipitation and neutralization reactions. Mass spectrometric and quantum chemical studies of such systems offer new opportunities to study the size-dependent evolution of cluster structures, the occurrence of magic number species as well as their fundamental properties. The work here presents new results for the stability, abundance and structure of pure [Na(NaClm)]+ , [K(KCl)m]+ and mixed [Na(NaCl)p(KCl)q]+ metal halide clusters with m<23 and p+q<14, respectively, using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS) in combination with the Gn and CBS-x multistep ab initio methods. Ion-cluster experiments were conducted on a modified 7T Bruker FT-ICR/MS equipped with electrospray ionization (ESI) sources and a custom-designed solvent gas inlet interface. In ESI FT-ICR/MS experiments performed with solutions containing NaCl and KCl salts (1mM; 80/20 CH3CN/H2O), singly and doubly charged salt clusters were generated up to a cluster size of [Na(NaCl)22]+, [K(KCl)17]+ and [K2(KCl)21,23]2+, respectively, including “magic number” clusters that correspond to the completed cluster cuboids with the dimensions 3x3x1 (m=4), 3x3x2+3 (m=10) 3x3x3 (m=13) and 3x3x5 (m=22) (see Figure). On the other hand, no pure clusters except [K(KCl)1-3]+ were generated when alkali halides were electrosprayed from 1mM NaCl/KCl solutions. Instead, mixed [Na(NaCl)p(KCl)q]+ clusters are generated up to p+q=14, which are the largest mixed alkali halide clusters yet generated in mass spectrometric experiments, including a suite of ionic species that are generated via CH3CN fragmentation and charge transfer in [Na(CH3CN)n]+ to yield the clusters [Na(NaCN)(CH3CN)n-1]+. We describe our ESI FT-ICR/MS experiments and discuss ion cluster abundances and extent of clustering

  20. Laserspray and Matrix-Assisted Ionization Inlet Coupled to High-Field FT-ICR Mass Spectrometry for Peptide and Protein Analysis

    NASA Astrophysics Data System (ADS)

    Nyadong, Leonard; Inutan, Ellen D.; Wang, Xu; Hendrickson, Christopher L.; Trimpin, Sarah; Marshall, Alan G.

    2013-03-01

    We present the first coupling of laser spray ionization inlet (LSII) and matrix assisted ionization inlet (MAII) to high-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for generation of electrospray-like ions to take advantage of increased sensitivity, mass range, and mass resolving power afforded by multiple charging. We apply the technique to top-down protein analysis and characterization of metalloproteins. We also present a novel method for generation of multiply-charged copper-peptide complexes with varying degrees of copper adduction by LSII. We show an application of the generated copper-peptide complexes for protein charge state and molecular weight determination, particularly useful for an instrument such as a linear ion trap mass analyzer. [Figure not available: see fulltext.

  1. Nontarget analysis of Murchison soluble organic matter by high-field NMR spectroscopy and FTICR mass spectrometry.

    PubMed

    Hertkorn, N; Harir, M; Schmitt-Kopplin, Ph

    2015-09-01

    High-field NMR spectra of Murchison meteorite methanolic extracts revealed primarily aliphatic extraterrestrial organic matter (EOM) with near statistical branching of commonly C(3-5) units separated by heteroatoms and aromatic units. The ratios of CCH, OCH and C(sp2)H units were 89 : 8 : 3, whereas carbon-based aliphatic chain termination was in the order methyl >  -COOH >  -CH(CH3)COOH. Aliphatic methine carbon was abundant, but its weak NMR signatures were primarily deduced from JRES (J-resolved) NMR spectra. Carbon NMR spectra were dominated by methylene and methyl carbon; strong apodization revealed methine carbon, of which about 20% was aromatic. Extrapolation provided 5-7% aromatic carbon present in Murchison soluble EOM. Compositional heterogeneity in Murchison methanolic extracts was visible in NMR and Fourier transform ion cyclotron (FTICR) mass spectra obtained from a few cubic millimeters of solid Murchison meteorite; increasing sample size enhanced uniformity of NMR spectra. Intrinsic chemical diversity and pH-dependent chemical shift variance contributed to the disparity of NMR spectra. FTICR mass spectra provided distinct clustering of CHO/CHOS and CHNO/CHNOS molecular series and confirmed the prevalence of aliphatic/alicyclic (73%) over single aromatic (21%) and polyaromatic (6%) molecular compositions, suggesting extensive aliphatic substitution of aromatic units as proposed by NMR. Murchison soluble EOM molecules feature a center with enhanced aromatic and heteroatom content, which provides rather diffuse and weak NMR signatures resulting from a huge overall chemical diversity. The periphery of Murchison EOM molecules comprises flexible branched aliphatic chains and aliphatic carboxylic acids. These project on narrow ranges of chemical shift, facilitating observation in one-dimensional and two-dimensional NMR spectra. The conformational entropy provided by these flexible surface moieties facilitates the solubility of EOM.

  2. Intact and Top-Down Characterization of Biomolecules and Direct Analysis Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Coupled to FT-ICR Mass Spectrometry

    PubMed Central

    Sampson, Jason S.; Murray, Kermit K.; Muddiman, David C.

    2013-01-01

    We report the implementation of an infrared laser onto our previously reported matrix-assisted laser desorption electrospray ionization (MALDESI) source with ESI post-ionization yielding multiply charged peptides and proteins. Infrared (IR)-MALDESI is demonstrated for atmospheric pressure desorption and ionization of biological molecules ranging in molecular weight from 1.2 to 17 kDa. High resolving power, high mass accuracy single-acquisition Fourier transform ion cyclotron resonance (FT-ICR) mass spectra were generated from liquid-and solid-state peptide and protein samples by desorption with an infrared laser (2.94 µm) followed by ESI post-ionization. Intact and top-down analysis of equine myoglobin (17 kDa) desorbed from the solid state with ESI post-ionization demonstrates the sequencing capabilities using IR-MALDESI coupled to FT-ICR mass spectrometry. Carbohydrates and lipids were detected through direct analysis of milk and egg yolk using both UV- and IR-MALDESI with minimal sample preparation. Three of the four classes of biological macromolecules (proteins, carbohydrates, and lipids) have been ionized and detected using MALDESI with minimal sample preparation. Sequencing of O-linked glycans, cleaved from mucin using reductive β-elimination chemistry, is also demonstrated. PMID:19185512

  3. Pharmacokinetic and pharmacometabolomic study of pirfenidone in normal mouse tissues using high mass resolution MALDI-FTICR-mass spectrometry imaging.

    PubMed

    Sun, Na; Fernandez, Isis E; Wei, Mian; Wu, Yin; Aichler, Michaela; Eickelberg, Oliver; Walch, Axel

    2016-02-01

    Given the importance of pirfenidone as the first worldwide-approved drug for idiopathic pulmonary fibrosis treatment, its pharmacodynamic properties and the metabolic response to pirfenidone treatment have not been fully elucidated. The aim of the present study was to get molecular insights of pirfenidone-related pharmacometabolomic response using MALDI-FTICR-MSI. Quantitative MALDI-FTICR-MSI was carried out for determining the pharmacokinetic properties of pirfenidone and its related metabolites 5-hydroxymethyl pirfenidone and 5-carboxy pirfenidone in lung, liver and kidney. To monitor the effect of pirfenidone administration on endogenous cell metabolism, additional in situ endogenous metabolite imaging was performed in lung tissue sections. While pirfenidone is highly abundant and delocalized across the whole micro-regions of lung, kidney and liver, 5-hydroxymethyl pirfenidone and 5-carboxy pirfenidone demonstrate heterogeneous distribution patterns in lung and kidney. In situ endogenous metabolite imaging study of lung tissue indicates no significant effects of pirfenidone on metabolic pathways. Remarkably, we found 129 discriminative m/z values which represent clear differences between control and treated lungs, the majority of which are currently unknown. PCA analysis and heatmap view can accurately distinguish control and treated groups. This is the first pharmacokinetic study to investigate the tissue distribution of orally administered pirfenidone and its related metabolites simultaneously in organs without labeling. The combination of pharmametabolome with histological features provides detailed mapping of drug effects on metabolism as response of healthy lung tissue to pirfenidone treatment.

  4. Oligomers formed through in-cloud methylglyoxal reactions: Chemical composition, properties, and mechanisms investigated by ultra-high resolution FT-ICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Altieri, K. E.; Seitzinger, S. P.; Carlton, A. G.; Turpin, B. J.; Klein, G. C.; Marshall, A. G.

    Secondary organic aerosol (SOA) is a substantial component of total atmospheric organic particulate matter, but little is known about the composition of SOA formed through cloud processing. We conducted aqueous phase photo-oxidation experiments of methylglyoxal and hydroxyl radical to simulate cloud processing. In addition to predicted organic acid monomers, oligomer formation from methylglyoxal-hydroxyl radical reactions was detected by electrospray ionization mass spectrometry (ESI-MS). The chemical composition of the oligomers and the mechanism of their formation were investigated by ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and LCQ DUO ion trap mass spectrometry (ESI-MS-MS). Reaction products included 415 compounds detected in the mass range 245-800 Da and the elemental composition of all 415 compounds were determined by ultra-high resolution FT-ICR MS. The ratio of total organic molecular weight per organic carbon weight (OM:OC) of the oligomers (1.0-2.5) was lower than the OM:OC of the organic acid monomers (2.3-3.8) formed, suggesting that the oligomers are less hygroscopic than the organic acid monomers formed from methylglyoxal-hydroxyl radical reaction. The OM:OC of the oligomers (average=2.0) is consistent with that of aged atmospheric aerosols and atmospheric humic-like substances (HULIS). A mechanism is proposed in which the organic acid monomers formed through hydroxyl radical reactions oligomerize through esterification. The mechanism is supported by the existence of series of oligomers identified by elemental composition from FT-ICR MS and ion fragmentation patterns from ESI-MS-MS. Each oligomer series starts with an organic acid monomer formed from hydroxyl radical oxidation, and increases in molecular weight and total oxygen content through esterification with a hydroxy acid (C 3H 6O 3) resulting in multiple additions of 72.02113 Da (C 3H 4O 2) to the parent organic acid monomer. Methylglyoxal is

  5. Hydrothermal liquefaction oil and hydrotreated product from pine feedstock characterized by heteronuclear two-dimensional NMR spectroscopy and FT-ICR mass spectrometry

    SciTech Connect

    Sudasinghe, Nilusha; Cort, John R.; Hallen, Richard; Olarte, Mariefel; Schmidt, Andrew; Schaub, Tanner

    2014-12-01

    Hydrothermal liquefaction (HTL) crude oil and hydrotreated product from pine tree farm waste (forest product residual, FPR) have been analyzed by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) in both positive- and negative-ionization modes and high-resolution twodimensional heteronuclear 1H-13C NMR spectroscopy. FT-ICR MS resolves thousands of compounds in complex oils and provides unparalleled compositional details for individual molecules for identification of compound class (heteroatom content), type (number of rings plus double bonds to carbon or double bond equivalents (DBE) and carbon number (degree of alkylation). Heteronuclear 1H-13C NMR spectroscopy provides one-bond and multiple-bond correlations between pairs of 1H and 13C chemical shifts that are characteristic of different organic functional groups. Taken together this information provides a picture of the chemical composition of these oils. Pyrolysis crude oil product from pine wood was characterized for comparison. Generally, pyrolysis oil is comprised of a more diverse distribution of heteroatom classes with higher oxygen number relative to HTL oil as shown by both positive- and negative-ion ESI FT-ICR MS. A total of 300 N1, 594 O1 and 267 O2 compounds were observed as products of hydrotreatment. The relative abundance of N1O1, N1O2, N1O3, N2, N2O1, N2O2 and O3 compounds are reduced to different degrees after hydrotreatment and other higher heteroatom containing species (O4-O10, N1O4, N1O5 and N2O3) are completely removed by hydrotreatment.

  6. Assessing drug and metabolite detection in liver tissue by UV-MALDI and IR-MALDESI mass spectrometry imaging coupled to FT-ICR MS

    PubMed Central

    Barry, Jeremy A.; Groseclose, M. Reid; Robichaud, Guillaume; Castellino, Stephen; Muddiman, David C.

    2014-01-01

    Determining the distribution of a drug and its metabolites within tissue is a key facet of evaluating drug candidates. Drug distribution can have a significant implication in appraising drug efficacy and potential toxicity. The specificity and sensitivity of mass spectrometry imaging (MSI) make it a perfect complement to the analysis of drug distributions in tissue. The detection of lapatinib as well as several of its metabolites in liver tissue was determined by MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to high resolving power Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. IR-MALDESI required minimal sample preparation while maintaining high sensitivity. The effect of the electrospray solvent composition on IR-MALDESI MSI signal from tissue analysis was investigated and an empirical comparison of IR-MALDESI and UV-MALDI for MSI analysis is also presented. PMID:26056514

  7. Rapid Screening for Potential Epitopes Reactive with a Polycolonal Antibody by Solution-Phase H/D Exchange Monitored by FT-ICR Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Qian; Noble, Kyle A.; Mao, Yuan; Young, Nicolas L.; Sathe, Shridhar K.; Roux, Kenneth H.; Marshall, Alan G.

    2013-07-01

    The potential epitopes of a recombinant food allergen protein, cashew Ana o 2, reactive to polyclonal antibodies, were mapped by solution-phase amide backbone H/D exchange (HDX) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Ana o 2 polyclonal antibodies were purified in the serum from a goat immunized with cashew nut extract. Antibodies were incubated with recombinant Ana o 2 (rAna o 2) to form antigen:polyclonal antibody (Ag:pAb) complexes. Complexed and uncomplexed (free) rAna o 2 were then subjected to HDX-MS analysis. Four regions protected from H/D exchange upon pAb binding are identified as potential epitopes and mapped onto a homologous model.

  8. High field NMR Spectroscopy and FTICR Mass Spectrometry: Powerful Discovery Tools for the Characterization of Marine Dissolved Organic Matter

    NASA Astrophysics Data System (ADS)

    Hertkorn, N.; Harir, M.; Koch, B. P.; Michalke, B.; Grill, P.; Schmitt-Kopplin, P.

    2012-04-01

    water depths. Eventually, olefinic unsaturation in marine DOM will be more directly traceable to ultimate biogenic precursors than aromatic unsaturation. The conformity of key NMR signatures suggests the presence of a numerous set of identical molecules throughout the entire ocean column even if the investigated water masses belonged to different oceanic regimes and currents. High field (12 T) negative electrospray ionization FTICR mass spectra showed abundant CHO, CHNO, CHOS and CHNOS molecular series with slightly increasing numbers of mass peaks and average mass from surface to bottom SPE-DOM. The proportion of CHO and CHNO molecular series increased from surface to depth whereas CHOS and especially CHNOS molecular series markedly declined. The exhaustive characterization of complex unknowns in marine DOM will enable a meaningful assessment of individual marine biogeosignatures which carry the holistic memory of the oceanic water masses.

  9. Petroleomics by electrospray ionization FT-ICR mass spectrometry coupled to partial least squares with variable selection methods: prediction of the total acid number of crude oils.

    PubMed

    Terra, Luciana A; Filgueiras, Paulo R; Tose, Lílian V; Romão, Wanderson; de Souza, Douglas D; de Castro, Eustáquio V R; de Oliveira, Mirela S L; Dias, Júlio C M; Poppi, Ronei J

    2014-10-07

    Negative-ion mode electrospray ionization, ESI(-), with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was coupled to a Partial Least Squares (PLS) regression and variable selection methods to estimate the total acid number (TAN) of Brazilian crude oil samples. Generally, ESI(-)-FT-ICR mass spectra present a power of resolution of ca. 500,000 and a mass accuracy less than 1 ppm, producing a data matrix containing over 5700 variables per sample. These variables correspond to heteroatom-containing species detected as deprotonated molecules, [M - H](-) ions, which are identified primarily as naphthenic acids, phenols and carbazole analog species. The TAN values for all samples ranged from 0.06 to 3.61 mg of KOH g(-1). To facilitate the spectral interpretation, three methods of variable selection were studied: variable importance in the projection (VIP), interval partial least squares (iPLS) and elimination of uninformative variables (UVE). The UVE method seems to be more appropriate for selecting important variables, reducing the dimension of the variables to 183 and producing a root mean square error of prediction of 0.32 mg of KOH g(-1). By reducing the size of the data, it was possible to relate the selected variables with their corresponding molecular formulas, thus identifying the main chemical species responsible for the TAN values.

  10. Chromatographic enrichment and subsequent separation of nickel and vanadyl porphyrins from natural seeps and molecular characterization by positive electrospray ionization FT-ICR mass spectrometry.

    PubMed

    Putman, Jonathan C; Rowland, Steven M; Corilo, Yuri E; McKenna, Amy M

    2014-11-04

    We report a novel chromatographic method to enrich and separate nickel and vanadyl porphyrins from a natural seep sample and combine molecular level characterization by positive-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Vanadyl and nickel porphyrin model compound elution from primary secondary amine (PSA) stationary phase combined with UV-vis spectroscopy confirms enrichment and subsequent fractionation of nickel and vanadyl porphyrins into polarity-based subfractions. A more than 100-fold increase in signal-to-noise ratio for nickel porphyrins enables unequivocal elemental composition assignment confirmed by isotopic fine structure for all isotopes >1% relative abundance, and the first mass spectral identification of (61)Ni porphyrin isotopologues derived from natural seeps. Oxygen-containing vanadyl porphyrins and sulfur-containing vanadyl porphyrins are isolated in the same fraction simultaneously from the same sample. We provide the first chromatographic evidence of carboxylic acid functionalities peripheral to the porphyrin core, in agreement with previous studies.

  11. Mapping the contact surfaces in the Lamin A:AIMP3 complex by hydrogen/deuterium exchange FT-ICR mass spectrometry

    PubMed Central

    Tao, Yeqing; Fang, Pengfei; Kim, Sunghoon; Guo, Min; Young, Nicolas L.; Marshall, Alan G.

    2017-01-01

    Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyl-tRNA synthetases. Recent reports reveal a novel function of AIMP3 as a tumor suppressor by accelerating cellular senescence and causing defects in nuclear morphology. AIMP3 specifically mediates degradation of mature Lamin A (LmnA), a major component of the nuclear envelope matrix; however, the mechanism of how AIMP3 interacts with LmnA is unclear. Here we report solution-phase hydrogen/deuterium exchange (HDX) for AIMP3, LmnA, and AIMP3 in association with the LmnA C-terminus. Reversed-phase LC coupled with LTQ 14.5 T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results in high mass accuracy and resolving power for comparing the D-uptake profiles for AIMP3, LmnA, and their complex. The results show that the AIMP3-LmnA interaction involves one of the two putative binding sites and an adjacent novel interface on AIMP3. LmnA binds AIMP3 via its extreme C-terminus. Together these findings provide a structural insight for understanding the interaction between AIMP3 and LmnA in AIMP3 degradation. PMID:28797100

  12. Mapping a Noncovalent Protein-Peptide Interface by Top-Down FTICR Mass Spectrometry Using Electron Capture Dissociation

    NASA Astrophysics Data System (ADS)

    Clarke, David J.; Murray, Euan; Hupp, Ted; Mackay, C. Logan; Langridge-Smith, Pat R. R.

    2011-08-01

    Noncovalent protein-ligand and protein-protein complexes are readily detected using electrospray ionization mass spectrometry (ESI MS). Furthermore, recent reports have demonstrated that careful use of electron capture dissociation (ECD) fragmentation allows covalent backbone bonds of protein complexes to be dissociated without disruption of noncovalent protein-ligand interactions. In this way the site of protein-ligand interfaces can be identified. To date, protein-ligand complexes, which have proven tractable to this technique, have been mediated by ionic electrostatic interactions, i.e., ion pair interactions or salt bridging. Here we extend this methodology by applying ECD to study a protein-peptide complex that contains no electrostatics interactions. We analyzed the complex between the 21 kDa p53-inhibitor protein anterior gradient-2 and its hexapeptide binding ligand (PTTIYY). ECD fragmentation of the 1:1 complex occurs with retention of protein-peptide binding and analysis of the resulting fragments allows the binding interface to be localized to a C-terminal region between residues 109 and 175. These finding are supported by a solution-phase competition assay, which implicates the region between residues 108 and 122 within AGR2 as the PTTIYY binding interface. Our study expands previous findings by demonstrating that top-down ECD mass spectrometry can be used to determine directly the sites of peptide-protein interfaces. This highlights the growing potential of using ECD and related top-down fragmentation techniques for interrogation of protein-protein interfaces.

  13. High-field NMR spectroscopy and FTICR mass spectrometry: powerful discovery tools for the molecular level characterization of marine dissolved organic matter

    NASA Astrophysics Data System (ADS)

    Hertkorn, N.; Harir, M.; Koch, B. P.; Michalke, B.; Schmitt-Kopplin, P.

    2013-03-01

    resolution and depicted resolved molecular signatures in excess of a certain minimum abundance. Classical methyl groups terminating aliphatic chains represented ~15% of total methyl in all samples investigated. A noticeable fraction of methyl (~2%) was bound to olefinic carbon. Methyl ethers were abundant in surface marine SPE-DOM, and the chemical diversity of carbohydrates was larger than that of freshwater and soil DOM. In all samples, we identified sp2-hybridized carbon chemical environments with discrimination of isolated and conjugated olefins and α,β-unsaturated double bonds. Olefinic proton and carbon atoms were more abundant than aromatic ones; olefinic unsaturation in marine SPE-DOM will be more directly traceable to ultimate biogenic precursors than aromatic unsaturation. The abundance of furan, pyrrol and thiophene derivatives was marginal, whereas benzene derivatives, phenols and six-membered nitrogen heterocycles were prominent; a yet unassigned set of six-membered N-heterocycles with likely more than one single nitrogen occurred in all samples. Various key polycyclic aromatic hydrocarbon substructures suggested the presence of thermogenic organic matter at all water depths. Progressive NMR cross-peak attenuation from surface to deep marine SPE-DOM was particularly strong in COSY NMR spectra and indicated a continual disappearance of biosignatures as well as entropy gain from an ever increased molecular diversity. Nevertheless, a specific near-seafloor SPE-DOM signature of unsaturated molecules recognized in both NMR and Fourier transform ion cyclotron mass spectrometry (FTICR/MS) possibly originated from sediment leaching. The conformity of key NMR and FTICR/MS signatures suggested the presence of a large set of identical molecules throughout the entire ocean column even though the investigated water masses belonged to different oceanic regimes and currents. FTICR/MS showed abundant CHO, CHNO, CHOS and CHNOS molecular series with slightly increasing numbers

  14. Molecular characterization and comparison of shale oils generated by different pyrolysis methods using FT-ICR mass spectrometry

    USGS Publications Warehouse

    Jin, J.M.; Kim, S.; Birdwell, J.E.

    2011-01-01

    Fourier transform ion cyclotron resonance mass spectrometry (FT ICR-MS) was applied in the analysis of shale oils generated using two different pyrolysis systems under laboratory conditions meant to simulate surface and in situ oil shale retorting. Significant variations were observed in the shale oils, particularly the degree of conjugation of the constituent molecules. Comparison of FT ICR-MS results to standard oil characterization methods (API gravity, SARA fractionation, gas chromatography-flame ionization detection) indicated correspondence between the average Double Bond Equivalence (DBE) and asphaltene content. The results show that, based on the average DBE values and DBE distributions of the shale oils examined, highly conjugated species are enriched in samples produced under low pressure, high temperature conditions and in the presence of water.

  15. High-field FT-ICR mass spectrometry and NMR spectroscopy to characterize DOM removal through a nanofiltration pilot plant.

    PubMed

    Cortés-Francisco, Nuria; Harir, Mourad; Lucio, Marianna; Ribera, Gemma; Martínez-Lladó, Xavier; Rovira, Miquel; Schmitt-Kopplin, Philipe; Hertkorn, Norbert; Caixach, Josep

    2014-12-15

    Ultrahigh resolution Fourier transform ion cyclotron mass spectrometry and nuclear magnetic resonance spectroscopy were combined to evaluate the molecular changes of dissolved organic matter (DOM) through an ultrafiltration-nanofiltration (UF-NF) pilot plant, using two dissimilar NF membranes tested in parallel. The sampling was performed on seven key locations within the pilot plant: pretreated water, UF effluent, UF effluent after addition of reagents, permeate NF 1, permeate NF 2, brine NF 1 and brine NF 2, during two sampling campaigns. The study showed that there is no significant change in the nature of DOM at molecular level, when the water was treated with UF and/or with the addition of sodium metabisulfite and antiscaling agents. However, enormous decrease of DOM concentration was observed when the water was treated on the NF membranes. The NF process preferentially removed compounds with higher oxygen and nitrogen content (more hydrophilic compounds), whereas molecules with longer pure aliphatic chains and less content of oxygen were the ones capable of passing through the membranes. Moreover, slight molecular selectivity between the two NF membranes was also observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Molecular Characterization and Reactivity of Dissolved Organic Matter by High Resolution Nanospray Ionization Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry (FTICR-MS)

    NASA Astrophysics Data System (ADS)

    Sleighter, R. L.; Hatcher, S. A.; Hatcher, P. G.

    2006-12-01

    The ultrahigh resolving power of FTICR-MS allows for the intense characterization of dissolved organic matter (DOM). DOM is the largest reactive component of the global carbon cycle, and an improved understanding of its composition is necessary to determine the transport and eventual fate of pollutants. The seasonal and spatial variations in DOM composition are investigated by taking surface water samples from five different sampling sites, four times a year. Water sampling begins at the Dismal Swamp in North Carolina, continues north up the Elizabeth River to the Chesapeake Bay, and concludes approximately ten miles off the coast in the Atlantic Ocean. DOM was extracted from the water samples using C18 extraction disks and were prepared in 50:50 methanol:water. Ammonium hydroxide was added prior to nanospray in order to solubilize the DOM as well as to increase the ionization efficiency. The samples were continuously infused into the Apollo II ion source with an Advion TriVersa NanoMate system of a Bruker 12 Tesla Apex QE FTICR-MS with resolving powers exceeding 400,000. All samples were analyzed in negative ion mode and were externally and internally calibrated prior to data analysis. Our DOM mass spectra consist of a multitude of peaks spanning the range of 200-850 m/z. Complexity is apparent from the detection of up to 20 peaks per nominal mass at nearly every mass throughout that range. A molecular formula calculator generated molecular formula matches from which van Krevelen plots were constructed for characterization purposes. A wide range of molecules were observed each containing oxygen, sulfur and nitrogen functional groups. We utilize the van Krevelen diagram to assist in clustering the molecules according to their functional group compositions. To test the hypothesis that formation of adducts to DOM serve to protect peptides from bacterial degradation, microcosm experiments were performed with a small isotopically enriched peptide, GGGR. This peptide

  17. High field NMR spectroscopy and FTICR mass spectrometry: powerful discovery tools for the molecular level characterization of marine dissolved organic matter from the South Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Hertkorn, N.; Harir, M.; Koch, B. P.; Michalke, B.; Grill, P.; Schmitt-Kopplin, P.

    2012-01-01

    to bottom DOM and similar fractions (~50%) of assigned molecular compositions throughout all DOM samples. The average mass increased from surface to bottom DOM by about 10 Dalton. The limited variance of FTICR mass spectra probably resulted from a rather inherent conformity of marine DOM at the mandatory level of intrinsic averaging provided by FTICR mass spectrometry, when many isomers unavoidably project on single nominal mass peaks. In addition, averaging from ion suppression added to the accordance observed. The proportion of CHO and CHNO molecular series increased from surface to depth whereas CHOS and especially CHNOS molecular series markedly declined. The abundance of certain aromatic CHOS compounds declined with water depth. For future studies, COSY NMR spectra appear best suited to assess organic molecular complexity of marine DOM and to define individual DOM molecules of yet unknown structure and function. Non-target organic structural spectroscopy at the level demonstrated here covered nearly all carbon present in marine DOM. The exhaustive characterization of complex unknowns in marine DOM will reveal a meaningful assessment of individual marine biogeosignatures which carry the holistic memory of the oceanic water masses (Koch et al., 2011).

  18. High-Throughput Proteomics Using High Efficiency Multiple-Capillary Liquid Chromatography With On-Line High-Performance ESI FTICR Mass Spectrometry

    SciTech Connect

    Shen, Yufeng ); Tolic, Nikola ); Zhao, Rui; Pasa Tolic, Ljiljana ); Li, Lingjun; Berger, Scott J.; Harkewicz, Richard ); Anderson, Gordon A. ); Belov, Mikhail E. ); Smith, Richard D. )

    2000-12-01

    We report on the design and application of a high-efficiency multiple-capillary liquid chromatography (LC) system for high-throughput proteome analysis. The multiple-capillary LC system was operated at the pressure of 10,000 psi using commercial LC pumps to deliver the mobile phase and newly developed passive feedback valves to switch the mobile phase flow and introduce samples. The multiple-capillary LC system was composed of several serially connected dual-capillary column devices. The dual-capillary column approach was designed to eliminate the time delay for regeneration (or equilibrium) of the capillary column after its use under the mobile phase gradient condition (i.e. one capillary column was used in separation and the other was washed using mobile phase A). The serially connected dual-capillary columns and ESI sources were operated independently, and could be used for either''backup'' operation or with other mass spectrometer(s). This high-efficiency multiple-capillary LC system uses switching valves for all operations and is highly amenable to automation. The separations efficiency of dual-capillary column device, optimal capillary dimensions (column length and packed particle size), suitable mobile phases for electrospray, and the capillary re-generation were investigated. A high magnetic field (11.5 tesla) Fourier transform ion cyclotron resonance (FTICR) mass spectrometer was coupled on-line with this high-efficiency multiple-capillary LC system through an electrospray ionization source. The capillary LC provided a peak capacity of {approx}600, and the 2-D capillary LC-FTICR provided a combined resolving power of > 6 x 10 7 polypeptide isotopic distributions. For yeast cellular tryptic digests, > 100,000 polypeptides were typically detected, and {approx}1,000 proteins can be characterized in a single run.

  19. Increasing Polyaromatic Hydrocarbon (PAH) Molecular Coverage during Fossil Oil Analysis by Combining Gas Chromatography and Atmospheric-Pressure Laser Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS).

    PubMed

    Benigni, Paolo; DeBord, J Daniel; Thompson, Christopher J; Gardinali, Piero; Fernandez-Lima, Francisco

    2016-01-21

    Thousands of chemically distinct compounds are encountered in fossil oil samples that require rapid screening and accurate identification. In the present paper, we show for the first time, the advantages of gas chromatography (GC) separation in combination with atmospheric-pressure laser ionization (APLI) and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for the screening of polyaromatic hydrocarbons (PAHs) in fossil oils. In particular, reference standards of organics in shale oil, petroleum crude oil, and heavy sweet crude oil were characterized by GC-APLI-FT-ICR MS and APLI-FT-ICR MS. Results showed that, while APLI increases the ionization efficiency of PAHs, when compared to other ionization sources, the complexity of the fossil oils reduces the probability of ionizing lower-concentration compounds during direct infusion. When gas chromatography precedes APLI-FT-ICR MS, an increase (more than 2-fold) in the ionization efficiency and an increase in the signal-to-noise ratio of lower-concentration fractions are observed, giving better molecular coverage in the m/z 100-450 range. That is, the use of GC prior to APLI-FT-ICR MS resulted in higher molecular coverage, higher sensitivity, and the ability to separate and characterize molecular isomers, while maintaining the ultrahigh resolution and mass accuracy of the FT-ICR MS separation.

  20. Applications of Fourier Transform Ion Cyclotron Resonance (FT-ICR) and Orbitrap Based High Resolution Mass Spectrometry in Metabolomics and Lipidomics

    PubMed Central

    Ghaste, Manoj; Mistrik, Robert; Shulaev, Vladimir

    2016-01-01

    Metabolomics, along with other “omics” approaches, is rapidly becoming one of the major approaches aimed at understanding the organization and dynamics of metabolic networks. Mass spectrometry is often a technique of choice for metabolomics studies due to its high sensitivity, reproducibility and wide dynamic range. High resolution mass spectrometry (HRMS) is a widely practiced technique in analytical and bioanalytical sciences. It offers exceptionally high resolution and the highest degree of structural confirmation. Many metabolomics studies have been conducted using HRMS over the past decade. In this review, we will explore the latest developments in Fourier transform mass spectrometry (FTMS) and Orbitrap based metabolomics technology, its advantages and drawbacks for using in metabolomics and lipidomics studies, and development of novel approaches for processing HRMS data. PMID:27231903

  1. Identification of glucosinolates in capers by LC-ESI-hybrid linear ion trap with Fourier transform ion cyclotron resonance mass spectrometry (LC-ESI-LTQ-FTICR MS) and infrared multiphoton dissociation.

    PubMed

    Bianco, Giuliana; Lelario, Filomena; Battista, Fabio Giuseppe; Bufo, Sabino A; Cataldi, Tommaso R I

    2012-09-01

    An liquid chromatography-mass spectrometry method using electrospray ionization in negative ion mode coupled with a hybrid quadrupole linear ion trap and Fourier transform ion cyclotron resonance (FTICR) mass spectrometer was applied to characterize of intact glucosinolates (GLSs) in crude sample extracts of wild bud flowers of Capparis spinosa (Capparis species, family Capparaceae). Structural information of GLSs was obtained upon precursor ions' isolation within the FTICR trapping cell and subsequent fragmentation induced by infrared multiphoton dissociation (IRMPD). Such a fragmentation was found very useful in terms of chemical identification of all precursor ions [M-H](-) including sulfur-rich GLSs reported here for the first time. Along with most common GLSs already found in capers such as glucocapparin, isopropyl/n-propyl-GLS, mercapto-glucocapparin, and two indolic GLS, i.e., 4-hydroxyglucobrassicin and glucobrassicin, the occurrence of the uncommon glycinyl-glucocapparin as well as two sulfur-rich GLSs is reported. IRMPD showed an increased selectivity towards disulfide bond cleavages with thiol migration, suggesting the side chain structure of non-targeted compounds, i.e., disulfanyl-glucocapparin and trisulfanyl-glucocapparin. Glucocapparin [2.05 ± 0.25 mg/g, dry weight (dw)] was the most abundant GLS, followed by glucobrassicin (232 ± 18 µg/g, dw) and 4-hydroxyglucobrassicin (89 ± 12 µg/g, dw). All other compounds were present at very low content ranging from 0.5 to 1.5 µg/g dw. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Biodegradation of carbamazepine and clarithromycin by Trichoderma harzianum and Pleurotus ostreatus investigated by liquid chromatography - high-resolution tandem mass spectrometry (FTICR MS-IRMPD).

    PubMed

    Buchicchio, Alessandro; Bianco, Giuliana; Sofo, Adriano; Masi, Salvatore; Caniani, Donatella

    2016-07-01

    In this study, the capability of pharmaceutical biodegradation of fungus Trichoderma harzianum was evaluated through the comparison with the well-known biodegradation capability of white-rot fungus Pleurotus ostreatus. The study was performed in aqueous phase under aerobic conditions, using two of the most frequently detected drugs in water bodies: carbamazepine and clarithromycin, with concentrations commonly found in treated wastewater (4μg/l and 0.03μg/l respectively). For the first time, we demonstrated that T. harzianum is able to remove carbamazepine and clarithromycin. The analyses were performed by reversed-phase liquid chromatography/mass spectrometry, using high-resolution Fourier-transform ion cyclotron resonance mass spectrometry upon electrospray ionization in positive ion mode. The high selectivity and mass accuracy provided by high-resolution mass spectrometry, allowed us to identify some unknown metabolites. On the basis of our study, the major metabolites detected in liquid culture treated by T. harzianum were: 14-hydroxy-descladinosyl- and descladinosyl-clarithromycin, which are pharmacologically inactive products not dangerous for the environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Characterization and identification of the chemical constituents from tartary buckwheat (Fagopyrum tataricum Gaertn) by high performance liquid chromatography/photodiode array detector/linear ion trap FTICR hybrid mass spectrometry.

    PubMed

    Ren, Qiang; Wu, Caisheng; Ren, Yan; Zhang, Jinlan

    2013-02-15

    In recent years tartary buckwheat has become popular healthful food due to its antioxidant, antidiabetic and antitumor activities. However, its chemical constituents have not yet been fully characterized and identified. In this paper, a novel high performance liquid chromatography coupled with photodiode array detector and linear ion trap FTICR hybrid mass spectrometry (HPLC-PDA/LTQ-FTICRMS) method was established to characterize and identify a total of 36 compounds by a single run. The retention time, maximum UV absorption wavelength, accurate mass weight and characteristic fragment ions were collected on line. To confirm the structures, 11 compounds were isolated and identified by MS and NMR experiments. 1, 3, 6, 6'-tetra-feruloyl sucrose named taroside was a new phenlypropanoid glycoside, together with 3, 6-di-p-coumaroyl-1, 6'-di-feruloyl sucrose, 1, 6, 6'-tri-feruloyl-3-p-coumaroyl sucrose, N-trans-feruloyltyramine and quercetin-3-O-[β-D-xyloxyl-(1→2)-α-L-rhamnoside] were isolated for the first time from the Fagopyrum species. The research enriched the chemical information of tartary buckwheat. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Binding of an organo-osmium(II) anticancer complex to guanine and cytosine on DNA revealed by electron-based dissociations in high resolution Top-Down FT-ICR mass spectrometry.

    PubMed

    Wootton, Christopher A; Sanchez-Cano, Carlos; Liu, Hong-Ke; Barrow, Mark P; Sadler, Peter J; O'Connor, Peter B

    2015-02-28

    The Os(II) arene anticancer complex [(η(6)-bip)Os(en)Cl](+) (Os1-Cl; where bip = biphenyl, and en = ethylenediamine) binds strongly to DNA. Here we investigate reactions between Os1-Cl and the self-complementary 12-mer oligonucleotide 5'-TAGTAATTACTA-3' (DNA12) using ultra high resolution Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Identification of the specific sites of DNA osmiation with {(η(6)-bip)Os(en)}(2+) was made possible by the use of Electron Detachment Dissociation (EDD) which produced a wide range of assignable osmiated MS/MS fragments. In contrast, the more commonly used CAD and IRMPD techniques produced fragments which lose the bound osmium. These studies reveal that not only is guanine G3 a strong binding site for {(η(6)-bip)Os(en)}(2+) but, unexpectedly, so too is cytosine C10. Interestingly, the G3/C10 di-osmiated adduct of DNA12 also formed readily but did not undergo such facile fragmentation by EDD, perhaps due to folding induced by van der Waal's interactions of the bound osmium arene species. These new insights into osmium arene DNA adducts should prove valuable for the design of new organometallic drugs and contribute to understanding the lack of cross resistance of this organometallic anticancer complex with cisplatin.

  5. MALDI FTICR IMS of intact proteins: Using mass accuracy to link protein images with proteomics data

    PubMed Central

    Spraggins, Jeffrey M.; Rizzo, David G.; Moore, Jessica L.; Rose, Kristie L.; Hammer, Neal D.; Skaar, Eric P.; Caprioli, Richard M.

    2015-01-01

    MALDI imaging mass spectrometry is a highly sensitive and selective tool used to visualize biomolecules in tissue. However, identification of detected proteins remains a difficult task. Indirect identifications strategies have been limited by insufficient mass accuracy to confidently link ion images to proteomics data. Here we demonstrate the capabilities of MALDI FTICR MS for imaging intact proteins. MALDI FTICR IMS provides an unprecedented combination of mass resolving power (∼75,000 at m/z 5,000) and accuracy (<5 ppm) for proteins up to ∼12 kDa enabling identification based on correlation with LC-MS/MS proteomics data. Analysis of rat brain tissue was performed as a proof-of-concept highlighting the capabilities of this approach by imaging and identifying a number of proteins including N-terminally acetylated Thymosin β4 (m/z 4,963.502, 0.6 ppm) and ATP Synthase subunit ε (m/z 5,636.074, −2.3 ppm). MALDI FTICR IMS was also used to differentiate a series of oxidation products of S100A8 (m/z 10,164.03, −2.1 ppm), a subunit of the heterodimer calprotectin, in kidney tissue from mice infected with Staphylococcus aureus. S100A8 – M37O/C42O3 (m/z 10228.00, −2.6 ppm) was found to co-localize with bactierial microcolonies at the center of infectious foci. The ability of MALDI FTICR IMS to distinguish S100A8 modifications is critical to understanding calprotectin’s roll in nutritional immunity. PMID:25904064

  6. MALDI FTICR IMS of Intact Proteins: Using Mass Accuracy to Link Protein Images with Proteomics Data

    NASA Astrophysics Data System (ADS)

    Spraggins, Jeffrey M.; Rizzo, David G.; Moore, Jessica L.; Rose, Kristie L.; Hammer, Neal D.; Skaar, Eric P.; Caprioli, Richard M.

    2015-06-01

    MALDI imaging mass spectrometry is a highly sensitive and selective tool used to visualize biomolecules in tissue. However, identification of detected proteins remains a difficult task. Indirect identification strategies have been limited by insufficient mass accuracy to confidently link ion images to proteomics data. Here, we demonstrate the capabilities of MALDI FTICR MS for imaging intact proteins. MALDI FTICR IMS provides an unprecedented combination of mass resolving power (~75,000 at m/z 5000) and accuracy (<5ppm) for proteins up to ~12kDa, enabling identification based on correlation with LC-MS/MS proteomics data. Analysis of rat brain tissue was performed as a proof-of-concept highlighting the capabilities of this approach by imaging and identifying a number of proteins including N-terminally acetylated thymosin β4 ( m/z 4,963.502, 0.6ppm) and ATP synthase subunit ɛ ( m/z 5,636.074, -2.3ppm). MALDI FTICR IMS was also used to differentiate a series of oxidation products of S100A8 ( m/z 10,164.03, -2.1ppm), a subunit of the heterodimer calprotectin, in kidney tissue from mice infected with Staphylococcus aureus. S100A8 - M37O/C42O3 ( m/z 10228.00, -2.6ppm) was found to co-localize with bacterial microcolonies at the center of infectious foci. The ability of MALDI FTICR IMS to distinguish S100A8 modifications is critical to understanding calprotectin's roll in nutritional immunity.

  7. 4 Years after the Deepwater Horizon Spill: Molecular Transformation of Macondo Well Oil in Louisiana Salt Marsh Sediments Revealed by FT-ICR Mass Spectrometry.

    PubMed

    Chen, Huan; Hou, Aixin; Corilo, Yuri E; Lin, Qianxin; Lu, Jie; Mendelssohn, Irving A; Zhang, Rui; Rodgers, Ryan P; McKenna, Amy M

    2016-09-06

    Gulf of Mexico saltmarsh sediments were heavily impacted by Macondo well oil (MWO) released from the 2010 Deepwater Horizon (DWH) oil spill. Detailed molecular-level characterization of sediment extracts collected over 48 months post-spill highlights the chemical complexity of highly polar, oxygen-containing compounds that remain environmentally persistent. Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), combined with chromatographic prefractionation, correlates bulk chemical properties to elemental compositions of oil-transformation products as a function of time. Carboxylic acid incorporation into parent MWO hydrocarbons detected in sediment extracts (corrected for mass loss relative to C30 hopane) proceeds with an increase of ∼3-fold in O2 species after 9 months to a maximum of a ∼5.5-fold increase after 36 months, compared to the parent MWO. More importantly, higher-order oxygenated compounds (O4-O6) not detected in the parent MWO increase in relative abundance with time as lower-order oxygenated species are transformed into highly polar, oxygen-containing compounds (Ox, where x > 3). Here, we present the first molecular-level characterization of temporal compositional changes that occur in Deepwater Horizon derived oil contamination deposited in a saltmarsh ecosystem from 9 to 48 months post-spill and identify highly oxidized Macondo well oil compounds that are not detectable by routine gas-chromatography-based techniques.

  8. Fast Reversed-Phase Liquid Chromatography to Reduce Back Exchange and Increase Throughput in H/D Exchange Monitored by FT-ICR Mass Spectrometry

    PubMed Central

    Zhang, Hui-Min; Bou-Assaf, George M.; Emmett, Mark R.; Marshall, Alan G.

    2009-01-01

    In solution-phase hydrogen/deuterium exchange (HDX), it is essential to minimize the back exchange level of H for D after the exchange has been quenched, to accurately assign protein conformation and protein-protein or protein-ligand interactions. Reversed-phase HPLC is conducted at low pH and low temperature to desalt and separate proteolytic fragments. However, back exchange averages ∼30% due to long exposure to H2O in the mobile phase. In this paper, we first show that there is no significant backbone amide hydrogen back exchange during quenching and digestion; backbone exchange occurs primarily during subsequent LC separation. We then show that a rapid reversed-phase separation reduces back exchange for HDX by at least 25%, due to dramatically reduced retention time of the peptide fragments on the column. The influence of retention time on back exchange was also evaluated. The rapid separation coupled with high resolution FT-ICR MS at 14.5T provides high amino acid sequence coverage, high sample throughput, and high reproducibility and reliability. PMID:19095461

  9. Nucleotide-induced conformational changes of tetradecameric GroEL mapped by H/D exchange monitored by FT-ICR mass spectrometry

    PubMed Central

    Zhang, Qian; Chen, Jin; Kuwajima, Kunihiro; Zhang, Hui-Min; Xian, Feng; Young, Nicolas L.; Marshall, Alan G.

    2013-01-01

    Here we employ hydrogen/deuterium exchange mass spectrometry (HDX-MS) to access E. coli chaperonin GroEL conformation. The ~800 kDa tetradecameric GroEL plays an essential role in the proper folding of many proteins. Previous studies of the structural dynamics of GroEL upon ATP binding have been inconsistent, showing either minimal or major allosteric changes. Our results, based on the native, non-mutated, protein under physiological conditions in solution demonstrate substantial changes in conformation and/or flexibility upon ATP binding. We capture the pivotal step in its functional cycle by use of a non-hydrolyzable ATP analog, ATPγS, to mimic the ATP-bound GroEL state. Comparison of HDX-MS results for apo GroEL and GroEL-ATPγS enables the characterization of the nucleotide-regulated conformational changes throughout the entire protein with high sequence resolution. The 14-mer GroEL complex is the largest protein assembly yet accessed by HDX-MS, with sequence resolution of segments of as few as five amino acids. PMID:23409238

  10. Characterizing the secondary organic aerosol products of ozone and α-pinene using ultrahigh-resolution FT-ICR mass spectrometry

    NASA Astrophysics Data System (ADS)

    Putman, A.; Offenberg, J. H.; Fisseha, R.; Kundu, S.; Rahn, T.; Mazzoleni, L. R.

    2011-12-01

    Three samples of secondary organic aerosol (SOA) were generated by reacting a-pinene and ozone in the presence of variable concentrations of hydroxyl radical scavenging cyclohexane and were characterized by ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS). The reactions were performed in the presence of different concentrations of hydroxyl radical scavenger. This provided an opportunity to examine the molecular level differences of SOA. More than 900 chemical formulas for negative ions were identified over the mass range of 100 to 820 u. The experimental reproducibility of the SOA composition and the technical reproducibility of the mass spectra were evaluated. Similar chemical formulas with similar relative abundances were observed in all three experiments. A few exceptions were particular high relative abundance signals such as m/z 357, 367 and 539, whose production efficiency increased in the presence of cyclohexane, and m/z 185, 199, 215, 231 and 261, whose production efficiency decreased in the presence of cyclohexane. In general, the composition of a-pinene SOA was only slightly influenced by the concentration of the hydroxyl radical scavenger, cyclohexane. The negative ion spectra of the SOA contained four groups of peaks over the following mass ranges: 150 < n < 300, 300 < n < 475, 475 < n < 600, 600 < n < 850. As the molecular weight increased, a variety of changes occurred. The number of individual compounds within one nominal mass increased. The range of oxygen to carbon and hydrogen ratios decreased from group I to IV. Likewise, the mean values of oxygen to carbon decreased from 0.55 to 0.42. The mean value of hydrogen to carbon, approximately 1.5, did not change with respect to molecular weight, although the range of values did decrease. The chemical formulas of groups I and II with the highest relative abundances contained 5-7 and 7-10 oxygen atoms and double bond equivalents (DBE) of 3-4 and 5

  11. A Novel 9.4 Tesla FTICR Mass Spectrometer with Improved Sensitivity, Mass Resolution, and Mass Range

    NASA Astrophysics Data System (ADS)

    Kaiser, Nathan K.; Quinn, John P.; Blakney, Gregory T.; Hendrickson, Christopher L.; Marshall, Alan G.

    2011-08-01

    Fourier transform ion cyclotron resonance (FTICR) mass spectrometry provides unparalleled mass measurement accuracy and resolving power. However, propagation of the technique into new analytical fields requires continued advances in instrument speed and sensitivity. Here, we describe a substantial redesign of our custom-built 9.4 tesla FTICR mass spectrometer that improves sensitivity, acquisition speed, and provides an optimized platform for future instrumentation development. The instrument was designed around custom vacuum chambers for improved ion optical alignment, minimized distance from the external ion trap to magnetic field center, and high conductance for effective differential pumping. The length of the transfer optics is 30% shorter than the prior system, for reduced time-of-flight mass discrimination and increased ion transmission and trapping efficiency at the ICR cell. The ICR cell, electrical vacuum feedthroughs, and cabling have been improved to reduce the detection circuit capacitance (and improve detection sensitivity) 2-fold. The design simplifies access to the ICR cell, and the modular vacuum flange accommodates new ICR cell technology, including linearized excitation, high surface area detection, and tunable electrostatic trapping potential.

  12. Mass spectrometry.

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Johanson, G. A.

    1972-01-01

    Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

  13. Mass spectrometry.

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Johanson, G. A.

    1972-01-01

    Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

  14. SIEMENS ADVANCED QUANTRA FTICR MASS SPECTROMETER FOR ULTRA HIGH RESOLUTION AT LOW MASS

    SciTech Connect

    Spencer, W; Laura Tovo, L

    2008-07-08

    The Siemens Advanced Quantra Fourier Transform Ion Cyclotron Resonance (FTICR) mass spectrometer was evaluated as an alternative instrument to large double focusing mass spectrometers for gas analysis. High resolution mass spectrometers capable of resolving the common mass isomers of the hydrogen isotopes are used to provide data for accurate loading of reservoirs and to monitor separation of tritium, deuterium, and helium. Conventional double focusing magnetic sector instruments have a resolution that is limited to about 5000. The Siemens FTICR instrument achieves resolution beyond 400,000 and could possibly resolve the tritium ion from the helium-3 ion, which differ by the weight of an electron, 0.00549 amu. Working with Y-12 and LANL, SRNL requested Siemens to modify their commercial Quantra system for low mass analysis. To achieve the required performance, Siemens had to increase the available waveform operating frequency from 5 MHz to 40 MHz and completely redesign the control electronics and software. However, they were able to use the previous ion trap, magnet, passive pump, and piezo-electric pulsed inlet valve design. NNSA invested $1M in this project and acquired four systems, two for Y-12 and one each for SRNL and LANL. Siemens claimed a $10M investment in the Quantra systems. The new Siemens Advanced Quantra demonstrated phenomenal resolution in the low mass range. Resolution greater than 400,000 was achieved for mass 2. The new spectrometer had a useful working mass range to 500 Daltons. However, experiments found that a continuous single scan from low mass to high was not possible. Two useful working ranges were established covering masses 1 to 6 and masses 12 to 500 for our studies. A compromise performance condition enabled masses 1 to 45 to be surveyed. The instrument was found to have a dynamic range of about three orders of magnitude and quantitative analysis is expected to be limited to around 5 percent without using complex fitting algorithms

  15. FT-ICR mass spectrometric and density functional theory studies of sulfate prenucleation clusters

    NASA Astrophysics Data System (ADS)

    Lemke, K. H.

    2012-12-01

    Recent mass spectrometric1 and relaxation spectroscopic studies2 of metal sulfate salts have demonstrated that aqueous clusters play an important role in sulfate prenucleation processes. While such studies provide evidence that that ion clusters are nucleation relevant species, ultra-high resolution mass spectrumetry, in particular, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS) can provide additional valuable information about the molecular composition and stability of individual ion clusters. Prompted by the above studies, our group has begun a systematic survey of metal sulfate clusters using FT-ICR mass spectrometry. Here, I report stoichiometries, structures and thermodynamic properties of calcium sulfate ion clusters, both "dry" and microsolvated, using electrospray ionization FT-ICR mass spectrometry in combination with semi-empirical methods and M062X/aug-cc-PVXZ level density functional theory calculations. In electrosprayed dilute aqueous solutions of CaSO4 (1-20mM), droplet desolvation results in the formation of stable doubly-charged clusters of [Ca(CaSO4)m(H2O)n]+2 (m≤10 & n≤9) as well as larger quadruply-charged ion clusters [Ca2(CaSO4)m(H2O)n]+4 with m≤23 and n≤10, demonstrating considerable sulfate nucleation potential in undersaturated electrolyte solutions. An attempt was also made to assess the extent of ion cluster aggregation in solution prior to electrospray ionization by measuring ion mass spectra at different solution concentrations. In brief, an increase in calcium sulfate concentration from 1-10mM results in a continuous increase in polynuclear ion cluster species, while smaller clusters, for instance, Ca[CaSO4]+2 and corresponding hydrated forms, become increasingly less abundant. Building on semi-empirical methods, M062X calculations have been applied to predict calcium sulfate cluster geometries, both "dry" and microsolvated, as well as the size-dependent evolution of clustering and hydration energies. 1

  16. Secondary Ion Mass Spectrometry Imaging of Dictyostelium discoideum Aggregation Streams

    SciTech Connect

    Debord, J. Daniel; Smith, Donald F.; Anderton, Christopher R.; Heeren, Ronald M.; Pasa-Tolic, Ljiljana; Gomer, Richard H.; Fernandez-Lima, Francisco A.

    2014-06-09

    High resolution imaging mass spectrometry could become a valuable tool for cell and developmental biology, but both, high spatial and mass spectral resolution are needed to enable this. In this report, we employed Bi3 bombardment time-of-flight (Bi3 ToF-SIMS) and C60 bombardment Fourier transform ion cyclotron resonance secondary ion mass spectrometry (C60 FTICR-SIMS) to image Dictyostelium discoideum aggregation streams. Nearly 300 lipid species were identified from the aggregation streams. High resolution mass spectrometry imaging (FTICR-SIMS) enabled the generation of multiple molecular ion maps at the nominal mass level and provided good coverage for fatty acyls, prenol lipids, and sterol lipids. The comparison of Bi3 ToF-SIMS and C60 FTICR-SIMS suggested that while the first provides fast, high spatial resolution molecular ion images, the chemical complexity of biological samples warrants the use of high resolution analyzers for accurate ion identification.

  17. Fourier transform ion cyclotron resonance mass spectrometry

    NASA Astrophysics Data System (ADS)

    Marshall, Alan G.

    1998-06-01

    As for Fourier transform infrared (FT-IR) interferometry and nuclear magnetic resonance (NMR) spectroscopy, the introduction of pulsed Fourier transform techniques revolutionized ion cyclotron resonance mass spectrometry: increased speed (factor of 10,000), increased sensitivity (factor of 100), increased mass resolution (factor of 10,000-an improvement not shared by the introduction of FT techniques to IR or NMR spectroscopy), increased mass range (factor of 500), and automated operation. FT-ICR mass spectrometry is the most versatile technique for unscrambling and quantifying ion-molecule reaction kinetics and equilibria in the absence of solvent (i.e., the gas phase). In addition, FT-ICR MS has the following analytically important features: speed (~1 second per spectrum); ultrahigh mass resolution and ultrahigh mass accuracy for analysis of mixtures and polymers; attomole sensitivity; MSn with one spectrometer, including two-dimensional FT/FT-ICR/MS; positive and/or negative ions; multiple ion sources (especially MALDI and electrospray); biomolecular molecular weight and sequencing; LC/MS; and single-molecule detection up to 108 Dalton. Here, some basic features and recent developments of FT-ICR mass spectrometry are reviewed, with applications ranging from crude oil to molecular biology.

  18. High resolution FT-ICR mass spectral analysis of bio-oil and residual water soluble organics produced by hydrothermal liquefaction of the marine microalga Nannochloropsis salina

    SciTech Connect

    Sudasinghe, Nilusha; Dungan, Barry; Lammers, Peter; Albrecht, Karl O.; Elliott, Douglas C.; Hallen, Richard T.; Schaub, Tanner

    2014-03-01

    We report a detailed compositional characterization of a bio-crude oil and aqueous by-product from hydrothermal liquefaction of Nannochloropsis salina by direct infusion Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) in both positive- and negative-ionization modes. The FT-ICR MS instrumentation approach facilitates direct assignment of elemental composition to >7000 resolved mass spectral peaks and three-dimensional mass spectral images for individual heteroatom classes highlight compositional diversity of the two samples and provide a baseline description of these materials. Aromatic nitrogen compounds and free fatty acids are predominant species observed in both the bio-oil and aqueous fraction. Residual organic compounds present in the aqueous fraction show distributions that are slightly lower in both molecular ring and/or double bond value and carbon number relative to those found in the bio-oil, albeit with a high degree of commonality between the two compositions.

  19. Front-End Electron Transfer Dissociation Coupled to a 21 Tesla FT-ICR Mass Spectrometer for Intact Protein Sequence Analysis

    NASA Astrophysics Data System (ADS)

    Weisbrod, Chad R.; Kaiser, Nathan K.; Syka, John E. P.; Early, Lee; Mullen, Christopher; Dunyach, Jean-Jacques; English, A. Michelle; Anderson, Lissa C.; Blakney, Greg T.; Shabanowitz, Jeffrey; Hendrickson, Christopher L.; Marshall, Alan G.; Hunt, Donald F.

    2017-07-01

    High resolution mass spectrometry is a key technology for in-depth protein characterization. High-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) enables high-level interrogation of intact proteins in the most detail to date. However, an appropriate complement of fragmentation technologies must be paired with FTMS to provide comprehensive sequence coverage, as well as characterization of sequence variants, and post-translational modifications. Here we describe the integration of front-end electron transfer dissociation (FETD) with a custom-built 21 tesla FT-ICR mass spectrometer, which yields unprecedented sequence coverage for proteins ranging from 2.8 to 29 kDa, without the need for extensive spectral averaging (e.g., 60% sequence coverage for apo-myoglobin with four averaged acquisitions). The system is equipped with a multipole storage device separate from the ETD reaction device, which allows accumulation of multiple ETD fragment ion fills. Consequently, an optimally large product ion population is accumulated prior to transfer to the ICR cell for mass analysis, which improves mass spectral signal-to-noise ratio, dynamic range, and scan rate. We find a linear relationship between protein molecular weight and minimum number of ETD reaction fills to achieve optimum sequence coverage, thereby enabling more efficient use of instrument data acquisition time. Finally, real-time scaling of the number of ETD reactions fills during method-based acquisition is shown, and the implications for LC-MS/MS top-down analysis are discussed.

  20. MASS SPECTROMETRY

    DOEpatents

    Nier, A.O.C.

    1959-08-25

    A voltage switching apparatus is described for use with a mass spectrometer in the concentratron analysis of several components of a gas mixture. The system automatically varies the voltage on the accelerating electrode of the mass spectrometer through a program of voltages which corresponds to the particular gas components under analysis. Automatic operation may be discontinued at any time to permit the operator to manually select any desired predetermined accelerating voltage. Further, the system may be manually adjusted to vary the accelerating voltage over a wide range.

  1. MASS SPECTROMETRY

    DOEpatents

    Friedman, L.

    1962-01-01

    method is described for operating a mass spectrometer to improve its resolution qualities and to extend its period of use substantially between cleanings. In this method, a small amount of a beta emitting gas such as hydrogen titride or carbon-14 methane is added to the sample being supplied to the spectrometer for investigation. The additive establishes leakage paths on the surface of the non-conducting film accumulating within the vacuum chamber of the spectrometer, thereby reducing the effect of an accumulated static charge on the electrostatic and magnetic fields established within the instrument. (AEC)

  2. Protein Identification Via Surface-Induced Dissociation in an FT-ICR Mass Spectrometer and a Patchwork Sequencing Approach

    SciTech Connect

    Fernandez, Facundo; Wysocki, Vicki H.; Futrell, Jean H.; Laskin, Julia

    2006-05-01

    Surface-induced dissociation (SID) and collision-induced dissociation (CID) are ion activation techniques based on energetic collisions with a surface or gas molecules, respectively. One noticeable difference between CID and SID is that SID does not require a collision gas for ion activation and is therefore directly compatible with the high vacuum requirement of Fourier Transform Ion Cyclotron Resonance mass spectrometers (FT-ICR MS). Eliminating the introduction of collision gas into the ICR cell for collisional activation dramatically shortens the acquisition time for MS/MS experiments, suggesting that SID could be utilized for high-throughput MS/MS studies in FT-ICR MS. We demonstrate for the first time the utility of SID combined with FT-ICR MS for protein identification. Tryptic digests of standard proteins were analyzed using a hybrid 6-Tesla FT-ICR MS with SID and CID capabilities. SID spectra of mass-selected singly and doubly charged peptides were obtained using a diamond-coated target mounted at the rear trapping plate of the ICR cell. The broad internal energy distribution deposited into the precursor ion following collision with the diamond surface allowed a variety of fragmentation channels to be accessed by SID. Composition and sequence qualifiers produced by SID of tryptic peptides were used to improve the statistical significance of database searches. Protein identification MASCOT scores obtained using SID were comparable or better than scores obtained using sustained off-resonance irradiation collision-induced dissociation (SORI-CID) –the conventional ion activation technique in FT-ICR MS.

  3. Front-End Electron Transfer Dissociation Coupled to a 21 Tesla FT-ICR Mass Spectrometer for Intact Protein Sequence Analysis

    NASA Astrophysics Data System (ADS)

    Weisbrod, Chad R.; Kaiser, Nathan K.; Syka, John E. P.; Early, Lee; Mullen, Christopher; Dunyach, Jean-Jacques; English, A. Michelle; Anderson, Lissa C.; Blakney, Greg T.; Shabanowitz, Jeffrey; Hendrickson, Christopher L.; Marshall, Alan G.; Hunt, Donald F.

    2017-09-01

    High resolution mass spectrometry is a key technology for in-depth protein characterization. High-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) enables high-level interrogation of intact proteins in the most detail to date. However, an appropriate complement of fragmentation technologies must be paired with FTMS to provide comprehensive sequence coverage, as well as characterization of sequence variants, and post-translational modifications. Here we describe the integration of front-end electron transfer dissociation (FETD) with a custom-built 21 tesla FT-ICR mass spectrometer, which yields unprecedented sequence coverage for proteins ranging from 2.8 to 29 kDa, without the need for extensive spectral averaging (e.g., 60% sequence coverage for apo-myoglobin with four averaged acquisitions). The system is equipped with a multipole storage device separate from the ETD reaction device, which allows accumulation of multiple ETD fragment ion fills. Consequently, an optimally large product ion population is accumulated prior to transfer to the ICR cell for mass analysis, which improves mass spectral signal-to-noise ratio, dynamic range, and scan rate. We find a linear relationship between protein molecular weight and minimum number of ETD reaction fills to achieve optimum sequence coverage, thereby enabling more efficient use of instrument data acquisition time. Finally, real-time scaling of the number of ETD reactions fills during method-based acquisition is shown, and the implications for LC-MS/MS top-down analysis are discussed. [Figure not available: see fulltext.

  4. Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems

    PubMed Central

    Gamble, Lara J.; Anderton, Christopher R.

    2016-01-01

    Secondary ion mass spectrometry (SIMS) is a technique capable of imaging tissues, single cells, and microbes revealing chemical species with sub-micrometer spatial resolution. The recently developed Fourier transform ion cyclotron resonance (FTICR) SIMS instrument provides high mass resolving power and mass accuracy, ToF-SIMS can generate chemical maps with an order of magnitude better lateral resolution than the FTICR-SIMS, and the NanoSIMS instrument offers sub-100 nm spatial resolution in chemical imaging. Many commercial ToF-SIMS instruments are also capable of depth profiling that allows three-dimensional reconstructions of cell and tissue structure. PMID:27660591

  5. Application of Fourier transform ion cyclotron resonance mass spectrometry to oligosaccharides.

    PubMed

    Park, Youmie; Lebrilla, Carlito B

    2005-01-01

    The application of Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) to the structural elucidation of oligosaccharides is described. This review covers the analyses of oligosaccharides in the context of the unique features of FTICR MS and the improvements in instrumentation that make it possible to study this class of compounds. It consists of work performed initially to understand the fundamental aspects of oligosaccharide ionization and unimolecular fragmentation. More recent investigation includes the application of the technique to samples of direct biological origin. Chemical and enzymatic degradation methods in conjunction with mass spectrometry (MS) and the use front-end methods with FTICR MS are also discussed. The current applications including the characterization of bacterial lipooligosaccharides and phosporylated carbohydrates are described.

  6. Instrumentation and methodology for simultaneous excitation/detection of ions in an FTICR mass spectrometer

    PubMed

    Schmidt; Fiorentino; Arkin; Laude

    2000-08-01

    A method for direct and continuous detection of ion motion during different perturbation events of the fourier transform ion cyclotron resonance (FTICR) experiment is demonstrated. The modifications necessary to convert an ordinary FTICR cell into one capable of performing simultaneous excitation/detection (SED) using a capacitive network are outlined. With these modifications, a 200-fold reduction in the detection of the coupled excitation signal is achieved. This allows the unique ability not only to observe the response to the perturbation but to observe the perturbation event itself. SED is used successfully to monitor the ion cyclotron transient during single-frequency excitation, remeasurement and exciter-excite experiments.

  7. Towards analytically useful two-dimensional Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    van Agthoven, Maria A; Delsuc, Marc-André; Bodenhausen, Geoffrey; Rolando, Christian

    2013-01-01

    Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) achieves high resolution and mass accuracy, allowing the identification of the raw chemical formulae of ions in complex samples. Using ion isolation and fragmentation (MS/MS), we can obtain more structural information, but MS/MS is time- and sample-consuming because each ion must be isolated before fragmentation. In 1987, Pfändler et al. proposed an experiment for 2D FT-ICR MS in order to fragment ions without isolating them and to visualize the fragmentations of complex samples in a single 2D mass spectrum, like 2D NMR spectroscopy. Because of limitations of electronics and computers, few studies have been conducted with this technique. The improvement of modern computers and the use of digital electronics for FT-ICR hardware now make it possible to acquire 2D mass spectra over a broad mass range. The original experiments used in-cell collision-induced dissociation, which caused a loss of resolution. Gas-free fragmentation modes such as infrared multiphoton dissociation and electron capture dissociation allow one to measure high-resolution 2D mass spectra. Consequently, there is renewed interest to develop 2D FT-ICR MS into an efficient analytical method. Improvements introduced in 2D NMR spectroscopy can also be transposed to 2D FT-ICR MS. We describe the history of 2D FT-ICR MS, introduce recent improvements, and present analytical applications to map the fragmentation of peptides. Finally, we provide a glossary which defines a few keywords for the 2D FT-ICR MS field.

  8. Petroleomics by EASI(+/-) FT-ICR MS.

    PubMed

    Corilo, Yuri E; Vaz, Boniek G; Simas, Rosineide C; Nascimento, Heliara D Lopes; Klitzke, Clécio F; Pereira, Rosana C L; Bastos, Wagner L; Santos Neto, Eugênio V; Rodgers, Ryan P; Eberlin, Marcos N

    2010-05-15

    An ambient ionization/desorption technique, namely, easy ambient sonic-spray ionization mass spectrometry (EASI), has been applied to crude oil samples. From a single droplet of the sample placed on an inert surface, EASI(+/-) is shown to promote efficient desorption and ionization of a myriad of polar components via the action of its cloud of very minute supersonic bipolar charged droplets. The gaseous [M + H](+) and [M - H](-) ions concurrently formed by EASI(+/-) were analyzed by Fourier transform mass spectrometry (FT-ICR MS), and a total of approximately 6000 acidic and basic components have been attributed. EASI(+/-) FT-ICR MS of crude oils is show to be almost as fast as ESI(+)/ESI(-) FT-ICR MS, providing similar compositional information of polar components and spectral quality comparable to that of a commercial nonochip-based robotic ESI device. EASI(+/-) requires no sample workup thus eliminating risks of contamination during sample manipulation and memory effects because of carry over in pumping ESI lines. More importantly, EASI(+/-) is a voltage-free ionization technique therefore eliminating risks of redox processes or duality of ionization mechanisms that can be observed in voltage-assisted processes. Data visualization via typical petroleomic plots confirms the similarity of the compositional information provided by EASI(+/-) compared to ESI(+)/ESI(-). The ambient EASI(+/-) FT-ICR MS method requires no voltage switching in changing the ion polarity mode, offering a workup, heating and voltage-free protocol for petroleomic studies performed at open atmosphere directly on the undisturbed crude oil sample.

  9. Fourier Transform Mass Spectrometry.

    ERIC Educational Resources Information Center

    Gross, Michael L.; Rempel, Don L.

    1984-01-01

    Discusses the nature of Fourier transform mass spectrometry and its unique combination of high mass resolution, high upper mass limit, and multichannel advantage. Examines its operation, capabilities and limitations, applications (ion storage, ion manipulation, ion chemistry), and future applications and developments. (JN)

  10. Mass Spectrometry for the Masses

    ERIC Educational Resources Information Center

    Persinger, Jared D.; Hoops, Geoffrey, C.; Samide, Michael J.

    2004-01-01

    A simple, qualitative experiment is developed for implementation, where the gas chromatography-mass spectrometry (GC-MS) plays an important role, into the laboratory curriculum of a chemistry course designed for nonscience majors. This laboratory experiment is well suited for the students as it helps them to determine the validity of their…

  11. Mass Spectrometry for the Masses

    ERIC Educational Resources Information Center

    Persinger, Jared D.; Hoops, Geoffrey, C.; Samide, Michael J.

    2004-01-01

    A simple, qualitative experiment is developed for implementation, where the gas chromatography-mass spectrometry (GC-MS) plays an important role, into the laboratory curriculum of a chemistry course designed for nonscience majors. This laboratory experiment is well suited for the students as it helps them to determine the validity of their…

  12. Forensic Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hoffmann, William D.; Jackson, Glen P.

    2015-07-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.

  13. Forensic Mass Spectrometry.

    PubMed

    Hoffmann, William D; Jackson, Glen P

    2015-01-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.

  14. Ambient ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lebedev, A. T.

    2015-07-01

    Ambient ionization mass spectrometry emerged as a new scientific discipline only about ten years ago. A considerable body of information has been reported since that time. Keeping the sensitivity, performance and informativity of classical mass spectrometry methods, the new approach made it possible to eliminate laborious sample preparation procedures and triggered the development of miniaturized instruments to work directly in the field. The review concerns the theoretical foundations and design of ambient ionization methods. Their advantages and drawbacks, as well as prospects for application in chemistry, biology, medicine, environmetal analysis, etc., are discussed. The bibliography includes 194 references.

  15. Analytical mass spectrometry

    SciTech Connect

    Not Available

    1990-01-01

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  16. Analytical mass spectrometry. Abstracts

    SciTech Connect

    Not Available

    1990-12-31

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  17. Developments in FT-ICR MS instrumentation, ionization techniques, and data interpretation methods for petroleomics.

    PubMed

    Cho, Yunju; Ahmed, Arif; Islam, Annana; Kim, Sunghwan

    2015-01-01

    Because of the increasing importance of heavy and unconventional crude oil as an energy source, there is a growing need for petroleomics: the pursuit of more complete and detailed knowledge of the chemical compositions of crude oil. Crude oil has an extremely complex nature; hence, techniques with ultra-high resolving capabilities, such as Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), are necessary. FT-ICR MS has been successfully applied to the study of heavy and unconventional crude oils such as bitumen and shale oil. However, the analysis of crude oil with FT-ICR MS is not trivial, and it has pushed analysis to the limits of instrumental and methodological capabilities. For example, high-resolution mass spectra of crude oils may contain over 100,000 peaks that require interpretation. To visualize large data sets more effectively, data processing methods such as Kendrick mass defect analysis and statistical analyses have been developed. The successful application of FT-ICR MS to the study of crude oil has been critically dependent on key developments in FT-ICR MS instrumentation and data processing methods. This review offers an introduction to the basic principles, FT-ICR MS instrumentation development, ionization techniques, and data interpretation methods for petroleomics and is intended for readers having no prior experience in this field of study. © 2014 Wiley Periodicals, Inc.

  18. Mass spectrometry with accelerators.

    PubMed

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  19. Desorption in Mass Spectrometry.

    PubMed

    Usmanov, Dilshadbek Tursunbayevich; Ninomiya, Satoshi; Chen, Lee Chuin; Saha, Subhrakanti; Mandal, Mridul Kanti; Sakai, Yuji; Takaishi, Rio; Habib, Ahsan; Hiraoka, Kenzo; Yoshimura, Kentaro; Takeda, Sen; Wada, Hiroshi; Nonami, Hiroshi

    2017-01-01

    In mass spectrometry, analytes must be released in the gas phase. There are two representative methods for the gasification of the condensed samples, i.e., ablation and desorption. While ablation is based on the explosion induced by the energy accumulated in the condensed matrix, desorption is a single molecular process taking place on the surface. In this paper, desorption methods for mass spectrometry developed in our laboratory: flash heating/rapid cooling, Leidenfrost phenomenon-assisted thermal desorption (LPTD), solid/solid friction, liquid/solid friction, electrospray droplet impact (EDI) ionization/desorption, and probe electrospray ionization (PESI), will be described. All the methods are concerned with the surface and interface phenomena. The concept of how to desorb less-volatility compounds from the surface will be discussed.

  20. Desorption in Mass Spectrometry

    PubMed Central

    Usmanov, Dilshadbek Tursunbayevich; Ninomiya, Satoshi; Chen, Lee Chuin; Saha, Subhrakanti; Mandal, Mridul Kanti; Sakai, Yuji; Takaishi, Rio; Habib, Ahsan; Hiraoka, Kenzo; Yoshimura, Kentaro; Takeda, Sen; Wada, Hiroshi; Nonami, Hiroshi

    2017-01-01

    In mass spectrometry, analytes must be released in the gas phase. There are two representative methods for the gasification of the condensed samples, i.e., ablation and desorption. While ablation is based on the explosion induced by the energy accumulated in the condensed matrix, desorption is a single molecular process taking place on the surface. In this paper, desorption methods for mass spectrometry developed in our laboratory: flash heating/rapid cooling, Leidenfrost phenomenon-assisted thermal desorption (LPTD), solid/solid friction, liquid/solid friction, electrospray droplet impact (EDI) ionization/desorption, and probe electrospray ionization (PESI), will be described. All the methods are concerned with the surface and interface phenomena. The concept of how to desorb less-volatility compounds from the surface will be discussed. PMID:28337398

  1. Biological Cluster Mass Spectrometry

    PubMed Central

    Winograd, Nicholas; Garrison, Barbara J.

    2010-01-01

    This article reviews the new physics and new applications of secondary ion mass spectrometry using cluster ion probes. These probes, particularly C60, exhibit enhanced molecular desorption with improved sensitivity owing to the unique nature of the energy-deposition process. In addition, these projectiles are capable of eroding molecular solids while retaining the molecular specificity of mass spectrometry. When the beams are microfocused to a spot on the sample, bioimaging experiments in two and three dimensions are feasible. We describe emerging theoretical models that allow the energy-deposition process to be understood on an atomic and molecular basis. Moreover, experiments on model systems are described that allow protocols for imaging on biological materials to be implemented. Finally, we present recent applications of imaging to biological tissue and single cells to illustrate the future directions of this methodology. PMID:20055679

  2. MASS SPECTROMETRY IN ENVIRONMENTAL SCIENCES

    EPA Science Inventory

    This review covers applications of mass spectrometry to the environmental sciences. From the early applications of mass spectrometry to environmental research in the 1960s and 1970s, mass spectrometry has played an important role in aiding our understanding of environmental poll...

  3. MASS SPECTROMETRY IN ENVIRONMENTAL SCIENCES

    EPA Science Inventory

    This review covers applications of mass spectrometry to the environmental sciences. From the early applications of mass spectrometry to environmental research in the 1960s and 1970s, mass spectrometry has played an important role in aiding our understanding of environmental poll...

  4. Gated Trapped Ion Mobility Spectrometry Coupled to Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

    PubMed

    Ridgeway, Mark E; Wolff, Jeremy J; Silveira, Joshua A; Lin, Cheng; Costello, Catherine E; Park, Melvin A

    2016-09-01

    Analysis of molecules by ion mobility spectrometry coupled with mass spectrometry (IMS-MS) provides chemical information on the three dimensional structure and mass of the molecules. The coupling of ion mobility to trapping mass spectrometers has historically been challenging due to the large differences in analysis time between the two devices. In this paper we present a modification of the trapped ion mobility (TIMS) analysis scheme termed "Gated TIMS" that allows efficient coupling to a Fourier Transform Ion Cyclotron Resonance (FT-ICR) analyzer. Analyses of standard compounds and the influence of source conditions on the TIMS distributions produced by ion mobility spectra of labile ubiquitin protein ions are presented. Ion mobility resolving powers up to 100 are observed. Measured collisional cross sections of ubiquitin ions are in excellent qualitative and quantitative agreement to previous measurements. Gated TIMS FT-ICR produces results comparable to those acquired using TIMS/time-of-flight MS instrument platforms as well as numerous drift tube IMS-MS studies published in the literature.

  5. Hybrid instruments for mass spectrometry/mass spectrometry

    SciTech Connect

    Glish, G.L.; McLuckey, S.A.

    1986-01-01

    In order to refine further the technique of mass spectrometry/mass spectrometry efforts are being made to combine the desirable features of sector based tandem instruments with those of triple quadrupole mass spectrometers. This has resulted in the construction of tandem mass spectrometers which incorporate both sector type analyzers and quadrupole mass filters. These so-called hybrid instruments, designed specifically for mass spectrometry/mass spectrometry applications, are appearing in a variety of geometries each with unique features. This review describes the hybrid instruments reported to data and discusses general considerations for evaluating hybrid instruments with regard to application. 100 references.

  6. Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry.

    PubMed

    Prokai, Laszlo; Stevens, Stanley M

    2016-01-16

    Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae.

  7. Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry

    PubMed Central

    Prokai, Laszlo; Stevens, Stanley M.

    2016-01-01

    Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae. PMID:26784186

  8. High-Throughput Metabolic Profiling of Soybean Leaves by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

    PubMed

    Yilmaz, Ali; Rudolph, Heather L; Hurst, Jerod J; Wood, Troy D

    2016-01-19

    As a relatively recent research field, plant metabolomics has gained increasing interest in the past few years and has been applied to answer biological questions through large-scale qualitative and quantitative analyses of the plant metabolome. The combination of sensitivity and selectivity offered by mass spectrometry (MS) for measurement of many metabolites in a single shot makes it an indispensable platform in metabolomics. In this regard, Fourier-transform ion cyclotron resonance (FTICR) has the unique advantage of delivering high mass resolving power and mass accuracy simultaneously, making it ideal for the study of complex mixtures such as plant extracts. Here we optimize soybean leaf extraction methods compatible with high-throughput reproducible MS-based metabolomics. In addition, matrix-assisted laser desorption ionization (MALDI) and direct LDI of soybean leaves are compared for metabolite profiling. The extraction method combined with electrospray (ESI)-FTICR is supported by the significant reduction of chlorophyll and its related metabolites as the growing season moves from midsummer to the autumn harvest day. To our knowledge for the first time, the use of ESI-FTICR MS and MALDI-FTICR MS is described in a complementary manner with the aim of metabolic profiling of plant leaves that have been collected at different time points during the growing season.

  9. "Magic" Ionization Mass Spectrometry.

    PubMed

    Trimpin, Sarah

    2016-01-01

    The systematic study of the temperature and pressure dependence of matrix-assisted ionization (MAI) led us to the discovery of the seemingly impossible, initially explained by some reviewers as either sleight of hand or the misinterpretation by an overzealous young scientist of results reported many years before and having little utility. The “magic” that we were attempting to report was that with matrix assistance, molecules, at least as large as bovine serum albumin (66 kDa), are lifted into the gas phase as multiply charged ions simply by exposure of the matrix:analyte sample to the vacuum of a mass spectrometer. Applied heat, a laser, or voltages are not necessary to achieve charge states and ion abundances only previously observed with electrospray ionization (ESI). The fundamentals of how solid phase volatile or nonvolatile compounds are converted to gas-phase ions without added energy currently involves speculation providing a great opportunity to rethink mechanistic understanding of ionization processes used in mass spectrometry. Improved understanding of the mechanism(s) of these processes and their connection to ESI and matrix-assisted laser desorption/ionization may provide opportunities to further develop new ionization strategies for traditional and yet unforeseen applications of mass spectrometry. This Critical Insights article covers developments leading to the discovery of a seemingly magic ionization process that is simple to use, fast, sensitive, robust, and can be directly applied to surface characterization using portable or high performance mass spectrometers.

  10. "Magic" Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Trimpin, Sarah

    2016-01-01

    The systematic study of the temperature and pressure dependence of matrix-assisted ionization (MAI) led us to the discovery of the seemingly impossible, initially explained by some reviewers as either sleight of hand or the misinterpretation by an overzealous young scientist of results reported many years before and having little utility. The "magic" that we were attempting to report was that with matrix assistance, molecules, at least as large as bovine serum albumin (66 kDa), are lifted into the gas phase as multiply charged ions simply by exposure of the matrix:analyte sample to the vacuum of a mass spectrometer. Applied heat, a laser, or voltages are not necessary to achieve charge states and ion abundances only previously observed with electrospray ionization (ESI). The fundamentals of how solid phase volatile or nonvolatile compounds are converted to gas-phase ions without added energy currently involves speculation providing a great opportunity to rethink mechanistic understanding of ionization processes used in mass spectrometry. Improved understanding of the mechanism(s) of these processes and their connection to ESI and matrix-assisted laser desorption/ionization may provide opportunities to further develop new ionization strategies for traditional and yet unforeseen applications of mass spectrometry. This Critical Insights article covers developments leading to the discovery of a seemingly magic ionization process that is simple to use, fast, sensitive, robust, and can be directly applied to surface characterization using portable or high performance mass spectrometers.

  11. Characterization of petroleum products by laser-induced acoustic desorption in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer

    NASA Astrophysics Data System (ADS)

    Pinkston, David S.

    Many petroleum products, in particular large nonpolar saturated hydrocarbons, have proven difficult to analyze via mass spectrometry due to their low volatility, lack of basic or acidic groups needed for most ionization methods, and low activation energies for fragmentation after ionization. The above limitation has been addressed by using laser-induced acoustic desorption (LIAD) to evaporate nonvolatile and thermally labile petroleum components for analysis in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The gaseous neutral analytes were ionized by electron impact. Model compounds were studied first to test the viability of this method. After that, different types of asphaltenes were characterized successfully. For example, the molecular weight distribution of a North American asphaltene was determined. A comparison between asphaltene samples obtained from different geographical locations showed distinct molecular weight characteristics, possibly allowing for the determination of an unknown asphaltene sample's geographic origin. Asphaltenes were also characterized via electrospray ionization (ESI) in a linear quadrupole ion trap (LQIT). The observed molecular weight distribution had an extended tail past 2000 Da. Collision-activated dissociation (CAD) experiments on isolated ions revealed that water aggregation was present in this analysis. The observed molecular weight distribution of asphaltenes reduced dramatically when water was eliminated from the system. The usefulness of a new chemical ionization reagent, ClMn(H2O) +, is also discussed. This reagent has been shown to ionize hydrocarbons without fragmentation to yield [ClMnR]+, where R is the hydrocarbon, thus providing molecular weight information. CAD of the [ClMnR]+ ions is demonstrated to allow the differentiation of isomeric hydrocarbons. Finally, the LIAD/ClMn(H2O)+ mass spectrometric method was applied to the successful analysis of various petroleum fractions and asphaltene

  12. Single event mass spectrometry

    DOEpatents

    Conzemius, Robert J.

    1990-01-16

    A means and method for single event time of flight mass spectrometry for analysis of specimen materials. The method of the invention includes pulsing an ion source imposing at least one pulsed ion onto the specimen to produce a corresponding emission of at least one electrically charged particle. The emitted particle is then dissociated into a charged ion component and an uncharged neutral component. The ion and neutral components are then detected. The time of flight of the components are recorded and can be used to analyze the predecessor of the components, and therefore the specimen material. When more than one ion particle is emitted from the specimen per single ion impact, the single event time of flight mass spectrometer described here furnis This invention was made with Government support under Contract No. W-7405-ENG82 awarded by the Department of Energy. The Government has certain rights in the invention.

  13. Petroleum crude oil characterization by IMS-MS and FTICR MS.

    PubMed

    Fernandez-Lima, Francisco A; Becker, Christopher; McKenna, Amy M; Rodgers, Ryan P; Marshall, Alan G; Russell, David H

    2009-12-15

    Here, complementary ion mobility/mass spectrometry (IM/MS) and ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS analyses of light, medium, and heavy petroleum crude oils yielded distributions of the heteroatom-containing hydrocarbons, as well as multiple conformational classes. The IM/MS technique provides unique fingerprints for fast identification of signature conformational/compositional patterns, whereas FTICR MS analysis provides comprehensive heteroatom class distributions. IM/MS and FTICR MS results reveal an increase in compositional complexity in proceeding from light to medium to heavy crude oils. Inspection of the mobility results shows a high structural diversity for the C(n)H(h)XY (XY = N(1), S(1), N(1), O(1), NS, SO(1-2), NO(1-2), etc.) series, as well as a shift from planar to more compact three-dimensional structures with increasing mass.

  14. Isotope dilution mass spectrometry

    NASA Astrophysics Data System (ADS)

    Heumann, Klaus G.

    1992-09-01

    In the past isotope dilution mass spectrometry (IDMS) has usually been applied using the formation of positive thermal ions of metals. Especially in calibrating other analytical methods and for the certification of standard reference materials this type of IDMS became a routine method. Today, the progress in this field lies in the determination of ultra trace amounts of elements, e.g. of heavy metals in Antarctic ice and in aerosols in remote areas down to the sub-pg g-1 and sub-pg m-3 levels respectively, in the analysis of uranium and thorium at concentrations of a few pg g-1 in sputter targets for the production of micro- electronic devices or in the determination of sub-picogram amounts of230Th in corals for geochemical age determinations and of226Ra in rock samples. During the last few years negative thermal ionization IDMS has become a frequently used method. The determination of very small amounts of selenium and technetium as well as of other transition metals such as vanadium, chromium, molybdenum and tungsten are important examples in this field. Also the measurement of silicon in connection with a re-determination of Avogadro's number and osmium analyses for geological age determinations by the Re/Os method are of special interest. Inductively-coupled plasma mass spectrometry is increasingly being used for multi-element analyses by the isotope dilution technique. Determinations of heavy metals in samples of marine origin are representative examples for this type of multi-element analysis by IDMS. Gas chromatography-mass spectrometry systems have also been successfully applied after chelation of metals (for example Pt determination in clinical samples) or for the determination of volatile element species in the environment, e.g. dimethyl sulfide. However, IDMS--specially at low concentration levels in the environment--seems likely to be one of the most powerful analytical methods for speciation in the future. This has been shown, up to now, for species of

  15. Chemical Diversity and Complexity of Scotch Whisky as Revealed by High-Resolution Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kew, Will; Goodall, Ian; Clarke, David; Uhrín, Dušan

    2017-01-01

    Scotch Whisky is an important product, both culturally and economically. Chemically, Scotch Whisky is a complex mixture, which comprises thousands of compounds, the nature of which are largely unknown. Here, we present a thorough overview of the chemistry of Scotch Whisky as observed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Eighty-five whiskies, representing the majority of Scotch Whisky produced and sold, were analyzed by untargeted high-resolution mass spectrometry. Thousands of chemical formulae were assigned for each sample based on parts-per-billion mass accuracy of FT-ICR MS spectra. For the first time, isotopic fine structure analysis was used to confirm the assignment of high molecular weight CHOS species in Scotch Whisky. The assigned spectra were compared using a number of visualization techniques, including van Krevelen diagrams, double bond equivalence (DBE) plots, as well as heteroatomic compound class distributions. Additionally, multivariate analysis, including PCA and OPLS-DA, was used to interpret the data, with key compounds identified for discriminating between types of whisky (blend or malt) or maturation wood type. FT-ICR MS analysis of Scotch Whisky was shown to be of significant potential in further understanding of the complexity of mature spirit drinks and as a tool for investigating the chemistry of the maturation processes.

  16. International Mass Spectrometry Society (IMSS).

    PubMed

    Cooks, R G; Gelpi, E; Nibbering, N M

    2001-02-01

    This paper gives a brief description of the recently formalized International Mass Spectrometry Society (IMSS). It is presented here in order to increase awareness of the opportunities for collaboration in mass spectrometry in an international context. It also describes the recent 15th International Mass Spectrometry Conference, held August/September 2000, in Barcelona. Each of the authors is associated with the IMSS. The 15th Conference, which covers all of mass spectrometry on a triennial basis, was chaired by Professor Emilio Gelpi of the Instituto de Investigaciones Biomedicas, Barcelona. The outgoing and founding President of the IMSS is Professor Graham Cooks, Purdue University, and the incoming President is Professor Nico Nibbering, University of Amsterdam. Similar material has been provided to the Editors of other journals that cover mass spectrometry.

  17. Vacuum compatible sample positioning device for matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging

    PubMed Central

    Aizikov, Konstantin; Smith, Donald F.; Chargin, David A.; Ivanov, Sergei; Lin, Tzu-Yung; Heeren, Ron M. A.; O’Connor, Peter B.

    2011-01-01

    The high mass accuracy and resolving power of Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS) make them ideal mass detectors for mass spectrometry imaging (MSI), promising to provide unmatched molecular resolution capabilities. The intrinsic low tolerance of FT-ICR MS to RF interference, however, along with typically vertical positioning of the sample, and MSI acquisition speed requirements present numerous engineering challenges in creating robotics capable of achieving the spatial resolution to match. This work discusses a two-dimensional positioning stage designed to address these issues. The stage is capable of operating in ∼1 × 10–8 mbar vacuum. The range of motion is set to 100 mm × 100 mm to accommodate large samples, while the positioning accuracy is demonstrated to be less than 0.4 micron in both directions under vertical load over the entire range. This device was integrated into three different matrix assisted laser desorption/ionization (MALDI) FT-ICR instruments and showed no detectable RF noise. The “oversampling” MALDI-MSI experiments, under which the sample is completely ablated at each position, followed by the target movement of the distance smaller than the laser beam, conducted on the custom-built 7T FT-ICR MS demonstrate the stability and positional accuracy of the stage robotics which delivers high spatial resolution mass spectral images at a fraction of the laser spot diameter. PMID:21639522

  18. Vacuum compatible sample positioning device for matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging

    SciTech Connect

    Aizikov, Konstantin; Lin, Tzu-Yung; Smith, Donald F.; Heeren, Ron M. A.; Chargin, David A.; Ivanov, Sergei; O'Connor, Peter B.

    2011-05-15

    The high mass accuracy and resolving power of Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS) make them ideal mass detectors for mass spectrometry imaging (MSI), promising to provide unmatched molecular resolution capabilities. The intrinsic low tolerance of FT-ICR MS to RF interference, however, along with typically vertical positioning of the sample, and MSI acquisition speed requirements present numerous engineering challenges in creating robotics capable of achieving the spatial resolution to match. This work discusses a two-dimensional positioning stage designed to address these issues. The stage is capable of operating in {approx}1 x 10{sup -8} mbar vacuum. The range of motion is set to 100 mm x 100 mm to accommodate large samples, while the positioning accuracy is demonstrated to be less than 0.4 micron in both directions under vertical load over the entire range. This device was integrated into three different matrix assisted laser desorption/ionization (MALDI) FT-ICR instruments and showed no detectable RF noise. The ''oversampling'' MALDI-MSI experiments, under which the sample is completely ablated at each position, followed by the target movement of the distance smaller than the laser beam, conducted on the custom-built 7T FT-ICR MS demonstrate the stability and positional accuracy of the stage robotics which delivers high spatial resolution mass spectral images at a fraction of the laser spot diameter.

  19. Repeatability and reproducibility of product ion abundances in electron capture dissociation mass spectrometry of peptides.

    PubMed

    Ben Hamidane, Hisham; Vorobyev, Aleksey; Tsybin, Yury O

    2011-01-01

    Site-specific reproducibility and repeatability of electron capture dissociation (ECD) in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) are of fundamental importance for product ion abundance (PIA)-based peptide and protein structure analysis. However, despite the growing interest in ECD PIA-based applications, these parameters have not yet been investigated in a consistent manner. Here, we first provide a detailed description of the experimental parameters for ECD-based tandem mass spectrometry performed on a hybrid linear ion trap (LTQ) FT-ICR MS. In the following, we describe the evaluation and comparison of ECD and infrared multiphoton dissociation (IRMPD) PIA methodologies upon variation of a number of experimental parameters, for example, cathode potential (electron energy), laser power, electron and photon irradiation periods and pre- irradiation delays, as well as precursor ion number. Ranges of experimental parameters that yielded an average PIA variation below 5% and 15% were determined for ECD and IRMPD, respectively. We report cleavage site-dependent ECD PIA variation below 20% and correlation coefficients between fragmentation patterns superior to 0.95 for experiments performed on three FT-ICR MS instruments. Overall, the encouraging results obtained for ECD PIA reproducibility and repeatability support the use of ECD PIA as a complementary source of information to m/z data in radical-induced dissociation applied for peptide and protein structure analysis.

  20. Accelerator mass spectrometry.

    PubMed

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples. Copyright 2008 Wiley Periodicals, Inc.

  1. Mass spectrometry in environmental toxicology.

    PubMed

    Groh, Ksenia J; Suter, Marc J-F

    2014-01-01

    In environmental toxicology, mass spectrometry can be applied to evaluate both exposure to chemicals as well as their effects in organisms. Various ultra-trace techniques are employed today to measure pollutants in different environmental compartments. Increasingly, effect-directed analysis is being applied to focus chemical monitoring on sites of ecotoxicological concern. Mass spectrometry is also very instrumental for studying the interactions of chemicals with organisms on the molecular and cellular level, providing new insights into mechanisms of toxicity. In the future, diverse mass spectrometry-based techniques are expected to become even more widely used in this field, contributing to the refinement of currently used environmental risk assessment strategies.

  2. Ion mobility-mass spectrometry.

    PubMed

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

    2008-01-01

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

  3. Review: mass spectrometry in Russia.

    PubMed

    Zaikin, Vladimir G; Sysoev, Alexander A

    2013-01-01

    The present review covers the main research in the area of mass spectrometry from the 1990s which was about the same time as the Russian Federation emerged from the collapse of the Soviet Union (USSR). It consists of two main parts-application of mass spectrometry to chemistry and related fields and creation and development of mass spectrometric technique. Both traditional and comparatively new mass spectrometric methods were used to solve various problems in organic chemistry (reactivity of gas-phase ions, structure elucidation and problems of identification, quantitative and trace analysis, differentiation of stereoisomers, derivatization approaches etc.), biochemistry (proteomics and peptidomics, lipidomics), medical chemistry (mainly the search of biomarkers, pharmacology, doping control), environmental, petrochemistry, polymer chemistry, inorganic and physical chemistry, determination of natural isotope ratio etc. Although a lot of talented mass spectrometrists left Russia and moved abroad after the collapse of the Soviet Union, the vitality of the mass spectral community proved to be rather high, which allowed the continuation of new developments in the field of mass spectrometric instrumentation. They are devoted to improvements in traditional magnetic sector mass spectrometers and the development of new ion source types, to analysis and modification of quadrupole, time-of-flight (ToF) and ion cyclotron resonance (ICR) analyzers. The most important achievements are due to the creation of multi-reflecting ToF mass analyzers. Special attention was paid to the construction of compact mass spectrometers, particularly for space exploration, of combined instruments, such as ion mobility spectrometer/mass spectrometer and accelerating mass spectrometers. The comparatively young Russian Mass Spectrometry Society is working hard to consolidate the mass spectrometrists from Russia and foreign countries, to train young professionals on new appliances and regularly

  4. Towards high-throughput metabolomics using ultrahigh-field Fourier transform ion cyclotron resonance mass spectrometry

    PubMed Central

    Han, Jun; Danell, Ryan M.; Patel, Jayanti R.; Gumerov, Dmitry R.; Scarlett, Cameron O.; Speir, J. Paul; Parker, Carol E.; Rusyn, Ivan; Zeisel, Steven; Borchers, Christoph H.

    2008-01-01

    With unmatched mass resolution, mass accuracy, and exceptional detection sensitivity, Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR-MS) has the potential to be a powerful new technique for high-throughput metabolomic analysis. In this study, we examine the properties of an ultrahigh-field 12-Tesla (12T) FTICR-MS for the identification and absolute quantitation of human plasma metabolites, and for the untargeted metabolic fingerprinting of inbred-strain mouse serum by direct infusion (DI). Using internal mass calibration (mass error ≤1 ppm), we determined the rational elemental compositions (incorporating unlimited C, H, N and O, and a maximum of two S, three P, two Na, and one K per formula) of approximately 250 out of 570 metabolite features detected in a 3-min infusion analysis of aqueous extract of human plasma, and were able to identify more than 100 metabolites. Using isotopically-labeled internal standards, we were able to obtain excellent calibration curves for the absolute quantitation of choline with sub-pmol sensitivity, using 500 times less sample than previous LC/MS analyses. Under optimized serum dilution conditions, chemical compounds spiked into mouse serum as metabolite mimics showed a linear response over a 600-fold concentration range. DI/FTICR-MS analysis of serum from 26 mice from 2 inbred strains, with and without acute trichloroethylene (TCE) treatment, gave a relative standard deviation (RSD) of 4.5%. Finally, we extended this method to the metabolomic fingerprinting of serum samples from 49 mice from 5 inbred strains involved in an acute alcohol toxicity study, using both positive and negative electrospray ionization (ESI). Using these samples, we demonstrated the utility of this method for high-throughput metabolomics, with more than 400 metabolites profiled in only 24 h. Our experiments demonstrate that DI/FTICR-MS is well-suited for high-throughput metabolomic analysis. PMID:19081807

  5. Linear electric field mass spectrometry

    DOEpatents

    McComas, David J.; Nordholt, Jane E.

    1992-01-01

    A mass spectrometer and methods for mass spectrometry. The apparatus is compact and of low weight and has a low power requirement, making it suitable for use on a space satellite and as a portable detector for the presence of substances. High mass resolution measurements are made by timing ions moving through a gridless cylindrically symmetric linear electric field.

  6. Linear electric field mass spectrometry

    DOEpatents

    McComas, D.J.; Nordholt, J.E.

    1992-12-01

    A mass spectrometer and methods for mass spectrometry are described. The apparatus is compact and of low weight and has a low power requirement, making it suitable for use on a space satellite and as a portable detector for the presence of substances. High mass resolution measurements are made by timing ions moving through a gridless cylindrically symmetric linear electric field. 8 figs.

  7. Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging.

    PubMed

    Kiss, András; Smith, Donald F; Jungmann, Julia H; Heeren, Ron M A

    2013-12-30

    Microscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high-speed imaging of biomolecules from complex surfaces. Technological developments such as new position-sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra-high spatial resolution, sample throughput and sensitivity. In this work, a C60 primary source was combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high-voltage post-acceleration capabilities. The system's mass spectral and imaging performance is tested with various benchmark samples and thin tissue sections. The high secondary ion yield (with respect to 'traditional' monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal-to-noise ratio are improved compared with other microscope mode imaging systems, all at high spatial resolution. We have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Application of printed circuit board technology to FT-ICR MS analyzer cell construction and prototyping.

    PubMed

    Leach, Franklin E; Norheim, Randolph; Anderson, Gordon; Pasa-Tolic, Ljiljana

    2014-12-01

    Although Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) remains the mass spectrometry platform that provides the highest levels of performance for mass accuracy and resolving power, there is room for improvement in analyzer cell design as the ideal quadrupolar trapping potential has yet to be generated for a broadband MS experiment. To this end, analyzer cell designs have improved since the field's inception, yet few research groups participate in this area because of the high cost of instrumentation efforts. As a step towards reducing this barrier to participation and allowing for more designs to be physically tested, we introduce a method of FT-ICR analyzer cell prototyping utilizing printed circuit boards at modest vacuum conditions. This method allows for inexpensive devices to be readily fabricated and tested over short intervals and should open the field to laboratories lacking or unable to access high performance machine shop facilities because of the required financial investment.

  9. Mass spectrometry. [in organic chemistry

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

    1978-01-01

    A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

  10. Mass spectrometry. [in organic chemistry

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

    1978-01-01

    A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

  11. Instrumentation for mass spectrometry: 1997

    SciTech Connect

    McLuckey, S.A.

    1997-08-01

    All mass spectrometry experiments involve the manipulation of material, an interface with the mass spectrometer, ionization, ion manipulation/analysis, detection and data collection/reduction. Each of these elements involve instrumentation. The wide range of species now amenable to mass spectrometry and the diverse areas of physical science in which it plays a role have led to a seemingly unlimited array of instrumental combinations. However, only a limited number of mass analyzers, and their combinations, dominate. The dominant analyzers include time-of-flight, Fourier transform ion cyclotron resonance, the Paul trap, the mass filter, and the sector mass spectrometer. Why there are so few (or so many, depending upon one`s point of view) can be understood upon consideration of a set of mass analyzer figures of merit. These include mass resolution, mass accuracy, mass range, dynamic range, abundance sensitivity, precision, efficiency, speed, MS{sup n} capability, compatibility with the ionizer, cost, and size. The most appropriate form of mass spectrometry is determined by the priorities of the particular measurement placed on the various mass analyzer characteristics and the relative strengths of the analyzers in meeting the requirements. Each of the analyzer types has a unique set of figures of merit that makes it optimally suited for particular applications. This paper discusses these figures of merit, provides data illustrating recent developments for each analyzer type, and gives the figures of merit of each type of analyzer as they stand in 1997. 101 refs., 24 figs.

  12. Mass spectrometry guided structural biology.

    PubMed

    Liko, Idlir; Allison, Timothy M; Hopper, Jonathan Ts; Robinson, Carol V

    2016-10-01

    With the convergence of breakthroughs in structural biology, specifically breaking the resolution barriers in cryo-electron microscopy and with continuing developments in crystallography, novel interfaces with other biophysical methods are emerging. Here we consider how mass spectrometry can inform these techniques by providing unambiguous definition of subunit stoichiometry. Moreover recent developments that increase mass spectral resolution enable molecular details to be ascribed to unassigned density within high-resolution maps of membrane and soluble protein complexes. Importantly we also show how developments in mass spectrometry can define optimal solution conditions to guide downstream structure determination, particularly of challenging biomolecules that refuse to crystallise.

  13. Imaging mass spectrometry in microbiology

    PubMed Central

    Watrous, Jeramie D.; Dorrestein, Pieter C.

    2013-01-01

    Mass spectrometry tools which allow for the 2-D visualization of the distribution of trace metals, metabolites, surface lipids, peptides and proteins directly from biological samples without the need for chemical tagging or antibodies are becoming increasingly useful for microbiology applications. These tools, comprised of different imaging mass spectrometry techniques, are ushering in an exciting new era of discovery by allowing for the generation of chemical hypotheses based on of the spatial mapping of atoms and molecules that can correlate to or transcend observed phenotypes. In this review, we explore the wide range of imaging mass spectrometry techniques available to microbiologists and describe their unique applications to microbiology with respect to the types of microbiology samples to be investigated. PMID:21822293

  14. Mass spectrometry for malaria diagnosis.

    PubMed

    Demirev, Plamen A

    2004-11-01

    A physical method currently being developed for malaria parasite detection and diagnosis in blood is reviewed in this article. The method - direct laser desorption mass spectrometry - is based on the detection of heme (iron protoporphyrin) as a unique qualitative and quantitative molecular biomarker for malaria. In infected erythrocytes, the parasite sequesters heme in a molecular crystal (hemozoin) - a volume of highly concentrated and purified biomarker molecules. Laser desorption mass spectrometry detects only heme from hemozoin in parasite-infected blood, and not heme that is bound to hemoglobin or other proteins in uninfected blood samples. The method requires only a drop of blood with minimal sample preparation. Laser desorption mass spectrometry may become a rapid and high-throughput tool for specific and sensitive pan-malaria detection at levels below 10 parasites/mul of blood.

  15. Symposium on accelerator mass spectrometry

    SciTech Connect

    1981-01-01

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base.

  16. Mass spectrometry for biomarker development

    SciTech Connect

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  17. Central ring electrode for trapping and excitation/detection in Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Ostrander, C M; Arkin, C R; Laude, D

    2001-01-01

    The use of a central trapping ring electrode for Fourier transform ion cyclotron resonance (FTICR) mass spectrometry is demonstrated. Ions are trapped with an oppositely biased static potential superimposed on both the excite and detect electrodes and maintained throughout the experiment, including the application of a dipolar rf excite waveform and the image current ion detection event. The use of a central trapping electrode for FTICR coupled with an open cell design retains the advantages of high ion throughput and gas conductance, while simplifying the electrode geometry and reducing the overall dimensions of the cell. This allows the central trapping electrode to be of utility in volume-limited vacuum chambers including FTICR instrument miniaturization. Presented here are the preliminary experimental results using the central trapping electrode as an FTICR cell in which the excitation and detection electrodes also create a trapping depression to constrain the z-axis motion of the ions. The cell overcomes the principle limitation of an earlier single trapping electrode design by producing a 91% effective potential well depth compared to 19% for the single trapping electrode and 33% for standard open cells. This allows the central trapping electrode configuration to achieve an order of magnitude improvement in ion capacity compared to more conventional open cell designs.

  18. 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.

  19. High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids

    PubMed Central

    Anderson, David M. G.; Ablonczy, Zsolt; Koutalos, Yiannis; Spraggins, Jeffrey; Crouch, Rosalie K.; Caprioli, Richard M.; Schey, Kevin L.

    2014-01-01

    Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism’s surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 μm retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina including age related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4−/− knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers. PMID:24819461

  20. High resolution MALDI imaging mass spectrometry of retinal tissue lipids.

    PubMed

    Anderson, David M G; Ablonczy, Zsolt; Koutalos, Yiannis; Spraggins, Jeffrey; Crouch, Rosalie K; Caprioli, Richard M; Schey, Kevin L

    2014-08-01

    Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism's surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 μm retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4(-/-) knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers.

  1. High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids

    NASA Astrophysics Data System (ADS)

    Anderson, David M. G.; Ablonczy, Zsolt; Koutalos, Yiannis; Spraggins, Jeffrey; Crouch, Rosalie K.; Caprioli, Richard M.; Schey, Kevin L.

    2014-08-01

    Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism's surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 μm retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4 -/- knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers.

  2. Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Kelly, Ryan T.; Marginean, Ioan; Tang, Keqi

    2014-06-13

    Electrospray Ionization (ESI) is a process whereby gas phase ions are created from molecules in solution. As a solution exits a narrow tube in the presence of a strong electric field, an aerosol of charged droplets are is formed that produces gas phase ions as they it desolvates. ESI-MS comprises the creation of ions by ESI and the determination of their mass to charge ratio (m/z) by MS.

  3. "EMERGING" POLLUTANTS, MASS SPECTROMETRY, AND ...

    EPA Pesticide Factsheets

    A foundation for Environmental Science - Mass Spectrometry: Historically fundamental to amassing our understanding of environmental processes and chemical pollution is the realm of mass spectrometry - the mainstay of analytical chemistry - the workhorse that supplies much of the definitive data that environmental scientists rely upon for identifying the molecular compositions (and ultimately the structures) of chemicals. This is not to ignore the complementary, critical roles played by the adjunct practices of sample enrichment (via any of various means of selective extraction) and analyte separation (via the myriad forms of chromatography and electrophoresis).While the power of mass spectrometry has long been highly visible to the practicing environmental chemist, it borders on continued obscurity to the lay public and most non-chemists. Even though mass spectrometry has played a long, historic (and largely invisible) role in establishing or undergirdidng our existing knowledge about environmental processes and pollution, what recognition it does enjoy is usually relegated to that of a tool. It is ususally the relevance of ssignificance of the knowledge acquired from the application of the tool that has ultimate meaning to the public and science at large - not how the knowledge was acquired. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in

  4. Perceiving the chemical language of Gram-negative bacteria: listening by high-resolution mass spectrometry.

    PubMed

    Cataldi, Tommaso R I; Bianco, Giuliana; Fonseca, Juliano; Schmitt-Kopplin, Philippe

    2013-01-01

    Gram-negative bacteria use N-acylhomoserine lactones (AHLs) as their command language to coordinate population behavior during invasion and colonization of higher organisms. Although many different bacterial bioreporters are available for AHLs monitoring, in which a phenotypic response, e.g. bioluminescence, violacin production, and β-galactosidase activity, is exploited, mass spectrometry (MS) is the most versatile detector for rapid analysis of AHLs in complex microbial samples, with or without prior separation steps. In this paper we critically review recent advances in the application of high-resolution MS to analysis of the quorum sensing (QS) signaling molecules used by Gram-negative bacteria, with much emphasis on AHLs. A critical review of the use of bioreporters in the study of AHLs is followed by a short methodological survey of the capabilities of high-resolution mass spectrometry (HRMS), including Fourier-transform ion cyclotron resonance (FTICR) MS and quadrupole time-of-flight (qTOF) MS. Use of infusion electrospray ultrahigh-resolution FTICR MS (12 Tesla) enables accurate mass measurements for determination of the elemental formulas of AHLs in Acidovorax sp. N35 and Burkholderia ubonensis AB030584. Results obtained by coupling liquid chromatography with a hybrid quadrupole linear ion trap-FTICR mass spectrometer (LC-LTQ-FTICRMS, 7-T) for characterization of acylated homoserine lactones in the human pathogen Pseudomonas aeruginosa are presented. UPLC-ESI-qTOF MS has also proved to be suitable for identification of 3O-C(10)HSL in Pseudomonas putida IsoF cell culture supernatant. Aspects of sample preparation and the avoidance of analytical pitfalls are also emphasized.

  5. Developments in FTICR-MS and Its Potential for Body Fluid Signatures

    PubMed Central

    Nicolardi, Simone; Bogdanov, Bogdan; Deelder, André M.; Palmblad, Magnus; van der Burgt, Yuri E. M.

    2015-01-01

    Fourier transform mass spectrometry (FTMS) is the method of choice for measurements that require ultra-high resolution. The establishment of Fourier transform ion cyclotron resonance (FTICR) MS, the availability of biomolecular ionization techniques and the introduction of the Orbitrap™ mass spectrometer have widened the number of FTMS-applications enormously. One recent example involves clinical proteomics using FTICR-MS to discover and validate protein biomarker signatures in body fluids such as serum or plasma. These biological samples are highly complex in terms of the type and number of components, their concentration range, and the structural identity of each species, and thus require extensive sample cleanup and chromatographic separation procedures. Clearly, such an elaborate and multi-step sample preparation process hampers high-throughput analysis of large clinical cohorts. A final MS read-out at ultra-high resolution enables the analysis of a more complex sample and can thus simplify upfront fractionations. To this end, FTICR-MS offers superior ultra-high resolving power with accurate and precise mass-to-charge ratio (m/z) measurement of a high number of peptides and small proteins (up to 20 kDa) at isotopic resolution over a wide mass range, and furthermore includes a wide variety of fragmentation strategies to characterize protein sequence and structure, including post-translational modifications (PTMs). In our laboratory, we have successfully applied FTICR “next-generation” peptide profiles with the purpose of cancer disease classifications. Here we will review a number of developments and innovations in FTICR-MS that have resulted in robust and routine procedures aiming for ultra-high resolution signatures of clinical samples, exemplified with state-of-the-art examples for serum and saliva. PMID:26580595

  6. Use of high resolution mass spectrometry for analysis of polymeric excipients in drug delivery formulations.

    PubMed

    Perez Hurtado, Pilar; Lam, Pui Yiu; Kilgour, David; Bristow, Anthony; McBride, Eileen; O'Connor, Peter B

    2012-10-16

    Two polymeric excipients, typically used in enabling drug delivery approaches, are Gelucire 44/14 (a product of Gattefosse s.a, St Priest, France) and polysorbate 80; these are known to improve solubility of poorly water-soluble drugs and, hence, increase their effective bioavailability. In addition to the use of Gelucire 44/14 and polysorbate 80 as excipients in drugs, they are also widely used as cosmetic and food additives. In general, complex structures and compositions of drug excipients impact performance of the formulation in vivo and consequently affect drug absorption. Therefore, a comparison between excipients from different suppliers and batches to batch would provide an indication of the impact on drug product performance and also the study of the effectiveness of the system and any problems associated with the formulation. In this study, high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) is used to compare two different batches of Gelucire 44/14 and polysorbate 80. With the high resolving power of FTICR MS, it was possible to differentiate between batches of excipients from differences in the identified components. The improved resolution offered by FTICR MS allowed assignment of four polymeric series differences in the two batches of polysorbate 80 and the presence of one compound and three polymeric series differences in the two batches of Gelucire 44/14. The increase in the number of components assigned in the excipients batch using FTICR-MS, compared to the numbers previously assigned by lower resolution TOF MS, underlines the importance of high resolution techniques in analysis of highly complex mixtures.

  7. Accelerator mass spectrometry

    SciTech Connect

    Vogel, J.S.; Turteltaub, K.W.; Finkel, R.; Nelson, D.E.

    1995-06-01

    Accelerator mass spectroscopy (AMS) can be used for efficient detection of long-lived isotopes at part-per-quadrillion sensitivities with good precision. In this article we present an overview of AMS and its recent use in archaeology, geochemistry and biomolecular tracing. All AMS systems use cesium sputter ion sources to produce negative ions from a small button of a solid sample containing the element of interest, such as graphite, metal halide, or metal oxide, often mixed with a metal powder as binder and thermal conductor. Experience shows that both natural and biomedical samples are compatible in a single AMS system, but few other AMS sites make routine {sup 14}C measurements for both dating and tracing. AMS is, in one sense, just `a very sensitive decay counter`, but if AMS sensitivity is creatively coupled to analytical chemistry of certain isotopes, whole new areas of geosciences, archaeology, and life sciences can be explored. 29 refs., 2 figs., 1 tab.

  8. MASS SPECTROMETRY-BASED METABOLOMICS

    PubMed Central

    Dettmer, Katja; Aronov, Pavel A.; Hammock, Bruce D.

    2007-01-01

    This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very diverse physico-chemical properties and occur at different abundance levels. Consequently, comprehensive metabolomics investigations are primarily a challenge for analytical chemistry and specifically mass spectrometry has vast potential as a tool for this type of investigation. Metabolomics require special approaches for sample preparation, separation, and mass spectrometric analysis. Current examples of those approaches are described in this review. It primarily focuses on metabolic fingerprinting, a technique that analyzes all detectable analytes in a given sample with subsequent classification of samples and identification of differentially expressed metabolites, which define the sample classes. To perform this complex task, data analysis tools, metabolite libraries, and databases are required. Therefore, recent advances in metabolomics bioinformatics are also discussed. PMID:16921475

  9. Direct mass spectrometric analysis of intact proteins of the yeast large ribosomal subunit using capillary LC/FTICR

    PubMed Central

    Lee, Sang-Won; Berger, Scott J.; Martinović, Suzana; Paša-Tolić, Ljiljana; Anderson, Gordon A.; Shen, Yufeng; Zhao, Rui; Smith, Richard D.

    2002-01-01

    Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry coupled with capillary reverse-phase liquid chromatography was used to characterize intact proteins from the large subunit of the yeast ribosome. High mass measurement accuracy, achieved by “mass locking” with an internal standard from a dual electrospray ionization source, allowed identification of ribosomal proteins. Analyses of the intact proteins revealed information on cotranslational and posttranslational modifications of the ribosomal proteins that included loss of the initiating methionine, acetylation, methylation, and proteolytic maturation. High-resolution separations permitted differentiation of protein isoforms having high structural similarity as well as proteins from their modified forms, facilitating unequivocal assignments. The study identified 42 of the 43 core large ribosomal subunit proteins and 58 (of 64 possible) core large subunit protein isoforms having unique masses in a single analysis. These results demonstrate the basis for the high-throughput analyses of complex mixtures of intact proteins, which we believe will be an important complement to other approaches for defining protein modifications and their changes resulting from physiological processes or environmental perturbations. PMID:11983894

  10. Mass spectrometry of aerospace materials

    NASA Technical Reports Server (NTRS)

    Colony, J. A.

    1976-01-01

    Mass spectrometry is used for chemical analysis of aerospace materials and contaminants. Years of analytical aerospace experience have resulted in the development of specialized techniques of sampling and analysis which are required in order to optimize results. This work has resulted in the evolution of a hybrid method of indexing mass spectra which include both the largest peaks and the structurally significant peaks in a concise format. With this system, a library of mass spectra of aerospace materials was assembled, including the materials responsible for 80 to 90 percent of the contamination problems at Goddard Space Flight Center during the past several years.

  11. Mass spectrometry and renal calculi

    PubMed Central

    Purcarea, VL; Sisu, I; Sisu, E

    2010-01-01

    The present review represents a concise and complete survey of the literature covering 2004–2009, concerning the mass spectrometric techniques involved in the structural investigation of renal calculi. After a short presentation of the fundamental mass spectrometric techniques (MALDI–TOF, QTOF, MS–MS) as well as hyphenated methods (GC–MS, LC–MS, CE–MS), an extensive study of the urinary proteome analysis as well as the detection and quantification by mass spectrometry of toxins, drugs and metabolites from renal calculi is presented. PMID:20968197

  12. Mass spectrometry and tandem mass spectrometry of citrus limonoids.

    PubMed

    Tian, Qingguo; Schwartz, Steven J

    2003-10-15

    Methods for atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) of citrus limonoid aglycones and electrospray ionization tandem mass spectrometry (ESI-MS/MS) of limonoid glucosides are reported. The fragmentation patterns of four citrus limonoid aglycones (limonin, nomilin, obacunone, and deacetylnomilin) and six limonoid glucosides, that is, limonin 17-beta-D-glucopyranoside (LG), nomilin 17-beta-D-glucopyranoside (NG), nomilinic acid 17-beta-D-glucopyranoside (NAG), deacetyl nomilinic acid 17-beta-D-glucopyranoside (DNAG), obacunone 17-beta-D-glucopyranoside (OG), and obacunoic acid 17-beta-D-glucopyranoside (OAG) were investigated using a quadruple mass spectrometer in low-energy collisionally activated dissociation (CAD). The four limonoid aglycones and four limonoid glucosides (LG, OG, NAG, and DNAG) were purified from citrus seeds; the other two limonoid glucosides (NG and OAG) were tentatively identified in the crude extract of grapefruit seeds by ESI mass spectrometry in both positive and negative ion analysis. Ammonium hydroxide or acetic acid was added to the mobile phase to facilitate ionization. During positive ion APCI analysis of limonoid aglycones, protonated molecular ion, [M + H]+, or adduct ion, [M + NH3 + H]-, was formed as base peaks when ammonium hydroxide was added to the mobile phase. Molecular anions or adduct ions with acetic acid ([M + HOAc - H] and [M + HOAc]-) or a deprotonated molecular ion were produced during negative ion APCI analysis of limonoid aglycones, depending on the mobile-phase modifier used. Positive ion ESI-MS of limonoid glucosides produced adduct ions of [M + H + NH3]+, [M + Na]+, and [M + K]+ when ammonium hydroxide was added to the mobile phase. After collisionally activated dissociation (CAD) of the limonoid aglycone molecular ions in negative ion APCI analysis, fragment ions indicated structural information of the precursor ions, showing the presence of methyl, carboxyl, and oxygenated ring

  13. Analysis of low molecular weight compounds by MALDI-FTICR-MS.

    PubMed

    Wang, Hao-Yang; Chu, Xu; Zhao, Zhi-Xiong; He, Xiao-Shuang; Guo, Yin-Long

    2011-05-15

    This review focuses on recent applications of matrix-assisted laser desorption ionization-Fourier-transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) in qualitative and quantitative analysis of low molecular weight compounds. The scope of the work includes amino acids, small peptides, mono and oligosaccharides, lipids, metabolic compounds, small molecule phytochemicals from medicinal herbs and even the volatile organic compounds from tobacco. We discuss both direct analysis and analysis following derivatization. In addition we review sample preparation strategies to reduce interferences in the low m/z range and to improve sensitivities by derivatization with charge tags. We also present coupling of head space techniques with MALDI-FTICR-MS. Furthermore, omics analyses based on MALDI-FTICR-MS were also discussed, including proteomics, metabolomics and lipidomics, as well as the relative MS imaging for bio-active low molecular weight compounds. Finally, we discussed the investigations on dissociation/rearrangement processes of low molecular weight compounds by MALDI-FTICR-MS.

  14. Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging.

    PubMed

    Lou, Sha; Balluff, Benjamin; Cleven, Arjen H G; Bovée, Judith V M G; McDonnell, Liam A

    2017-02-01

    Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival (m/z 180.9436 and 241.0118) and metastasis-free survival (m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine. Graphical Abstract ᅟ.

  15. Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    Lou, Sha; Balluff, Benjamin; Cleven, Arjen H. G.; Bovée, Judith V. M. G.; McDonnell, Liam A.

    2017-02-01

    Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival ( m/z 180.9436 and 241.0118) and metastasis-free survival ( m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

  16. EMERGING POLLUTANTS, MASS SPECTROMETRY, AND ...

    EPA Pesticide Factsheets

    Historically fundamental to amassing our understanding of environmental processes and chemical pollution is the realm of mass spectrometry (MS) - the mainstay of analytical chemistry - the workhorse that supplies definitive data that environmental scientists and engineers reply upon for identifying molecular compositions (and ultimately structures) of chemicals. While the power of MS has long been visible to the practicing environmental chemist, it borders on obscurity to the lay public and many scientists. While MS has played a long, historic (and largely invisible) role in establishing our knowledge of environmental processes and pollution, what recognition it does enjoy is usually relegated to that of a tool. It is usually the relevance or significance of the knowledge acquired from the application of the tool that has ultimate meaning to the public and science at large - not how the data were acquired. Methods (736/800): Mass Spectrometry and the

  17. Imaging Mass Spectrometry in Neuroscience

    PubMed Central

    2013-01-01

    Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging. PMID:23530951

  18. Estimating Probabilities of Peptide Database Identifications to LC-FTICR-MS Observations

    SciTech Connect

    Anderson, Kevin K.; Monroe, Matthew E.; Daly, Don S.

    2006-02-24

    One of the grand challenges in the post-genomic era is proteomics, the characterization of the proteins expressed in a cell under specific conditions. A promising technology for high-throughput proteomics is mass spectrometry, specifically liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS). The accuracy and certainty of the determinations of peptide identities and abundances provided by LC-FTICR-MS are an important and necessary component of systems biology research. Methods: After a tryptically digested protein mixture is analyzed by LC-FTICR-MS, the observed masses and normalized elution times of the detected features are statistically matched to the theoretical masses and elution times of known peptides listed in a large database. The probability of matching is estimated for each peptide in the reference database using statistical classification methods assuming bivariate Gaussian probability distributions on the uncertainties in the masses and the normalized elution times. A database of 69,220 features from 32 LC-FTICR-MS analyses of a tryptically digested bovine serum albumin (BSA) sample was matched to a database populated with 97% false positive peptides. The percentage of high confidence identifications was found to be consistent with other database search procedures. BSA database peptides were identified with high confidence on average in 14.1 of the 32 analyses. False positives were identified on average in just 2.7 analyses. Using a priori probabilities that contrast peptides from expected and unexpected proteins was shown to perform better in identifying target peptides than using equally likely a priori probabilities. This is because a large percentage of the target peptides were similar to unexpected peptides which were included to be false positives. The use of triplicate analyses with a ''2 out of 3'' reporting rule was shown to have excellent rejection of false positives.

  19. Simultaneous molecular formula determinations of natural compounds in a plant extract using 15 T Fourier transform ion cyclotron resonance mass spectrometry

    PubMed Central

    2013-01-01

    Background Plant extracts are a reservoir of pharmacologically active substances; however, conventional analytical methods can analyze only a small portion of an extract. Here, we report a high-throughput analytical method capable of determining most phytochemicals in a plant extract and of providing their molecular formulae from a single experiment using ultra-high-resolution electrospray ionization mass spectrometry (UHR ESI MS). UHR mass profiling was used to analyze natural compounds in a 70% ethanol ginseng extract, which was directly infused into a 15 T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer for less than 10 min without a separation process. Results The UHR FT-ICR MS yielded a mass accuracy of 0.5 ppm and a mass resolving power (m/Δm) of 1,000,000–270,000 for the range m/z 290–1,100. The mass resolution was sufficient to resolve the isotopic fine structure (IFS) of many compounds in the extract. After noise removal from 1,552 peaks, 405 compounds were detected. The molecular formulae of 123 compounds, including 33 ginsenosides, were determined using the observed IFS, exact monoisotopic mass, and exact mass difference. Liquid chromatography (LC)/FT-ICR MS of the extract was performed to compare the high-throughput performance of UHR ESI FT-ICR MS. The LC/FT-ICR MS detected only 129 compounds, including 19 ginsenosides. The result showed that UHR ESI FT-ICR MS identified three times more compounds than LC/FT-ICR MS and in a relatively shorter time. The molecular formula determination by UHR FT-ICR MS was validated by LC and tandem MS analyses of three known ginsenosides. Conclusions UHR mass profiling of a plant extract by 15 T FT-ICR MS showed that multiple compounds were simultaneously detected and their molecular formulae were decisively determined by a single experiment with ultra-high mass resolution and mass accuracy. Simultaneous molecular determination of multiple natural products by UHR ESI FT-ICR MS would be a

  20. Simultaneous molecular formula determinations of natural compounds in a plant extract using 15 T Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Park, Kyu Hwan; Kim, Min Sun; Baek, Sun Jong; Bae, Ik Hyun; Seo, Sang-Wan; Kim, Jongjin; Shin, Yong Kook; Lee, Yong-Moon; Kim, Hyun Sik

    2013-01-01

    Plant extracts are a reservoir of pharmacologically active substances; however, conventional analytical methods can analyze only a small portion of an extract. Here, we report a high-throughput analytical method capable of determining most phytochemicals in a plant extract and of providing their molecular formulae from a single experiment using ultra-high-resolution electrospray ionization mass spectrometry (UHR ESI MS). UHR mass profiling was used to analyze natural compounds in a 70% ethanol ginseng extract, which was directly infused into a 15 T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer for less than 10 min without a separation process. The UHR FT-ICR MS yielded a mass accuracy of 0.5 ppm and a mass resolving power (m/Δm) of 1,000,000-270,000 for the range m/z 290-1,100. The mass resolution was sufficient to resolve the isotopic fine structure (IFS) of many compounds in the extract. After noise removal from 1,552 peaks, 405 compounds were detected. The molecular formulae of 123 compounds, including 33 ginsenosides, were determined using the observed IFS, exact monoisotopic mass, and exact mass difference. Liquid chromatography (LC)/FT-ICR MS of the extract was performed to compare the high-throughput performance of UHR ESI FT-ICR MS. The LC/FT-ICR MS detected only 129 compounds, including 19 ginsenosides. The result showed that UHR ESI FT-ICR MS identified three times more compounds than LC/FT-ICR MS and in a relatively shorter time. The molecular formula determination by UHR FT-ICR MS was validated by LC and tandem MS analyses of three known ginsenosides. UHR mass profiling of a plant extract by 15 T FT-ICR MS showed that multiple compounds were simultaneously detected and their molecular formulae were decisively determined by a single experiment with ultra-high mass resolution and mass accuracy. Simultaneous molecular determination of multiple natural products by UHR ESI FT-ICR MS would be a powerful method to profile a wide

  1. Mass spectrometry. [review of techniques

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Kimble, B. J.; Derrick, P. J.

    1976-01-01

    Advances in mass spectrometry (MS) and its applications over the past decade are reviewed in depth, with annotated literature references. New instrumentation and techniques surveyed include: modulated-beam MS, chromatographic MS on-line computer techniques, digital computer-compatible quadrupole MS, selected ion monitoring (mass fragmentography), and computer-aided management of MS data and interpretation. Areas of application surveyed include: organic MS and electron impact MS, field ionization kinetics, appearance potentials, translational energy release, studies of metastable species, photoionization, calculations of molecular orbitals, chemical kinetics, field desorption MS, high pressure MS, ion cyclotron resonance, biochemistry, medical/clinical chemistry, pharmacology, and environmental chemistry and pollution studies.

  2. Mass spectrometry. [review of techniques

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Kimble, B. J.; Derrick, P. J.

    1976-01-01

    Advances in mass spectrometry (MS) and its applications over the past decade are reviewed in depth, with annotated literature references. New instrumentation and techniques surveyed include: modulated-beam MS, chromatographic MS on-line computer techniques, digital computer-compatible quadrupole MS, selected ion monitoring (mass fragmentography), and computer-aided management of MS data and interpretation. Areas of application surveyed include: organic MS and electron impact MS, field ionization kinetics, appearance potentials, translational energy release, studies of metastable species, photoionization, calculations of molecular orbitals, chemical kinetics, field desorption MS, high pressure MS, ion cyclotron resonance, biochemistry, medical/clinical chemistry, pharmacology, and environmental chemistry and pollution studies.

  3. Glycosaminoglycan Glycomics Using Mass Spectrometry*

    PubMed Central

    Zaia, Joseph

    2013-01-01

    The fact that sulfated glycosaminoglycans (GAGs) are necessary for the functioning of all animal physiological systems drives the need to understand their biology. This understanding is limited, however, by the heterogeneous nature of GAG chains and their dynamic spatial and temporal expression patterns. GAGs have a regulated structure overlaid by heterogeneity but lack the detail necessary to build structure/function relationships. In order to provide this information, we need glycomics platforms that are sensitive, robust, high throughput, and information rich. This review summarizes progress on mass-spectrometry-based GAG glycomics methods. The areas covered include disaccharide analysis, oligosaccharide profiling, and tandem mass spectrometric sequencing. PMID:23325770

  4. Utilizing a Robotic Sprayer for High Lateral and Mass Resolution MALDI FT-ICR MSI of Microbial Cultures

    SciTech Connect

    Anderton, Christopher R.; Chu, Rosalie K.; Tolic, Nikola; Creissen, Alain V.; Pasa-Tolic, Ljiljana

    2016-01-07

    The ability to visualize biochemical interactions between microbial communities using MALDI MSI has provided tremendous insights into a variety of biological fields. Matrix application using a sieve proved to be incredibly useful, but it had many limitations that include uneven matrix coverage and limitation in the types of matrices one could employ in their studies. Recently, there has been a concerted effort to improve matrix application for studying agar plated microbial cultures, many of which utilized automated matrix sprayers. Here, we describe the usefulness of using a robotic sprayer for matrix application. The robotic sprayer has two-dimensional control over where matrix is applied and a heated capillary that allows for rapid drying of the applied matrix. This method provided a significant increase in MALDI sensitivity over the sieve method, as demonstrated by FT-ICR MS analysis, facilitating the ability to gain higher lateral resolution MS images of Bacillus Subtilis than previously reported. This method also allowed for the use of different matrices to be applied to the culture surfaces.

  5. Utilizing a Robotic Sprayer for High Lateral and Mass Resolution MALDI FT-ICR MSI of Microbial Cultures

    NASA Astrophysics Data System (ADS)

    Anderton, Christopher R.; Chu, Rosalie K.; Tolić, Nikola; Creissen, Alain; Paša-Tolić, Ljiljana

    2016-03-01

    The ability to visualize biochemical interactions between microbial communities using MALDI MSI has provided tremendous insights into a variety of biological fields. Matrix application using a sieve proved to be incredibly useful, but it has many limitations that include uneven matrix coverage and limitation in the types of matrices that could be employed in studies. Recently, there has been a concerted effort to improve matrix application for studying agar plated microbial cultures, many of which utilized automated matrix sprayers. Here, we describe the usefulness of using a robotic sprayer for matrix application. The robotic sprayer has two-dimensional control over where matrix is applied, and a heated capillary that allows for rapid drying of the applied matrix. This method provided a significant increase in MALDI sensitivity over the sieve method, as demonstrated by FT-ICR MS analysis, facilitating the ability to gain higher lateral resolution MS images of Bacillus subtilis than previously reported. This method also allowed for the use of different matrices to be applied to the culture surfaces.

  6. Trapping Ring Electrode Cell: A FTICR Mass Spectrometer Cell for Improved Signal-to-Noise and Resolving Power

    PubMed Central

    Weisbrod, Chad R.; Kaiser, Nathan K.; Skulason, Gunnar E.; Bruce, James E.

    2010-01-01

    A novel FTICR cell called the trapping ring electrode cell (TREC) has been conceived, simulated, developed, and tested. The performance of the TREC is compared to a closed cylindrical cell at different excited cyclotron radii. The TREC permits the ability to maintain coherent ion motion at larger initial excited cyclotron radii by decreasing the change in radial electric field with respect to z-axis position in the cell. This is accomplished through postexcitation modulation of the trapping potentials applied to segmented trap plates. Resolving power approaching the theoretical limit was achieved using the novel TREC technology; over 420 000 resolving power was observed on melittin [M + 4H]4+ species when employed under modest magnetic field strength (3T) and a data acquisition duration of 13 s. A 10-fold gain in signal-to-noise ratio is demonstrated over the closed cylindrical cell optimized with common potentials on all ring electrodes. The observed frequency drift during signal acquisition over long time periods was also significantly reduced, resulting in improved resolving power. PMID:18681460

  7. A mass spectrometry primer for mass spectrometry imaging

    PubMed Central

    Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2011-01-01

    Mass spectrometry imaging (MSI), a rapidly growing subfield of chemical imaging, employs mass spectrometry (MS) technologies to create single- and multi-dimensional localization maps for a variety of atoms and molecules. Complimentary to other imaging approaches, MSI provides high chemical specificity and broad analyte coverage. This powerful analytical toolset is capable of measuring the distribution of many classes of inorganics, metabolites, proteins and pharmaceuticals in chemically and structurally complex biological specimens in vivo, in vitro, and in situ. The MSI approaches highlighted in this Methods in Molecular Biology volume provide flexibility of detection, characterization, and identification of multiple known and unknown analytes. The goal of this chapter is to introduce investigators who may be unfamiliar with MS to the basic principles of the mass spectrometric approaches as used in MSI. In addition to guidelines for choosing the most suitable MSI method for specific investigations, cross-references are provided to the chapters in this volume that describe the appropriate experimental protocols. PMID:20680583

  8. Quantitative mass spectrometry: an overview

    NASA Astrophysics Data System (ADS)

    Urban, Pawel L.

    2016-10-01

    Mass spectrometry (MS) is a mainstream chemical analysis technique in the twenty-first century. It has contributed to numerous discoveries in chemistry, physics and biochemistry. Hundreds of research laboratories scattered all over the world use MS every day to investigate fundamental phenomena on the molecular level. MS is also widely used by industry-especially in drug discovery, quality control and food safety protocols. In some cases, mass spectrometers are indispensable and irreplaceable by any other metrological tools. The uniqueness of MS is due to the fact that it enables direct identification of molecules based on the mass-to-charge ratios as well as fragmentation patterns. Thus, for several decades now, MS has been used in qualitative chemical analysis. To address the pressing need for quantitative molecular measurements, a number of laboratories focused on technological and methodological improvements that could render MS a fully quantitative metrological platform. In this theme issue, the experts working for some of those laboratories share their knowledge and enthusiasm about quantitative MS. I hope this theme issue will benefit readers, and foster fundamental and applied research based on quantitative MS measurements. This article is part of the themed issue 'Quantitative mass spectrometry'.

  9. Application of mass spectrometry in the characterization of chemicals in coal-derived liquids.

    PubMed

    Liu, Fang-Jing; Fan, Maohong; Wei, Xian-Yong; Zong, Zhi-Min

    2016-04-13

    Coal-derived liquids (CDLs) are primarily generated from pyrolysis, carbonization, gasification, direct liquefaction, low-temperature extraction, thermal dissolution, and mild oxidation. CDLs are important feedstocks for producing value-added chemicals and clean liquid fuels as well as high performance carbon materials. Accordingly, the compositional characterization of chemicals in CDLs at the molecular level with advanced analytical techniques is significant for the efficient utilization of CDLs. Although reviews on advancements have been rarely reported, great progress has been achieved in this area by using gas chromatography/mass spectrometry (GC/MS), two-dimensional GC-time of flight mass spectrometry (GC × GC-TOFMS), and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). This review focuses on characterizing hydrocarbon, oxygen-containing, nitrogen-containing, sulfur-containing, and halogen-containing chemicals in various CDLs with these three mass spectrometry techniques. Small molecular (< 500 u), volatile and semi-volatile, and less polar chemicals in CDLs have been identified with GC/MS and GC × GC-TOFMS. By equipped with two-dimensional GC, GC × GC-TOFMS can achieve a clearly chromatographic separation of complex chemicals in CDLs without prior fractionation, and thus can overcome the disadvantages of co-elution and serious peak overlap in GC/MS analysis, providing much more compositional information. With ultrahigh resolving power and mass accuracy, FT-ICR MS reveals a huge number of compositionally distinct compounds assigned to various chemical classes in CDLs. It shows excellent performance in resolving and characterizing higher-molecular, less volatile, and polar chemicals that cannot be detected by GC/MS and GC × GC-TOFMS. The application of GC × GC-TOFMS and FT-ICR MS to chemical characterization of CDLs is not as prevalent as that of petroleum and largely remains to be developed in many respects

  10. Coded Apertures in Mass Spectrometry.

    PubMed

    Amsden, Jason J; Gehm, Michael E; Russell, Zachary E; Chen, Evan X; Di Dona, Shane T; Wolter, Scott D; Danell, Ryan M; Kibelka, Gottfried; Parker, Charles B; Stoner, Brian R; Brady, David J; Glass, Jeffrey T

    2017-06-12

    The use of coded apertures in mass spectrometry can break the trade-off between throughput and resolution that has historically plagued conventional instruments. Despite their very early stage of development, coded apertures have been shown to increase throughput by more than one order of magnitude, with no loss in resolution in a simple 90-degree magnetic sector. This enhanced throughput can increase the signal level with respect to the underlying noise, thereby significantly improving sensitivity to low concentrations of analyte. Simultaneous resolution can be maintained, preventing any decrease in selectivity. Both one- and two-dimensional (2D) codes have been demonstrated. A 2D code can provide increased measurement diversity and therefore improved numerical conditioning of the mass spectrum that is reconstructed from the coded signal. This review discusses the state of development, the applications where coding is expected to provide added value, and the various instrument modifications necessary to implement coded apertures in mass spectrometers.

  11. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, Brian D.; Fought, Eric R.

    1987-01-01

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface.

  12. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, B.D.; Fought, E.R.

    1987-11-10

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface. 8 figs.

  13. Affinity membrane introduction mass spectrometry

    SciTech Connect

    Xu, C.; Patrick, J.S.; Cooks, R.G. )

    1995-02-15

    A new technique, affinity membrane introduction mass spectrometry, is described. In this method, a chemically modified membrane is used to selectively adsorb analytes bearing a particular functional group and concentrate them from solution. Release of the bound analyte results in its transfer across the membrane and allows it to be monitored mass spectrometrically, using, in the present case, a benchtop ion trap instrument. Alkylamine-modified cellulose membranes are used to bind substituted benzaldehydes through imine formation at high pH. Release of the bound aldehyde is achieved by acid hydrolysis of the surface-bound imine. Benzaldehyde is detected with excellent specificity at 10 ppm in a complex mixture using this method. Using the enrichment capability of the membrane, a full mass spectrum of benzaldehyde can be measured at a concentration of 10 ppb. The behavior of a variety of other aldehydes is also discussed to illustrate the capabilities of the method. 21 refs., 5 figs., 2 tabs.

  14. Fourier Transform Ion Cyclotron Resonance Mass Spectrometry at the Cyclotron Frequency

    NASA Astrophysics Data System (ADS)

    Nagornov, Konstantin O.; Kozhinov, Anton N.; Tsybin, Yury O.

    2017-02-01

    The phenomenon of ion cyclotron resonance allows for determining mass-to-charge ratio, m/z, of an ensemble of ions by means of measurements of their cyclotron frequency, ω c . In Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), the ω c quantity is usually unavailable for direct measurements: the resonant state is located close to the reduced cyclotron frequency (ω+), whereas the ω c and the corresponding m/z values may be calculated via theoretical derivation from an experimental estimate of the ω+ quantity. Here, we describe an experimental observation of a new resonant state, which is located close to the ω c frequency and is established because of azimuthally-dependent trapping electric fields of the recently developed ICR cells with narrow aperture detection electrodes. We show that in mass spectra, peaks close to ω+ frequencies can be reduced to negligible levels relative to peaks close to ω c frequencies. Due to reduced errors with which the ω c quantity is obtained, the new resonance provides a means of cyclotron frequency measurements with precision greater than that achieved when ω+ frequency peaks are employed. The described phenomenon may be considered for a development into an FT-ICR MS technology with increased mass accuracy for applications in basic research, life, and environmental sciences.

  15. Fourier Transform Ion Cyclotron Resonance Mass Spectrometry at the Cyclotron Frequency.

    PubMed

    Nagornov, Konstantin O; Kozhinov, Anton N; Tsybin, Yury O

    2017-04-01

    The phenomenon of ion cyclotron resonance allows for determining mass-to-charge ratio, m/z, of an ensemble of ions by means of measurements of their cyclotron frequency, ω c . In Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), the ω c quantity is usually unavailable for direct measurements: the resonant state is located close to the reduced cyclotron frequency (ω+), whereas the ω c and the corresponding m/z values may be calculated via theoretical derivation from an experimental estimate of the ω+ quantity. Here, we describe an experimental observation of a new resonant state, which is located close to the ω c frequency and is established because of azimuthally-dependent trapping electric fields of the recently developed ICR cells with narrow aperture detection electrodes. We show that in mass spectra, peaks close to ω+ frequencies can be reduced to negligible levels relative to peaks close to ω c frequencies. Due to reduced errors with which the ω c quantity is obtained, the new resonance provides a means of cyclotron frequency measurements with precision greater than that achieved when ω+ frequency peaks are employed. The described phenomenon may be considered for a development into an FT-ICR MS technology with increased mass accuracy for applications in basic research, life, and environmental sciences. Graphical Abstract ᅟ.

  16. Neuroscience and Accelerator Mass Spectrometry

    SciTech Connect

    Palmblad, M N; Buchholz, B A; Hillegonds, D J; Vogel, J S

    2004-08-02

    Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as {sup 3}H, {sup 14}C, {sup 26}Al, {sup 36}Cl and {sup 41}Ca, with zepto- or attomole sensitivity and high precision and throughput, enabling safe human pharmacokinetic studies involving: microgram doses, agents having low bioavailability, or toxicology studies where administered doses must be kept low (<1 {micro}g/kg). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the timescale of decades. We will here review how AMS is applied in neurotoxicology and neuroscience.

  17. Neuroscience and accelerator mass spectrometry.

    PubMed

    Palmblad, Magnus; Buchholz, Bruce A; Hillegonds, Darren J; Vogel, John S

    2005-02-01

    Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had a great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as 3H, 14C, 26Al, 36Cl and 41Ca, with zepto- or attomole sensitivity and high precision and throughput, allowing safe human pharmacokinetic studies involving microgram doses, agents having low bioavailability or toxicology studies where administered doses must be kept low (<1 microg kg(-1)). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the time-scale of decades. We review here how AMS is applied in neurotoxicology and neuroscience.

  18. Mass Spectrometry Applications for Toxicology.

    PubMed

    Mbughuni, Michael M; Jannetto, Paul J; Langman, Loralie J

    2016-12-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MS(n)) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

  19. Mass spectrometry in combinatorial chemistry.

    PubMed

    Enjalbal, C; Martinez, J; Aubagnac, J L

    2000-01-01

    In the fast expanding field of combinatorial chemistry, profiling libraries has always been a matter of concern--as illustrated by the buoyant literature over the past seven years. Spectroscopic methods, including especially mass spectrometry and to a lesser extent IR and NMR, have been applied at different levels of combinatorial library synthesis: in the rehearsal phase to optimize the chemistry prior to library generation, to confirm library composition, and to characterize after screening each structure that exhibits positive response. Most of the efforts have been concentrated on library composition assessment. The difficulties of such analyses have evolved from the infancy of the combinatorial concept, where large mixtures were prepared, to the recent parallel syntheses of collections of discrete compounds. Whereas the complexity of the analyses has diminished, an increased degree of automation was simultaneously required to achieve efficient library component identification and quantification. In this respect, mass spectrometry has been found to be the method of choice, providing rapid, sensitive, and informative analyses, especially when coupled to chromatographic separation. Fully automated workstations able to cope with several hundreds of compounds per day have been designed. After a brief introduction to describe the combinatorial approach, library characterization will be discussed in detail, considering first the solution-based methodologies and secondly the support-bound material analyses.

  20. Mass Spectrometry Applications for Toxicology

    PubMed Central

    Mbughuni, Michael M.; Jannetto, Paul J.

    2016-01-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology. PMID:28149262

  1. Distributed computing strategies for processing of FT-ICR MS imaging datasets for continuous mode data visualization

    SciTech Connect

    Smith, Donald F.; Schulz, Carl; Konijnenburg, Marco; Kilic, Mehmet; Heeren, Ronald M.

    2015-03-01

    High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging enables the spatial mapping and identification of biomolecules from complex surfaces. The need for long time-domain transients, and thus large raw file sizes, results in a large amount of raw data (“big data”) that must be processed efficiently and rapidly. This can be compounded by largearea imaging and/or high spatial resolution imaging. For FT-ICR, data processing and data reduction must not compromise the high mass resolution afforded by the mass spectrometer. The continuous mode “Mosaic Datacube” approach allows high mass resolution visualization (0.001 Da) of mass spectrometry imaging data, but requires additional processing as compared to featurebased processing. We describe the use of distributed computing for processing of FT-ICR MS imaging datasets with generation of continuous mode Mosaic Datacubes for high mass resolution visualization. An eight-fold improvement in processing time is demonstrated using a Dutch nationally available cloud service.

  2. Distributed computing strategies for processing of FT-ICR MS imaging datasets for continuous mode data visualization.

    PubMed

    Smith, Donald F; Schulz, Carl; Konijnenburg, Marco; Kilic, Mehmet; Heeren, Ron M A

    2015-03-01

    High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging enables the spatial mapping and identification of biomolecules from complex surfaces. The need for long time-domain transients, and thus large raw file sizes, results in a large amount of raw data ("big data") that must be processed efficiently and rapidly. This can be compounded by large-area imaging and/or high spatial resolution imaging. For FT-ICR, data processing and data reduction must not compromise the high mass resolution afforded by the mass spectrometer. The continuous mode "Mosaic Datacube" approach allows high mass resolution visualization (0.001 Da) of mass spectrometry imaging data, but requires additional processing as compared to feature-based processing. We describe the use of distributed computing for processing of FT-ICR MS imaging datasets with generation of continuous mode Mosaic Datacubes for high mass resolution visualization. An eight-fold improvement in processing time is demonstrated using a Dutch nationally available cloud service.

  3. Feasibility Assessment of a MALDI FTICR Imaging Approach for the 3D Reconstruction of a Mouse Lung

    NASA Astrophysics Data System (ADS)

    Jones, E. Ellen; Quiason, Cristine; Dale, Stephanie; Shahidi-Latham, Sheerin K.

    2017-08-01

    Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has proven to be a quick, robust, and label-free tool to produce two-dimensional (2D) ion-density maps representing the distribution of a variety of analytes across a tissue section of interest. In addition, three-dimensional (3D) imaging mass spectrometry workflows have been developed that are capable of visualizing these same analytes throughout an entire volume of a tissue rather than a single cross-section. Until recently, the use of Fourier transform ion cyclotron resonance (FTICR) mass spectrometers for 3D volume reconstruction has been impractical due to software limitations, such as inadequate capacity to manipulate the extremely large data files produced during an imaging experiment. Fortunately with recent software and hardware advancements, 3D reconstruction from MALDI FTICR IMS datasets is now feasible. Here we describe the first proof of principle study for a 3D volume reconstruction of an entire mouse lung using data collected on a FTICR mass spectrometer. Each lung tissue section was analyzed with high mass resolution and mass accuracy, and considered as an independent dataset. Each subsequent lung section image, or lung dataset, was then co-registered to its adjacent section to reconstruct a 3D volume. Volumes representing various endogenous lipid species were constructed, including sphingolipids and phosphatidylcholines (PC), and species confirmation was performed with on-tissue collision induced dissociation (CID).

  4. Quantitative mass spectrometry: an overview

    PubMed Central

    2016-01-01

    Mass spectrometry (MS) is a mainstream chemical analysis technique in the twenty-first century. It has contributed to numerous discoveries in chemistry, physics and biochemistry. Hundreds of research laboratories scattered all over the world use MS every day to investigate fundamental phenomena on the molecular level. MS is also widely used by industry—especially in drug discovery, quality control and food safety protocols. In some cases, mass spectrometers are indispensable and irreplaceable by any other metrological tools. The uniqueness of MS is due to the fact that it enables direct identification of molecules based on the mass-to-charge ratios as well as fragmentation patterns. Thus, for several decades now, MS has been used in qualitative chemical analysis. To address the pressing need for quantitative molecular measurements, a number of laboratories focused on technological and methodological improvements that could render MS a fully quantitative metrological platform. In this theme issue, the experts working for some of those laboratories share their knowledge and enthusiasm about quantitative MS. I hope this theme issue will benefit readers, and foster fundamental and applied research based on quantitative MS measurements. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644965

  5. Clinical Application of Ambient Ionization Mass Spectrometry

    PubMed Central

    Li, Li-Hua; Hsieh, Hua-Yi; Hsu, Cheng-Chih

    2017-01-01

    Ambient ionization allows mass spectrometry analysis directly on the sample surface under atmospheric pressure with almost zero sample pretreatment. Since the development of desorption electrospray ionization (DESI) in 2004, many other ambient ionization techniques were developed. Due to their simplicity and low operation cost, rapid and on-site clinical mass spectrometry analysis becomes real. In this review, we will highlight some of the most widely used ambient ionization mass spectrometry approaches and their applications in clinical study. PMID:28337399

  6. Complementary nontargeted and targeted mass spectrometry techniques to determine bioaccumulation of halogenated contaminants in freshwater species.

    PubMed

    Myers, Anne L; Watson-Leung, Trudy; Jobst, Karl J; Shen, Li; Besevic, Sladjana; Organtini, Kari; Dorman, Frank L; Mabury, Scott A; Reiner, Eric J

    2014-12-02

    Assessing the toxicological significance of complex environmental mixtures is challenging due to the large number of unidentified contaminants. Nontargeted analytical techniques may serve to identify bioaccumulative contaminants within complex contaminant mixtures without the use of analytical standards. This study exposed three freshwater organisms (Lumbriculus variegatus, Hexagenia spp., and Pimephales promelas) to a highly contaminated soil collected from a recycling plant fire site. Biota extracts were analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and mass defect filtering to identify bioaccumulative halogenated contaminants. Specific bioaccumulative isomers were identified by comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry (GCxGC-HRToF). Targeted analysis of mixed brominated/chlorinated dibenzo-p-dioxins and dibenzofurans (PXDD/PXDFs, X = Br and Cl) was performed by atmospheric pressure gas chromatography tandem mass spectrometry (APGC-MS/MS). Relative sediment and biota instrument responses were used to estimate biota-sediment accumulation factors (BSAFs). Bioaccumulating contaminants varied among species and included polychlorinated naphthalenes (PCNs), polychlorinated dibenzofurans (PCDFs), chlorinated and mixed brominated/chlorinated anthracenes/phenanthrenes, and pyrenes/fluoranthenes (Cl-PAHs and X-PAHs, X = Br and Cl), as well as PXDD/PXDFs. Bioaccumulation potential among isomers also varied. This study demonstrates how complementary high-resolution mass spectrometry techniques identify persistent and bioaccumulative contaminants (and specific isomers) of environmental concern.

  7. Identification of sites of ubiquitination in proteins: a fourier transform ion cyclotron resonance mass spectrometry approach.

    PubMed

    Cooper, Helen J; Heath, John K; Jaffray, Ellis; Hay, Ronald T; Lam, Tukiet T; Marshall, Alan G

    2004-12-01

    Structural elucidation of posttranslationally modified peptides and proteins is of key importance in the understanding of an array of biological processes. Ubiquitination is a reversible modification that regulates many cellular functions. Consequences of ubiquitination depend on whether a single ubiquitin or polyubiquitin chain is added to the tagged protein. The lysine residue through which the polyubiquitin chain is formed is also critical for biological activity. Robust methods are therefore required to identify sites of ubiquitination modification, both in the target protein and in ubiquitin. Here, we demonstrate the suitability of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, in conjunction with activated ion electron capture dissociation (AI ECD) or infrared multiphoton dissociation (IRMPD), for the analysis of ubiquitinated proteins. Polyubiquitinated substrate protein GST-Ubc5 was generated in vitro. Tryptic digests of polyubiquitinated species contain modified peptides in which the ubiquitin C-terminal Gly-Gly residues are retained on the modified lysine residues. Direct infusion microelectrospray FT-ICR of the digest and comparison with an in silico digest enables identification of modified peptides and therefore sites of ubiquitination. Fifteen sites of ubiquitination were identified in GST-Ubc5 and four sites in ubiquitin. Assignments were confirmed by AI ECD or IRMPD. The Gly-Gly modification is stable and both tandem mass spectrometric techniques are suitable, providing extensive sequence coverage and retention of the modification on backbone fragments.

  8. Does deamidation cause protein unfolding? A top-down tandem mass spectrometry study

    PubMed Central

    Soulby, Andrew J; Heal, Jack W; Barrow, Mark P; Roemer, Rudolf A; O'Connor, Peter B

    2015-01-01

    Deamidation is a nonenzymatic post-translational modification of asparagine to aspartic acid or glutamine to glutamic acid, converting an uncharged amino acid to a negatively charged residue. It is plausible that deamidation of asparagine and glutamine residues would result in disruption of a proteins' hydrogen bonding network and thus lead to protein unfolding. To test this hypothesis Calmodulin and B2M were deamidated and analyzed using tandem mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). The gas phase hydrogen bonding networks of deamidated and nondeamidated protein isoforms were probed by varying the infra-red multi-photon dissociation laser power in a linear fashion and plotting the resulting electron capture dissociation fragment intensities as a melting curve at each amino acid residue. Analysis of the unfolding maps highlighted increased fragmentation at lower laser powers localized around heavily deamidated regions of the proteins. In addition fragment intensities were decreased across the rest of the proteins which we propose is because of the formation of salt-bridges strengthening the intramolecular interactions of the central regions. These results were supported by a computational flexibility analysis of the mutant and unmodified proteins, which would suggest that deamidation can affect the global structure of a protein via modification of the hydrogen bonding network near the deamidation site and that top down FTICR-MS is an appropriate technique for studying protein folding. PMID:25653127

  9. Identification of Mercury and Dissolved Organic Matter Complexes Using Ultrahigh Resolution Mass Spectrometry

    DOE PAGES

    Chen, Hongmei; Johnston, Ryne C.; Mann, Benjamin F.; ...

    2016-12-22

    The chemical speciation and bioavailability of mercury (Hg) is markedly influenced by its complexation with naturally dissolved organic matter (DOM) in aquatic environments. To date, however, analytical methodologies capable of identifying such complexes are scarce. Here in this paper, we utilize ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) coupled with electrospray ionization to identify individual Hg–DOM complexes. The measurements were performed by direct infusion of DOM in a 1:1 methanol:water solution at a Hg to dissolved organic carbon (DOC) molar ratio of 3 × 10–4. Heteroatomic molecules, especially those containing multiple S and N atoms, were foundmore » to be among the most important in forming strong complexes with Hg. Major Hg–DOM complexes of C10H21N2S4Hg+ and C8H17N2S4Hg+ were identified based on both the exact molecular mass and patterns of Hg stable isotope distributions detected by FTICR-MS. Density functional theory was used to predict the solution-phase structures of candidate molecules. Finally, these findings represent the first step to unambiguously identify specific DOM molecules in Hg binding, although future studies are warranted to further optimize and validate the methodology so as to explore detailed molecular compositions and structures of Hg–DOM complexes that affect biological uptake and transformation of Hg in the environment.« less

  10. Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems

    SciTech Connect

    Anderton, Christopher R.; Gamble, Lara J.

    2016-03-01

    Mass spectrometry imaging (MSI) techniques are increasingly being utilized within many biological fields, including medicine, pathology, microbial ecology, and more. Of the MSI methods available, secondary ion mass spectrometry (SIMS) offers the highest lateral resolution of any technique. Moreover, SIMS versatility in the number of different operating modes and types of mass spectrometers available has made it an increasing popular method for bio-related measurements. Here, we discuss SIMS ability to image tissues, single cells, and microbes with a particular emphasis on the types chemical and spatial information that can be ascertained by the different types of SIMS instruments and methods. The recently developed Fourier transform ion cyclotron resonance (FTICR) SIMS located at PNNL is capable of generating molecular maps of tissues with an unprecedented mass resolving power and mass accuracy, with respect to SIMS measurements. ToF-SIMS can generate chemical maps, where detection of small molecules and fragments can be acquired with an order of magnitude better lateral resolution than the FTICR-SIMS. Furthermore, many of commercially available ToF-SIMS instruments are capable of depth profiling measurements, offering the ability to attain three-dimensional information of one’s sample. The NanoSIMS instrument offers the highest lateral resolution of any MSI method available. In practice, NanoSIMS regularly achieves sub-100 nm resolution of atomic and diatomic secondary ions within biological samples. The strengths of the different SIMS methods are more and more being leveraged in both multimodal-imaging endeavors that use complementary MSI techniques as well with optical, fluorescence, and force microscopy methods.

  11. Counting Molecules by Desorption Ionization and Mass Spectrometry/Mass Spectrometry.

    ERIC Educational Resources Information Center

    Cooks, R. G.; Busch, K. L.

    1982-01-01

    Discusses two newer methods in mass spectrometry and shows how they can increase signal and signal-to-noise ratios, respectively. The first method, desorption ionization (DI), increases sensitivity while the second method, mass spectrometry/mass spectrometry (MS/MS), increases specificity. Together, the two methods offer improved analytical…

  12. INFRARED MATRIX-ASSISTED LASER DESORPTION ELECTROSPRAY IONIZATION (IR-MALDESI) IMAGING SOURCE COUPLED TO A FT-ICR MASS SPECTROMETER

    PubMed Central

    Robichaud, Guillaume; Barry, Jeremy A.; Garrard, Kenneth P.; Muddiman, David C.

    2013-01-01

    Mass spectrometry imaging (MSI) allows for the direct monitoring of the abundance and spatial distribution of chemical compounds over the surface of a tissue sample. This technology has opened the field of mass spectrometry to numerous innovative applications over the past 15 years. First used with SIMS and MALDI MS that operate under vacuum, interest has grown for mass spectrometry ionization sources that allow for effective imaging but where the analysis can be performed at ambient pressure with minimal or no sample preparation. We introduce here a versatile source for MALDESI imaging analysis coupled to a hybrid LTQ-FT-ICR mass spectrometer. The imaging source offers single shot or multi-shot capability per pixel with full control over the laser repetition rate and mass spectrometer scanning cycle. Scanning rates can be as fast as 1 pixel/second and a spatial resolution of 45 μm was achieved with oversampling. PMID:23208743

  13. Analysis of cancer cell lipids using matrix-assisted laser desorption/ionization 15-T Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Yang, Hyo-Jik; Park, Kyu Hwan; Lim, Dong Wan; Kim, Hyun Sik; Kim, Jeongkwon

    2012-03-30

    A combination of methodologies using the extremely high mass accuracy and resolution of 15-T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) was introduced for the identification of intact cancer cell phospholipids. Lipids from a malignant glioma cell line were initially analyzed at a resolution of >200,000 and identified by setting the mass tolerance to ±1 mDa using matrix-assisted laser desorption/ionization (MALDI) 15-T FT-ICR MS in positive ion mode. In most cases, a database search of potential lipid candidates using the exact masses of the lipids yielded only one possible chemical composition. Extremely high mass accuracy (<0.1 ppm) was then attained by using previously identified lipids as internal standards. This, combined with an extremely high resolution (>800,000), yielded well-resolved isotopic fine structures allowing for the identification of lipids by MALDI 15-T FT-ICR MS without using tandem mass spectrometric (MS/MS) analysis. Using this method, a total of 38 unique lipids were successfully identified.

  14. Inorganic trace analysis by mass spectrometry

    NASA Astrophysics Data System (ADS)

    Becker, Johanna Sabine; Dietze, Hans-Joachim

    1998-10-01

    Mass spectrometric methods for the trace analysis of inorganic materials with their ability to provide a very sensitive multielemental analysis have been established for the determination of trace and ultratrace elements in high-purity materials (metals, semiconductors and insulators), in different technical samples (e.g. alloys, pure chemicals, ceramics, thin films, ion-implanted semiconductors), in environmental samples (waters, soils, biological and medical materials) and geological samples. Whereas such techniques as spark source mass spectrometry (SSMS), laser ionization mass spectrometry (LIMS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), glow discharge mass spectrometry (GDMS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS) have multielemental capability, other methods such as thermal ionization mass spectrometry (TIMS), accelerator mass spectrometry (AMS) and resonance ionization mass spectrometry (RIMS) have been used for sensitive mono- or oligoelemental ultratrace analysis (and precise determination of isotopic ratios) in solid samples. The limits of detection for chemical elements using these mass spectrometric techniques are in the low ng g -1 concentration range. The quantification of the analytical results of mass spectrometric methods is sometimes difficult due to a lack of matrix-fitted multielement standard reference materials (SRMs) for many solid samples. Therefore, owing to the simple quantification procedure of the aqueous solution, inductively coupled plasma mass spectrometry (ICP-MS) is being increasingly used for the characterization of solid samples after sample dissolution. ICP-MS is often combined with special sample introduction equipment (e.g. flow injection, hydride generation, high performance liquid chromatography (HPLC) or electrothermal vaporization) or an off-line matrix separation and enrichment of trace impurities (especially for characterization of

  15. Visualization of 57Fe-Labeled Heme Isotopic Fine Structure and Localization of Regions of Erythroblast Maturation in Mouse Spleen by MALDI FTICR-MS Imaging

    NASA Astrophysics Data System (ADS)

    Kihara, Makoto; Matsuo-Tezuka, Yukari; Noguchi-Sasaki, Mariko; Yorozu, Keigo; Kurasawa, Mitsue; Shimonaka, Yasushi; Hirata, Michinori

    2017-08-01

    Epoetin beta pegol (continuous erythropoiesis receptor activator; C.E.R.A.), or methoxy-polyethylene glycol-modified epoetin beta, is a long-acting erythropoiesis stimulating agent (ESA) that effectively maintains hemoglobin levels. It promotes proliferation of erythroid progenitor cells in hematopoietic organs and leads to increased reticulocyte and hemoglobin levels. However, the detailed erythropoietic effects of various ESAs on their target organs have yet to be clarified, and new approaches are needed to analyze tissue iron localization with structural information. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) techniques are widely used in basic pharmaceutical research. High-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) imaging enables the spatial mapping and identification of biomolecules. In this study, mice administered with C.E.R.A. were fed a diet containing the stable iron isotope 57Fe. The 57Fe-heme+ isotopic fine structure peak (m/z 617.1772) was separated from the non-labeled heme+ isotopic peak (Δ0.0029) by FTICR-MS with a resolving power of more than 500,000. We optimized the platform to analyze the distribution of 57Fe-heme in the spleen using MALDI FTICR-MS imaging. The combination of the ultrahigh resolution power of FTICR-MS and a stable isotope labeling technique has the potential to be very effective in basic pharmaceutical research. [Figure not available: see fulltext.

  16. Normalization Approaches for Removing Systematic Biases Associated with Mass Spectrometry and Label-Free Proteomics

    SciTech Connect

    Callister, Stephen J.; Barry, Richard C.; Adkins, Joshua N.; Johnson, Ethan T.; Qian, Weijun; Webb-Robertson, Bobbie-Jo M.; Smith, Richard D.; Lipton, Mary S.

    2006-02-01

    Central tendency, linear regression, locally weighted regression, and quantile techniques were investigated for normalization of peptide abundance measurements obtained from high-throughput liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR MS). Arbitrary abundances of peptides were obtained from three sample sets, including a standard protein sample, two Deinococcus radiodurans samples taken from different growth phases, and two mouse striatum samples from control and methamphetamine-stressed mice (strain C57BL/6). The selected normalization techniques were evaluated in both the absence and presence of biological variability by estimating extraneous variability prior to and following normalization. Prior to normalization, replicate runs from each sample set were observed to be statistically different, while following normalization replicate runs were no longer statistically different. Although all techniques reduced systematic bias, assigned ranks among the techniques revealed significant trends. For most LC-FTICR MS analyses, linear regression normalization ranked either first or second among the four techniques, suggesting that this technique was more generally suitable for reducing systematic biases.

  17. Characterization of microbial siderophores by mass spectrometry.

    PubMed

    Pluháček, Tomáš; Lemr, Karel; Ghosh, Dipankar; Milde, David; Novák, Jiří; Havlíček, Vladimír

    2016-01-01

    Siderophores play important roles in microbial iron piracy, and are applied as infectious disease biomarkers and novel pharmaceutical drugs. Inductively coupled plasma and molecular mass spectrometry (ICP-MS) combined with high resolution separations allow characterization of siderophores in complex samples taking advantages of mass defect data filtering, tandem mass spectrometry, and iron-containing compound quantitation. The enrichment approaches used in siderophore analysis and current ICP-MS technologies are reviewed. The recent tools for fast dereplication of secondary metabolites and their databases are reported. This review on siderophores is concluded with their recent medical, biochemical, geochemical, and agricultural applications in mass spectrometry context.

  18. Mass Spectrometry Imaging Quick View

    SciTech Connect

    2013-01-24

    MSI QuickView is a software designed to provide a graphical user interface (GUI) for greatly speeding up experimental feedback (visualization and analysis) of mass spectrometry imaging (MSI or IMS) data during data acquisition. Often different software loads the entire data set, i.e., all lines of data into computer memory (RAM). This causes out of memory errors for larger datasets. We solved this in MSI QuickView by reading in the data one line at a time. Only the required information (e.g. the final pixel values for that line of heat map) is maintained in RAM. Interim analysis options include the mean intensity vs. m/z spectrum, intensity vs. time spectrums for up to 6 different m/z values or ranges chosen by the user and heat maps for each line. This assists in validating the usefulness of the particular experiment after scanning the first few lines. In addition, the tool facilitates further processing and analysis of the massive datasets. The user can manually pick different m/z values, time ranges, scroll through the spectra for any line in the data without having to load it in manually, save multiple images, change aspect ratios for the heat maps, and process the heat maps in multiple ways including overlaying images at different m/z values, displaying up to 9 different heat maps, alignment of scans along each line etc. There is no manipulation of the data required by the user to visualize the data.

  19. Mass spectrometry of extracellular vesicles.

    PubMed

    Pocsfalvi, Gabriella; Stanly, Christopher; Vilasi, Annalisa; Fiume, Immacolata; Capasso, Giovambattista; Turiák, Lilla; Buzas, Edit I; Vékey, Károly

    2016-01-01

    The review briefly summaries main features of extracellular vesicles, a joint terminology for exosomes, microvesicles, and apoptotic vesicles. These vesicles are in the center of interest in biology and medical sciences, and form a very active field of research. Mass spectrometry (MS), with its specificity and sensitivity, has the potential to identify and characterize molecular composition of these vesicles; but as yet there are only a limited, but fast-growing, number of publications that use MS workflows in this field. MS is the major tool to assess protein composition of extracellular vesicles: qualitative and quantitative proteomics approaches are both reviewed. Beside proteins, lipid and metabolite composition of vesicles might also be best assessed by MS techniques; however there are few applications as yet in this respect. The role of alternative analytical approaches, like gel-based proteomics and antibody-based immunoassays, are also mentioned. The objective of the review is to give an overview of this fast-growing field to help orient MS-based research on extracellular vesicles. © 2015 Wiley Periodicals, Inc.

  20. Broadband Analysis of Bioagents by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Fenselau, Catherine; Wynne, Colin; Edwards, Nathan

    Mass spectrometry was first reported to provide analysis of intact metabolite biomarkers from whole cells in 1975.1 Since then advances in ionization techniques have extended our capabilities to polar lipids and, eventually, to proteins.2, 3 Mass spectrometry provides a broadband detection system, which, however, has great specificity. Bioinformatics plays an important role in providing flexible and rapid characterization of species, based on protein and peptide mass spectra collected in the field.

  1. Mass spectrometry analysis of nucleosides and nucleotides.

    PubMed

    Dudley, Ed; Bond, Liz

    2014-01-01

    Mass spectrometry has been widely utilised in the study of nucleobases, nucleosides and nucleotides as components of nucleic acids and as bioactive metabolites in their own right. In this review, the application of mass spectrometry to such analysis is overviewed in relation to various aspects regarding the analytical mass spectrometric and chromatographic techniques applied and also the various applications of such analysis. © 2013 Wiley Periodicals, Inc.

  2. Application of mass spectrometry in proteomics.

    PubMed

    Guerrera, Ida Chiara; Kleiner, Oliver

    2005-01-01

    Mass spectrometry has arguably become the core technology in proteomics. The application of mass spectrometry based techniques for the qualitative and quantitative analysis of global proteome samples derived from complex mixtures has had a big impact in the understanding of cellular function. Here, we give a brief introduction to principles of mass spectrometry and instrumentation currently used in proteomics experiments. In addition, recent developments in the application of mass spectrometry in proteomics are summarised. Strategies allowing high-throughput identification of proteins from highly complex mixtures include accurate mass measurement of peptides derived from total proteome digests and multidimensional peptide separations coupled with mass spectrometry. Mass spectrometric analysis of intact proteins permits the characterisation of protein isoforms. Recent developments in stable isotope labelling techniques and chemical tagging allow the mass spectrometry based differential display and quantitation of proteins, and newly established affinity procedures enable the targeted characterisation of post-translationally modified proteins. Finally, advances in mass spectrometric imaging allow the gathering of specific information on the local molecular composition, relative abundance and spatial distribution of peptides and proteins in thin tissue sections.

  3. Aerosol Organic Matter-Trace Metal Relationships Revealed by Ultra-High Resolution Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Wozniak, A. S.; Sleighter, R. L.; Morton, P. L.; Landing, W. M.; Shelley, R. U.; Hatcher, P. G.

    2011-12-01

    Atmospheric delivery of aerosols is important for the biogeochemical cycling of organic matter (OM) and trace elements in marine environments. Aerosols over marine environments can be derived from marine sources or transported from continental regions of variable vegetative cover and anthropogenic influence. These different sources are key determinants of aerosol OM composition, as well as trace metal amounts and characteristics. Dust-influenced aerosols typically contain higher amounts of Fe than anthropogenic-influenced aerosols but have lesser % of soluble Fe (%FeS), believed to be the bioavailable form of Fe for marine phytoplankton. Four samples from the 2008 GEOTRACES intercalibration experiments (Miami, FL, USA) were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and related to both air mass back trajectories and %FeS. Three samples showed aerosol sources from the east consistent with Saharan dust inputs, while the fourth sample was derived in part from air masses to the north, influenced by the North American continent. This North American-influenced sample was collected following the 3 day period with the highest %FeS (1.3-1.7%) of the 11 day intercalibration experiment (mean = 0.4-1.1%). FT-ICR mass spectra showed 795 peaks common to the dust-influenced samples but absent from the North American-influenced sample. These peaks were assigned molecular formulas characterized by CHO and CHON compounds with lower H/C and O/C ratios than the 1257 formulas common to all 4 samples, suggesting that the dust-influenced aerosols carry OM that is less oxygenated and more condensed in structure along with Fe of lesser solubility. Air mass trajectory analyses revealed samples collected during a 2010 cruise in the North Atlantic Ocean to be characterized by European-influenced (anthropogenic), African-influenced (dust), and primarily marine air masses, making them ideal for further exploration of the

  4. Elucidating the site of protein-ATP binding by top-down mass spectrometry.

    PubMed

    Yin, Sheng; Loo, Joseph A

    2010-06-01

    A Fourier-transform ion cyclotron resonance (FT-ICR) top-down mass spectrometry strategy for determining the adenosine triphosphate (ATP)-binding site on chicken adenylate kinase is described. Noncovalent protein-ligand complexes are readily detected by electrospray ionization mass spectrometry (ESI-MS), but the ability to detect protein-ligand complexes depends on their stability in the gas phase. Previously, we showed that collisionally activated dissociation (CAD) of protein-nucleotide triphosphate complexes yield products from the dissociation of a covalent phosphate bond of the nucleotide with subsequent release of the nucleotide monophosphate (Yin, S. et al., J. Am. Soc. Mass Spectrom. 2008, 19, 1199-1208). The intrinsic stability of electrostatic interactions in the gas phase allows the diphosphate group to remain noncovalently bound to the protein. This feature is exploited to yield positional information on the site of ATP-binding on adenylate kinase. CAD and electron capture dissociation (ECD) of the adenylate kinase-ATP complex generate product ions bearing mono- and diphosphate groups from regions previously suggested as the ATP-binding pocket by NMR and crystallographic techniques. Top-down MS may be a viable tool to determine the ATP-binding sites on protein kinases and identify previously unknown protein kinases in a functional proteomics study. Copyright 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  5. Glycosylation characterization of therapeutic mAbs by top- and middle-down mass spectrometry.

    PubMed

    Tran, Bao Quoc; Barton, Christopher; Feng, Jinhua; Sandjong, Aimee; Yoon, Sung Hwan; Awasthi, Shivangi; Liang, Tao; Khan, Mohd M; Kilgour, David P A; Goodlett, David R; Goo, Young Ah

    2016-03-01

    A reference monoclonal antibody IgG1 and a fusion IgG protein were analyzed by top- and middle-down mass spectrometry with multiple fragmentation techniques including electron transfer dissociation (ETD) and matrix-assisted laser desorption ionization in-source decay (MALDI-ISD) to investigate heterogeneity of glycosylated protein species. Specifically, glycan structure, sites, relative abundance levels, and termini structural conformation were investigated by use of Fourier transform ion cyclotron resonance (FT-ICR) or high performance liquid chromatography electrospray ionization (HPLC-ESI) linked to an Orbitrap. Incorporating a limited enzymatic digestion by immunoglobulin G-degrading enzyme Streptococcus pyogenes (IdeS) with MALDI-ISD analysis extended sequence coverage of the internal region of the proteins without pre-fractionation. The data in this article is associated with the research article published in Journal of Proteomics (Tran et al., 2015) [1].

  6. Methods for recalibration of mass spectrometry data

    DOEpatents

    Tolmachev, Aleksey V.; Smith, Richard D.

    2009-03-03

    Disclosed are methods for recalibrating mass spectrometry data that provide improvement in both mass accuracy and precision by adjusting for experimental variance in parameters that have a substantial impact on mass measurement accuracy. Optimal coefficients are determined using correlated pairs of mass values compiled by matching sets of measured and putative mass values that minimize overall effective mass error and mass error spread. Coefficients are subsequently used to correct mass values for peaks detected in the measured dataset, providing recalibration thereof. Sub-ppm mass measurement accuracy has been demonstrated on a complex fungal proteome after recalibration, providing improved confidence for peptide identifications.

  7. Extension of the analytical window for characterizing aromatic compounds in oils using a comprehensive suite of high-resolution mass spectrometry techniques and double bond equivalence versus carbon number plot

    USGS Publications Warehouse

    Cho, Yunju; Birdwell, Justin E.; Hur, Manhoi; Lee, Joonhee; Kim, Byungjoo; Kim, Sunghwan

    2017-01-01

    In this study, comprehensive two-dimensional (2D) gas chromatography–mass spectrometry (GC–MS), atmospheric pressure photoionization (APPI) quadrupole-Orbitrap mass spectrometry (MS), and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) were used to study the aromatic fractions of crude oil and oil shale pyrolysates (shale oils). The collected data were compared and combined in the double bond equivalence (DBE) versus carbon number plot to obtain a more complete understanding of the composition of the oil fractions. The numbers of peaks observed by each technique followed the order 2D GC–MS < Orbitrap MS < FT-ICR MS. The class distributions observed by Orbitrap MS and FT-ICR MS were similar to each other but different from that observed by 2D GC–MS. The DBE and carbon number distributions of the 2D GC–MS and Orbitrap MS data were similar for crude oil aromatics. The FT-ICR MS plots of DBE and carbon number showed an extended range of higher values relative to the other methods. For the aromatic fraction of an oil shale pyrolysate generated by the Fischer assay, only a few nitrogen-containing compounds were observed by 2D GC–MS but a large number of these compounds were detected by Orbitrap MS and FT-ICR MS. This comparison clearly shows that the data obtained from these three techniques can be combined to more completely characterize oil composition. The data obtained by Orbitrap MS and FT-ICR MS agreed well with one another, and the combined DBE versus carbon number plot provided more complete coverage of compounds present in the fractions. In addition, the chemical structure information provided by 2D GC–MS could be matched with the chemical formulas in the DBE versus carbon number plots, providing information not available in ultrahigh-resolution MS results. It was therefore concluded that the combination of 2D GC–MS, Orbitrap MS, and FT-ICR MS in the DBE versus carbon number space facilitates structural assignment of heavy

  8. Analysis of carbon and nitrogen co-metabolism in yeast by ultrahigh-resolution mass spectrometry applying 13C- and 15N-labeled substrates simultaneously.

    PubMed

    Blank, Lars M; Desphande, Rahul R; Schmid, Andreas; Hayen, Heiko

    2012-06-01

    Alternative metabolic pathways inside a cell can be deduced using stable isotopically labeled substrates. One prerequisite is accurate measurement of the labeling pattern of targeted metabolites. Experiments are generally limited to the use of single-element isotopes, mainly (13)C. Here, we demonstrate the application of direct infusion nanospray, ultrahigh-resolution Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS) for metabolic studies using differently labeled elemental isotopes simultaneously--i.e., (13)C and (15)N--in amino acids of a total protein hydrolysate. The optimized strategy for the analysis of metabolism by a hybrid linear ion trap-FTICR-MS comprises the collection of multiple adjacent selected ion monitoring scans. By limiting both the width of the mass range and the number of ions entering the ICR cell with automated gain control, sensitive measurements of isotopologue distribution were possible without compromising mass accuracy and isotope intensity mapping. The required mass-resolving power of more than 60,000 is only achievable on a routine basis by FTICR and Orbitrap mass spectrometers. Evaluation of the method was carried out by comparison of the experimental data to the natural isotope abundances of selected amino acids and by comparison to GC/MS results obtained from a labeling experiment with (13)C-labeled glucose. The developed method was used to shed light on the complexity of the yeast Saccharomyces cerevisiae carbon-nitrogen co-metabolism by administering both (13)C-labeled glucose and (15)N-labeled alanine. The results indicate that not only glutamate but also alanine acts as an amino donor during alanine and valine synthesis. Metabolic studies using FTICR-MS can exploit new possibilities by the use of multiple-labeled elemental isotopes.

  9. Universal Mass Spectrometry-Based Life Detection

    NASA Astrophysics Data System (ADS)

    Cleaves, H. J.; Giri, C.

    2017-02-01

    The search for ET life will be an important 21st century solar system exploration goal. Mass spectrometry offers a comprehensive, rapid way of "chemotyping" environmental samples. Preparation of a reference catalogue of abiotic and biological samples is described.

  10. Plasma Desorption Mass Spectrometry: Coming of Age.

    ERIC Educational Resources Information Center

    Cotter, Robert J.

    1988-01-01

    Discusses the history and development of Plasma Desorption Mass Spectrometry to determine molecular weights and structures of proteins and polymers. Outlines theory, instrumentation, and sample preparation commonly used. Gives several examples of resulting spectra. (ML)

  11. Plasma Desorption Mass Spectrometry: Coming of Age.

    ERIC Educational Resources Information Center

    Cotter, Robert J.

    1988-01-01

    Discusses the history and development of Plasma Desorption Mass Spectrometry to determine molecular weights and structures of proteins and polymers. Outlines theory, instrumentation, and sample preparation commonly used. Gives several examples of resulting spectra. (ML)

  12. A low noise single-transistor transimpedance preamplifier for Fourier-transform mass spectrometry using a T feedback network

    PubMed Central

    Lin, Tzu-Yung; Green, Roger J.; O’Connor, Peter B.

    2012-01-01

    A novel single-transistor transimpedance preamplifier has been introduced for improving performance in Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry. A low noise junction field-effect transistor (JFET), BF862, is used as the main amplification stage of this trans-impedance preamplifier, and a T-shaped feedback network is introduced as both the feedback and the gate biasing solutions. The T feedback network has been studied using an operational amplifier (Op Amp), AD8099. Such a feedback system allows ∼100-fold less feedback resistance at a given transimpedance, hence preserving bandwidth, which is beneficial to applications demanding high gain. The single-transistor preamplifier yields a tested transimpedance of ∼104 Ω (80 dBΩ) in the frequency range between 1 kHz and 1 MHz (mass-to-charge ratio, m/z, of around 180-180k for a 12-T FT-ICR system), with a low power consumption of ∼6 mW, which implies that this preamplifier is well suited to a 12-T FT-ICR mass spectrometer. In trading noise performance for higher trans-impedance, an alternative preamplifier design, an AD8099 preamplifier with the T feedback network, has also been studied with a capability of ∼106 Ω (120 dBΩ) transimpedance in the same frequency range. The resistive components in the T feedback network reported here can be replaced by complex impedances, which allows adaptation of this feedback system to other frequency, transimpedance, and noise characteristics for applications not only in other mass spectrometers, such as Orbitrap, time-of-flight (TOF), and ion trap systems, but also in other charge/current detecting systems such as spectroscopy systems, microscopy systems, optical communication systems, or charge-coupled devices (CCDs). PMID:23020394

  13. Rapid Analysis of Microalgal Triacylglycerols with Direct-Infusion Mass Spectrometry

    SciTech Connect

    Christensen, Earl; Sudasinghe, Nilusha; Dandamudi, Kodanda Phani Raj; Sebag, Robert; Schaub, Tanner; Laurens, Lieve M. L.

    2015-09-01

    Cultivation of microalgae has the potential to provide lipid-derived feedstocks for conversion to liquid transportation fuels. Lipid extracts from microalgae are significantly more complex than those of traditional seed oils, and their composition changes significantly throughout the microalgal growth period. With three acyl side chains per molecule, triglycerides (TAGs) are an important fuel precursor, and the distribution of acyl chain composition for TAGs has a significant impact on fuel properties and processing. Therefore, determination of the distribution of microalgal TAG production is needed to assess the value of algal extracts designed for fuel production and to optimize strain, cultivation, and harvesting practices. Methods utilized for TAG speciation commonly involve complicated and time-consuming chromatographic techniques. Here we present a method for TAG speciation and quantification based on direct-infusion mass spectrometry, which provides rapid characterization of TAG profiles without chromatographic separation. Specifically, we utilize Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to provide a reference library of TAGs for the microalgae Nannochloropsis sp. that provides the basis for high-throughput TAG quantitation by time-of-flight mass spectrometry (TOF MS). In conclusion, we demonstrate the application of this novel approach for lipid characterization with respect to TAG compound distribution, which informs both immediate and future strain and process optimization strategies.

  14. Rapid Analysis of Microalgal Triacylglycerols with Direct-Infusion Mass Spectrometry

    DOE PAGES

    Christensen, Earl; Sudasinghe, Nilusha; Dandamudi, Kodanda Phani Raj; ...

    2015-09-01

    Cultivation of microalgae has the potential to provide lipid-derived feedstocks for conversion to liquid transportation fuels. Lipid extracts from microalgae are significantly more complex than those of traditional seed oils, and their composition changes significantly throughout the microalgal growth period. With three acyl side chains per molecule, triglycerides (TAGs) are an important fuel precursor, and the distribution of acyl chain composition for TAGs has a significant impact on fuel properties and processing. Therefore, determination of the distribution of microalgal TAG production is needed to assess the value of algal extracts designed for fuel production and to optimize strain, cultivation, andmore » harvesting practices. Methods utilized for TAG speciation commonly involve complicated and time-consuming chromatographic techniques. Here we present a method for TAG speciation and quantification based on direct-infusion mass spectrometry, which provides rapid characterization of TAG profiles without chromatographic separation. Specifically, we utilize Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to provide a reference library of TAGs for the microalgae Nannochloropsis sp. that provides the basis for high-throughput TAG quantitation by time-of-flight mass spectrometry (TOF MS). In conclusion, we demonstrate the application of this novel approach for lipid characterization with respect to TAG compound distribution, which informs both immediate and future strain and process optimization strategies.« less

  15. Accounting for isotopic clustering in Fourier transform mass spectrometry data analysis for clinical diagnostic studies.

    PubMed

    Kakourou, Alexia; Vach, Werner; Nicolardi, Simone; van der Burgt, Yuri; Mertens, Bart

    2016-10-01

    Mass spectrometry based clinical proteomics has emerged as a powerful tool for high-throughput protein profiling and biomarker discovery. Recent improvements in mass spectrometry technology have boosted the potential of proteomic studies in biomedical research. However, the complexity of the proteomic expression introduces new statistical challenges in summarizing and analyzing the acquired data. Statistical methods for optimally processing proteomic data are currently a growing field of research. In this paper we present simple, yet appropriate methods to preprocess, summarize and analyze high-throughput MALDI-FTICR mass spectrometry data, collected in a case-control fashion, while dealing with the statistical challenges that accompany such data. The known statistical properties of the isotopic distribution of the peptide molecules are used to preprocess the spectra and translate the proteomic expression into a condensed data set. Information on either the intensity level or the shape of the identified isotopic clusters is used to derive summary measures on which diagnostic rules for disease status allocation will be based. Results indicate that both the shape of the identified isotopic clusters and the overall intensity level carry information on the class outcome and can be used to predict the presence or absence of the disease.

  16. Natural Organic Matter and the Event Horizon of Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hertkorn, N.; Frommberger, M.; Witt, M.; Koch, B. P.; Schmitt-Kopplin, P.; Perdue, E. M.

    2009-05-01

    Soils, sediments, freshwaters and marine waters contain natural organic matter (NOM) - an exceedingly complex mixture of organic compounds that collectively exhibit a nearly continuous range of properties (size- reactivity continuum). NOM is composed mainly of carbon, hydrogen and oxygen, with minor contributions from heteroatoms such as sulphur and phosphorus. Suwannee River fulvic acid (SuwFA) is a fraction of NOM that is relatively depleted in heteroatoms. Ultrahigh resolution Fourier transform ion cyclotron (FTICR) mass spectra of SuwFA reveal several thousand molecular formulae, corresponding in turn to several hundred thousand distinct chemical environments of carbon even without accountancy of isomers. The mass difference m among adjoining C,H,O-molecules between and within clusters of nominal mass is inversely related to molecular dissimilarity: any decrease of m imposes an ever growing mandatory difference in molecular composition. Molecular formulae that are expected for likely biochemical precursor molecules are notably absent from these spectra, indicating that SuwFA is the product of diagenetic reactions that have altered the major components of biomass beyond the point of recognition. The degree of complexity of SuwFA can be brought into sharp focus through comparison with the theoretical limits of chemical complexity, as constrained and quantized by the fundamentals of chemical binding. The theoretical C,H,O-compositional space denotes the isomer-filtered complement of the entire, very vast space of molecular structures composed solely of carbon, hydrogen and oxygen. The molecular formulae within SuwFA occupy a sizable proportion of the theoretical C,H,O-compositional space. A one-hundred percent coverage of the theoretically feasible C,H,O-compositional space by SuwFA molecules is attained throughout a sizable range of mass, H/C and O/C elemental ratios. The substantial differences between (and complementarity of) the SuwFA molecular formulae that

  17. The Use of Accurate Mass Tags based upon High-Throughput Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Global Proteomic Characterization

    SciTech Connect

    Camp, David G.; Smith, Richard D.

    2004-07-30

    In this review, we describe the technological basis and progress towards a new global proteomics strategy that uses peptide accurate mass measurements augmented by information from separations (e.g. LC retention times) to provide large improvements in sensitivity, dynamic range, comprehensiveness and throughput. The use of ?accurate mass and time? (AMT) tags serves to eliminate the need for routine MS/MS measurements [#4109]. As the case study, we use our own research efforts to illustrate the role of AMTs within the broader context of a state-of-the-art proteomics effort. Our strategy exploits high-resolution capillary LC separations combined with Fourier transform ion cyclotron resonance mass spectrometry (FTICR). AMTs represent peptide biomarkers and can be used to confidently identify proteins based on the high mass measurement accuracy provided by FTICR combined with LC elution times. Once identified using MS/MS, these biomarkers provide the foundation for subsequent high throughput studies using only AMT tags to identify and quantify the proteins expressed within a cell system. Key attractions of this approach include the feasibility of completely automated high confidence protein identifications, extensive proteome coverage, and the capability for exploiting stable-isotope labeling methods for high precision abundance measurements [#4019]. Additional developments described in this review include methods for more effective coverage of membrane proteins [#4184], for dynamic range expansion of proteome measurements [#4012], and for multi-stage separations that promise to enable more focused analyses, further extend the quality of measurements, and also extend measurements to more complex proteomes.

  18. Mass spectrometry in the home and garden.

    PubMed

    Pulliam, Christopher J; Bain, Ryan M; Wiley, Joshua S; Ouyang, Zheng; Cooks, R Graham

    2015-02-01

    Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application.

  19. Mass Spectrometry in the Home and Garden

    NASA Astrophysics Data System (ADS)

    Pulliam, Christopher J.; Bain, Ryan M.; Wiley, Joshua S.; Ouyang, Zheng; Cooks, R. Graham

    2015-02-01

    Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application.

  20. Characterization of Polyolefin Pyrolysis Species Produced Under Ambient Conditions by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Ion Mobility-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Farenc, Mathilde; Witt, Matthias; Craven, Kirsten; Barrère-Mangote, Caroline; Afonso, Carlos; Giusti, Pierre

    2017-03-01

    Polyolefins such as polyethylene (PE) and polypropylene (PP) are often characterized from their pyrolysis products by Py-MS. Nowadays the development of plasma-based direct probe atmospheric pressure sources allow the direct analysis of these polymers. These sources operate at atmospheric pressure, which implies a limited control of the ionization conditions. It was shown that side reactions could occur with species present in air, such as O2, which may lead to the formation of oxidized compounds. In this work, ion mobility-mass spectrometry (IM-MS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR) were used for the exhaustive characterization of the PP and PE pyrolysis ions produced using plasma-based atmospheric pressure ion sources. Both PP and PE yielded distributions of pyrolysis products presenting different amounts of unsaturation but also different numbers of oxygen atoms. In addition, the ions produced from PP presented a lower collision cross-section (CCS) than those produced from PE. In the same way, both PP and PE present repeated patterns separated by 14 m/z in the bidimensional drift time versus m/z plots. Within these plots, several trend lines can be evidenced, which are specific of each polymer investigated. Differences were observed between isotactic and atactic samples concerning the pyrolysis profile relative abundance and collision cross-section.

  1. Characterization of Polyolefin Pyrolysis Species Produced Under Ambient Conditions by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Ion Mobility-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Farenc, Mathilde; Witt, Matthias; Craven, Kirsten; Barrère-Mangote, Caroline; Afonso, Carlos; Giusti, Pierre

    2017-01-01

    Polyolefins such as polyethylene (PE) and polypropylene (PP) are often characterized from their pyrolysis products by Py-MS. Nowadays the development of plasma-based direct probe atmospheric pressure sources allow the direct analysis of these polymers. These sources operate at atmospheric pressure, which implies a limited control of the ionization conditions. It was shown that side reactions could occur with species present in air, such as O2, which may lead to the formation of oxidized compounds. In this work, ion mobility-mass spectrometry (IM-MS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR) were used for the exhaustive characterization of the PP and PE pyrolysis ions produced using plasma-based atmospheric pressure ion sources. Both PP and PE yielded distributions of pyrolysis products presenting different amounts of unsaturation but also different numbers of oxygen atoms. In addition, the ions produced from PP presented a lower collision cross-section (CCS) than those produced from PE. In the same way, both PP and PE present repeated patterns separated by 14 m/z in the bidimensional drift time versus m/z plots. Within these plots, several trend lines can be evidenced, which are specific of each polymer investigated. Differences were observed between isotactic and atactic samples concerning the pyrolysis profile relative abundance and collision cross-section.

  2. Reactivity and Selectivity of Charged Phenyl Radicals Toward Amino Acids in a Fourier-Transform Ion Cyclotron Resonance (FT-ICR) Mass Spectrometer

    PubMed Central

    Pates, George O.; Guler, Leonard; Nash, John J.; Kenttämaa, Hilkka I.

    2011-01-01

    The reactivity of ten charged phenyl radicals toward several amino acids was examined in the gas phase in a dual-cell Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. All radicals abstract a hydrogen atom from the amino acids, as expected. The most electrophilic radicals (with a greater calculated vertical electron affinity (EA) at the radical site) also react with these amino acids via NH2 abstraction (a nonradical nucleophilic addition-elimination reaction). Both the radical (hydrogen atom abstraction) and nonradical (NH2 abstraction) reaction efficiencies were found to increase with the electrophilicity (EA) of the radical. However, NH2 abstraction is more strongly influenced by EA. In contrast to an earlier report, the ionization energies of the amino acids do not appear to play a general reactivity controlling role. Studies using several partially deuterium-labeled amino acids revealed that abstraction of a hydrogen atom from the α-carbon is only preferred for glycine; for the other amino acids, a hydrogen atom is preferentially abstracted from the side chain. The electrophilicity of the radicals does not appear to have a major influence on the site from which the hydrogen atom is abstracted. Hence, the regioselectivity of hydrogen atom abstraction appears to be independent of the structure of the radical but dependent on the structure of the amino acid. Surprisingly, abstraction of two hydrogen atoms was observed for the 3-nitro-5-dehydrophenyl pyridinium radical, indicating that substituents on the radical not only influence the EA of the radical but also can be involved in the reaction. In disagreement with an earlier report, proline was found to display several unprecedented reaction pathways that likely do not proceed via a radical mechanism but rather by a nucleophilic addition-elimination mechanism. Both NH2 and 15NH2 groups were abstracted from lysine labeled with 15N on the side-chain, indicating that NH2 abstraction occurs both

  3. Letter: High-mass capabilities of positive-ion and negative-ion direct analysis in real time mass spectrometry.

    PubMed

    Gross, Jürgen H

    2016-01-01

    Of the ionic liquid 1-butyl-3-methylimidazolium (C(+)) tricyanomethide (A(-)) high-mass cluster ions of both positive ([C(n)A(n-1)](+)) and negative ([C(n-1)A(n)](-)) charge were generated and detected by direct analysis in real time (DART) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS). After optimization of the settings of the DART ionization source and of the mass analyzer ions of m/z values unprecedented in DART-MS were detected. Thus, the upper m/z limits of positive-ion and negative-ion DART- MS were substantially expanded. Negative-ion DART-MS delivered cluster ions up to [C(15)A(16)](-), m/z 3527 (nominal mass of monoisotopic ion), while positive-ion DART-MS even yielded ions up to [C(30)A(29)](+), m/z 6784. The identification of the cluster ions is supported by their accurate mass and exact mass differences corresponding to CA between adjacent cluster ion peaks.

  4. Epitope Structure of the Carbohydrate Recognition Domain of Asialoglycoprotein Receptor to a Monoclonal Antibody Revealed by High-Resolution Proteolytic Excision Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Stefanescu, Raluca; Born, Rita; Moise, Adrian; Ernst, Beat; Przybylski, Michael

    2011-01-01

    Recent studies suggest that the H1 subunit of the carbohydrate recognition domain (H1CRD) of the asialoglycoprotein receptor is used as an entry site into hepatocytes by hepatitis A and B viruses and Marburg virus. Thus, molecules binding specifically to the CRD might exert inhibition towards these diseases by blocking the virus entry site. We report here the identification of the epitope structure of H1CRD to a monoclonal antibody by proteolytic epitope excision of the immune complex and high-resolution MALDI-FTICR mass spectrometry. As a prerequisite of the epitope determination, the primary structure of the H1CRD antigen was characterised by ESI-FTICR-MS of the intact protein and by LC-MS/MS of tryptic digest mixtures. Molecular mass determination and proteolytic fragments provided the identification of two intramolecular disulfide bridges (seven Cys residues), and a Cys-mercaptoethanol adduct formed by treatment with β-mercaptoethanol during protein extraction. The H1CRD antigen binds to the monoclonal antibody in both native and Cys-alkylated form. For identification of the epitope, the antibody was immobilized on N-hydroxysuccinimide (NHS)-activated Sepharose. Epitope excision and epitope extraction with trypsin and FTICR-MS of affinity-bound peptides provided the identification of two specific epitope peptides (5-16) and (17-23) that showed high affinity to the antibody. Affinity studies of the synthetic epitope peptides revealed independent binding of each peptide to the antibody.

  5. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

    SciTech Connect

    Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

    2015-03-01

    Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

  6. Glossary of terms for separations coupled to mass spectrometry.

    PubMed

    Murray, Kermit K

    2010-06-18

    This document is a glossary of terms for separations coupled to mass spectrometry. It covers gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and supercritical fluid chromatography/mass spectrometry and the sample introduction, ionization, and data analysis methods used with these combined techniques. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Mass spectrometry: a revolution in clinical microbiology?

    PubMed

    Lavigne, Jean-Philippe; Espinal, Paula; Dunyach-Remy, Catherine; Messad, Nourredine; Pantel, Alix; Sotto, Albert

    2013-02-01

    Recently, different bacteriological laboratory interventions that decrease reporting time have been developed. These promising new broad-based techniques have merit, based on their ability to identify rapidly many bacteria, organisms difficult to grow or newly emerging strains, as well as their capacity to track disease transmission. The benefit of rapid reporting of identification and/or resistance of bacteria can greatly impact patient outcomes, with an improvement in the use of antibiotics, in the reduction of the emergence of multidrug resistant bacteria and in mortality rates. Different techniques revolve around mass spectrometry (MS) technology: matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), PCR combined with electrospray ionization-mass spectrometry (PCR/ESIMS), iPLEX MassArray system and other new evolutions combining different techniques. This report emphasizes the (r)evolution of these technologies in clinical microbiology.

  8. Mass Spectrometry of Intact Membrane Protein Complexes

    PubMed Central

    Laganowsky, Arthur; Reading, Eamonn; Hopper, Jonathan T.S.; Robinson, Carol V.

    2014-01-01

    Mass spectrometry of intact soluble protein complexes has emerged as a powerful technique to study the stoichiometry, structure-function and dynamics of protein assemblies. Recent developments have extended this technique to the study of membrane protein complexes where it has already revealed subunit stoichiometries and specific phospholipid interactions. Here, we describe a protocol for mass spectrometry of membrane protein complexes. The protocol begins with preparation of the membrane protein complex enabling not only the direct assessment of stoichiometry, delipidation, and quality of the target complex, but also evaluation of the purification strategy. A detailed list of compatible non-ionic detergents is included, along with a protocol for screening detergents to find an optimal one for mass spectrometry, biochemical and structural studies. This protocol also covers the preparation of lipids for protein-lipid binding studies and includes detailed settings for a Q-ToF mass spectrometer after introduction of complexes from gold-coated nanoflow capillaries. PMID:23471109

  9. Analytical aspects of hydrogen exchange mass spectrometry

    PubMed Central

    Engen, John R.; Wales, Thomas E.

    2016-01-01

    The analytical aspects of measuring hydrogen exchange by mass spectrometry are reviewed. The nature of analytical selectivity in hydrogen exchange is described followed by review of the analytical tools required to accomplish fragmentation, separation, and the mass spectrometry measurements under restrictive exchange quench conditions. In contrast to analytical quantitation that relies on measurements of peak intensity or area, quantitation in hydrogen exchange mass spectrometry depends on measuring a mass change with respect to an undeuterated or deuterated control, resulting in a value between zero and the maximum amount of deuterium that could be incorporated. Reliable quantitation is a function of experimental fidelity and to achieve high measurement reproducibility, a large number of experimental variables must be controlled during sample preparation and analysis. The method also reports on important qualitative aspects of the sample, including conformational heterogeneity and population dynamics. PMID:26048552

  10. Mass Spectrometry: A Technique of Many Faces

    PubMed Central

    Olshina, Maya A.; Sharon, Michal

    2016-01-01

    Protein complexes form the critical foundation for a wide range of biological process, however understanding the intricate details of their activities is often challenging. In this review we describe how mass spectrometry plays a key role in the analysis of protein assemblies and the cellular pathways which they are involved in. Specifically, we discuss how the versatility of mass spectrometric approaches provides unprecedented information on multiple levels. We demonstrate this on the ubiquitin-proteasome proteolytic pathway, a process that is responsible for protein turnover. We follow the various steps of this degradation route and illustrate the different mass spectrometry workflows that were applied for elucidating molecular information. Overall, this review aims to stimulate the integrated use of multiple mass spectrometry approaches for analyzing complex biological systems. PMID:28100928

  11. Application of Printed Circuit Board Technology to FT-ICR MS Analyzer Cell Construction and Prototyping

    SciTech Connect

    Leach, Franklin E.; Norheim, Randolph V.; Anderson, Gordon A.; Pasa-Tolic, Ljiljana

    2014-12-01

    Although Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS) remains themass spectrometry platform that provides the highest levels of performance for mass accuracy and resolving power, there is room for improvement in analyzer cell design as the ideal quadrupolar trapping potential has yet to be generated for a broadband MS experiment. To this end, analyzer cell designs have improved since the field’s inception, yet few research groups participate in this area because of the high cost of instrumentation efforts. As a step towards reducing this barrier to participation and allowing for more designs to be physically tested, we introduce a method of FT-ICR analyzer cell prototyping utilizing printed circuit boards at modest vacuum conditions. This method allows for inexpensive devices to be readily fabricated and tested over short intervals and should open the field to laboratories lacking or unable to access high performance machine shop facilities because of the required financial investment.

  12. Capillary electrophoresis electrospray ionization mass spectrometry interface

    DOEpatents

    Smith, Richard D.; Severs, Joanne C.

    1999-01-01

    The present invention is an interface between a capillary electrophoresis separation capillary end and an electrospray ionization mass spectrometry emitter capillary end, for transporting an anolyte sample from a capillary electrophoresis separation capillary to a electrospray ionization mass spectrometry emitter capillary. The interface of the present invention has: (a) a charge transfer fitting enclosing both of the capillary electrophoresis capillary end and the electrospray ionization mass spectrometry emitter capillary end; (b) a reservoir containing an electrolyte surrounding the charge transfer fitting; and (c) an electrode immersed into the electrolyte, the electrode closing a capillary electrophoresis circuit and providing charge transfer across the charge transfer fitting while avoiding substantial bulk fluid transfer across the charge transfer fitting. Advantages of the present invention have been demonstrated as effective in providing high sensitivity and efficient analyses.

  13. Identification of Mercury and Dissolved Organic Matter Complexes Using Ultrahigh Resolution Mass Spectrometry

    SciTech Connect

    Chen, Hongmei; Johnston, Ryne C.; Chu, Rosalie K.; Tolic, Nikola; Parks, Jerry M.

    2016-12-22

    The chemical speciation and bioavailability of mercury (Hg) is markedly influenced by its complexation with naturally dissolved organic matter (DOM) in aquatic environments. To date, however, analytical methodologies capable of identifying such complexes are scarce. Here in this paper, we utilize ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) coupled with electrospray ionization to identify individual Hg–DOM complexes. The measurements were performed by direct infusion of DOM in a 1:1 methanol:water solution at a Hg to dissolved organic carbon (DOC) molar ratio of 3 × 10–4. Heteroatomic molecules, especially those containing multiple S and N atoms, were found to be among the most important in forming strong complexes with Hg. Major Hg–DOM complexes of C10H21N2S4Hg+ and C8H17N2S4Hg+ were identified based on both the exact molecular mass and patterns of Hg stable isotope distributions detected by FTICR-MS. Density functional theory was used to predict the solution-phase structures of candidate molecules. Finally, these findings represent the first step to unambiguously identify specific DOM molecules in Hg binding, although future studies are warranted to further optimize and validate the methodology so as to explore detailed molecular compositions and structures of Hg–DOM complexes that affect biological uptake and transformation of Hg in the environment.

  14. Arabica and robusta coffees: identification of major polar compounds and quantification of blends by direct-infusion electrospray ionization-mass spectrometry.

    PubMed

    Garrett, Rafael; Vaz, Boniek G; Hovell, Ana Maria C; Eberlin, Marcos N; Rezende, Claudia M

    2012-05-02

    Considering that illegal admixture of robusta coffee into high-quality arabica coffee is an important task in coffee analysis, we evaluated the use of direct-infusion electrospray ionization-mass spectrometry (ESI-MS) data combined with the partial least-squares (PLS) multivariate calibration technique as a fast way to detect and quantify arabica coffee adulterations by robusta coffee. A total of 16 PLS models were built using ESI± quadrupole time-of-flight (QTOF) and ESI± Fourier transform ion cyclotron resonance (FT-ICR) MS data from hot aqueous extracts of certified coffee samples. The model using the 30 more abundant ions detected by ES+ FT-ICR MS produced the most accurate coffee blend percentage prediction, and thus, it was later successfully employed to predict the blend composition of commercial robusta and arabica coffee. In addition, ESI± FT-ICR MS analysis allowed for the identification of 22 compounds in the arabica coffee and 20 compounds in the robusta coffee, mostly phenolics.

  15. Comparing Laser Desorption Ionization and Atmospheric Pressure Photoionization Coupled to Fourier Transform Ion Cyclotron Resonance Mass Spectrometry To Characterize Shale Oils at the Molecular Level

    USGS Publications Warehouse

    Cho, Yunjo; Jin, Jang Mi; Witt, Matthias; Birdwell, Justin E.; Na, Jeong-Geol; Roh, Nam-Sun; Kim, Sunghwan

    2013-01-01

    Laser desorption ionization (LDI) coupled to Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to analyze shale oils. Previous work showed that LDI is a sensitive ionization technique for assessing aromatic nitrogen compounds, and oils generated from Green River Formation oil shales are well-documented as being rich in nitrogen. The data presented here demonstrate that LDI is effective in ionizing high-double-bond-equivalent (DBE) compounds and, therefore, is a suitable method for characterizing compounds with condensed structures. Additionally, LDI generates radical cations and protonated ions concurrently, the distribution of which depends upon the molecular structures and elemental compositions, and the basicity of compounds is closely related to the generation of protonated ions. This study demonstrates that LDI FT-ICR MS is an effective ionization technique for use in the study of shale oils at the molecular level. To the best of our knowledge, this is the first time that LDI FT-ICR MS has been applied to shale oils.

  16. Accurate mass analysis of N-acyl-homoserine-lactones and cognate lactone-opened compounds in bacterial isolates of Pseudomonas aeruginosa PAO1 by LC-ESI-LTQ-FTICR-MS.

    PubMed

    Cataldi, Tommaso R I; Bianco, Giuliana; Abate, Salvatore

    2009-02-01

    N-acyl-homoserine-lactones (AHSLs) are widely conserved signal molecules present in quorum sensing systems of Gram-negative bacteria such as Pseudomonas aeruginosa. We present here the results obtained with a hybrid linear trap/Fourier transform ion cyclotron resonance (LTQ-FTICR) mass spectrometer used to investigate the occurrence of AHSLs and cognate N-acyl-homoserines (AHSs) in bacterial isolates of P. aeruginosa (strain PAO1). Two hydrolysed AHSs were found in significant amounts, most likely formed through the lactone opening of N-3-oxo-decanoyl-L-homoserine-lactone (3OC10-HSL) and N-3-oxo-dodecanoyl-L-homoserine-lactone (3OC12-HSL). Structure elucidation of these ring-opened molecules, i.e. N-3-oxo-decanoyl-L-homoserine (3OC10-HS), and N-3-oxo-dodecanoyl-L-homoserine (3OC12-HS), which are not detected by bacterial biosensors, was performed by high-resolution and accurate mass measurements upon liquid chromatography (LC) and confirmed by tandem MS in the LTQ analyser. Assignment of chemical formula, with mass spectra in the form of [M+H]+, was significantly expedited by extracted ion chromatograms (XICs) because the number of potentially plausible formulae for each protonated signalling molecule was considerably reduced a priori by the LC behaviour, the high mass measurement accuracy available in FTICR mass spectra and the isotopic patterns. At least two concentration levels were observed in spent culture supernatants of P. aeruginosa: compounds at a relatively high content (5-15 microM) that is C4-HSL, 3OC10-HS, and 3OC12-HS and those occurring at a lower content (<0.2 microM) that is C6-HSL and C8-HSL. The implications of this work extend to a great variety of Gram-negative bacteria.

  17. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

    Discusses reactions and characteristics of fast atom bombardment (FAB) mass spectroscopy in which samples are ionized in a condensed state by bombardment with xenon or argon atoms, yielding positive/negative secondary ions. Includes applications of FAB to structural problems and considers future developments using the technique. (Author/JN)

  18. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

    Discusses reactions and characteristics of fast atom bombardment (FAB) mass spectroscopy in which samples are ionized in a condensed state by bombardment with xenon or argon atoms, yielding positive/negative secondary ions. Includes applications of FAB to structural problems and considers future developments using the technique. (Author/JN)

  19. Enumeration of carboxyl groups carried on individual components of humic systems using deuteromethylation and Fourier transform mass spectrometry.

    PubMed

    Zherebker, Alexander; Kostyukevich, Yury; Kononikhin, Alexey; Kharybin, Oleg; Konstantinov, Andrey I; Zaitsev, Kirill V; Nikolaev, Eugene; Perminova, Irina V

    2017-03-01

    Here, we report a novel approach to enumeration of carboxylic groups carried by individual molecules of humic substances using selective chemical modification and isotopic labeling (deuteromethylation) and high-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS). Esterification was conducted with a use of thionyl chloride-deuteromethanol reagent under mild conditions to avoid transesterification. The deuteromethylated products were subjected to solid phase extraction using PPL Bond Elute cartridges prior to FTICR MS analysis. An amount of carboxyl groups in the individual molecular component was estimated from the length of identified deuteromethylation series. The method allowed for discerning between compounds with close elemental compositions possessing different protolytic properties. We found that different carboxylic moieties occupy distinct regions in molecular space of humic substances (HS) projected onto Van Krevelen diagram. These locations do not depend on the source of the humic material and can be assigned to carboxyl-rich alicyclic molecules (5 to 6 COOH), hydrolyzable tannins (3-4 COOH), lignins (1 to 2 COOH), condensed tannins and lignans (0 to 1 COOH), and carbohydrates (0 COOH). At the same time, the alignment pattern of these carboxylated species along the structural evolution lines in Van Krevelen diagrams was characteristic to the specific transformation processes undergone by the humic materials in the different environments. The obtained data enable mapping of molecular ensemble of HS with regards to their specific acidic compartments and might be used for directed fractionation of HS. Graphical abstract Selective isotopic labeling followed by FTICR MS enables discerning between humic molecules with close elemental compositions carrying different numbers of carboxylic groups.

  20. A "screened" electrostatic ion trap for enhanced mass resolution, mass accuracy, reproducibility, and upper mass limit in Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Wang, M; Marshall, A G

    1989-06-01

    Until now, it was thought that the optimal static electromagnetic ion trap for Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry should be designed to produce a quadrupolar electrical potential, for which the ion cyclotron frequency is independent of the ion's preexcitation location within the trap. However, a quadrupolar potential results in a transverse (to the magnetic field) electric field that increases linearly with distance from the center of the trap. That radially linear electric field shifts the observed ICR frequency, increases the ICR orbital radius, and ultimately limits the highest mass-to-charge ratio ion that can be contained within the trap. In this paper, we propose a new static electromagnetic ion "trap" in which grounded screens placed just inside the usual "trapping" plates produce a good approximation to a "particle-in-a-box" potential (rather than the quadrupolar "harmonic oscillator" potential). SIMION calculations confirm that the electric potential of the screened trap is near zero almost everywhere within the trap. For our screened orthorhombic (2.5 in. X 2 in. X 2 in.) trap, the experimental ICR frequency shift due to trapping voltage is reduced by a factor of approximately 100, and the experimental variation of ICR frequency with ICR radius is reduced by a factor of approximately 10 compared to a conventional (unscreened) 2-in. cubic ion trap.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. A history of mass spectrometry in Australia.

    PubMed

    Downard, Kevin M; de Laeter, John R

    2005-09-01

    An interest in mass spectrometry in Australia can be traced back to the 1920s with an early correspondence with Francis Aston who first visited these shores a decade earlier. The region has a rich tradition in both the development of the field and its application, from early measurements of ionization and appearance potentials by Jim Morrison at the Council for Scientific and Industrial Research (CSIR) around 1950 to the design and construction of instrumentation including the first use of a triple quadrupole mass spectrometer for tandem mass spectrometry, the first suite of programs to simulate ion optics (SIMION), the development of early TOF/TOF instruments and orthogonal acceleration and the local design and construction of several generations of a sensitive high-resolution ion microprobe (SHRIMP) instrument. Mass spectrometry has been exploited in the study and characterization of the constituents of this nation's unique flora and fauna from Australian apples, honey, tea plant and eucalyptus oil, snake, spider, fish and frog venoms, coal, oil, sediments and shale, environmental studies of groundwater to geochronological dating of limestone and granite, other terrestrial and meteoritic rocks and coral from the Great Barrier Reef. Peter Jeffery's establishment of geochronological dating techniques in Western Australia in the early 1950s led to the establishment of geochronology research both at the Australian National University and at what is now the Curtin Institute of Technology in the 1960s. This article traces the history of mass spectrometry in its many guises and applications in the island continent of Australia. An article such as this can never be complete. It instead focuses on contributions of scientists who played a major role in the early establishment of mass spectrometry in Australia. In general, those who are presently active in the field, and whose histories are incomplete, have been mentioned at best only briefly despite their important

  2. Targeted Quantitation of Proteins by Mass Spectrometry

    PubMed Central

    2013-01-01

    Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

  3. Laser desorption mass spectrometry for molecular diagnosis

    NASA Astrophysics Data System (ADS)

    Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Allman, S. L.; Tang, K.; Matteson, K. J.; Chang, L. Y.; Chung, C. N.; Martin, Steve; Haff, Lawrence

    1996-04-01

    Laser desorption mass spectrometry has been used for molecular diagnosis of cystic fibrosis. Both 3-base deletion and single-base point mutation have been successfully detected by clinical samples. This new detection method can possibly speed up the diagnosis by one order of magnitude in the future. It may become a new biotechnology technique for population screening of genetic disease.

  4. Pyrolysis Mass Spectrometry of Complex Organic Materials.

    ERIC Educational Resources Information Center

    Meuzelaar, Henk L. C.; And Others

    1984-01-01

    Illustrates the state of the art in pyrolysis mass spectrometry techniques through applications in: (1) structural determination and quality control of synthetic polymers; (2) quantitative analysis of polymer mixtures; (3) classification and structural characterization of fossil organic matter; and (4) nonsupervised numerical extraction of…

  5. Pyrolysis Mass Spectrometry of Complex Organic Materials.

    ERIC Educational Resources Information Center

    Meuzelaar, Henk L. C.; And Others

    1984-01-01

    Illustrates the state of the art in pyrolysis mass spectrometry techniques through applications in: (1) structural determination and quality control of synthetic polymers; (2) quantitative analysis of polymer mixtures; (3) classification and structural characterization of fossil organic matter; and (4) nonsupervised numerical extraction of…

  6. Nanostructure-initiator mass spectrometry biometrics

    DOEpatents

    Leclerc, Marion; Bowen, Benjamin; Northen, Trent

    2015-09-08

    Several embodiments described herein are drawn to methods of identifying an analyte on a subject's skin, methods of generating a fingerprint, methods of determining a physiological change in a subject, methods of diagnosing health status of a subject, and assay systems for detecting an analyte and generating a fingerprint, by nanostructure-initiator mass spectrometry (NIMS).

  7. Higher-Resolution Data-Dependent Selective External Ion Accumulation for Capillary LC-FTICR.

    SciTech Connect

    Belov, Mikhail E. ); Anderson, Gordon A. ); Smith, Richard D. )

    2002-07-15

    Data-dependent selective external ion ejection with improved resolution is demonstrated with a 3.5 tesla FTICR instrument employing DREAMS (Dynamic Range Enhancement Applied to Mass Spectrometry) technology. To correct for the fringing rf-field aberrations each rod of the selection quadrupole has been segmented into three sections, so that ion excitation and ejection was performed by applying auxiliary rf-only waveforms in the region of the middle segments. Two different modes of external ion trapping and ejection were studied with the mixtures of model peptides and a tryptic digest of bovine serum albumin. A mass resolution of about 100 has been attained for rf-only dipolar ejection in a quadrupole operating at a Mathieu parameter q of{approx} 0.45. LC-ESI-DREAMS-FTICR analysis of a 0.1 mg/mL solution of bovine serum albumin digest resulted in detection of 82 unique tryptic peptides with mass measurement errors lower than 5 ppm, providing 100% sequence coverage of the protein.

  8. Higher-Resolution Data-Dependent Selective External ION Accumulation for Capillary LC-FTICR

    SciTech Connect

    Belov, Mikhail E.; Anderson, Gordon A.; Smith, Richard D.

    2002-07-15

    Data-dependent selective external ion ejection with improved resolution is demonstrated with a 3.5 tesla FTICR instrument employing DREAMS (Dynamic Range Enhancement Applied to Mass Spectrometry) technology. To correct for the fringing rf-field aberrations each rod of the selection quadrupole has been segmented into three sections, so that ion excitation and ejection was performed by applying auxiliary rf-only waveforms in the region of the middle segments. Two different modes of external ion trapping and ejection were studied with the mixtures of model peptides and a tryptic digest of bovine serum albumin. A mass resolution of about 100 had been attained for rf-only dipolar ejection in a quadrupole operating at a Mathieu parameter q of ~0.45. LC-ESI-DREAMS-FTICR analysis of a 0.1 mg/mL solution of bovine serum albumin digest resulted in detection of 82 unique tryptic peptides with mass measurement errors lower than 5 ppm, providing 100 % sequence coverage of the protein.

  9. Optimization Of A Mass Spectrometry Process

    SciTech Connect

    Lopes, Jose; Alegria, F. Correa; Redondo, Luis; Barradas, N. P.; Alves, E.; Rocha, Jorge

    2011-06-01

    In this paper we present and discuss a system developed in order to optimize the mass spectrometry process of an ion implanter. The system uses a PC to control and display the mass spectrum. The operator interacts with the I/O board, that interfaces with the computer and the ion implanter by a LabVIEW code. Experimental results are shown and the capabilities of the system are discussed.

  10. The significance of monoisotopic and carbon-13 isobars for the identification of a 19-component dodecapeptide library by positive ion electrospray Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Ramjit, H G; Kruppa, G H; Spier, J P; Ross, C W; Garsky, V M

    2000-01-01

    Harnessing the ultra high resolution capabilities of Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and positive ion electrospray, we have demonstrated the significance and utility of cumulative mass defect high resolution mass separation stable isotope distribution, exact mass measurement and elemental formula as a means of simultaneously identifying 19 components of the dodecapeptide library Ac-ANKISYQS[X]STE-NH(2). With an instrument resolution of 275 000 (average), isobaric multiplets attributed to monoisotopic and carbon-13 components of peptides: Ac approximately SLS approximately NH(2); Ac approximately SNS approximately NH(2); Ac approximately SOS approximately NH(2); Ac approximately SDS approximately NH(2); within the mass window of 1380-1385 Da, and Ac approximately SQS approximately NH(2); Ac approximately SKS approximately NH(2); Ac approximately SES approximately NH(2); Ac approximately SMS approximately NH(2), within the mass window 1395-1400 Da, were mass resolved, accurately mass measured and identified from the computed molecular formulas. This experimental procedure enabled the separation of monoisotopic and carbon-13 isobars yielding enhanced selectivity and specificity and serves to illustrate the significance of monoisotopic and carbon-13 isobars in final product analysis. Chromatographic separation (HPLC) was of limited utility except for monitoring the overall extent of reaction and apparent product distribution. Positive ion electrospray-FTICR-MS and fast atom bombardment (FAB) MS were used to assess final product quality and apparent component distribution.

  11. MALDI Imaging Mass Spectrometry Spatially Maps Age-Related Deamidation and Truncation of Human Lens Aquaporin-0

    PubMed Central

    Wenke, Jamie L.; Rose, Kristie L.; Spraggins, Jeffrey M.; Schey, Kevin L.

    2015-01-01

    Purpose To spatially map human lens Aquaporin-0 (AQP0) protein modifications, including lipidation, truncation, and deamidation, from birth through middle age using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). Methods Human lens sections were water-washed to facilitate detection of membrane protein AQP0. We acquired MALDI images from eight human lenses ranging in age from 2 months to 63 years. In situ tryptic digestion was used to generate peptides of AQP0 and peptide images were acquired on a 15T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Peptide extracts were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and database searched to identify peptides observed in MALDI imaging experiments. Results Unmodified, truncated, and fatty acid–acylated forms of AQP0 were detected in protein imaging experiments. Full-length AQP0 was fatty acid acylated in the core and cortex of young (2- and 4-month) lenses. Acylated and unmodified AQP0 were C-terminally truncated in older lens cores. Deamidated tryptic peptides (+0.9847 Da) were mass resolved from unmodified peptides by FTICR MS. Peptide images revealed differential localization of un-, singly-, and doubly-deamidated AQP0 C-terminal peptide (239–263). Deamidation was present at 4 months and increases with age. Liquid chromatography–MS/MS results indicated N246 undergoes deamidation more rapidly than N259. Conclusions Results indicated AQP0 fatty acid acylation and deamidation occur during early development. Progressive age-related AQP0 processing, including deamidation and truncation, was mapped in human lenses as a function of age. The localization of these modified AQP0 forms suggests where AQP0 functions may change throughout lens development and aging. PMID:26574799

  12. Application of mass spectrometry for metabolite identification.

    PubMed

    Ma, Shuguang; Chowdhury, Swapan K; Alton, Kevin B

    2006-06-01

    Metabolism studies play a pivotal role in drug discovery and development. Characterization of metabolic "hot-spots" as well as reactive and pharmacologically active metabolites is critical to designing new drug candidates with improved metabolic stability, toxicological profile and efficacy. Metabolite identification in the preclinical species used for safety evaluation is required in order to determine whether human metabolites have been adequately tested during non-clinical safety assessment. From an instrumental standpoint, high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) dominates all analytical tools used for metabolite identification. The general strategies employed for metabolite identification in both drug discovery and drug development settings together with sample preparation techniques are reviewed herein. These include a discussion of the various ionization methods, mass analyzers, and tandem mass spectrometry (MS/MS) techniques that are used for structural characterization in a modern drug metabolism laboratory. Mass spectrometry-based techniques, such as stable isotope labeling, on-line H/D exchange, accurate mass measurement to enhance metabolite identification and recent improvements in data acquisition and processing for accelerating metabolite identification are also described. Rounding out this review, we offer additional thoughts about the potential of alternative and less frequently used techniques such as LC-NMR/MS, CRIMS and ICPMS.

  13. Continuous summer export of nitrogen-rich organic matter from the Greenland Ice Sheet inferred by ultrahigh resolution mass spectrometry.

    PubMed

    Lawson, Emily C; Bhatia, Maya P; Wadham, Jemma L; Kujawinski, Elizabeth B

    2014-12-16

    Runoff from glaciers and ice sheets has been acknowledged as a potential source of bioavailable dissolved organic matter (DOM) to downstream ecosystems. This source may become increasingly significant as glacial melt rates increase in response to future climate change. Recent work has identified significant concentrations of bioavailable carbon and iron in Greenland Ice Sheet (GrIS) runoff. The flux characteristics and export of N-rich DOM are poorly understood. Here, we employed electrospray ionization (ESI) coupled to Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to determine the elemental compositions of DOM molecules in supraglacial water and subglacial runoff from a large GrIS outlet glacier. We provide the first detailed temporal analysis of the molecular composition of DOM exported over a full melt season. We find that DOM pools in supraglacial and subglacial runoff are compositionally diverse and that N-rich material is continuously exported throughout the melt season, as the snowline retreats further inland. Identification of protein-like compounds and a high proportion of N-rich DOM, accounting for 27-41% of the DOM molecules identified by ESI FT-ICR MS, may suggest a microbial provenance and high bioavailability of glacially exported DOM to downstream microbial communities.

  14. Isotope ratio measurements by secondary ion mass spectrometry (SIMS) and glow discharge mass spectrometry (GDMS)

    NASA Astrophysics Data System (ADS)

    Betti, Maria

    2005-04-01

    The basic principles of secondary ion mass spectrometry and glow discharge mass spectrometry have been shortly revisited. The applications of both techniques as exploited for the isotope ratio measurements in several matrices have been reviewed. Emphasis has been given to research fields in expansions such as solar system studies, medicine, biology, environment and nuclear forensic. The characteristics of the two techniques are discussed in terms of sensitivity and methodology of quantification. Considerations on the different detection possibilities in SIMS are also presented.

  15. Microbial proteomics using mass spectrometry.

    PubMed

    Hines, Harry B

    2012-01-01

    Proteomic analyses involve a series of intricate, interdependent steps involving approaches and technical issues that must be fully coordinated to obtain the optimal amount of required information about the test subject. Fortunately, many of these steps are common to most test subjects, requiring only modifications to or, in some cases, substitution of some of the steps to ensure they are relevant to the desired objective of a study. This fortunate occurrence creates an essential core of proteomic approaches and techniques that are consistently available for most studies, regardless of test subject. In this chapter, an overview of some of these core approaches, techniques, and mass spectrometric instrumentation is given, while indicating how such steps are useful for and applied to bacterial investigations. To exemplify how such proteomic concepts and techniques are applicable to bacterial investigations, a practical, quantitative method useful for bacterial proteomic analysis is presented with a discussion of possibilities, pitfalls, and some emerging technology to provide a compilation of information from the diverse literature that is intermingled with experimental experience.

  16. Space Applications of Mass Spectrometry. Chapter 31

    NASA Technical Reports Server (NTRS)

    Hoffman, John H.; Griffin, Timothy P.; Limero, Thomas; Arkin, C. Richard

    2010-01-01

    Mass spectrometers have been involved in essentially all aspects of space exploration. This chapter outlines some of these many uses. Mass spectrometers have not only helped to expand our knowledge and understanding of the world and solar system around us, they have helped to put man safely in space and expand our frontier. Mass spectrometry continues to prove to be a very reliable, robust, and flexible analytical instrument, ensuring that its use will continue to help aid our investigation of the universe and this small planet that we call home.

  17. Initial results of positron ionization mass spectrometry

    NASA Technical Reports Server (NTRS)

    Donohue, D. L.; Hulett, L. D., Jr.; Mcluckey, S. A.; Glish, G. L.; Eckenrode, B. A.

    1990-01-01

    The use of monoenergetic positrons for the ionization of organic molecules in the gas phase is described. The ionic products are analyzed with a time-of-flight mass spectrometer and detected to produce a mass spectrum. The ionization mechanisms which can be studied in this way include positron impact at energies above the ionization limit of the target molecules, positronium formation in the Ore gap energy range, and positron attachment at energies less than 1eV. The technique of positron ionization mass spectrometry (PIMS) may have analytical utility in that chemical selectivity is observed for one or more of these processes.

  18. Nuclear applications of inorganic mass spectrometry.

    PubMed

    De Laeter, John

    2010-01-01

    There are several basic characteristics of mass spectrometry that are not always fully appreciated by the science community. These characteristics include the distinction between relative and absolute isotope abundances, and the influence of isotope fractionation on the accuracy of isotopic measurements. These characteristics can be illustrated in the field of nuclear physics with reference to the measurement of nuclear parameters, which involve the use of enriched isotopes, and to test models of s-, r-, and p-process nucleosynthesis. The power of isotope-dilution mass spectrometry (IDMS) to measure trace elements in primitive meteorites to produce accurate Solar System abundances has been essential to the development of nuclear astrophysics. The variety of mass spectrometric instrumentation used to measure the isotopic composition of elements has sometimes been accompanied by a lack of implementation of basic mass spectrometric protocols which are applicable to all instruments. These metrological protocols are especially important in atomic weight determinations, but must also be carefully observed in cases where the anomalies might be very small, such as in studies of the daughter products of extinct radionuclides to decipher events in the early history of the Solar System. There are occasions in which misleading conclusions have been drawn from isotopic data derived from mass spectrometers where such protocols have been ignored. It is important to choose the mass spectrometer instrument most appropriate to the proposed experiment. The importance of the integrative nature of mass spectrometric measurements has been demonstrated by experiments in which long, double beta decay and geochronological decay half-lives have been measured as an alternative to costly radioactive-counting experiments. This characteristic is also illustrated in the measurement of spontaneous fission yields, which have accumulated over long periods of time. Mass spectrometry is also a

  19. Linking Mass Spectrometry with Toxicology for Emerging Water Contaminants

    EPA Science Inventory

    This overview presentation will discuss the benefits of combining mass spectrometry with toxicology. These benefits will be described for 3 main areas: (1) Toxicity assays used to test new environmental contaminants previously identified using mass spectrometry, such that furth...

  20. Linking Mass Spectrometry with Toxicology for Emerging Water Contaminants

    EPA Science Inventory

    This overview presentation will discuss the benefits of combining mass spectrometry with toxicology. These benefits will be described for 3 main areas: (1) Toxicity assays used to test new environmental contaminants previously identified using mass spectrometry, such that furth...

  1. Observation of vanadyl porphyrins and sulfur-containing vanadyl porphyrins in a petroleum asphaltene by atmospheric pressure photonionization Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Qian, Kuangnan; Mennito, Anthony S; Edwards, Kathleen E; Ferrughelli, Dave T

    2008-07-01

    Vanadyl (VO) porphyrins and sulfur-containing vanadyl (VOS) porphyrins of a wide carbon number range (C(26) to C(52)) and Z-number range (-28 to -54) were detected and identified in a petroleum asphaltene by atmospheric pressure photonionization (APPI) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). APPI provides soft ionization of asphaltene molecules (including VO and VOS porphyrins), generating primarily molecular ions (M(+.)). The ultra-high mass resolving power (m/Delta m(FWHM) approximately 500 K) of FTICR-MS enabled resolution and positive identification of elemental formulae for the entire family of VO and VOS porphyrins in a complicated asphaltene matrix. Deocophylerythro-etioporphyrin (DPEP) is found to be the most prevalent structure, followed by etioporphyrins (etio)- and rhodo (benzo)-DPEP. The characteristic Z-distribution of VO porphyrins suggests benzene and naphthene increment in the growth of porphyrin ring structures. Bimodal carbon number distributions of VO porphyrins suggest possible different origins of low and high molecular weight species. To our knowledge, the observation of VOS porphyrins in a petroleum product has not previously been reported. The work is also the first direct identification of the entire vanadyl porphyrin family by ultra-high resolution mass spectrometry without chromatographic separation or demetallation.

  2. Mass Spectrometry Imaging under Ambient Conditions

    PubMed Central

    Wu, Chunping; Dill, Allison L.; Eberlin, Livia S.; Cooks, R. Graham; Ifa, Demian R.

    2012-01-01

    Mass spectrometry imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information, without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of spatial distribution. In addition to now standard methods involving MSI in vacuum, recently developed ambient ionization techniques allow MSI to be performed under atmospheric pressure on untreated samples outside the mass spectrometer. Here we review recent developments and applications of MSI emphasizing the ambient ionization techniques of desorption electrospray ionization (DESI), laser ablation electrospray ionization (LAESI), probe electrospray ionization (PESI), desorption atmospheric pressure photoionization (DAPPI), femtosecond laser desorption ionization (fs-LDI), laser electrospray mass spectrometry (LEMS), infrared laser ablation metastable-induced chemical ionization (IR-LAMICI), liquid microjunction surface sampling probe mass spectrometry (LMJ-SSP MS), nanospray desorption electrospray ionization (nano-DESI), and plasma sources such as the low temperature plasma (LTP) probe and laser ablation coupled to flowing atmospheric-pressure afterglow (LA-FAPA). Included are discussions of some of the features of ambient MSI including the ability to implement chemical reactions with the goal of providing high abundance ions characteristic of specific compounds of interest and the use of tandem mass spectrometry to either map the distribution of targeted molecules with high specificity or to provide additional MS information in the structural identification of compounds. We also describe the role of bioinformatics in acquiring and interpreting the chemical and spatial information obtained through MSI, especially in biological applications for tissue

  3. Ultrahigh-Mass Mass Spectrometry of Single Biomolecules and Bioparticles

    NASA Astrophysics Data System (ADS)

    Chang, Huan-Cheng

    2009-07-01

    Since the advent of soft ionization methods, mass spectrometry (MS) has found widespread application in the life sciences. Mass is now known to be a critical parameter for characterization of biomolecules and their complexes; it is also a useful parameter to characterize bioparticles such as viruses and cells. However, because of the genetic diversity of these entities, it is necessary to measure their masses individually and to obtain the corresponding mean masses and mass distributions. Here, I review recent technological developments that enable mass measurement of ultrahigh-mass biomolecules and bioparticles at the single-ion level. Some representative examples include cryodetection time-of-flight MS of single-megadalton protein ions, Millikan-type mass measurements of single viruses in a cylindrical ion trap, and charge-detection quadrupole ion trap MS of single whole cells. I also discuss the promises and challenges of these new technologies in real-world applications.

  4. Biological particle analysis by mass spectrometry

    NASA Technical Reports Server (NTRS)

    Vilker, V. L.; Platz, R. M.

    1983-01-01

    An instrument that analyzes the chemical composition of biological particles in aerosol or hydrosol form was developed. Efforts were directed toward the acquisition of mass spectra from aerosols of biomolecules and bacteria. The filament ion source was installed on the particle analysis by mass spectrometry system. Modifications of the vacuum system improved the sensitivity of the mass spectrometer. After the modifications were incorporated, detailed mass spectra of simple compounds from the three major classes of biomolecules, proteins, nucleic acids, and carbohydrates were obtained. A method of generating bacterial aerosols was developed. The aerosols generated were collected and examined in the scanning electron microscope to insure that the bacteria delivered to the mass spectrometer were intact and free from debris.

  5. Laser-Cooling-Assisted Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Schneider, Christian; Schowalter, Steven J.; Chen, Kuang; Sullivan, Scott T.; Hudson, Eric R.

    2014-09-01

    Mass spectrometry is used in a wide range of scientific disciplines including proteomics, pharmaceutics, forensics, and fundamental physics and chemistry. Given this ubiquity, there is a worldwide effort to improve the efficiency and resolution of mass spectrometers. However, the performance of all techniques is ultimately limited by the initial phase-space distribution of the molecules being analyzed. Here, we dramatically reduce the width of this initial phase-space distribution by sympathetically cooling the input molecules with laser-cooled, cotrapped atomic ions, improving both the mass resolution and detection efficiency of a time-of-flight mass spectrometer by over an order of magnitude. Detailed molecular-dynamics simulations verify the technique and aid with evaluating its effectiveness. This technique appears to be applicable to other types of mass spectrometers.

  6. Mass spectrometry in Chronic Kidney Disease research

    PubMed Central

    Merchant, Michael L.

    2010-01-01

    Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass spectrometer and its application to analyze biological samples. Our need to understand both the identity of proteins and their abundance has led to improvements in mass spectrometers and their ability to analyze complex tryptic peptide mixtures with high sensitivity and high mass accuracy in a high throughput fashion (such as the LTQ-Orbitrap). It should not be surprising that this occurred coincident with dramatic improvements in our understanding chronic kidney disease (CKD), the mechanisms through which CKD progresses and the development of candidate CKD biomarkers. This review attempts to present a basic framework for the operational components of mass spectrometers, basic insight into how they are used in renal research and a discussion of CKD research that was driven by mass spectrometry. PMID:21044768

  7. Ionization and fragmentation of humic substances in electrospray ionization Fourier transform-ion cyclotron resonance mass spectrometry.

    PubMed

    Stenson, Alexandra C; Landing, William M; Marshall, Alan G; Cooper, William T

    2002-09-01

    Electrospray ionization (ESI) was combined with ultra-high-resolution Fourier transform-ion cyclotron resonance mass spectrometry (FTICR MS) to characterize complex humic and fulvic acid mixtures. Lower than expected molecular weight distributions previously observed for humics when analyzed by ESI-MS have fueled speculation about a bias in favor of low molecular weight. Multiply charged ions, ionization suppression, and sample fragmentation have all been suggested as sources of this low molecular weight bias. In this work, resolution of the individual components of humic mixtures within a 1 mass-to-charge unit window was accomplished by FTICR MS at 9.4 T. At mass resolving powers between 60,000 (high mass) and 120,000 (low mass), it was possible to determine that virtually all ions present in spectra of Suwannee River fulvic and humic acid are singly charged, thus eliminating inadequate accounting for multiply charged ions as a primary source of any low molecular weight bias. The high-resolution mass spectra also revealed the presence of molecular families containing ions that differ from each other in degree of saturation, functional group substitution (primarily CH vs N and CH4 vs O), and number of CH2 groups. Ionization suppression and ion fragmentation were addressed for humic and fulvic acid mixtures and well-characterized poly(ethylene glycol) (PEG) mixtures with average molecular weights of 8000 and 10,000. Although these high molecular weight PEG mixtures fragment extensively under traditional positive-ion mode ESI conditions, similar fragmentation could not be confirmed for humic and fulvic acid mixtures.

  8. Single-Cell Imaging Mass Spectrometry

    PubMed Central

    Passarelli, Melissa K.; Ewing, Andrew G.

    2013-01-01

    Single-cell imaging mass spectrometry (IMS) is a powerful technique used to map the distributions of endogenous biomolecules with sub-cellular resolution. Currently, secondary ion mass spectrometry is the predominant technique for single-cell IMS, thanks to its sub-micron lateral resolution and surface sensitivity. However, recent methodological and technological developments aimed at improving the spatial resolution of matrix assisted laser desorption ionization (MALDI) have made this technique a potential platform of single-cell IMS. MALDI opens the field of single-cell IMS to new possibilities, including single cell proteomic imaging and atmospheric pressure analyses; however, sensitivity is a challenge. In this report, we estimate the availability of proteins and lipids in a single cell and discuss strategies employed to improve sensitivity at the single-cell level. PMID:23948695

  9. Dissecting the ubiquitin pathway by mass spectrometry

    PubMed Central

    Xu, Ping; Peng, Junmin

    2007-01-01

    Summary Protein modification by ubiquitin is a central regulatory mechanism in eukaryotic cells. Recent proteomics developments in mass spectrometry enable systematic analysis of cellular components in the ubiquitin pathway. Here, we review the advances in analyzing ubiquitinated substrates, determining modified lysine residues, quantifying polyubiquitin chain topologies, as well as profiling deubiquitinating enzymes based on the activity. Moreover, proteomic approaches have been developed for probing the interactome of proteasome and for identifying proteins with ubiquitin-binding domains. Similar strategies have been applied on the studies of the modification by ubiquitin-like proteins as well. These strategies are discussed with respect to their advantages, limitations and potential improvements. While the utilization of current methodologies has rapidly expanded the scope of protein modification by the ubiquitin family, a more active role is anticipated in the functional studies with the emerging of quantitative mass spectrometry. PMID:17055348

  10. Impact of automation on mass spectrometry.

    PubMed

    Zhang, Yan Victoria; Rockwood, Alan

    2015-10-23

    Mass spectrometry coupled to liquid chromatography (LC-MS and LC-MS/MS) is an analytical technique that has rapidly grown in popularity in clinical practice. In contrast to traditional technology, mass spectrometry is superior in many respects including resolution, specificity, multiplex capability and has the ability to measure analytes in various matrices. Despite these advantages, LC-MS/MS remains high cost, labor intensive and has limited throughput. This specialized technology requires highly trained personnel and therefore has largely been limited to large institutions, academic organizations and reference laboratories. Advances in automation will be paramount to break through this bottleneck and increase its appeal for routine use. This article reviews these challenges, shares perspectives on essential features for LC-MS/MS total automation and proposes a step-wise and incremental approach to achieve total automation through reducing human intervention, increasing throughput and eventually integrating the LC-MS/MS system into the automated clinical laboratory operations.

  11. Top-Down Protein Identification of Proteasome Proteins with nanoLC FT-ICR MS Employing Data-Independent Fragmentation Methods

    PubMed Central

    Lakshmanan, Rajeswari; Wolff, Jeremy J.; Alvarado, Rudy; Loo, Joseph A.

    2014-01-01

    A comparison of different data-independent fragmentation methods combined with liquid chromatography (LC) coupled to high resolution Fourier-transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry (MS) is presented for top-down MS of protein mixtures. Proteins composing the 20S and 19S proteasome complex and their post-translational modifications were identified using a 15-Tesla FT-ICR mass spectrometer. The data-independent fragmentation modes with LC timescales allowed for higher duty cycle measurements that better suit on-line LC-FT-ICR-MS. Protein top-down dissociation was effected by funnel-skimmer collisionally activated dissociation (FS-CAD) and CASI (Continuous Accumulation of Selected Ions)-CAD. The N-terminus for 9 out of the 14 20S proteasome proteins were found to be modified, and the α3 protein was found to be phosphorylated; these results are consistent with previous reports. Mass measurement accuracy with the LC-FT-ICR system for the 20–30 kDa 20S proteasome proteins was 1 ppm. The intact mass of the 100 kDa Rpn1 subunit from the 19S proteasome complex regulatory particle was measured with a deviation of 17 ppm. The CASI-CAD technique is a complementary tool for intact protein fragmentation and is an effective addition to the growing inventory of dissociation methods which are compatible with on-line protein separation coupled to FT-ICR MS. PMID:24478249

  12. Unraveling the Complexity of Atmospheric Aerosol: Insights from Ultrahigh Resolution Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mazzoleni, Lynn R.; Zhao, Yunzhu; Samburova, Vera; Gannet Hallar, A.; Lowenthal, Douglas

    2016-04-01

    Atmospheric aerosol organic matter (AOM) is a complex mixture of thousands of organic compounds, which may have significant influence on the climate-relevant properties of atmospheric aerosols. An improved understanding of the molecular composition of AOM is needed to evaluate the effect of aerosol composition upon aerosol physical properties. Products of gas, aqueous and particle phase reactions contribute to the aerosol organic mass. Thus, ambient aerosols carry a complex array of AOM components with variable chemical signatures depending upon its origin and aerosol life-cycle processes. In this work, ultrahigh-resolution Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to characterize ambient aerosol AOM collected at the Storm Peak Laboratory (3210 m a.s.l.) near Steamboat Springs, CO. Thousands of molecular formulas were assigned in the mass range of m/z 100-800 after negative-ion electrospray ionization. Using multivariate statistical analysis, correlations between the site meteorological conditions and specific molecular compositions were identified. For example, days with strong UV radiation and high temperature were found to contain large numbers of biogenic SOA molecular formulas. Similarly, days with high relative humidity and high sulfate concentrations were found to contain many sulfur-containing compounds, suggesting their aqueous phase formation.

  13. Accelerator mass spectrometry - from DNA to astrophysics

    NASA Astrophysics Data System (ADS)

    Kutschera, Walter

    2013-12-01

    A brief review of accelerator mass spectrometry (AMS) is presented. The present work touches on a few technical aspects and recent developments of AMS, and describes two specific applications of AMS, the dating of human DNA with the 14C bomb peak and the search for superheavy elements in nature. Since two extended general reviews on technical developments in AMS [1] and applications of AMS [2] will appear in 2013, frequent reference to these reviews is made.

  14. Monolithic multinozzle emitters for nanoelectrospray mass spectrometry

    DOEpatents

    Wang, Daojing; Yang, Peidong; Kim, Woong; Fan, Rong

    2011-09-20

    Novel and significantly simplified procedures for fabrication of fully integrated nanoelectrospray emitters have been described. For nanofabricated monolithic multinozzle emitters (NM.sup.2 emitters), a bottom up approach using silicon nanowires on a silicon sliver is used. For microfabricated monolithic multinozzle emitters (M.sup.3 emitters), a top down approach using MEMS techniques on silicon wafers is used. The emitters have performance comparable to that of commercially-available silica capillary emitters for nanoelectrospray mass spectrometry.

  15. Radiation Biomarker Research Using Mass Spectrometry

    DTIC Science & Technology

    2007-07-01

    The data was of insufficient quality to obtain definitive biomarkers. Trips were also made to AFRL/HEDR at Brooks City Base to assist with their...sample analysis using the Finnigan LTQ located there. Mr. Mullens and Ms. Nagore assisted with training personnel at AFRL/HEDR and when necessary...techniques with saliva samples and matrix- assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), we have been able to

  16. [Photon burst mass spectrometry technique.] Final report

    SciTech Connect

    Fairbank, W.M. Jr

    1996-04-01

    The basic tools have been developed and demonstrated for selective detection of Kr isotopes in the Photon Burst Mass Spectrometry technique. The effort is divided into: photon burst measurements on Mg{sup +} demonstrating high isotopic selectivity, charge exchange of Kr{sup +} with Cs and Rb to produce metastable Kr atoms, development of a diode laser system for photon burst detection of Kr{sup +}, and measurements of photon bursts detection of Kr.

  17. [Sample preparation and bioanalysis in mass spectrometry].

    PubMed

    Bourgogne, Emmanuel; Wagner, Michel

    2015-01-01

    The quantitative analysis of compounds of clinical interest of low molecular weight (<1000 Da) in biological fluids is currently in most cases performed by liquid chromatography-mass spectrometry (LC-MS). Analysis of these compounds in biological fluids (plasma, urine, saliva, hair...) is a difficult task requiring a sample preparation. Sample preparation is a crucial part of chemical/biological analysis and in a sense is considered the bottleneck of the whole analytical process. The main objectives of sample preparation are the removal of potential interferences, analyte preconcentration, and converting (if needed) the analyte into a more suitable form for detection or separation. Without chromatographic separation, endogenous compounds, co-eluted products may affect a quantitative method in mass spectrometry performance. This work focuses on three distinct parts. First, quantitative bioanalysis will be defined, different matrices and sample preparation techniques currently used in bioanalysis by mass spectrometry of/for small molecules of clinical interest in biological fluids. In a second step the goals of sample preparation will be described. Finally, in a third step, sample preparation strategies will be made either directly ("dilute and shoot") or after precipitation.

  18. Identification and quantification of the phosphorylated ovalbumin by high resolution mass spectrometry under dry-heating treatment.

    PubMed

    Wang, Hui; Tu, Zong-Cai; Liu, Guang-Xian; Zhang, Lu; Chen, Yuan

    2016-11-01

    The specific phosphorylation sites and degree of phosphorylation (DP) at each site are directly related to protein's structure and functional properties. Thus, characterizing the introduced phosphate groups is of great importance. This study was to monitor the phosphorylation sites, DP and the number of phosphorylation sites in P-Oval achieved by dry heating in the presence of pyrophosphate for 1, 2 and 5days by using Fourier transform ion cyclotron mass spectrometry (FTICR MS). Two phosphorylation sites were found in natural ovalbumin, but the number of phosphorylation sites increased to 8, 8 and 10 after dry-heating phosphorylation for 1, 2 and 5days, respectively. In addition, dual-phosphorylated peptides were detected for samples without extensive heating. The phosphorylation sites were found to be mainly on Ser residues, which could be the preferred phosphorylation site for dry heating in the presence of pyrophosphate.

  19. Determining the Binding Sites of β-Cyclodextrin and Peptides by Electron-Capture Dissociation High Resolution Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Qi, Yulin; Geib, Timon; Volmer, Dietrich A.

    2015-07-01

    Cyclodextrins (CDs) are a group of cyclic oligosaccharides, which readily form inclusion complexes with hydrophobic compounds to increase bioavailability, thus making CDs ideal drug excipients. Recent studies have also shown that CDs exhibit a wide range of protective effects, preventing proteins from aggregation, degradation, and folding. These effects strongly depend on the binding sites on the protein surface. CDs only exhibit weak interactions with amino acids, however; conventional analytical techniques therefore usually fail to reveal the exact location of the binding sites. Moreover, some studies even suggest that CD inclusion complexes are merely electrostatic adducts. Here, electron capture dissociation (ECD) was applied in this proof-of-concept study to examine the exact nature of the CD/peptide complexes, and CD binding sites were unambiguously located for the first time via Fourier-transform ion cyclotron resonance (FTICR) tandem mass spectrometry.

  20. Determining the Binding Sites of β-Cyclodextrin and Peptides by Electron-Capture Dissociation High Resolution Tandem Mass Spectrometry.

    PubMed

    Qi, Yulin; Geib, Timon; Volmer, Dietrich A

    2015-07-01

    Cyclodextrins (CDs) are a group of cyclic oligosaccharides, which readily form inclusion complexes with hydrophobic compounds to increase bioavailability, thus making CDs ideal drug excipients. Recent studies have also shown that CDs exhibit a wide range of protective effects, preventing proteins from aggregation, degradation, and folding. These effects strongly depend on the binding sites on the protein surface. CDs only exhibit weak interactions with amino acids, however; conventional analytical techniques therefore usually fail to reveal the exact location of the binding sites. Moreover, some studies even suggest that CD inclusion complexes are merely electrostatic adducts. Here, electron capture dissociation (ECD) was applied in this proof-of-concept study to examine the exact nature of the CD/peptide complexes, and CD binding sites were unambiguously located for the first time via Fourier-transform ion cyclotron resonance (FTICR) tandem mass spectrometry.

  1. Mass Spectrometry of Proteins in Liquids

    NASA Astrophysics Data System (ADS)

    Baltz-Knorr, Michelle; Papantonakis, Michael; Ermer Haglund, David, Jr.

    1999-11-01

    Infrared matrix assisted laser desorption/ionization mass spectrometry (IR-MALDI) is an effective technique for mass identification and structural analysis of biomolecules. We are using liquid glycerol/water matrices in a reflectron time-of-flight mass spectrometer equipped with a liquid nitrogen cooled sample stage to provide a more natural environment for biomolecules. An Er:YAG laser (2.94 μm) and also a tunable free electron laser (2-9 μm) are used to induce desorption and ionization by exciting the O-H and CH2 stretching vibrations in the glycerol. This vibrationally enhanced ionization makes IR-MALDI very efficient, as observed in the mass spectra of small peptides. This work is a first step toward using mass spectrometry to study noncovalently bound protein complexes in vitro and to study proteins in their cellular environment. Supported by the Medical Free Electron Laser Program of the Office of Naval Research and the Vanderbilt Molecular Biophysics Training Grant of the National Institutes of Health

  2. Toward Single-Molecule Nanomechanical Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Roukes, Michael

    2009-03-01

    Mass spectrometry (MS) has become a preeminent methodology of proteomics since it provides rapid and quantitative identification of protein species with relatively low sample consumption. Yet with the trend toward biological analysis at increasingly smaller scales, ultimately down to the volume of an individual cell, MS with few-to-single molecule resolution will be required. We report the first realization of MS based on single-biological-molecule detection with nanoelectromechanical systems (NEMS). NEMS provide unparalleled mass resolution, now sufficient for detection of individual molecular species in real time. However, high sensitivity is only one of several components required for MS. We demonstrate a first complete prototype NEMS-MS system for single-molecule mass spectrometry providing proof-of-principle for this new technique. Nanoparticles and protein species are introduced by electrospray injection from the fluid phase in ambient conditions into vacuum and subsequently delivered to the NEMS detector by hexapole ion optics . Mass measurements are then recorded in real-time as analytes adsorb, one-by-one, onto a phase-locked, ultrahigh frequency (UHF) NEMS resonator. These first NEMS-MS spectra, obtained with modest resolution from only several hundred mass adsorption events, presage the future capabilities of this methodology. We outline the substantial improvements feasible in near term, through recent advances and technological avenues that are unique to NEMS-MS.

  3. Mass spectrometry with direct supercritical fluid injection

    SciTech Connect

    Smith, R.D.; Udseth, H.R.

    1983-12-01

    Direct fluid injection mass spectrometry utilizes supercritical fluids for solvation and transfer of materials to a mass spectrometer chemical ionization (CI) source. Available data suggest that any material soluble in a supercritical fluid is transferred efficiently to the ionization region. Mass spectra are presented for mycotoxins of the trichothecene group obtained by use of supercritical carbon dioxide with isobutane as the CI reagent gas. Direct fluid injection MS/MS is also illustrated for major ions in the isobutane chemical ionization of T-2 toxin. The effect of pressure and temperature upon solubility in supercritical fluids is described and illustrated for diacetoxycirpenol. A potential method is also demonstrated for on-line fraction during MS analysis using pressure to control supercritical fluid solubility. Mass spectra are also presented for polar compounds, using supercritical ammonia, and the extension to complex mixtures is described. The fundamental basis and experimental requirements of the direct fluid injection process are discussed. 34 references, 11 figures, 1 table.

  4. Mass spectrometry with direct supercritical fluid injection

    SciTech Connect

    Smith, R.D.; Udseth, H.R.

    1983-12-01

    Direct fluid injection mass spectrometry utilizes supercritical fluids for solvation and transfer of materials to a mass spectrometer chemical ionization (CI) source. Available data suggest that any material soluble in a supercritical fluid is transferred efficiently to the ionization region. Mass spectra are presented for mycotoxins of the trichothecene group obtained by use of supercritical carbon dioxide with isobutane as the CI reagent gas. Direct fluid injection MS/MS is also illustrated for major ions in the isobutane chemical ionization of T-2 toxin. The effect of pressure and temperature upon solubility in supercritical fluids is described and illustrated for diacetoxyscirpenol. A potential method is also demonstrated for ''on-line fractionation'' during MS analysis using pressure to control supercritical fluid solubility. Mass spectra are also presented for polar compounds, using supercritical ammonia, and the extension to complex mixtures is described. The fundamental basis and experimental requirements of the direct fluid injection process are discussed. 1 figure, 11 tables.

  5. Study of cluster anions generated by laser ablation of titanium oxides: a high resolution approach based on Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Barthen, Nicolas; Millon, Eric; Aubriet, Frédéric

    2011-03-01

    Laser ablation of titanium oxides at 355 nm and ion-molecule reactions between [(TiO(2))(x)](-•) cluster anions and H(2)O or O(2) were investigated by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) with an external ion source. The detected anions correspond to [(TiO(2))(x)(H(2)O)(y)OH](-) and [(TiO(2))(x)(H(2)O)(y)O(2)](-•) oxy-hydroxide species with x=1 to 25 and y=1, 2, or 3 and were formed by a two step process: (1) laser ablation, which leads to the formation of [(TiO(2))(x)](-•) cluster anions as was previously reported, and (2) ion-molecule reactions during ion storage. Reactions of some [(TiO(2))(x)](-•) cluster anions with water and dioxygen conducted in the FTICR cell confirm this assessment. Tandem mass spectrometry experiments were also performed in sustained off-resonance irradiation collision-induced dissociation (SORI-CID) mode. Three fragmentation pathways were observed: (1) elimination of water molecules, (2) O(2) loss for radical anions, and (3) fission of the cluster. Density functional theory (DFT) calculations were performed to explain the experimental data.

  6. Structural Characterization of Monohydroxyeicosatetraenoic Acids and Dihydroxy- and Trihydroxyeicosatrienoic Acids by ESI-FTICR

    PubMed Central

    Cui, Lijie; Isbell, Marilyn A.; Chawengsub, Yuttana; Falck, John R.; Campbell, William B.; Nithipatikom, Kasem

    2008-01-01

    The fragmentation characteristics of monohydroxyeicosatetraenoic acids and dihydroxy- and trihydroxyeicosatrienoic acids were investigated by electrospray ionization - Fourier transform ion cyclotron resonance (FTICR) mass spectrometry using sustained off-resonance irradiation collision-induced dissociation (SORI-CID) and infrared multiphoton dissociation (IRMPD). The fragmentation patterns of these compounds were associated with the number and positions of the hydroxyl substituents. The fragmentation is more complicated with increasing number of the hydroxyl groups of the compounds. In general, the major carbon-carbon cleavage of [M-H]− ions occurred at the α-position to the hydroxyl group, and the carbon-carbon cleavage occurred when there was a double bond at the β-position to the hydroxyl group. SORI-CID and IRMPD produced some common fragmentation patterns; however, each technique provided some unique patterns that are useful for structural identification of these compounds. This study demonstrated the application of FTICR via the identification of regioisomers of trihydroxyeicosatrienoic acids in rabbit aorta samples. PMID:18296063

  7. Pathway Confirmation and Flux Analysis of Central Metabolic Pathways in Desulfovibrio vulgaris Hildenborough using Gas Chromatography-Mass Spectrometry and Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry▿ †

    PubMed Central

    Tang, Yinjie; Pingitore, Francesco; Mukhopadhyay, Aindrila; Phan, Richard; Hazen, Terry C.; Keasling, Jay D.

    2007-01-01

    Flux distribution in central metabolic pathways of Desulfovibrio vulgaris Hildenborough was examined using 13C tracer experiments. Consistent with the current genome annotation and independent evidence from enzyme activity assays, the isotopomer results from both gas chromatography-mass spectrometry (GC-MS) and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) indicate the lack of an oxidatively functional tricarboxylic acid (TCA) cycle and an incomplete pentose phosphate pathway. Results from this study suggest that fluxes through both pathways are limited to biosynthesis. The data also indicate that >80% of the lactate was converted to acetate and that the reactions involved are the primary route of energy production [NAD(P)H and ATP production]. Independently of the TCA cycle, direct cleavage of acetyl coenzyme A to CO and 5,10-methyl tetrahydrofuran also leads to production of NADH and ATP. Although the genome annotation implicates a ferredoxin-dependent oxoglutarate synthase, isotopic evidence does not support flux through this reaction in either the oxidative or the reductive mode; therefore, the TCA cycle is incomplete. FT-ICR MS was used to locate the labeled carbon distribution in aspartate and glutamate and confirmed the presence of an atypical enzyme for citrate formation suggested in previous reports [the citrate synthesized by this enzyme is the isotopic antipode of the citrate synthesized by the (S)-citrate synthase]. These findings enable a better understanding of the relation between genome annotation and actual metabolic pathways in D. vulgaris and also demonstrate that FT-ICR MS is a powerful tool for isotopomer analysis, overcoming the problems with both GC-MS and nuclear magnetic resonance spectroscopy. PMID:17114264

  8. Human Plasma N-Glycoproteome Analysis by Immunoaffinity Subtraction, Hydrazide Chemistry, and Mass Spectrometry

    SciTech Connect

    Liu, Tao; Qian, Weijun; Gritsenko, Marina A.; Camp, David G.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.

    2005-12-01

    The enormous complexity, wide dynamic range of relative protein abundance of interest (over 10 orders of magnitude), and tremendous heterogeneity (due to post-translational modifications, such as glycosylation) of the human blood plasma proteome severely challenges the capabilities of existing analytical methodologies. We describe here the comprehensive analysis of human plasma N-glycoproteins using the combination of immunoaffinity subtraction and glycoprotein capture to reduce both the protein concentration range and the overall sample complexity. Six high-abundance plasma proteins were simultaneously removed using a pre-packed, immobilized antibody column. N-linked glycoproteins were then captured from the depleted plasma using hydrazide resin, enzymatically digested, and the bound, N-linked glycopeptides were released using peptide-N-glycosidase F. Following strong cation exchange (SCX) fractionation, the deglycosylated peptides were analyzed by reversed-phase capillary liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A total of 2140 different N-glycopeptides were confidently identified using stringent criteria, covering 371 non-redundant N-glycoproteins with the majority of them being extracellular or membrane proteins. The strategy significantly improved the detection, enabling the identification of a number of low-abundance proteins, exemplified by interleukin-1 receptor antagonist protein ({approx}200 pg/mL), cathepsin L ({approx}1 ng/mL), and transforming growth factor beta 1 ({approx}2 ng/mL). A total of 712 N-glycosylation sites were identified and the confidence of these site identifications was further validated by accurate mass measurements using high resolution liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR). This study provides the basis for future high-throughput measurements using the accurate mass and time tag approach.

  9. Analysis of Glycosaminoglycans Using Mass Spectrometry

    PubMed Central

    Staples, Gregory O.; Zaia, Joseph

    2015-01-01

    The glycosaminoglycans (GAGs) are linear polysaccharides expressed on animal cell surfaces and in extracellular matrices. Their biosynthesis is under complex control and confers a domain structure that is essential to their ability to bind to protein partners. Key to understanding the functions of GAGs are methods to determine accurately and rapidly patterns of sulfation, acetylation and uronic acid epimerization that correlate with protein binding or other biological activities. Mass spectrometry (MS) is particularly suitable for the analysis of GAGs for biomedical purposes. Using modern ionization techniques it is possible to accurately determine molecular weights of GAG oligosaccharides and their distributions within a mixture. Methods for direct interfacing with liquid chromatography have been developed to permit online mass spectrometric analysis of GAGs. New tandem mass spectrometric methods for fine structure determination of GAGs are emerging. This review summarizes MS-based approaches for analysis of GAGs, including tissue extraction and chromatographic methods compatible with LC/MS and tandem MS. PMID:25705143

  10. Computational mass spectrometry for small molecules

    PubMed Central

    2013-01-01

    The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

  11. Computational mass spectrometry for small molecules.

    PubMed

    Scheubert, Kerstin; Hufsky, Franziska; Böcker, Sebastian

    2013-03-01

    : The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline.

  12. MALDI-FTICR MS Imaging as a Powerful Tool to Identify Paenibacillus Antibiotics Involved in the Inhibition of Plant Pathogens

    NASA Astrophysics Data System (ADS)

    Debois, Delphine; Ongena, Marc; Cawoy, Hélène; De Pauw, Edwin

    2013-08-01

    Nowadays, microorganisms are more and more often used as biocontrol agents for crop protection against diseases. Among them, bacteria of Bacillus and Paenibacillus genders are already used as commercial biocontrol agents. Their mode of action is supposed to be related to their production of antibiotics, such as cyclic lipopeptides, which exhibit great antimicrobial activities. We chose to work with a Paenibacillus polymyxa strain (Pp56) very resistant to various microorganisms. The bacteria were grown simultaneously with Fusarium oxysporum and we applied matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) mass spectrometry to identify the antibiotics compounds present in the fungus growth inhibition area. We, therefore, identified fusaricidins A, B, and C and numerous members of the LI-F antibiotics family. MALDI-FTICR mass spectrometry imaging was then used to follow the diffusion of lipopeptides involved in the inhibitory activity over time. We analyzed the molecular content of the inhibitory area at different Pp56 and Fusarium incubation durations and concluded that some lipopeptides such as fusaricidin B and a mixture of LI-F05b/06b/08a were mainly involved in the defense mechanism of Pp56. Our study confirms that MALDI imaging may be a powerful tool to quickly determine which molecular species is involved in an antagonism with another microorganism, avoiding time-consuming steps of extraction, purification, and activity tests, which are still commonly used in microbiology.

  13. Improving gene annotation using peptide mass spectrometry

    PubMed Central

    Tanner, Stephen; Shen, Zhouxin; Ng, Julio; Florea, Liliana; Guigó, Roderic; Briggs, Steven P.; Bafna, Vineet

    2007-01-01

    Annotation of protein-coding genes is a key goal of genome sequencing projects. In spite of tremendous recent advances in computational gene finding, comprehensive annotation remains a challenge. Peptide mass spectrometry is a powerful tool for researching the dynamic proteome and suggests an attractive approach to discover and validate protein-coding genes. We present algorithms to construct and efficiently search spectra against a genomic database, with no prior knowledge of encoded proteins. By searching a corpus of 18.5 million tandem mass spectra (MS/MS) from human proteomic samples, we validate 39,000 exons and 11,000 introns at the level of translation. We present translation-level evidence for novel or extended exons in 16 genes, confirm translation of 224 hypothetical proteins, and discover or confirm over 40 alternative splicing events. Polymorphisms are efficiently encoded in our database, allowing us to observe variant alleles for 308 coding SNPs. Finally, we demonstrate the use of mass spectrometry to improve automated gene prediction, adding 800 correct exons to our predictions using a simple rescoring strategy. Our results demonstrate that proteomic profiling should play a role in any genome sequencing project. PMID:17189379

  14. Biological accelerator mass spectrometry at Uppsala University.

    PubMed

    Salehpour, Mehran; Possnert, Göran; Bryhni, Helge; Palminger-Hallén, Ira; Ståhle, Lars

    2009-03-01

    A new research programme for the biological applications of accelerator mass spectrometry has been initiated at Uppsala University and the first results are presented. A (14)C-labelled pharmaceutical substance has been dissolved in human blood, plasma and urine and diluted over 3 orders of magnitude. The measured drug concentrations were found to be in good agreement with the predicted values. Furthermore, the effect of the sample preparation background contribution has been studied as the sample amount was varied down to sub-microl sizes.

  15. Accelerator mass spectrometry of the planetary elements

    NASA Astrophysics Data System (ADS)

    Fifield, L. K.; Clacher, A. P.; Morris, K.; King, S. J.; Cresswell, R. G.; Day, J. P.; Livens, F. R.

    1997-03-01

    Accelerator mass spectrometry has been applied for the first time to the detection of 237Np. Sensitivity approaches 105 atoms. A first measurement of the mobility of 237Np in a marine environment is reported, and lends support to the prediction that neptunium should be substantially more mobile than plutonium. Measurements of backgrounds and transmissions for plutonium and neptunium in different charge states are also reported. In addition, the relative negative ion formation probabilities for the monoxide ions of Th, U, Np and Pu have been measured.

  16. Isotopic trace analysis by atomic mass spectrometry

    SciTech Connect

    Stoffels, J.J.

    1993-12-01

    All the production facilities at Hanford are now shut down. However, the legacy from half a century of plutonium production includes 177 underground storage tanks of up to one million gallons each containing the largest accumulation of high-level radioactive waste in what used to be called ``the free world.`` Hanford`s new mission, in addition to a spectrum of ongoing research and development, is radioactive waste management and environmental restoration. Isotope-ratio mass spectrometry will continue to be an essential tool in monitoring the progress of that mission.

  17. Mass Determination of Entire Amyloid Fibrils by Using Mass Spectrometry.

    PubMed

    Doussineau, Tristan; Mathevon, Carole; Altamura, Lucie; Vendrely, Charlotte; Dugourd, Philippe; Forge, Vincent; Antoine, Rodolphe

    2016-02-12

    Amyloid fibrils are self-assembled protein structures with important roles in biology (either pathogenic or physiological), and are attracting increasing interest in nanotechnology. However, because of their high aspect ratio and the presence of some polymorphism, that is, the possibility to adopt various structures, their characterization is challenging and basic information such as their mass is unknown. Here we show that charge-detection mass spectrometry, recently developed for large self-assembled systems such as viruses, provides such information in a straightforward manner. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Native top-down mass spectrometry for the structural characterization of human hemoglobin

    SciTech Connect

    Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.; Loo, Joseph A.

    2015-06-09

    Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of the Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.

  19. Native top-down mass spectrometry for the structural characterization of human hemoglobin

    DOE PAGES

    Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.; ...

    2015-06-09

    Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

  20. Human Plasma N-Glycoproteome Analysis by Immunoaffinity Subtraction, Hydrazide Chemistry, and Mass Spectrometry

    PubMed Central

    Liu, Tao; Qian, Wei-Jun; Gritsenko, Marina A.; Camp, David G.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.

    2007-01-01

    The enormous complexity, wide dynamic range of relative protein abundances of interest (over 10 orders of magnitude), and tremendous heterogeneity (due to post-translational modifications, such as glycosylation) of the human blood plasma proteome severely challenge the capabilities of existing analytical methodologies. Here, we describe an approach for broad analysis of human plasma N-glycoproteins using a combination of immunoaffinity subtraction and glycoprotein capture to reduce both the protein concentration range and overall sample complexity. Six high-abundance plasma proteins were simultaneously removed using a pre-packed, immobilized antibody column. N-linked glycoproteins were then captured from the depleted plasma using hydrazide resin and enzymatically digested, and the bound N-linked glycopeptides were released using peptide-N-glycosidase F (PNGase F). Following strong cation exchange (SCX) fractionation, the deglycosylated peptides were analyzed by reversed-phase capillary liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Using stringent criteria, a total of 2053 different N-glycopeptides were confidently identified, covering 303 non-redundant N-glycoproteins. This enrichment strategy significantly improved detection and enabled identification of a number of low-abundance proteins, exemplified by interleukin-1 receptor antagonist protein (~200 pg/mL), cathepsin L (~1 ng/mL), and transforming growth factor beta 1 (~2 ng/mL). A total of 639 N-glycosylation sites were identified, and the overall high accuracy of these glycosylation site assignments as assessed by accurate mass measurement using high resolution liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR) is initially demonstrated. PMID:16335952

  1. Boundaries of Mass Resolution in Native Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Lössl, Philip; Snijder, Joost; Heck, Albert J. R.

    2014-06-01

    Over the last two decades, native mass spectrometry (MS) has emerged as a valuable tool to study intact proteins and noncovalent protein complexes. Studied experimental systems range from small-molecule (drug)-protein interactions, to nanomachineries such as the proteasome and ribosome, to even virus assembly. In native MS, ions attain high m/z values, requiring special mass analyzers for their detection. Depending on the particular mass analyzer used, instrumental mass resolution does often decrease at higher m/z but can still be above a couple of thousand at m/z 5000. However, the mass resolving power obtained on charge states of protein complexes in this m/z region is experimentally found to remain well below the inherent instrument resolution of the mass analyzers employed. Here, we inquire into reasons for this discrepancy and ask how native MS would benefit from higher instrumental mass resolution. To answer this question, we discuss advantages and shortcomings of mass analyzers used to study intact biomolecules and biomolecular complexes in their native state, and we review which other factors determine mass resolving power in native MS analyses. Recent examples from the literature are given to illustrate the current status and limitations.

  2. Molecular characterization of inhibiting biochar water-extractable substances using electrospray ionization fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Smith, Cameron R; Sleighter, Rachel L; Hatcher, Patrick G; Lee, James W

    2013-01-01

    Biochar has gained significant interest worldwide for its potential use as both a carbon sequestration technique and soil amendment. Recently, research has shown that pinewood-derived biochar water extracts inhibited the growth of aquatic photosynthetic microorganisms, both prokaryotic and eukaryotic algae, while chicken litter- and peanut shell-derived biochar water extracts showed no growth inhibition. With the use of electrodialysis, the pinewood-derived biochar water extract is separated into 3 fractions (anode-isolated, center chamber retained, and cathode-isolated substances) all with varying toxic effects. Because of its ultrahigh resolution and mass precision, electrospray ionization (ESI) coupled to Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is utilized in this study to analyze biochar water extracts at a molecular level to enhance our understanding of the toxic nature of pinewood-derived biochar water extracts as compared to benign peanut shell-derived biochar water extracts. The molecular composition of pinewood-derived biochar water extracts shows unique carbohydrate ligneous components and sulfur containing condensed ligneous components that are both absent from the peanut shell water extracts and more prevalent in the anode-isolated substances. Using Kendrick mass defect analysis, we also determine that the most likely inhibitor species contain carboxyl and hydroxyl homologous series, both of which are characteristic functional groups hypothesized in our previous research for the inhibitor species. We have suggested that inhibition of aquatic photosynthetic microorganism growth is most likely due to degraded lignin-like species rich in oxygen containing functionalities. From the study conducted here, we show the potential of ultrahigh resolution FTICR-MS as a valuable analytical technique for determining whether certain biochars are safe and benign for use as carbon sequestration and soil amendment.

  3. Mass Spectrometry for Rapid Characterization of Microorganisms

    NASA Astrophysics Data System (ADS)

    Demirev, Plamen A.; Fenselau, Catherine

    2008-07-01

    Advances in instrumentation, proteomics, and bioinformatics have contributed to the successful applications of mass spectrometry (MS) for detection, identification, and classification of microorganisms. These MS applications are based on the detection of organism-specific biomarker molecules, which allow differentiation between organisms to be made. Intact proteins, their proteolytic peptides, and nonribosomal peptides have been successfully utilized as biomarkers. Sequence-specific fragments for biomarkers are generated by tandem MS of intact proteins or proteolytic peptides, obtained after, for instance, microwave-assisted acid hydrolysis. In combination with proteome database searching, individual biomarker proteins are unambiguously identified from their tandem mass spectra, and from there the source microorganism is also identified. Such top-down or bottom-up proteomics approaches permit rapid, sensitive, and confident characterization of individual microorganisms in mixtures and are reviewed here. Examples of MS-based functional assays for detection of targeted microorganisms, e.g., Bacillus anthracis, in environmental or clinically relevant backgrounds are also reviewed.

  4. Liquid Chromatography Mass Spectrometry Profiling of Histones

    PubMed Central

    Su, Xiaodan; Jacob, Naduparambil K.; Amunugama, Ravindra; Lucas, David M.; Knapp, Amy R.; Ren, Chen; Davis, Melanie E.; Marcucci, Guido; Parthun, Mark R.; Byrd, John C.; Fishel, Richard A.; Freitas, Michael A.

    2007-01-01

    Here we describe the use of reverse-phase liquid chromatography mass spectrometry (RP-LC-MS) to simultaneously characterize variants and post-translationally modified isoforms for each histone. The analysis of intact proteins significantly reduces the time of sample preparation and simplifies data interpretation. LC-MS analysis and peptide mass mapping have previously been applied to identify histone proteins and to characterize their post-translational modifications. However, these studies provided limited characterization of both linker histones and core histones. The current LC-MS analysis allows for the simultaneous observation of all histone PTMs and variants (both replacement and bulk histones) without further enrichment, which will be valuable in comparative studies. Protein identities were verified by the analysis of histone H2A species using RPLC fractionation, AU-PAGE separation and nano-LC-MS/MS. PMID:17254850

  5. Study of odor recorder using Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Miura, Tomohiro; Nakamoto, Takamichi; Moriizumi, Toyosaka

    It is necessary to determine the recipe of a target odor with sufficient accuracy to realize an odor recorder for recording and reproducing it. We studied the recipe measurement method of a target odor using a mass spectrometry. It was confirmed that the linear superposition was valid when the binary mixture of the apple-flavor components such as isobutyric acid and ethyl valerate was measured. The superposition of a mass spectrum pattern may enable the recipe determination of a multi-component odor easily. In this research, we succeeded in the recipe determinations of orange flavor made up of 14 component odors when its typical recipe, the equalized, the citral-enhanced and the citronellol-enhanced ones were measured.

  6. FAPA mass spectrometry of designer drugs.

    PubMed

    Smoluch, Marek; Gierczyk, Blazej; Reszke, Edward; Babij, Michal; Gotszalk, Teodor; Schroeder, Grzegorz; Silberring, Jerzy

    2016-01-01

    Application of a flowing atmospheric-pressure afterglow ion source for mass spectrometry (FAPA-MS) for the analysis of designer drugs is described. In this paper, we present application of FAPA MS for identification of exemplary psychotropic drugs: JWH-122, 4BMC, Pentedrone, 3,4-DNNC and ETH-CAT. We have utilized two approaches for introducing samples into the plasma stream; first in the form of a methanolic aerosol from the nebulizer, and the second based on a release of vapors from the electrically heated crucible by thermal desorption. The analytes were ionized by FAPA and identified in the mass analyzer. The order of release of the compounds depends on their volatility. These methods offer fast and reliable structural information, without pre-separation, and can be an alternative to the Electron Impact, GC/MS, and ESI for fast analysis of designer-, and other psychoactive drugs.

  7. MALDI mass spectrometry imaging in rheumatic diseases.

    PubMed

    Rocha, Beatriz; Cillero-Pastor, Berta; Blanco, Francisco J; Ruiz-Romero, Cristina

    2017-07-01

    Mass spectrometry imaging (MSI) is a technique used to visualize the spatial distribution of biomolecules such as peptides, proteins, lipids or other organic compounds by their molecular masses. Among the different MSI strategies, MALDI-MSI provides a sensitive and label-free approach for imaging of a wide variety of protein or peptide biomarkers from the surface of tissue sections, being currently used in an increasing number of biomedical applications such as biomarker discovery and tissue classification. In the field of rheumatology, MALDI-MSI has been applied to date for the analysis of joint tissues such as synovial membrane or cartilage. This review summarizes the studies and key achievements obtained using MALDI-MSI to increase understanding on rheumatic pathologies and to describe potential diagnostic or prognostic biomarkers of these diseases. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Steroid Hormone Analysis by Tandem Mass Spectrometry

    PubMed Central

    Soldin, Steven J.; Soldin, Offie P.

    2013-01-01

    BACKGROUND New high-performance liquid chromatography/ tandem mass spectrometry (LC-MS/MS) methods are among the most successful approaches to improve specificity problems inherent in many immunoassays. CONTENT We emphasize problems with immunoassays for the measurement of steroids and review the emerging role of LC-MS/MS in the measurement of clinically relevant steroids. The latest generation of tandem mass spectrometers has superior limits of quantification, permitting omission of previously employed derivatization steps. The measurement of steroid profiles in the diagnosis and treatment of congenital adrenal hyperplasia, adrenal insufficiency, chronic pelvic pain and prostatitis, oncology (breast cancer), and athletes has important new applications. CONCLUSIONS LC-MS/MS now affords the specificity, imprecision, and limits of quantification necessary for the reliable measurement of steroids in human fluids, enhancing diagnostic capabilities, particularly when steroid profiles are available. PMID:19325015

  9. Protein Sequencing with Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ziady, Assem G.; Kinter, Michael

    The recent introduction of electrospray ionization techniques that are suitable for peptides and whole proteins has allowed for the design of mass spectrometric protocols that provide accurate sequence information for proteins. The advantages gained by these approaches over traditional Edman Degradation sequencing include faster analysis and femtomole, sometimes attomole, sensitivity. The ability to efficiently identify proteins has allowed investigators to conduct studies on their differential expression or modification in response to various treatments or disease states. In this chapter, we discuss the use of electrospray tandem mass spectrometry, a technique whereby protein-derived peptides are subjected to fragmentation in the gas phase, revealing sequence information for the protein. This powerful technique has been instrumental for the study of proteins and markers associated with various disorders, including heart disease, cancer, and cystic fibrosis. We use the study of protein expression in cystic fibrosis as an example.

  10. Radiocarbon positive-ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Freeman, Stewart P. H. T.; Shanks, Richard P.; Donzel, Xavier; Gaubert, Gabriel

    2015-10-01

    Proof-of-principle of a new mass spectrometric technique for radiocarbon measurement is demonstrated. Interfering nitrogen and hydrocarbon molecules are largely eliminated in a charge-exchange cell operating on non-metallic gas. The positive-to-negative ion conversion is the reverse of that conventionally used in accelerator mass spectrometry (AMS) and is compatible with plasma ion sources that may be significantly more efficient and capable of greater output than are AMS sputter ion sources. The Nanogan electron cyclotron resonance (ECR) ion source employed exhibited no sample memory and the >50 kyrs age range of AMS was reproduced. A bespoke prototype new instrument is now required to optimise the plasma and cell physics and to realise hypothetical performance gains over AMS.

  11. [Mass spectrometry in the clinical microbiology laboratory].

    PubMed

    Jordana-Lluch, Elena; Martró Català, Elisa; Ausina Ruiz, Vicente

    2012-12-01

    Infectious diseases are still a cause of high mortality and morbidity rates. Current microbiological diagnostic methods are based on culture and phenotypic identification of isolated microorganisms, which can be obtained in about 24-48 h. Given that the microbiological identification is of major importance for patient management, new diagnostic methods are needed in order to detect and identify microorganisms in a timely and accurate manner. Over the last few years, several molecular techniques based on the amplification of microbial nucleic acids have been developed with the aim of reducing the time needed for the identification of the microorganisms involved in different infectious processes. On the other hand, mass spectrometry has emerged as a rapid and consistent alternative to conventional methods for microorganism identification. This review describes the most widely used mass spectrometry technologies -matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization time-of-flight (ESI-TOF)-, both for protein and nucleic acid analysis, as well as the commercial platforms available. Related publications of most interest in clinical microbiology are also reviewed.

  12. Research Using Accelerator Mass Spectrometry at Arizona

    NASA Astrophysics Data System (ADS)

    Jull, A.; Donahue, D. J.; Burr, G. S.; Beck, W.; Hatheway, A. L.; Biddulph, D. L.; McHargue, L. R.

    2002-12-01

    An Accelerator Mass Spectrometry (AMS) facility has been operated at the University of Arizona since 1982. This is an excellent example of a facility which has benefitted from the NSF Earth Sciences Instrumentation and Facilities Program. AMS has many applications to the fields of geochronology, geoarchaeology, paleoclimatology. A wide range of climatic, geologic and archeological records can be characterized by measuring their 14C and 10Be concentrations, using accelerator mass spectrometry (AMS). These records are found not only in the traditional sampling sites such as lake sediments and ice cores, but also in diverse natural accumulates and biogeochemical products such as: loess/paleosol deposits, corals, speleothems, and forest-fire horizons. The in-situ production of cosmogenic radionuclides in terrestrial and extraterrestrial materials provides several possibilities of determining their chronology. Thes studies are important for understanding cosmic-ray production of radionuclides in rock surfaces, by which we can draw conclusions about exposure time and erosion. Studies on extraterrestrial materials such as lunar samples allow us to determine the solar and galactic cosmic-ray fluxes in the past, and the cosmogenic 14C and 10Be in meteorites can be used to determine terrestrial ages. In this paper, we will highlight some selected applications of AMS, including dating of some interesting art works and artifacts, to show some of the great range of studies which can be undertaken.

  13. Lipid imaging by mass spectrometry - a review.

    PubMed

    Gode, David; Volmer, Dietrich A

    2013-03-07

    Mass spectrometry imaging (MSI) has proven to be extremely useful for applications such as the spatial analysis of peptides and proteins in biological tissue, the performance assessment of drugs in vivo or the measurement of protein or metabolite expression as tissue classifiers or biomarkers from disease versus control tissue comparisons. The most popular MSI technique is MALDI mass spectrometry. First invented by Richard Caprioli in the mid-1990s, it is the highest performing MSI technique in terms of spatial resolution, sensitivity for intact biomolecules and application range today. The unique ability to identify and spatially resolve numerous compounds simultaneously, based on m/z values has inter alia been applied to untargeted and targeted chemical mapping of biological compartments, revealing changes of physiological states, disease pathologies and metabolic faith and distribution of xenobiotics. Many MSI applications focus on lipid species because of the lipids' diverse roles as structural components of cell membranes, their function in the surfactant cycle, and their involvement as second messengers in signalling cascades of tissues and cells. This article gives a comprehensive overview of lipid imaging techniques and applications using established MALDI and SIMS methods but also other promising MSI techniques such as DESI.

  14. [Application of mass spectrometry in mycobacteria].

    PubMed

    Alcaide, Fernando; Palop-Borrás, Begoña; Domingo, Diego; Tudó, Griselda

    2016-06-01

    To date, more than 170 species of mycobacteria have been described, of which more than one third may be pathogenic to humans, representing a significant workload for microbiology laboratories. These species must be identified in clinical practice, which has long been a major problem due to the shortcomings of conventional (phenotypic) methods and the limitations and complexity of modern methods largely based on molecular biology techniques. The aim of this review was to briefly describe different aspects related to the use of MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) for the identification of mycobacteria. Several difficulties are encountered with the use of this methodology in these microorganisms mainly due to the high pathogenicity of some mycobacteria and the peculiar structure of their cell wall, requiring inactivation and special protein extraction protocols. We also analysed other relevant aspects such as culture media, the reference methods employed (gold standard) in the final identification of the different species, the cut-off used to accept data as valid, and the databases of the different mass spectrometry systems available. MS has revolutionized diagnosis in modern microbiology; however, specific improvements are needed to consolidate the use of this technology in mycobacteriology. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  15. Mass Spectrometry on Future Mars Landers

    NASA Technical Reports Server (NTRS)

    Brinckerhoff, W. B.; Mahaffy, P. R.

    2011-01-01

    Mass spectrometry investigations on the 2011 Mars Science Laboratory (MSL) and the 2018 ExoMars missions will address core science objectives related to the potential habitability of their landing site environments and more generally the near-surface organic inventory of Mars. The analysis of complex solid samples by mass spectrometry is a well-known approach that can provide a broad and sensitive survey of organic and inorganic compounds as well as supportive data for mineralogical analysis. The science value of such compositional information is maximized when one appreciates the particular opportunities and limitations of in situ analysis with resource-constrained instrumentation in the context of a complete science payload and applied to materials found in a particular environment. The Sample Analysis at Mars (SAM) investigation on MSL and the Mars Organic Molecule Analyzer (MOMA) investigation on ExoMars will thus benefit from and inform broad-based analog field site work linked to the Mars environments where such analysis will occur.

  16. Isotope ratio mass spectrometry in nutrition research

    SciTech Connect

    Luke, A.H.

    1994-12-31

    Many of the biochemical pathways and processes that form the foundation of modern nutrition research was elucidated using stable isotopes as physiological tracers. Since the discovery of stable isotopes, improvements and innovations in mass spectrometry and chromatography have led to greatly expanded applications. This research project was designed to evaluate gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) as a tool for isotopic tracer studies and to delineate the operational parameters for the analysis of {sup 13}C-labeled cholesterol, leucine and {alpha}-ketoisocaproate. The same isotope ratio mass spectrometer was then used as the base instrument for the ratio mass spectrometer was then used as the base instrument for the development of two additional inlet systems: a continuous-flow inlet for the analyses of {sup 13}C and {sup 18}O as CO{sub 2} and a filament inlet for on-line combustion and isotopic analysis of non-volatile organic compounds. Each of these three inlets was evaluated and their utility in nutrition research illustrated. GC/C/IRMS was used to analyze cholesterol, leucine and {alpha}-ketoisocaproate with good accuracy, precision and little isotopic memory. For all three compounds the detection limits achieved well surpassed currently used technologies. For compounds that can be well separated by GC, GC/C/IRMS is a valuable analytical tool. The continuous-flow inlet provided good accuracy and precision for measurements of {sup 13}CO{sub 2} from breath tests and {sup 18}O as CO{sub 2} from total energy expenditure tests. Most importantly, the continuous-flow inlet increased sample throughput by at least a factor of three over conventional analytical techniques. The filament inlet provided accurate and precise {sup 13}C ratio measurements of both natural abundance and enriched standards of non-volatile organic compounds of physiological interest.

  17. Biomarker Candidates of Chlamydophila pneumoniae Proteins and Protein Fragments Identified by Affinity-Proteomics Using FTICR-MS and LC-MS/MS

    NASA Astrophysics Data System (ADS)

    Susnea, Iuliana; Bunk, Sebastian; Wendel, Albrecht; Hermann, Corinna; Przybylski, Michael

    2011-04-01

    We report here an affinity-proteomics approach that combines 2D-gel electrophoresis and immunoblotting with high performance mass spectrometry to the identification of both full length protein antigens and antigenic fragments of Chlamydophila pneumoniae (C. pneumoniae). The present affinity-mass spectrometry approach effectively utilized high resolution FTICR mass spectrometry and LC-tandem-MS for protein identification, and enabled the identification of several new highly antigenic C. pneumoniae proteins that were not hitherto reported or previously detected only in other Chlamydia species, such as Chlamydia trachomatis. Moreover, high resolution affinity-MS provided the identification of several neo-antigenic protein fragments containing N- and C-terminal, and central domains such as fragments of the membrane protein Pmp21 and the secreted chlamydial proteasome-like factor (Cpaf), representing specific biomarker candidates.

  18. Increasing Fragmentation of Disulfide-Bonded Proteins for Top-Down Mass Spectrometry by Supercharging

    PubMed Central

    Zhang, Jiang; Ogorzalek Loo, Rachel R.; Loo, Joseph A.

    2015-01-01

    The disulfide bond is an important post-translational modification to form and maintain the native structure and biological functions of proteins. Characterization of disulfide bond linkages is therefore of essential interest in the structural elucidation of proteins. Top-down mass spectrometry (MS) of disulfide-bonded proteins has been hindered by relatively low sequence coverage due to disulfide cross-linking. In this study, we employed top-down ESI-MS with Fourier-transform ion cyclotron resonance (FT-ICR) MS with electron capture dissociation (ECD) and collisionally activated dissociation (CAD) to study the fragmentation of supercharged proteins with multiple intramolecular disulfide bonds. With charge enhancement upon the addition of sulfolane to the analyte solution, improved protein fragmentation and disulfide bond cleavage efficiency was observed for proteins including bovine β-lactoglobulin, soybean trypsin inhibitor, human proinsulin, and chicken lysozyme. Both the number and relative abundances of product ions representing disulfide cleavage increase with increasing charge states for the proteins studied. Our studies suggest supercharging ESI-MS is a promising tool to aid in the top-down MS analysis of disulfide-bonded proteins, providing potentially useful information for the determination of disulfide bond linkages. PMID:26028988

  19. Isotope ratio analysis by Orbitrap mass spectrometry

    NASA Astrophysics Data System (ADS)

    Eiler, J. M.; Chimiak, L. M.; Dallas, B.; Griep-Raming, J.; Juchelka, D.; Makarov, A.; Schwieters, J. B.

    2016-12-01

    Several technologies are being developed to examine the intramolecular isotopic structures of molecules (i.e., site-specific and multiple substitution), but various limitations in sample size and type or (for IRMS) resolution have so far prevented the creation of a truly general technique. We will discuss the initial findings of a technique based on Fourier transform mass spectrometry, using the Thermo Scientific Q Exactive GC — an instrument that contains an Orbitrap mass analyzer. Fourier transform mass spectrometry is marked by exceptionally high mass resolutions (the Orbitrap reaches M/∆M in the range 250,000-1M in the mass range of greatest interest, 50-200 amu). This allows for resolution of a large range of nearly isobaric interferences for isotopologues of volatile and semi-volatile compounds (i.e., involving isotopes of H, C, N, O and S). It also provides potential to solve very challenging mass resolution problems for isotopic analysis of other, heavier elements. Both internal and external experimental reproducibilities of isotope ratio analyses using the Orbitrap typically conform to shot-noise limits down to levels of 0.2 ‰ (1SE), and routinely in the range 0.5-1.0 ‰, with similar accuracy when standardized to concurrently run reference materials. Such measurements can be made without modifications to the ion optics of the Q Exactive GC, but do require specially designed sample introduction devices to permit sample/standard comparison and long integration times. The sensitivity of the Q Exactive GC permits analysis of sub-nanomolar samples and quantification of multiply-substituted species. The site-specific capability of this instrument arises from the fact that mass spectra of molecular analytes commonly contain diverse fragment ion species, each of which samples a specific sub-set of molecular sites. We will present applications of this technique to the biological and abiological chemistry of amino acids, forensic identification of

  20. Combination of statistical methods and Fourier transform ion cyclotron resonance mass spectrometry for more comprehensive, molecular-level interpretations of petroleum samples.

    PubMed

    Hur, Manhoi; Yeo, Injoon; Park, Eunsuk; Kim, Young Hwan; Yoo, Jongshin; Kim, Eunkyoung; No, Myoung-han; Koh, Jaesuk; Kim, Sunghwan

    2010-01-01

    Complex petroleum mass spectra obtained by Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS) were successfully interpreted at the molecular level by applying principle component analysis (PCA) and hierarchical clustering analysis (HCA). A total of 40 mass spectra were obtained from 20 crude oil samples using both positive and negative atmospheric pressure photoionization (APPI). Approximately 400,000 peaks were identified at the molecular level. Conventional data analyses would have been impractical with so much data. However, PCA grouped samples into score plots based on their molecular composition. In this way, the overall compositional difference between samples could be easily displayed and identified by comparing score and loading plots. HCA was also performed to group and compare samples based on selected peaks that had been grouped by PCA. Subsequent heat map analyses revealed detailed compositional differences among grouped samples. This study demonstrates a promising new approach for studying multiple, complex petroleum samples at the molecular level.

  1. NITPICK: peak identification for mass spectrometry data

    PubMed Central

    Renard, Bernhard Y; Kirchner, Marc; Steen , Hanno; Steen, Judith AJ; Hamprecht , Fred A

    2008-01-01

    Background The reliable extraction of features from mass spectra is a fundamental step in the automated analysis of proteomic mass spectrometry (MS) experiments. Results This contribution proposes a sparse template regression approach to peak picking called NITPICK. NITPICK is a Non-greedy, Iterative Template-based peak PICKer that deconvolves complex overlapping isotope distributions in multicomponent mass spectra. NITPICK is based on fractional averagine, a novel extension to Senko's well-known averagine model, and on a modified version of sparse, non-negative least angle regression, for which a suitable, statistically motivated early stopping criterion has been derived. The strength of NITPICK is the deconvolution of overlapping mixture mass spectra. Conclusion Extensive comparative evaluation has been carried out and results are provided for simulated and real-world data sets. NITPICK outperforms pepex, to date the only alternate, publicly available, non-greedy feature extraction routine. NITPICK is available as software package for the R programming language and can be downloaded from . PMID:18755032

  2. Multinozzle Emitter Arrays for Nanoelectrospray Mass Spectrometry

    PubMed Central

    Mao, Pan; Wang, Hung-Ta; Yang, Peidong; Wang, Daojing

    2011-01-01

    Mass spectrometry (MS) is the enabling technology for proteomics and metabolomics. However, dramatic improvements in both sensitivity and throughput are still required to achieve routine MS-based single cell proteomics and metabolomics. Here, we report the silicon-based monolithic multinozzle emitter array (MEA), and demonstrate its proof-of-principle applications in high-sensitivity and high-throughput nanoelectrospray mass spectrometry. Our MEA consists of 96 identical 10-nozzle emitters in a circular array on a 3-inch silicon chip. The geometry and configuration of the emitters, the dimension and number of the nozzles, and the micropillar arrays embedded in the main channel, can be systematically and precisely controlled during the microfabrication process. Combining electrostatic simulation and experimental testing, we demonstrated that sharpened-end geometry at the stem of the individual multinozzle emitter significantly enhanced the electric fields at its protruding nozzle tips, enabling sequential nanoelectrospray for the high-density emitter array. We showed that electrospray current of the multinozzle emitter at a given total flow rate was approximately proportional to the square root of the number of its spraying-nozzles, suggesting the capability of high MS sensitivity for multinozzle emitters. Using a conventional Z-spray mass spectrometer, we demonstrated reproducible MS detection of peptides and proteins for serial MEA emitters, achieving sensitivity and stability comparable to the commercial capillary emitters. Our robust silicon-based MEA chip opens up the possibility of a fully-integrated microfluidic system for ultrahigh-sensitivity and ultrahigh-throughput proteomics and metabolomics. PMID:21728281

  3. Multinozzle Emitter Arrays for Nanoelectrospray Mass Spectrometry

    SciTech Connect

    Mao, Pan; Wang, Hung-Ta; Yang, Peidong; Wang, Daojing

    2011-06-16

    Mass spectrometry (MS) is the enabling technology for proteomics and metabolomics. However, dramatic improvements in both sensitivity and throughput are still required to achieve routine MS-based single cell proteomics and metabolomics. Here, we report the silicon-based monolithic multinozzle emitter array (MEA), and demonstrate its proof-of-principle applications in high-sensitivity and high-throughput nanoelectrospray mass spectrometry. Our MEA consists of 96 identical 10-nozzle emitters in a circular array on a 3-inch silicon chip. The geometry and configuration of the emitters, the dimension and number of the nozzles, and the micropillar arrays embedded in the main channel, can be systematically and precisely controlled during the microfabrication process. Combining electrostatic simulation and experimental testing, we demonstrated that sharpened-end geometry at the stem of the individual multinozzle emitter significantly enhanced the electric fields at its protruding nozzle tips, enabling sequential nanoelectrospray for the high-density emitter array. We showed that electrospray current of the multinozzle emitter at a given total flow rate was approximately proportional to the square root of the number of its spraying-nozzles, suggesting the capability of high MS sensitivity for multinozzle emitters. Using a conventional Z-spray mass spectrometer, we demonstrated reproducible MS detection of peptides and proteins for serial MEA emitters, achieving sensitivity and stability comparable to the commercial capillary emitters. Our robust silicon-based MEA chip opens up the possibility of a fully-integrated microfluidic system for ultrahigh-sensitivity and ultrahigh-throughput proteomics and metabolomics.

  4. Mass Spectrometry for Large Undergraduate Laboratory Sections

    NASA Astrophysics Data System (ADS)

    Illies, A.; Shevlin, P. B.; Childers, G.; Peschke, M.; Tsai, J.

    1995-08-01

    Mass spectrometry is routinely covered in undergraduate organic chemistry courses and a number of valuable laboratory experiments featuring its use have been discussed (1-7). Although such experiments work well at institutions with limited laboratory enrollments, we typically teach laboratories with enrollments of 160 or more in which it is difficult to allow each student to carry out a meaningful "hands on" mass spectrometry experiment. Since we feel that some practical experience with this technique is important, we have designed a simple gas chromatography-mass spectrometry (gc/ms) exercise that allows each student to analyze the products of a simple synthesis that they have performed. The exercise starts with the microscale SN2 synthesis of 1-bromobutane from 1-butanol as described by Williamson (8). The students complete the synthesis and place one drop of the distilled product in a screw capped vial. The vials are then sealed, labeled with the students name and taken to the mass spectrometry laboratory by a teaching assistant. Students are instructed to sign up for a 20-min block of time over the next few days in order to analyze their sample. When the student arrives at the laboratory, he or she adds 1 ml CH2Cl2 to the sample and injects 0.3 microliters of the solution into the gas chromatograph. The samples typically contain the 1-butanol starting material and the 1-bromobutane product along with traces of dibutyl ether. The figure shows a mass chromatogram along with the mass spectra of the starting material and product from an actual student run. For this analysis to be applicable to large numbers of students, the gc separation must be as rapid as possible. We have been able to analyze each sample in 6 minutes on a 30 m DB-5 capillary column with the following temperature program: 70 oC for 1 min, 70-80 oC at 10 oC/min, 86-140 oC at 67.5 oC/min, 140-210 oC at 70 oC/min, and 210 oC for 1 min. A mass range of 20-200 amu is scanned with a solvent delay of 2

  5. Targeted high-resolution ion mobility separation coupled to ultrahigh-resolution mass spectrometry of endocrine disruptors in complex mixtures.

    PubMed

    Benigni, Paolo; Thompson, Christopher J; Ridgeway, Mark E; Park, Melvin A; Fernandez-Lima, Francisco

    2015-04-21

    Traditional separation and detection of targeted compounds from complex mixtures from environmental matrices requires the use of lengthy prefractionation steps and high-resolution mass analyzers due to the large number of chemical components and their large structural diversity (highly isomeric). In the present work, selected accumulation trapped ion mobility spectrometry (SA-TIMS) is coupled to Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for direct separation and characterization of targeted endocrine-disrupting compounds (EDC) from a complex environmental matrix in a single analysis. In particular, targeted identification based on high-resolution mobility (R ∼ 70-120) and ultrahigh-resolution mass measurements (R > 400 000) of seven commonly targeted EDC and their isobars (e.g., bisphenol A, (Z)- and (E)-diethylstilbestrol, hexestrol, estrone, α-estradiol, and 17-ethynylestradiol) is shown from a complex mixture of water-soluble organic matter (e.g., Suwannee River Fulvic Acid Standard II) complemented with reference standard measurements and theoretical calculations (<3% error).

  6. Laser Microprobe Mass Spectrometry 1: Basic Principles and Performance Characteristics.

    ERIC Educational Resources Information Center

    Denoyer, Eric; And Others

    1982-01-01

    Describes the historical development, performance characteristics (sample requirements, analysis time, ionization characteristics, speciation capabilities, and figures of merit), and applications of laser microprobe mass spectrometry. (JN)

  7. Laser Microprobe Mass Spectrometry 1: Basic Principles and Performance Characteristics.

    ERIC Educational Resources Information Center

    Denoyer, Eric; And Others

    1982-01-01

    Describes the historical development, performance characteristics (sample requirements, analysis time, ionization characteristics, speciation capabilities, and figures of merit), and applications of laser microprobe mass spectrometry. (JN)

  8. Characterisation of DEFB107 by mass spectrometry

    NASA Astrophysics Data System (ADS)

    McCullough, Bryan J.; Eastwood, Hayden; Clark, Dave J.; Polfer, Nick C.; Campopiano, Dominic J.; Dorin, Julia A.; Maxwell, Alison; Langley, Ross J.; Govan, John R. W.; Bernstein, Summer L.; Bowers, Michael T.; Barran, Perdita E.

    2006-05-01

    Mammalian defensins are small endogenous cationic proteins which form a class of antimicrobial peptides that is part of the innate immune response of all mammalian species [R. Lehrer, Nat. Rev. Microbiol. 2 (9) (2004) 727; T. Ganz, R.I. Lehrer, Curr. Opin. Immunol. 6 (4) (1994) 584] [1] and [2]. We have developed mass spectrometry based strategies for characterising the structure-activity relationship of defensins [D.J. Campopiano, D.J. Clarke, N.C. Polfer, P.E. Barran, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, J. Biol. Chem. 279 (47) (2004) 48671; P.E. Barran, N.C. Polfer, D.J. Campopiano, D.J. Clarke, P.R.R. Langridge-Smith, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, R.P. Millar, M.T. Bowers, Int. J. Mass Spectrom. 240 (2005) 273] [3] and [4], and here we present data obtained from a five cysteine containing [beta]-defensin, DEFB107. The synthetic product of this human defensin exists with a glutathione capping group, its oxidation state and disulphide connectivity have been determined via accurate mass measurements and peptide mass mapping respectively, and despite possessing three disulphide bridges, it does not fit the [beta]-defensin canonical motif. With the use of molecular modelling, we have generated candidate geometries to discern the influence of disulphide bridging on the overall tertiary structure of DEFB107. These are compared with experimental results from ion mobility measurements. Defensins display activity against a wide variety of pathogens including both gram-negative and gram-positive bacteria. Their mechanism of mode of action is unknown, but is believed to involve defensin aggregation at cell surfaces, followed by cell permeabilisation and hence deathE To probe this mechanism, the localisation of DEFB107 in synthetic vesicles was studied using H/D exchange and mass spectrometry. The results obtained are used to analyse the antimicrobial activity of DEFB107.

  9. Interfacing membrane mimetics with mass spectrometry

    PubMed Central

    Marty, Michael T.; Hoi, Kin Kuan; Robinson, Carol V.

    2017-01-01

    Conspectus Membrane proteins play critical physiological roles and make up the majority of drug targets. Due to their generally low expression levels and amphipathic nature, membrane proteins represent challenging molecular entities for biophysical study. Mass spectrometry offers several sensitive approaches to study the biophysics of membrane proteins. By preserving noncovalent interactions in the gas phase and using collisional activation to remove solubilization agents inside the mass spectrometer, native mass spectrometry (MS) is capable of studying isolated assemblies that would be insoluble in aqueous solution, such as membrane protein oligomers and protein-lipid complexes. Conventional methods use detergent to solubilize the protein prior to electrospray ionization. Gas-phase activation inside the mass spectrometer removes the detergent to yield the isolated proteins with bound ligands. This approach has proven highly successful for ionizing membrane proteins. With the appropriate choice of detergents, membrane proteins with bound lipid species can be observed, which allows characterization of protein-lipid interactions. However, detergents have several limitations. They do not necessarily replicate the native lipid bilayer environment, and only a small number of protein-lipid interactions can be resolved. In this Account, we summarize the development of different membrane mimetics as cassettes for MS analysis of membrane proteins. Examples include amphipols, bicelles, and picodiscs with a special emphasis on lipoprotein Nanodiscs. Polydispersity and heterogeneity of the membrane mimetic cassette is a critical issue for study by MS. Ever more complex datasets consisting of overlapping protein charge states and multiple lipid-bound entities have required development of new computational, theoretical, and experimental approaches to interpret both mass and ion mobility spectra. We will present the rationale and limitations of these approaches. Starting with the

  10. Low molecular weight components in an aquatic humic substance as characterized by membrane dialysis and orbitrap mass spectrometry.

    PubMed

    Remucal, Christina K; Cory, Rose M; Sander, Michael; McNeill, Kristopher

    2012-09-04

    Suwannee River fulvic acid (SRFA) was dialyzed through a 100-500 molecular weight cutoff dialysis membrane, and the dialysate and retentate were analyzed by UV-visible absorption and high-resolution Orbitrap mass spectrometry (MS). A significant fraction (36% based on dissolved organic carbon) of SRFA passed through the dialysis membrane. The fraction of SRFA in the dialysate had a different UV-visible absorption spectrum and was enriched in low molecular weight molecules with a more aliphatic composition relative to the initial SRFA solution. Comparison of the SRFA spectra collected by Orbitrap MS and Fourier transform ion cyclotron resonance MS (FT-ICR MS) demonstrated that the mass accuracy of the Orbitrap MS is sufficient for determination of unique molecular formulas of compounds with masses <600 Da in a complex mixture, such as SRFA. The most intense masses detected by Orbitrap MS were found in the 100-200 Da mass range. Many of these low molecular masses corresponded to molecular formulas of previously identified compounds in organic matter, lignin, and plants, and the use of the standard addition method provided an upper concentration estimate of selected target compounds in SRFA. Collectively, these results provide evidence that SRFA contains low molecular weight components that are present individually or in loosely bound assemblies.

  11. Detection of gunshot residues using mass spectrometry.

    PubMed

    Taudte, Regina Verena; Beavis, Alison; Blanes, Lucas; Cole, Nerida; Doble, Philip; Roux, Claude

    2014-01-01

    In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR. Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further, modern MS instruments can detect and identify a number of explosives and additives which may require different ionization techniques. Finally, MS has been applied to the analysis of both OGSR and inorganic gunshot residue (IGSR), although the "gold standard" for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis.

  12. Mass Spectrometry Methodology in Lipid Analysis

    PubMed Central

    Li, Lin; Han, Juanjuan; Wang, Zhenpeng; Liu, Jian’an; Wei, Jinchao; Xiong, Shaoxiang; Zhao, Zhenwen

    2014-01-01

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease. PMID:24921707

  13. [Application of mass spectrometry in mycology].

    PubMed

    Quiles Melero, Inmaculada; Peláez, Teresa; Rezusta López, Antonio; Garcia-Rodríguez, Julio

    2016-06-01

    MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) is becoming an essential tool in most microbiology laboratories. At present, by using a characteristic fungal profile obtained from whole cells or through simple extraction protocols, MALDI-TOF MS allows the identification of pathogenic fungi with a high performance potential. This methodology decreases the laboratory turnaround time, optimizing the detection of mycoses. This article describes the state-of-the-art of the use of MALDI-TOF MS for the detection of human clinical fungal pathogens in the laboratory and discusses the future applications of this technology, which will further improve routine mycological diagnosis. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Live single-cell mass spectrometry.

    PubMed

    Masujima, Tsutomu

    2009-08-01

    The history from bio-imaging to live single-cell mass spectrometry (MS) is herein reviewed. The limitation of the current bio-imaging method is probing only known molecules, and a method for finding new molecules is needed for cells which, however, show individual behaviors even in the same incubation dish. Single-cell MALDI-TOF/MS has been developed, but it can detect only molecules that can be easily ionized, and not be exhaustive. Recently, the contents of a single cell have been sucked out by a nano-electro spray tip, and directly introduced into MS by nano-spray ionization. Thousands of molecular peaks have been successfully and exhaustively detected, and an extraction method for key molecules was also developed. This new method is now being widely applied to explore site- or state-specific molecules in various aspects of cell dynamisms.

  15. Recent trends in inorganic mass spectrometry

    SciTech Connect

    Smith, D.H.; Barshick, C.M.; Duckworth, D.C.; Riciputi, L.R.

    1996-10-01

    The field of inorganic mass spectrometry has seen substantial change in the author`s professional lifetime (over 30 years). Techniques in their infancy 30 years ago have matured; some have almost disappeared. New and previously unthought of techniques have come into being; some of these, such as ICP-MS, are reasonably mature now, while others have some distance to go before they can be so considered. Most of these new areas provide fertile fields for researchers, both in the development of new analytical techniques and by allowing fundamental studies to be undertaken that were previously difficult, impossible, or completely unforeseen. As full coverage of the field is manifestly impossible within the framework of this paper, only those areas with which the author has personal contact will be discussed. Most of the work originated in his own laboratory, but that of other laboratories is covered where it seemed appropriate.

  16. Characterization of Microorganisms by MALDI Mass Spectrometry

    SciTech Connect

    Petersen, Catherine E.; Valentine, Nancy B.; Wahl, Karen L.

    2008-10-02

    Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for characterization and analysis of microorganisms, specifically bacteria, is described here as a rapid screening tool. The objective of this technique is not comprehensive protein analysis of a microorganism but rather a rapid screening of the organism and the accessible protein pattern for characterization and distinction. This method is based on the ionization of the readily accessible and easily ionizable portion of the protein profile of an organism that is often characteristic of different bacterial species. The utility of this screening approach is yet to reach its full potential but could be applied to food safety, disease outbreak monitoring in hospitals, culture stock integrity and verification, microbial forensics or homeland security applications.

  17. [Future applications of mass spectrometry in microbiology].

    PubMed

    Vila, Jordi; Zboromyrska, Yuliya; Burillo, Almudena; Bouza, Emilio

    2016-06-01

    MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) has been vigorously introduced in many clinical microbiology laboratories for the rapid and accurate identification of bacteria and fungi. In fact, the implementation of this methodology can be considered a revolution in these laboratories. In addition to microbial identification, MALDI-TOF MS is being used for the detection of some mechanisms of antibiotic resistance and for the molecular typing of bacteria. A number of current and future applications that increase the versatility of this methodology may also be mentioned. Among these are its direct application on clinical samples, the detection of toxins or specific microbial antigens, and its application in the fields of virology and parasitology. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. Glass microfabricated nebulizer chip for mass spectrometry.

    PubMed

    Saarela, Ville; Haapala, Markus; Kostiainen, Risto; Kotiaho, Tapio; Franssila, Sami

    2007-05-01

    A microfluidic nebulizer chip for mass spectrometry is presented. It is an all-glass device which consists of fusion bonded Pyrex wafers with embedded flow channels and a nozzle at the chip edge. A platinum heater is located on the wafer backside. Fabrication of the chip is detailed, especially glass deep etching, wafer bonding, and metal patterning. Various process combinations of bonding and metallization have been considered (anodic bonding vs. fusion bonding; heater inside/outside channel; metallization before/after bonding; platinum lift-off vs. etching). The chip vaporizes the liquid sample (0.1-10 microL min(-1)) and mixes it with a nebulizer gas (ca. 100 sccm N2). Operating temperatures can go up to 500 degrees C ensuring efficient vaporization. Thermal insulation of the glass ensures low temperatures at the far end of the chip, enabling easy interconnections.

  19. Functional phosphoproteomic mass spectrometry-based approaches

    PubMed Central

    2012-01-01

    Mass Spectrometry (MS)-based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease. The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un-phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future. Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies. PMID:23369623

  20. Accelerator mass spectrometry (AMS) in plutonium analysis.

    PubMed

    Strumińska-Parulska, Dagmara I

    The paper summarizes the results of the (240)Pu/(239)Pu atomic ratio studies in atmospheric fallout samples collected in 1986 over Gdynia (Poland) as well as three Baltic fish species collected in 1997 using the accelerator mass spectrometry. A new generation of AMS has been developed during last years and this method is an efficient and good technique to measure long-lived radioisotopes in the environment and provides the most accurate determination of the atomic ratios between (240)Pu and (239)Pu. The nuclide compositions of plutonium in filter samples correspond to their means of production. AMS measurements of atmospheric fallout collected in April showed sufficient increase of the (240)Pu/(239)Pu atomic ratio from 0.28 from March to 0.47. Also such high increase of (240)Pu/(239)Pu atomic ratio, close to reactor core (240)Pu/(239)Pu atomic ratio, was observed in September and equaled 0.47.

  1. Mass Spectrometry Imaging in Oncology Drug Discovery.

    PubMed

    Goodwin, R J A; Bunch, J; McGinnity, D F

    2017-01-01

    Over the last decade mass spectrometry imaging (MSI) has been integrated in to many areas of drug discovery and development. It can have significant impact in oncology drug discovery as it allows efficacy and safety of compounds to be assessed against the backdrop of the complex tumour microenvironment. We will discuss the roles of MSI in investigating compound and metabolite biodistribution and defining pharmacokinetic -pharmacodynamic relationships, analysis that is applicable to all drug discovery projects. We will then look more specifically at how MSI can be used to understand tumour metabolism and other applications specific to oncology research. This will all be described alongside the challenges of applying MSI to industry research with increased use of metrology for MSI. © 2017 Elsevier Inc. All rights reserved.

  2. Mass spectrometry methodology in lipid analysis.

    PubMed

    Li, Lin; Han, Juanjuan; Wang, Zhenpeng; Liu, Jian'an; Wei, Jinchao; Xiong, Shaoxiang; Zhao, Zhenwen

    2014-06-11

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

  3. Mass spectrometry and Web 2.0.

    PubMed

    Murray, Kermit K

    2007-10-01

    The term Web 2.0 is a convenient shorthand for a new era in the Internet in which users themselves are both generating and modifying existing web content. Several types of tools can be used. With social bookmarking, users assign a keyword to a web resource and the collection of the keyword 'tags' from multiple users form the classification of these resources. Blogs are a form of diary or news report published on the web in reverse chronological order and are a popular form of information sharing. A wiki is a website that can be edited using a web browser and can be used for collaborative creation of information on the site. This article is a tutorial that describes how these new ways of creating, modifying, and sharing information on the Web are being used for on-line mass spectrometry resources.

  4. In situ secondary ion mass spectrometry analysis

    SciTech Connect

    Groenewold, G.S.; Applehans, A.D.; Ingram, J.C.; Delmore, J.E.; Dahl, D.A.

    1993-01-01

    The direct detection of tributyl phosphate (TBP) on rocks using molecular beam surface analysis [MBSA or in situ secondary ion mass spectrometry (SIMS)] is demonstrated. Quantities as low as 250 ng were detected on basalt and sandstone with little or no sample preparation. Detection of TBP on soil has proven to be more problematic and requires further study. Ethylenediaminetetraacetic acid (EDTA) is more difficult to detect because it is very reactive with surfaces of interest. Nevertheless, it is possible to detect EDTA if the acidity of the surface is controlled. The detection of EDTA-metal complexes is currently an open question, but evidence is presented for the detection of ions arising from a EDTA-lead complex. Carboxylic acids (i.e., citric, ascorbic, malic, succinic, malonic, and oxalic) give characteristic SIM spectra, but their detection on sample surfaces awaits evaluation.

  5. Dating silk by capillary electrophoresis mass spectrometry.

    PubMed

    Moini, Mehdi; Klauenberg, Kathryn; Ballard, Mary

    2011-10-01

    A new capillary electrophoresis mass spectrometry (CE-MS) technique is introduced for age estimation of silk textiles based on amino acid racemization rates. With an L to D conversion half-life of ~2500 years for silk (B. mori) aspartic acid, the technique is capable of dating silk textiles ranging in age from several decades to a few-thousand-years-old. Analysis required only ~100 μg or less of silk fiber. Except for a 2 h acid hydrolysis at 110 °C, no other sample preparation is required. The CE-MS analysis takes ~20 min, consumes only nanoliters of the amino acid mixture, and provides both amino acid composition profiles and D/L ratios for ~11 amino acids.

  6. Multiplex mass spectrometry imaging for latent fingerprints.

    PubMed

    Yagnik, Gargey B; Korte, Andrew R; Lee, Young Jin

    2013-01-01

    We have previously developed in-parallel data acquisition of orbitrap mass spectrometry (MS) and ion trap MS and/or MS/MS scans for matrix-assisted laser desorption/ionization MS imaging (MSI) to obtain rich chemical information in less data acquisition time. In the present study, we demonstrate a novel application of this multiplex MSI methodology for latent fingerprints. In a single imaging experiment, we could obtain chemical images of various endogenous and exogenous compounds, along with simultaneous MS/MS images of a few selected compounds. This work confirms the usefulness of multiplex MSI to explore chemical markers when the sample specimen is very limited. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Laser Ablation Inductively Coupled Plasma Mass Spectrometry

    PubMed Central

    Hutchinson, Robert W.; McLachlin, Katherine M.; Riquelme, Paloma; Haarer, Jan; Broichhausen, Christiane; Ritter, Uwe; Geissler, Edward K.; Hutchinson, James A.

    2015-01-01

    ABSTRACT New analytical techniques for multiparametric characterisation of individual cells are likely to reveal important information about the heterogeneity of immunological responses at the single-cell level. In this proof-of-principle study, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was applied to the problem of concurrently detecting 24 lineage and activation markers expressed by human leucocytes. This approach was sufficiently sensitive and specific to identify subpopulations of isolated T, B, and natural killer cells. Leucocyte subsets were also accurately detected within unfractionated peripheral blood mononuclear cells preparations. Accordingly, we judge LA-ICP-MS to be a suitable method for assessing expression of multiple tissue antigens in solid-phase biological specimens, such as tissue sections, cytospins, or cells grown on slides. These results augur well for future development of LA-ICP-MS–based bioimaging instruments for general users. PMID:27500232

  8. Deciphering the histone code using mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ueberheide, Beatrix M.; Mollah, Sahana

    2007-01-01

    During the past decade, studies surrounding chromatin research have grown exponentially. A major focus of chromatin biology is centered on understanding of how histone modifications alter chromatin structure at the molecular and mechanistic levels. Discoveries are being made at a rapid pace due to the advent of new and innovative techniques. Mass spectrometry has emerged as a powerful tool in the field of histone research due to its speed, sensitivity, and ease of use. This has resulted in the identification of a number of novel histone modification sites. In consequence, new roles in biological processes have been discovered and hypothetical models, such as the `histone code' have been reaffirmed or refined. One significant advantage to using mass spectrometric techniques is that the combinations of modifications on different sites can be determined which is crucial to deciphering the `histone code'. In this manuscript, the mass spectrometric approaches developed over the past decade for both qualitative and quantitative analysis of histone post-translational modifications (PTMs) are discussed.

  9. Atmospheric-pressure Penning ionization mass spectrometry.

    PubMed

    Hiraoka, Kenzo; Fujimaki, Susumu; Kambara, Shizuka; Furuya, Hiroko; Okazaki, Shigemitsu

    2004-01-01

    A preliminary study on the atmospheric-pressure Penning ionization (APP(e)I) of gaseous organic compounds with Ar* has been made. The metastable argon atoms (Ar*: 11.55 eV for (3)P(2) and 11.72 eV for (3)P(0)) were generated by the negative-mode corona discharge of atmospheric-pressure argon gas. By applying a high positive voltage (+500 to +1000 V) to the stainless steel capillary for the sample introduction (0.1 mm i.d., 0.3 mm o.d.), strong ion signals could be obtained. The ions formed were sampled through an orifice into the vacuum and mass-analyzed by an orthogonal time-of-flight mass spectrometer. The major ions formed by APP(e)I are found to be molecular-related ions for alkanes, aromatics, and oxygen-containing compounds. Because only the molecules with ionization energies less than the internal energy of Ar* are ionized, the present method will be a selective and highly sensitive interface for gas chromatography/mass spectrometry.

  10. Mass spectrometry-based quantitative proteomic profiling.

    PubMed

    Yan, Wei; Chen, Sharon S

    2005-05-01

    Quantitative proteomics involves the identification and quantitation of protein components in various biological systems. Stable isotope labelling technology, by both metabolic and chemical methods, has been the most commonly used approach for global proteome-wide profiling. Recently, its capability has been extended from labelled pairs to multiple labels, allowing for the simultaneous quantification of multiplex samples. The ion intensity-based quantitative approach has progressively gained more popularity as mass spectrometry performance has improved significantly. Although some success has been reported, it remains difficult comprehensively to characterise the global proteome, due to its enormous complexity and dynamic range. The use of sub-proteome fractionation techniques permits a simplification of the proteome and provides a practical step towards the ultimate dissection of the entire proteome. Further development of the technology for targeting sub-proteomes on a functional basis - such as selecting proteins with differential expression profiles from mass spectrometric analyses, for further mass spectrometric sequencing in an intelligent manner--is expected in the near future.

  11. Forensic applications of ambient ionization mass spectrometry.

    PubMed

    Ifa, Demian R; Jackson, Ayanna U; Paglia, Giuseppe; Cooks, R Graham

    2009-08-01

    This review highlights and critically assesses forensic applications in the developing field of ambient ionization mass spectrometry. Ambient ionization methods permit the ionization of samples outside the mass spectrometer in the ordinary atmosphere, with minimal sample preparation. Several ambient ionization methods have been created since 2004 and they utilize different mechanisms to create ions for mass-spectrometric analysis. Forensic applications of these techniques--to the analysis of toxic industrial compounds, chemical warfare agents, illicit drugs and formulations, explosives, foodstuff, inks, fingerprints, and skin--are reviewed. The minimal sample pretreatment needed is illustrated with examples of analysis from complex matrices (e.g., food) on various substrates (e.g., paper). The low limits of detection achieved by most of the ambient ionization methods for compounds of forensic interest readily offer qualitative confirmation of chemical identity; in some cases quantitative data are also available. The forensic applications of ambient ionization methods are a growing research field and there are still many types of applications which remain to be explored, particularly those involving on-site analysis. Aspects of ambient ionization currently undergoing rapid development include molecular imaging and increased detection specificity through simultaneous chemical reaction and ionization by addition of appropriate chemical reagents.

  12. Enantioselectivity of mass spectrometry: challenges and promises.

    PubMed

    Awad, Hanan; El-Aneed, Anas

    2013-01-01

    With the fast growing market of pure enantiomer drugs and bioactive molecules, new chiral-selective analytical tools have been instigated including the use of mass spectrometry (MS). Even though MS is one of the best analytical tools that has efficiently been used in several pharmaceutical and biological applications, traditionally MS is considered as a "chiral-blind" technique. This limitation is due to the MS inability to differentiate between two enantiomers of a chiral molecule based merely on their masses. Several approaches have been explored to assess the potential role of MS in chiral analysis. The first approach depends on the use of MS-hyphenated techniques utilizing fast and sensitive chiral separation tools such as liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled to MS detector. More recently, several alternative separation techniques have been evaluated such as supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC); the latter being a hybrid technique that combines the efficiency of CE with the selectivity of LC. The second approach is based on using the MS instrument solely for the chiral recognition. This method depends on the behavioral differences between enantiomers towards a foreign molecule and the ability of MS to monitor such differences. These behavioral differences can be divided into three types: (i) differences in the enantiomeric affinity for association with the chiral selector, (ii) differences of the enantiomeric exchange rate with a foreign reagent, and (iii) differences in the complex MS dissociation behaviors of the enantiomers. Most recently, ion mobility spectrometry was introduced to qualitatively and quantitatively evaluate chiral compounds. This article provides an overview of MS role in chiral analysis by discussing MS based methodologies and presenting the challenges and promises associated with each approach.

  13. Mapping of Neuropeptides in the Crustacean Stomatogastric Nervous System by Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve ( stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies.

  14. Nanospray ion mobility mass spectrometry of selected high mass species.

    PubMed

    Campuzano, Iain; Giles, Kevin

    2011-01-01

    The introduction of electrospray ionization (ESI) and in particular nano-electrospray (nESI) has enabled the routine mass spectrometric (MS) analysis of large protein complexes in native aqueous buffers. Time-of-flight (ToF) mass spectrometers, in particular the hybrid quadrupole time-of-flight (Q-ToF) instruments, are well suited to the analysis of large protein complexes. When ionized under native-MS conditions, protein complexes routinely exhibit multiple charge states in excess of m/z 6,000, well above the standard mass range of many quadrupole or ion cyclotron-based instruments. The research area of native MS has expanded considerably in the last decade and has shown particular relevance in the area of protein structure determination. Researchers are now able to routinely measure intact MS spectra of protein complexes above 1 MDa in mass. The advent of ion mobility mass spectrometry (IM-MS), in combination with molecular dynamics (MD) studies, is now allowing researchers to infer the shape of the protein complex being analyzed. Herein, we describe how to acquire IM-MS data that ranges from inorganic salt clusters of caesium iodide (CsI) to large biomolecular complexes such as the chaperone protein GroEL.

  15. Advances in imaging secondary ion mass spectrometry for biological samples

    SciTech Connect

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this has been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.

  16. Advantageous Uses of Mass Spectrometry for the Quantification of Proteins

    PubMed Central

    Hale, John E.

    2013-01-01

    Quantitative protein measurements by mass spectrometry have gained wide acceptance in research settings. However, clinical uptake of mass spectrometric protein assays has not followed suit. In part, this is due to the long-standing acceptance by regulatory agencies of immunological assays such as ELISA assays. In most cases, ELISAs provide highly accurate, sensitive, relatively inexpensive, and simple assays for many analytes. The barrier to acceptance of mass spectrometry in these situations will remain high. However, mass spectrometry provides solutions to certain protein measurements that are difficult, if not impossible, to accomplish by immunological methods. Cases where mass spectrometry can provide solutions to difficult assay development include distinguishing between very closely related protein species and monitoring biological and analytical variability due to sample handling and very high multiplexing capacity. This paper will highlight several examples where mass spectrometry has made certain protein measurements possible where immunological techniques have had a great difficulty. PMID:23365751

  17. Advances in imaging secondary ion mass spectrometry for biological samples

    DOE PAGES

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this hasmore » been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.« less

  18. Mass Spectrometry of Acoustically Levitated Droplets

    PubMed Central

    Westphall, Michael S.; Jorabchi, Kaveh; Smith, Lloyd M.

    2008-01-01

    Containerless sample handling techniques such as acoustic levitation offer potential advantages for mass spectrometry, by eliminating surfaces where undesired adsorption/desorption processes can occur. In addition, they provide a unique opportunity to study fundamental aspects of the ionization process as well as phenomena occurring at the air–droplet interface. Realizing these advantages is contingent, however, upon being able to effectively interface levitated droplets with a mass spectrometer, a challenging task that is addressed in this report. We have employed a newly developed charge and matrix-assisted laser desorption/ionization (CALDI) technique to obtain mass spectra from a 5-μL acoustically levitated droplet containing peptides and an ionic matrix. A four-ring electrostatic lens is used in conjunction with a corona needle to produce bursts of corona ions and to direct those ions toward the droplet, resulting in droplet charging. Analyte ions are produced from the droplet by a 337-nm laser pulse and detected by an atmospheric sampling mass spectrometer. The ion generation and extraction cycle is repeated at 20 Hz, the maximum operating frequency of the laser employed. It is shown in delayed ion extraction experiments that both positive and negative ions are produced, behavior similar to that observed for atmospheric pressure matrix-assisted laser absorption/ionization. No ion signal is observed in the absence of droplet charging. It is likely, although not yet proven, that the role of the droplet charging is to increase the strength of the electric field at the surface of the droplet, reducing chargere combination after ion desorption. PMID:18582090

  19. Mass spectrometry of acoustically levitated droplets.

    PubMed

    Westphall, Michael S; Jorabchi, Kaveh; Smith, Lloyd M

    2008-08-01

    Containerless sample handling techniques such as acoustic levitation offer potential advantages for mass spectrometry, by eliminating surfaces where undesired adsorption/desorption processes can occur. In addition, they provide a unique opportunity to study fundamental aspects of the ionization process as well as phenomena occurring at the air-droplet interface. Realizing these advantages is contingent, however, upon being able to effectively interface levitated droplets with a mass spectrometer, a challenging task that is addressed in this report. We have employed a newly developed charge and matrix-assisted laser desorption/ionization (CALDI) technique to obtain mass spectra from a 5-microL acoustically levitated droplet containing peptides and an ionic matrix. A four-ring electrostatic lens is used in conjunction with a corona needle to produce bursts of corona ions and to direct those ions toward the droplet, resulting in droplet charging. Analyte ions are produced from the droplet by a 337-nm laser pulse and detected by an atmospheric sampling mass spectrometer. The ion generation and extraction cycle is repeated at 20 Hz, the maximum operating frequency of the laser employed. It is shown in delayed ion extraction experiments that both positive and negative ions are produced, behavior similar to that observed for atmospheric pressure matrix-assisted laser absorption/ionization. No ion signal is observed in the absence of droplet charging. It is likely, although not yet proven, that the role of the droplet charging is to increase the strength of the electric field at the surface of the droplet, reducing charge recombination after ion desorption.

  20. Fourier Transform Mass Spectrometry and Nuclear Magnetic Resonance Analysis for the Rapid and Accurate Characterization of Hexacosanoylceramide

    PubMed Central

    Ross, Charles W.; Simonsick, William J.; Bogusky, Michael J.; Celikay, Recep W.; Guare, James P.; Newton, Randall C.

    2016-01-01

    Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential vaccine adjuvants in humans. Accurate analyses of these and related sphingosine analogues are important for the characterization of structure, biological function, and metabolism. We report the complementary use of direct laser desorption ionization (DLDI), sheath flow electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and high-field nuclear magnetic resonance (NMR) analysis for the rapid, accurate identification of hexacosanoylceramide and starting materials. DLDI does not require stringent sample preparation and yields representative ions. Sheath-flow ESI yields ions of the product and byproducts and was significantly better than monospray ESI due to improved compound solubility. Negative ion sheath flow ESI provided data of starting materials and products all in one acquisition as hexacosanoic acid does not ionize efficiently when ceramides are present. NMR provided characterization of these lipid molecules complementing the results obtained from MS analyses. NMR data was able to differentiate straight chain versus branched chain alkyl groups not easily obtained from mass spectrometry. PMID:27367671

  1. Top-Down Analysis of Highly Post-Translationally Modified Peptides by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Guerrero, Andres; Lerno, Larry; Barile, Daniela; Lebrilla, Carlito B.

    2015-03-01

    Bovine κ-caseinoglycomacropeptide (GMP) is a highly modified peptide from κ-casein produced during the cheese making process. The chemical nature of GMP makes analysis by traditional proteomic approaches difficult, as the peptide bears a strong net negative charge and a variety of post-translational modifications. In this work, we describe the use of electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) for the top-down analysis of GMP. The method allows the simultaneous detection of different GMP forms that result from the combination of amino acid genetic variations and post-translational modifications, specifically phosphorylation and O-glycosylation. The different GMP forms were identified by high resolution mass spectrometry in both negative and positive mode and confirmation was achieved by tandem MS. The results showed the predominance of two genetic variants of GMP that occur as either mono- or bi-phosphorylated species. Additionally, these four forms can be modified with up to two O-glycans generally sialylated. The results demonstrate the presence of glycosylated, bi-phosphorylated forms of GMP never described before.

  2. Fourier Transform Mass Spectrometry and Nuclear Magnetic Resonance Analysis for the Rapid and Accurate Characterization of Hexacosanoylceramide.

    PubMed

    Ross, Charles W; Simonsick, William J; Bogusky, Michael J; Celikay, Recep W; Guare, James P; Newton, Randall C

    2016-06-28

    Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential vaccine adjuvants in humans. Accurate analyses of these and related sphingosine analogues are important for the characterization of structure, biological function, and metabolism. We report the complementary use of direct laser desorption ionization (DLDI), sheath flow electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and high-field nuclear magnetic resonance (NMR) analysis for the rapid, accurate identification of hexacosanoylceramide and starting materials. DLDI does not require stringent sample preparation and yields representative ions. Sheath-flow ESI yields ions of the product and byproducts and was significantly better than monospray ESI due to improved compound solubility. Negative ion sheath flow ESI provided data of starting materials and products all in one acquisition as hexacosanoic acid does not ionize efficiently when ceramides are present. NMR provided characterization of these lipid molecules complementing the results obtained from MS analyses. NMR data was able to differentiate straight chain versus branched chain alkyl groups not easily obtained from mass spectrometry.

  3. Expansion of the analytical window for oil spill characterization by ultrahigh resolution mass spectrometry: beyond gas chromatography.

    PubMed

    McKenna, Amy M; Nelson, Robert K; Reddy, Christopher M; Savory, Joshua J; Kaiser, Nathan K; Fitzsimmons, Jade E; Marshall, Alan G; Rodgers, Ryan P

    2013-07-02

    Traditional tools for routine environmental analysis and forensic chemistry of petroleum have relied almost exclusively on gas chromatography-mass spectrometry (GC-MS), although many compounds in crude oil (and its transformation products) are not chromatographically separated or amenable to GC-MS due to volatility. To enhance current and future studies on the fate, transport, and fingerprinting of the Macondo well oil released from the 2010 Deepwater Horizon disaster, we created an extensive molecular library of the unadulterated petroleum to compare to a tar ball collected on the beach of Louisiana. We apply ultrahigh resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry to identify compositional changes at the molecular level between native and weathered crude oil samples and reveal enrichment in polar compounds inaccessible by GC-based characterization. The outlined approach provides unprecedented detail with the potential to enhance insight into the environmental fate of spilled oil, improved toxicology, molecular modeling of biotic/abiotic weathering, and comprehensive molecular characterization for petroleum-derived releases. Here, we characterize more than 30,000 acidic, basic, and nonpolar unique neutral elemental compositions for the Macondo well crude oil, to provide an archive for future chemical analyses of the environmental consequences of the oil spill.

  4. Measuring protein synthesis using metabolic ²H labeling, high-resolution mass spectrometry, and an algorithm.

    PubMed

    Kasumov, Takhar; Ilchenko, Serguey; Li, Ling; Rachdaoui, Nadia; Sadygov, Rovshan G; Willard, Belinda; McCullough, Arthur J; Previs, Stephen

    2011-05-01

    We recently developed a method for estimating protein dynamics in vivo with heavy water ((2)H(2)O) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) [16], and we confirmed that (2)H labeling of many hepatic free amino acids rapidly equilibrated with body water. Although this is a reliable method, it required modest sample purification and necessitated the determination of tissue-specific amino acid labeling. Another approach for quantifying protein kinetics is to measure the (2)H enrichments of body water (precursor) and protein-bound amino acid or proteolytic peptide (product) and to estimate how many copies of deuterium are incorporated into a product. In the current study, we used nanospray linear trap Fourier transform ion cyclotron resonance mass spectrometry (LTQ FT-ICR MS) to simultaneously measure the isotopic enrichment of peptides and protein-bound amino acids. A mathematical algorithm was developed to aid the data processing. The most notable improvement centers on the fact that the precursor/product labeling ratio can be obtained by measuring the labeling of water and a protein (or peptide) of interest, thereby minimizing the need to measure the amino acid labeling. As a proof of principle, we demonstrate that this approach can detect the effect of nutritional status on albumin synthesis in rats given (2)H(2)O. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Single-protein nanomechanical mass spectrometry in real time

    PubMed Central

    Hanay, M.S.; Kelber, S.; Naik, A.K.; Chi, D.; Hentz, S.; Bullard, E.C.; Colinet, E.; Duraffourg, L.; Roukes, M.L.

    2012-01-01

    Nanoelectromechanical systems (NEMS) resonators can detect mass with exceptional sensitivity. Previously, mass spectra from several hundred adsorption events were assembled in NEMS-based mass spectrometry using statistical analysis. Here, we report the first realization of single-molecule NEMS-based mass spectrometry in real time. As each molecule in the sample adsorbs upon the NEMS resonator, its mass and the position-of-adsorption are determined by continuously tracking two driven vibrational modes of the device. We demonstrate the potential of multimode NEMS-based mass spectrometry by analyzing IgM antibody complexes in real-time. NEMS-MS is a unique and promising new form of mass spectrometry: it can resolve neutral species, provides resolving power that increases markedly for very large masses, and allows acquisition of spectra, molecule-by-molecule, in real-time. PMID:22922541

  6. Laser ablation/Fourier transform mass spectrometry of polymers

    NASA Astrophysics Data System (ADS)

    Creasy, William R.; Brenna, J. T.

    1989-10-01

    Laser ablation/ionization followed by Fourier transform mass spectrometry is used to identify and characterize polymers. The mass spectra of several polymers are discussed, including polyimide, polyamic acid, Dupont Tefzel, and polyphenylene sulfide.

  7. Reliability of veterinary drug residue confirmation: high resolution mass spectrometry versus tandem mass spectrometry.

    PubMed

    Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M

    2015-01-26

    Confirmation of suspected residues has been a long time domain of tandem triple quadrupole mass spectrometry (QqQ). The currently most widely used confirmation strategy relies on the use of two selected reaction monitoring signals (SRM). The details of this confirmation procedure are described in detail in the Commission Decision 93/256/EC (CD). On the other hand, high resolution mass spectrometry (HRMS) is nowadays increasingly used for trace analysis. Yet its utility for confirmatory purposes has not been well explored and utilized, since established confirmation strategies like the CD do not yet include rules for modern HRMS technologies. It is the focus of this paper to evaluate the likelihood of false positive and false negative confirmation results, when using a variety of HRMS based measurement modes as compared to conventional QqQ mass spectrometry. The experimental strategy relies on the chromatographic separation of a complex blank sample (bovine liver extract) and the subsequent monitoring of a number of dummy transitions respectively dummy accurate masses. The term "dummy" refers to precursor and derived product ions (based on a realistic neutral loss) whose elemental compositions (CxHyNzOdCle) were produced by a random number generator. Monitoring a large number of such hypothetical SRM's, or accurate masses inevitably produces a number of mass traces containing chromatographic peaks (false detects) which are caused by eluting matrix compounds. The number and intensity of these peaks were recorded and standardized to permit a comparison among the two employed MS technologies. QqQ performance (compounds which happen to produce a response in two SRM traces at identical retention time) was compared with a number of different HRMS(1) and HRMS(2) detection based modes. A HRMS confirmation criterion based on two full scans (an unfragmented and an all ion fragmented) was proposed. Compared to the CD criteria, a significantly lower probability of false

  8. Fluxomics: mass spectrometry versus quantitative imaging

    PubMed Central

    Wiechert, Wolfgang; Schweissgut, Oliver; Takanaga, Hitomi; Frommer, Wolf B

    2010-01-01

    The recent development of analytic high-throughput technologies enables us to take a bird’s view of how metabolism is regulated in real time. We have known for a long time that metabolism is highly regulated at all levels, including transcriptional, posttranslational and allosteric controls. Flux through a metabolic or signaling pathway is determined by the activity of its individual components. Fluxomics aims to define the genes involved in regulation by following the flux. Two technologies are used to monitor fluxes. Pulse labeling of the organism or cell with a tracer, such as 13C, followed by mass spectrometric analysis of the partitioning of label into different compounds provides an efficient tool to study flux and to compare the effect of mutations on flux. The second approach is based on the use of flux sensors, proteins that respond with a conformational change to ligand binding. Fluorescence resonance energy transfer (FRET) detects the conformational change and serves as a proxy for ligand concentration. In contrast to the mass spectrometry assays, FRET nanosensors monitor only a single compound. Both methods provide high time resolution. The major advantages of FRET nanosensors are that they yield data with cellular and subcellular resolution and the method is minimally invasive. PMID:17481942

  9. Fluxomics: mass spectrometry versus quantitative imaging.

    PubMed

    Wiechert, Wolfgang; Schweissgut, Oliver; Takanaga, Hitomi; Frommer, Wolf B

    2007-06-01

    The recent development of analytic high-throughput technologies enables us to take a bird's view of how metabolism is regulated in real time. We have known for a long time that metabolism is highly regulated at all levels, including transcriptional, posttranslational and allosteric controls. Flux through a metabolic or signaling pathway is determined by the activity of its individual components. Fluxomics aims to define the genes involved in regulation by following the flux. Two technologies are used to monitor fluxes. Pulse labeling of the organism or cell with a tracer, such as 13C, followed by mass spectrometric analysis of the partitioning of label into different compounds provides an efficient tool to study flux and to compare the effect of mutations on flux. The second approach is based on the use of flux sensors, proteins that respond with a conformational change to ligand binding. Fluorescence resonance energy transfer (FRET) detects the conformational change and serves as a proxy for ligand concentration. In contrast to the mass spectrometry assays, FRET nanosensors monitor only a single compound. Both methods provide high time resolution. The major advantages of FRET nanosensors are that they yield data with cellular and subcellular resolution and the method is minimally invasive.

  10. Pushing the limits of accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Galindo-Uribarri, A.; Beene, J. R.; Danchev, M.; Doupé, J.; Fuentes, B.; Gomez del Campo, J.; Hausladen, P. A.; Juras, R. C.; Liang, J. F.; Litherland, A. E.; Liu, Y.; Meigs, M. J.; Mills, G. D.; Mueller, P. E.; Padilla-Rodal, E.; Pavan, J.; Sinclair, J. W.; Stracener, D. W.

    2007-06-01

    A renewed interest in Accelerator Mass Spectrometry (AMS) from nuclear physics laboratories is emerging in connection with Radioactive Ion Beams (RIBs). At the Holifield Radioactive Ion Beam Facility (HRIBF) at Oak Ridge National Laboratory (ORNL) we are exploring the AMS capabilities of the 25-MV tandem accelerator. Behind this effort is the realization that two fields of research - AMS and RIBs - complement each other in techniques. Development of effective and efficient beam purification techniques is of common interest to both AMS and the RIB program. Two main characteristics of the 25-MV tandem provide unique opportunities for performing the highest sensitivity measurements of AMS; namely (i) the highest operating voltage in the world, and (ii) a folded geometry which involves a 180° magnet in the terminal. For the RIB program, we have used AMS techniques to improve the sensitivity of detection of some radioactive species in the measurement of unknown masses of n-rich nuclei. For AMS, we have concentrated in exploring two important isotopes, 14C and 36Cl, for applications that require the highest sensitivity. We have successfully measured 36Cl/Cl ratios as low as a few times 10-16 in seawater samples demonstrating that our setup has the highest sensitivity for this isotope and proving that 36Cl can be measured at the levels required for a tracer in oceanography.

  11. Multifunctional Carbon Fiber Ionization Mass Spectrometry.

    PubMed

    Wu, Meng-Xi; Wang, Hao-Yang; Zhang, Jun-Ting; Guo, Yin-Long

    2016-10-04

    A carbon fiber ionization (CFI) technique was developed for the mass spectrometric analysis of various organic compounds with different polarities. The design of the CFI technique was based on the good compatibility and dispersion of samples and solutions in different solvents on carbon fiber. As a fast, convenient, and versatile ionization method, CFI-MS is especially efficient for analyzing many low/nonpolar organic compounds, such as polycyclic aromatic hydrocarbons, long-chain aliphatic aldehydes, sensitive steroids, terpenoids, and organometallic compounds. Some of these compounds may not be well-analyzed by electrospray ionization or electron ionization mass spectrometry. On the basis of our experimental results, the major ion formation mechanism of CFI-MS was suggested to involve desorption in a steam-distillation-like process, and then, ionization occurred mainly via corona discharge under high voltage. CFI-MS could not only work alone but also be coupled with separation techniques. It works well when coupled with supercritical fluid chromatography (SFC) as well as in the analysis of exhaled human air. The high flexibility and versatility of CFI-MS has extended its applications in many areas, such as fast chemical screening, clinical testing, and forensic analysis.

  12. Mass spectrometry in bioinorganic analytical chemistry.

    PubMed

    Lobiński, Ryszard; Schaumlöffel, Dirk; Szpunar, Joanna

    2006-01-01

    A considerable momentum has recently been gained by in vitro and in vivo studies of interactions of trace elements in biomolecules due to advances in inductively coupled plasma mass spectrometry (ICP MS) used as a detector in chromatography and capillary and planar electrophoresis. The multi-isotopic (including non-metals such as S, P, or Se) detection capability, high sensitivity, tolerance to matrix, and large linearity range regardless of the chemical environment of an analyte make ICP MS a valuable complementary technique to electrospray MS and MALDI MS. This review covers different facets of the recent progress in metal speciation in biochemistry, including probing in vitro interactions between metals and biomolecules, detection, determination, and structural characterization of heteroatom-containing molecules in biological tissues, and protein monitoring and quantification via a heteroelement (S, Se, or P) signal. The application areas include environmental chemistry, plant and animal biochemistry, nutrition, and medicine. (c) 2005 Wiley Periodicals, Inc. Mass Spec Rev 25:255-289, 2006.

  13. Chip-mass spectrometry for glycomic studies.

    PubMed

    Bindila, Laura; Peter-Katalinić, Jasna

    2009-01-01

    The introduction of micro- and nanochip front end technologies for electrospray mass spectrometry addressed a major challenge in carbohydrate analysis: high sensitivity structural determination and heterogeneity assessment in high dynamic range mixtures of biological origin. Chip-enhanced electrospray ionization was demonstrated to provide reproducible performance irrespective of the type of carbohydrate, while the amenability of chip systems for coupling with different mass spectrometers greatly advance the chip/MS technique as a versatile key tool in glycomic studies. A more accurate representation of the glycan repertoire to include novel biologically-relevant information was achieved in different biological sources, asserting this technique as a valuable tool in glycan biomarker discovery and monitoring. Additionally, the integration of various analytical functions onto chip devices and direct hyphenation to MS proved its potential for glycan analysis during the recent years, whereby a new analytical tool is on the verge of maturation: lab-on-chip MS glycomics. The achievements until early beginning of 2007 on the implementation of chip- and functional integrated chip/MS in systems glycobiology studies are reviewed here. (c) 2009 Wiley Periodicals, Inc.

  14. Detailed characterization of polar compounds of residual oil in contaminated soil revealed by Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Wang, Jian; Zhang, Xu; Li, Guanghe

    2011-10-01

    Effects of remediation technologies on polar compounds of crude oil in contaminated soils have not been well understood when compared to hydrocarbons. In this study, ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to characterize the changes in NSO polar compounds of crude oil and residual oil after long-term natural attenuation, biostimulation and subsequent ozonation following biostimulation of contaminated soils. N1 and O1 species, which were abundant in the crude oil, were selectively biodegraded, and species with higher double bond equivalent values and smaller carbon numbers appeared to be more resistant to microbial alteration. O2-O6 species were enriched by biodegradation and contained a large number of compounds with a high degree of unsaturation. Ozone could react with a variety of polar compounds in residual oil after biodegradation and showed high reactivity with polar species containing aromatic or multi-aliphatic rings, including the residual N1 and O1 species, naphthenic acids and unsaturated O3-O6 compounds. Fatty acids and O3-O8 species dominated by saturated alkyl compounds were resistant to ozonation or the primarily incomplete ozonation products. Principal component analysis of identified peaks in the FT-ICR MS spectra provided a comprehensive overview of the complex samples at the molecular level and the results were consistent with the detailed analysis. Taken together, these results showed the high complexity of polar compounds in residual oils after biodegradation or ozonation in contaminated soil and would contribute to a better understanding of bioremediation and ozonation processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Advanced solvent based methods for molecular characterization of soil organic matter by high-resolution mass spectrometry

    SciTech Connect

    Tfaily, Malak M.; Chu, Rosalie K.; Tolic, Nikola; Roscioli, Kristyn M.; Anderton, Christopher R.; Pasa-Tolic, Ljiljana; Robinson, Errol W.; Hess, Nancy J.

    2015-05-19

    Soil organic matter (SOM) a complex, heterogeneous mixture of above and belowground plant litter and animal and microbial residues at various degrees of decomposition, is a key reservoir for carbon (C) and nutrient biogeochemical cycling in soil based ecosystems. A limited understanding of the molecular composition of SOM limits the ability to routinely decipher chemical processes within soil and predict accurately how terrestrial carbon fluxes will response to changing climatic conditions and land use. To elucidate the molecular-level structure of SOM, we selectively extracted a broad range of intact SOM compounds by a combination of different organic solvents from soils with a wide range of C content. Our use of Electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and a suite of solvents with varying polarity significantly expands the inventory of the types of organic molecules present in soils. Specifically, we found that hexane is selective for lipid-like compounds with very low O:C ratios; water was selective for carbohydrates with high O:C ratios; acetonitrile preferentially extracts lignin, condensed structures, and tannin poly phenolic compounds with O:C > 0.5; methanol has higher selectivity towards compounds characterized with low O:C < 0.5; and hexane, MeOH, ACN and water solvents increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Our study of SOM molecules by ESI-FTICR MS revealed new insight into the molecular-level complexity of organics contained in soils.

  16. Deciphering the rhizosphere by liquid extraction surface analysis mass spectrometry (LESA-MS)

    NASA Astrophysics Data System (ADS)

    Chu, R. K.; Tfaily, M. M.; Handakumbura, P. P.; Paša-Tolić, L.; Anderton, C.

    2016-12-01

    Interactions of plants with their soil microenvironment and surrounding microbes are of major scientific importance for reasons ranging from understanding global carbon and nitrogen cycling to developing advanced crops. Gaining spatial information of the biochemical interactions that occur within the rhizosphere and other subsurface terrestrial ecosystems is an area of growing interest. Accordingly, development of analytical tools to probe and map molecular interactions in situ, and without intrusive and extensive sample preparation, would provide unique insights into the processes governing plant growth, nitrogen fixation and the metabolic exchange between the root and rhizobia, for example. Here, we will discuss the development of an application using LESA-MS—liquid extraction surface analysis mass spectrometry—that is capable of spatially characterizing molecular rhizospheric interactions in their native state and in a label-free manner. In LESA-MS, microextractions of a sample's surface are performed robotically, and we can either address points of interest (e.g., determined visually) or an entire area can be profiled in a serial fashion. Extracted molecules are then ionized by nanoelectrospray ionization (nano-ESI) and analyzed using high resolution and mass accuracy mass spectrometry (Fourier transform ion cyclotron resonance, FTICR MS). Because this analysis can be performed under ambient conditions, we are able to characterize the chemical distributions within the rhizosphere of a living plant. Here, we use Sorghum bicolor grown in a two-dimensional rhizobox that contains Turface clay as a model system, and used methanol-water as the solvent to characterize molecular distributions across the rhizosphere.

  17. Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine

    SciTech Connect

    Annesley, Thomas M.; Cooks, Robert G.; Herold, David A.; Hoofnagle, Andrew N.

    2016-01-04

    Each year the journal Clinical Chemistry publishes a January special issue on a topic that is relevant to the laboratory medicine community. In January 2016 the topic is mass spectrometry, and the issue is entitled “Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine”. One popular feature in our issues is a Q&A on a topic, clearly in this case mass spectrometry. The journal is assembling a panel of 5-6 experts from various areas of mass spectrometry ranging from instrument manufacturing to practicing clinical chemists. Dick Smith is one of the scientist requested to participate in this special issue Q&A on Mass Spectrometry. The Q&A Transcript is attached

  18. Applications of Mass Spectrometry to Lipids and Membranes

    PubMed Central

    Harkewicz, Richard; Dennis, Edward A.

    2012-01-01

    Lipidomics, a major part of metabolomics, constitutes the detailed analysis and global characterization, both spatial and temporal, of the structure and function of lipids (the lipidome) within a living system. As with proteomics, mass spectrometry has earned a central analytical role in lipidomics, and this role will continue to grow with technological developments. Currently, there exist two mass spectrometry-based lipidomics approaches, one based on a division of lipids into categories and classes prior to analysis, the “comprehensive lipidomics analysis by separation simplification” (CLASS), and the other in which all lipid species are analyzed together without prior separation, shotgun. In exploring the lipidome of various living systems, novel lipids are being discovered, and mass spectrometry is helping characterize their chemical structure. Deuterium exchange mass spectrometry (DXMS) is being used to investigate the association of lipids and membranes with proteins and enzymes, and imaging mass spectrometry (IMS) is being applied to the in situ analysis of lipids in tissues. PMID:21469951

  19. US Food and Drug Administration Perspectives on Clinical Mass Spectrometry.

    PubMed

    Lathrop, Julia Tait; Jeffery, Douglas A; Shea, Yvonne R; Scholl, Peter F; Chan, Maria M

    2016-01-01

    Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry-based devices and enhance their entry into the clinic.

  20. Molecular evidence of heavy-oil weathering following the M/V Cosco Busan spill: insights from Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Lemkau, Karin L; McKenna, Amy M; Podgorski, David C; Rodgers, Ryan P; Reddy, Christopher M

    2014-04-01

    Recent studies have highlighted a critical need to investigate oil weathering beyond the analytical window afforded by conventional gas chromatography (GC). In particular, techniques capable of detecting polar and higher molecular weight (HMW; > 400 Da) components abundant in crude and heavy fuel oils (HFOs) as well as transformation products. Here, we used atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI FT-ICR MS) to identify molecular transformations in oil-residue samples from the 2007 M/V Cosco Busan HFO spill (San Francisco, CA). Over 617 days, the abundance and diversity of oxygen-containing compounds increased relative to the parent HFO, likely from bio- and photodegradation. HMW, highly aromatic, alkylated compounds decreased in relative abundance concurrent with increased relative abundance of less alkylated stable aromatic structures. Combining these results with GC-based data yielded a more comprehensive understanding of oil spill weathering. For example, dealkylation trends and the overall loss of HMW species observed by FT-ICR MS has not previously been documented and is counterintuitive given losses of lower molecular weight species observed by GC. These results suggest a region of relative stability at the interface of these techniques, which provides new indicators for studying long-term weathering and identifying sources.

  1. Mass spectrometry innovations in drug discovery and development.

    PubMed

    Papac, D I; Shahrokh, Z

    2001-02-01

    This review highlights the many roles mass spectrometry plays in the discovery and development of new therapeutics by both the pharmaceutical and the biotechnology industries. Innovations in mass spectrometer source design, improvements to mass accuracy, and implementation of computer-controlled automation have accelerated the purification and characterization of compounds derived from combinatorial libraries, as well as the throughput of pharmacokinetics studies. The use of accelerator mass spectrometry, chemical reaction interface-mass spectrometry and continuous flow-isotope ratio mass spectrometry are promising alternatives for conducting mass balance studies in man. To meet the technical challenges of proteomics, discovery groups in biotechnology companies have led the way to development of instruments with greater sensitivity and mass accuracy (e.g., MALDI-TOF, ESI-Q-TOF, Ion Trap), the miniaturization of separation techniques and ion sources (e.g., capillary HPLC and nanospray), and the utilization of bioinformatics. Affinity-based methods coupled to mass spectrometry are allowing rapid and selective identification of both synthetic and biological molecules. With decreasing instrument cost and size and increasing reliability, mass spectrometers are penetrating both the manufacturing and the quality control arenas. The next generation of technologies to simplify the investigation of the complex fate of novel pharmaceutical entities in vitro and in vivo will be chip-based approaches coupled with mass spectrometry.

  2. Illustrating the Concepts of Isotopes and Mass Spectrometry in Introductory Courses: A MALDI-TOF Mass Spectrometry Laboratory Experiment

    ERIC Educational Resources Information Center

    Dopke, Nancy Carter; Lovett, Timothy Neal

    2007-01-01

    Mass spectrometry is a widely used and versatile tool for scientists in many different fields. Soft ionization techniques such as matrix-assisted laser desorption/ionization (MALDI) allow for the analysis of biomolecules, polymers, and clusters. This article describes a MALDI mass spectrometry experiment designed for students in introductory…

  3. Illustrating the Concepts of Isotopes and Mass Spectrometry in Introductory Courses: A MALDI-TOF Mass Spectrometry Laboratory Experiment

    ERIC Educational Resources Information Center

    Dopke, Nancy Carter; Lovett, Timothy Neal

    2007-01-01

    Mass spectrometry is a widely used and versatile tool for scientists in many different fields. Soft ionization techniques such as matrix-assisted laser desorption/ionization (MALDI) allow for the analysis of biomolecules, polymers, and clusters. This article describes a MALDI mass spectrometry experiment designed for students in introductory…

  4. Analysis of omnoponum by surface-ionization mass spectrometry and liquid chromatography tandem mass spectrometry methods.

    PubMed

    Usmanov, Dilshadbek; Khasanov, Usman; Pantsirev, Aleksey; Van Bocxlaer, Jan

    2010-12-01

    This paper provides the development of analytical capabilities of surface-ionization mass spectrometry (SI/MS) and high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) for narcotic analgesic omnoponum, which perfectly exemplifies a mixture of opium alkaloids. It has been revealed that the investigated opiates solution, omnoponum, is ionized by the surface ionization (SI) method with high sensitivity. In the SI mass spectrum, M+, (M-H)+, (M-H-2nH)+, (M-R)+ and (M-R-2nH)+ ion lines, where M is a molecule, H is the hydrogen atom and R is a radical, were observed. These ion lines consist of combined omnoponum mixture SI mass spectra, i.e. morphine, codeine, thebaine, papaverine, and narcotine. Moreover, while the study of omnoponum by HPLC/MS/MS methods has attested that the mixture really consists of 5 components, it has been demonstrated that the SI/MS method can be utilized for the analysis of this mixture without the necessity of its chromatographic separation. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  5. Mass Spectrometry Imaging: facts and perspectives from a non-mass spectrometrist point of view.

    PubMed

    Cameron, L C

    2012-08-01

    Mass Spectrometry Imaging (MSI, also called Imaging Mass Spectrometry) can be used to map molecules according to their chemical abundance and spatial distribution. This technique is not widely used in mass spectrometry circles and is barely known by other scientists. In this review, a brief overview of the mass spectrometer hardware used in MSI and some of the possible applications of this powerful technique are discussed. I intend to call attention to MSI uses from cell biology to histopathology for biological scientists who have little background in mass spectrometry. MSI facts and perspectives are presented from a non-mass spectrometrist point of view.

  6. Identification of Unknown Contaminants in Water Samples from ISS Employing Liquid Chromatography/Mass Spectrometry/Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Rutz, Jeffrey A.; Schultz, John R.

    2008-01-01

    Mass Spectrometry/Mass Spectrometry (MS/MS) is a powerful technique for identifying unknown organic compounds. For non-volatile or thermally unstable unknowns dissolved in liquids, liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) is often the variety of MS/MS used for the identification. One type of LC/MS/MS that is rapidly becoming popular is time-of-flight (TOF) mass spectrometry. This technique is now in use at the Johnson Space Center for identification of unknown nonvolatile organics in water samples from the space program. An example of the successful identification of one unknown is reviewed in detail in this paper. The advantages of time-of-flight instrumentation are demonstrated through this example as well as the strategy employed in using time-of-flight data to identify unknowns.

  7. [Application of mass spectrometry to bacterial identification].

    PubMed

    Hernández, Álvaro Pascual; Ballestero-Téllez, Mónica; Galán-Sánchez, Fátima; Iglesias, Manuel Rodríguez

    2016-06-01

    Correct and rapid identification of bacteria is essential for the correct diagnosis and treatment of infected patients. Until a few years ago, biochemical, colorimetric or even antibiotic sensitivity tests were used to identify genera and species. The main limitations of these methods were the time needed for their performance and the difficulty of distinguishing between microorganisms that were little reactive, highly similar, or difficult to culture. Many of these problems have been solved by the introduction of mass spectrometry (MS) in the laboratory with the use of MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight). Knowledge of the strengths and weaknesses of this technology is essential to be able to take maximum advantage of this technique. Not all microorganisms can be identified with the same ease and reliability by MALDI-TOF and microbiologists need to know how to interpret the results obtained with this technique and the available alternatives in order to identify the microorganisms causing the most problems. This article aims to summarise the available information on the correct identification of the main human pathogenic bacteria through the use of MALDI-TOF MS, focusing on Gram-negative, Grampositive and anaerobic microorganisms. The main factors that must be taken into account for the reliable identification of any bacterium are the conditions for culture, sample preparation with the ideal extraction method and especially the use of a correct and updated database. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. Detection of Gunshot Residues Using Mass Spectrometry

    PubMed Central

    Blanes, Lucas; Cole, Nerida; Doble, Philip; Roux, Claude

    2014-01-01

    In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR. Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further, modern MS instruments can detect and identify a number of explosives and additives which may require different ionization techniques. Finally, MS has been applied to the analysis of both OGSR and inorganic gunshot residue (IGSR), although the “gold standard” for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis. PMID:24977168

  9. Proton Dynamics in Protein Mass Spectrometry.

    PubMed

    Li, Jinyu; Lyu, Wenping; Rossetti, Giulia; Konijnenberg, Albert; Natalello, Antonino; Ippoliti, Emiliano; Orozco, Modesto; Sobott, Frank; Grandori, Rita; Carloni, Paolo

    2017-03-16

    Native electrospray ionization/ion mobility-mass spectrometry (ESI/IM-MS) allows an accurate determination of low-resolution structural features of proteins. Yet, the presence of proton dynamics, observed already by us for DNA in the gas phase, and its impact on protein structural determinants, have not been investigated so far. Here, we address this issue by a multistep simulation strategy on a pharmacologically relevant peptide, the N-terminal residues of amyloid-β peptide (Aβ(1-16)). Our calculations reproduce the experimental maximum charge state from ESI-MS and are also in fair agreement with collision cross section (CCS) data measured here by ESI/IM-MS. Although the main structural features are preserved, subtle conformational changes do take place in the first ∼0.1 ms of dynamics. In addition, intramolecular proton dynamics processes occur on the picosecond-time scale in the gas phase as emerging from quantum mechanics/molecular mechanics (QM/MM) simulations at the B3LYP level of theory. We conclude that proton transfer phenomena do occur frequently during fly time in ESI-MS experiments (typically on the millisecond time scale). However, the structural changes associated with the process do not significantly affect the structural determinants.

  10. Signatures for Mass Spectrometry Data Quality

    PubMed Central

    2014-01-01

    Ensuring data quality and proper instrument functionality is a prerequisite for scientific investigation. Manual quality assurance is time-consuming and subjective. Metrics for describing liquid chromatography mass spectrometry (LC–MS) data have been developed; however, the wide variety of LC–MS instruments and configurations precludes applying a simple cutoff. Using 1150 manually classified quality control (QC) data sets, we trained logistic regression classification models to predict whether a data set is in or out of control. Model parameters were optimized by minimizing a loss function that accounts for the trade-off between false positive and false negative errors. The classifier models detected bad data sets with high sensitivity while maintaining high specificity. Moreover, the composite classifier was dramatically more specific than single metrics. Finally, we evaluated the performance of the classifier on a separate validation set where it performed comparably to the results for the testing/training data sets. By presenting the methods and software used to create the classifier, other groups can create a classifier for their specific QC regimen, which is highly variable lab-to-lab. In total, this manuscript presents 3400 LC–MS data sets for the same QC sample (whole cell lysate of Shewanella oneidensis), deposited to the ProteomeXchange with identifiers PXD000320–PXD000324. PMID:24611607

  11. Accelerator Mass Spectrometry in Laboratory Nuclear Astrophysics

    NASA Astrophysics Data System (ADS)

    Nusair, O.; Bauder, W.; Gyürky, G.; Paul, M.; Collon, P.; Fülöp, Zs; Greene, J.; Kinoshita, N.; Palchan, T.; Pardo, R.; Rehm, K. E.; Scott, R.; Vondrasek, R.

    2016-01-01

    The extreme sensitivity and discrimination power of accelerator mass spectrometry (AMS) allows for the search and the detection of rare nuclides either in natural samples or produced in the laboratory. At Argonne National Laboratory, we are developing an AMS setup aimed in particular at the detection of medium and heavy nuclides, relying on the high ion energy achievable with the ATLAS superconducting linear accelerator and on gas-filled magnet isobaric separation. The setup was recently used for the detection of the 146Sm p-process nuclide and for a new determination of the 146Sm half-life (68.7 My). AMS plays an important role in the measurement of stellar nuclear reaction cross sections by the activation method, extending thus the technique to the study of production of long-lived radionuclides. Preliminary measurements of the 147Sm(γ,n)146Sm are described. A measurement of the 142Nd(α,γ)146Sm and 142Nd(α,n)145Sm reactions is in preparation. A new laser-ablation method for the feeding of the Electron Cyclotron Resonance (ECR) ion source is described.

  12. Accelerator mass spectrometry of small biological samples.

    PubMed

    Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran

    2008-12-01

    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of microg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A (12)C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

  13. Secondary Ion Mass Spectrometry SIMS XI

    NASA Astrophysics Data System (ADS)

    Gillen, G.; Lareau, R.; Bennett, J.; Stevie, F.

    2003-05-01

    This volume contains 252 contributions presented as plenary, invited and contributed poster and oral presentations at the 11th International Conference on Secondary Ion Mass Spectrometry (SIMS XI) held at the Hilton Hotel, Walt Disney World Village, Orlando, Florida, 7 12 September, 1997. The book covers a diverse range of research, reflecting the rapid growth in advanced semiconductor characterization, ultra shallow depth profiling, TOF-SIMS and the new areas in which SIMS techniques are being used, for example in biological sciences and organic surface characterization. Papers are presented under the following categories: Isotopic SIMS Biological SIMS Semiconductor Characterization Techniques and Applications Ultra Shallow Depth Profiling Depth Profiling Fundamental/Modelling and Diffusion Sputter-Induced Topography Fundamentals of Molecular Desorption Organic Materials Practical TOF-SIMS Polyatomic Primary Ions Materials/Surface Analysis Postionization Instrumentation Geological SIMS Imaging Fundamentals of Sputtering Ion Formation and Cluster Formation Quantitative Analysis Environmental/Particle Characterization Related Techniques These proceedings provide an invaluable source of reference for both newcomers to the field and experienced SIMS users.

  14. JAMSS: proteomics mass spectrometry simulation in Java.

    PubMed

    Smith, Rob; Prince, John T

    2015-03-01

    Countless proteomics data processing algorithms have been proposed, yet few have been critically evaluated due to lack of labeled data (data with known identities and quantities). Although labeling techniques exist, they are limited in terms of confidence and accuracy. In silico simulators have recently been used to create complex data with known identities and quantities. We propose Java Mass Spectrometry Simulator (JAMSS): a fast, self-contained in silico simulator capable of generating simulated MS and LC-MS runs while providing meta information on the provenance of each generated signal. JAMSS improves upon previous in silico simulators in terms of its ease to install, minimal parameters, graphical user interface, multithreading capability, retention time shift model and reproducibility. The simulator creates mzML 1.1.0. It is open source software licensed under the GPLv3. The software and source are available at https://github.com/optimusmoose/JAMSS. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 1912: a Titanic year for mass spectrometry.

    PubMed

    Downard, Kevin M

    2012-08-01

    The 1912 sinking of the Titanic continues to capture the imagination and fascination of the general public. The year coincides with the birth of mass spectrometry that began with the cathode ray experiments performed by Joseph John (J. J.) Thomson in Cambridge. Modifications made to Thomson's cathode ray apparatus by Francis William Aston, resulted in an increase in the brightness of the positive rays that aided their detection. This led to the discovery of heavy isotopes for many of the chemical elements in the ensuing decades. As the discovery of (22) Ne was reported in 1913, another of Thomson's students was taking part in an expedition to help save future ocean liners from the fate of the Titanic. Geoffrey Ingram Taylor took part in the first ice patrol of the North Atlantic in 1913 aboard the SS Scotia to investigate the formation and position of icebergs. This article, 100 years on, describes Taylor's work and its impact on safe ocean passage across the Atlantic. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Charging of Proteins in Native Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Susa, Anna C.; Xia, Zijie; Tang, Henry Y. H.; Tainer, John A.; Williams, Evan R.

    2017-02-01

    Factors that influence the charging of protein ions formed by electrospray ionization from aqueous solutions in which proteins have native structures and function were investigated. Protein ions ranging in molecular weight from 12.3 to 79.7 kDa and pI values from 5.4 to 9.6 were formed from different solutions and reacted with volatile bases of gas-phase basicities higher than that of ammonia in the cell of a Fourier-transform ion cyclotron resonance mass spectrometer. The charge-state distribution of cytochrome c ions formed from aqueous ammonium or potassium acetate is the same. Moreover, ions formed from these two solutions do not undergo proton transfer to 2-fluoropyridine, which is 8 kcal/mol more basic than ammonia. These results provide compelling evidence that proton transfer between ammonia and protein ions does not limit protein ion charge in native electrospray ionization. Both circular dichroism and ion mobility measurements indicate that there are differences in conformations of proteins in pure water and aqueous ammonium acetate, and these differences can account for the difference in the extent of charging and proton-transfer reactivities of protein ions formed from these solutions. The extent of proton transfer of the protein ions with higher gas-phase basicity bases trends with how closely the protein ions are charged to the value predicted by the Rayleigh limit for spherical water droplets approximately the same size as the proteins. These results indicate that droplet charge limits protein ion charge in native mass spectrometry and are consistent with these ions being formed by the charged residue mechanism.

  17. In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Switzar, Linda; Nicolardi, Simone; Rutten, Julie W.; Oberstein, Saskia A. J. Lesnik; Aartsma-Rus, Annemieke; van der Burgt, Yuri E. M.

    2016-01-01

    Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow. A key advantage of a LC-based strategy is the use of the retention time in identifying both intra- and interpeptide disulfide bonds. This is demonstrated by performing two sequential analyses of a certain protein digest, once without and once with electrochemical reduction. In this way, the "parent" disulfide-linked peptide detected in the first run has a retention time-based correlation with the EC-reduced peptides detected in the second run, thus simplifying disulfide bond mapping. Using this platform, both inter- and intra-disulfide-linked peptides were characterized in two different proteins, ß-lactoglobulin and ribonuclease B. In order to prevent disulfide reshuffling during the digestion process, proteins were digested at a relatively low pH, using (a combination of) the high specificity proteases trypsin and Glu-C. With this approach, disulfide bonds in ß-lactoglobulin and ribonuclease B were comprehensively identified and localized, showing that online LC-EC-MS is a useful tool for the characterization of protein disulfide bonds.

  18. Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

    SciTech Connect

    Wu, Si; Brown, Joseph N.; Tolic, Nikola; Meng, Da; Liu, Xiaowen; Zhang, Haizhen; Zhao, Rui; Moore, Ronald J.; Pevzner, Pavel A.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2014-05-31

    There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.

  19. 3D Imaging by Mass Spectrometry: A New Frontier

    PubMed Central

    Seeley, Erin H.; Caprioli, Richard M.

    2012-01-01

    Summary Imaging mass spectrometry can generate three-dimensional volumes showing molecular distributions in an entire organ or animal through registration and stacking of serial tissue sections. Here we review the current state of 3D imaging mass spectrometry as well as provide insights and perspectives on the process of generating 3D mass spectral data along with a discussion of the process necessary to generate a 3D image volume. PMID:22276611

  20. Mass spectrometry of Natural Products: Current, Emerging and Future Technologies

    PubMed Central

    Bouslimani, Amina; Sanchez, Laura M; Garg, Neha; Dorrestein, Pieter C

    2014-01-01

    Although mass spectrometry is a century old technology, we are entering into an exciting time for the analysis of molecular information directly from complex biological systems. In this viewpoint article, we highlight emerging mass spectrometric methods and tools used by the natural product community and give a perspective of future directions where the mass spectrometry field is migrating towards over the next decade. PMID:24801551

  1. Probing the exposure of the phosphate group in modified amino acids and peptides by ion-molecule reactions with triethoxyborane in Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Lanucara, Francesco; Fornarini, Simonetta; Eyers, Claire E; Crestoni, Maria Elisa

    2014-05-30

    Intramolecular hydrogen bonds between a phosphate group and charged residues play a crucial role in the chemistry of phosphorylated peptides, driving the species to specific conformations and affecting the exposure of the phosphate moiety. The nature and extent of these interactions can be investigated by measuring the reactivity of phosphate groups toward selected substrates in the gas phase. We used Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry (MS) to perform a systematic study on the gas-phase ionic reactivity of phosphorylated amino acids and peptides with triethoxyborane (TEB). Ions of interest were generated by electrospray ionization (ESI), isolated in the cell of the FT-ICR mass spectrometer, and allowed to react with a stationary pressure of TEB. The temporal evolution of the reaction was monitored and thermal rate constants were derived. The structure of the ionic products was confirmed by Collision-Induced Dissociation (CID) tandem mass spectrometry (MS/MS). TEB was found to react with the phosphate of protonated phosphorylated amino acids and peptides by an addition-elimination pathway. The kinetic efficiency of the reaction showed a positive correlation with the charge state of the reagent ion, suggesting the existence of charge-state-dependent exposure of the phosphate groups towards the incoming neutral during the reaction. Isomeric phosphorylated peptides, only differing for the position of the modified serine residue, showed markedly different kinetic efficiencies. The ability of a phosphorylated species to react with TEB depends on the ease of access to the phosphate moiety in the corresponding gaseous ion. Measuring the kinetic efficiency of such reactions can represent a valuable tool to explore the accessibility of phosphate groups in biomolecules. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Hydropathic influences on the quantification of equine heart cytochrome c using relative ion abundance measurements by electrospray ionization fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Gordon, E F; Mansoori, B A; Carroll, C F; Muddiman, D C

    1999-10-01

    The number of publications documenting the utility of electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) for the analysis of biological molecules has increased in geometric proportion spanning diverse areas of research. Currently, we are investigating the capabilities of ESI-FTICR to quantify relative molecular ion abundances of biopolymers, an area which has not been explored rigorously. We present here the results of an investigation of a two-component system utilizing equine heart cytochrome c (EH) as the analyte and bovine heart cytochrome c (BH) as a constant concentration internal standard. As these compounds are relatively large ( approximately 12 kDa), they will become multiply charged during the electrospray process. Using appropriate solution and instrument conditions, the 7(+) and 8(+) charge states were enhanced for both cytochrome c species. We report that using the average of the ion abundances for the two charge states observed for each species, the linear curve (intensity ratio vs concentration ratio) had a dynamic range of 0.045-2.348 microM (1.7 orders of magnitude). Linear least-squares regression analysis (LLSRA) of these averaged ion abundances (i.e. [(EH + 7H(+))(7+)/(BH + 7H(+))(7+) + (EH + 8H(+))(8+)/(BH + 8H(+))(8+)]/2) yielded the equation y = 1.005x + 0.027. The slope of the line with its calculated precision, reported as one standard deviation, is 1.005 +/- 0.0150, which is statistically ideal (i.e. equal to unity). However, LLSRA of the ion abundances of the two individual charge states were significantly different (i.e. the slope of the (EH + 7H(+))(7+)/(BH + 7H(+))(7+) peak intensity ratio vs molar ratio data was 0.885 +/- 0.0183 and the slope of the (EH + 8H(+))(8+)/(BH + 8H(+))(8+) data was 1.125 +/- 0.0308). We attribute this difference to the variation in primary amino acid sequence for the two cytochrome c species. Both have 104 amino acids, but there are three residue

  3. Analysis of perchlorate in groundwater by electrospray ionization mass spectrometry/mass spectrometry

    SciTech Connect

    Koester, C.J.; Beller, H.R.; Halden, R.U.

    2000-05-01

    An electrospray ionization mass spectrometry/mass spectrometry (ESI/MS/MS) method was developed to measure part-per-billion ({micro}g/L) concentrations of perchlorate in groundwater. Selective and sensitive perchlorate detection was achieved by operating the mass spectrometer in the negative ionization mode and by using MS/MS to monitor the CIO{sub 4}{sup {minus}} to ClO{sub 3}{sup {minus}} transition. The method of standard additions was used to address the considerable signal suppression caused by anions that are typically present in groundwater, such as bicarbonate and sulfate. ESI-MS/MS analysis was rapid, accurate, reproducible, and provided a detection limit of 0.5 {micro}g/L perchlorate in groundwater. Accuracy and precision of the ESI/MS/MS method were assessed by analyzing performance evaluation samples in a groundwater matrix and by comparing ion chromatography (IC) and ESI/MS/MS results for local groundwater samples. Results for the performance evaluation samples differed from the certified values by 4--13%, and precision ranged from 3 to 10% (relative standard deviation). The IC and ESI/MS/MS results were statistically indistinguishable for perchlorate concentrations above the detection limits of both methods.

  4. Characterization of Membrane Protein-Lipid Interactions by Mass Spectrometry Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Cong, Xiao; Liu, Wen; Laganowsky, Arthur

    2017-04-01

    Lipids in the biological membrane can modulate the structure and function of integral and peripheral membrane proteins. Distinguishing individual lipids that bind selectively to membrane protein complexes from an ensemble of lipid-bound species remains a daunting task. Recently, ion mobility mass spectrometry (IM-MS) has proven to be invaluable for interrogating the interactions between protein and individual lipids, where the complex undergoes collision induced unfolding followed by quantification of the unfolding pathway to assess the effect of these interactions. However, gas-phase unfolding experiments for membrane proteins are typically performed on the entire ensemble ( apo and lipid bound species), raising uncertainty to the contribution of individual lipids and the species that are ejected in the unfolding process. Here, we describe the application of mass spectrometry ion mobility mass spectrometry (MS-IM-MS) for isolating ions corresponding to lipid-bound states of a model integral membrane protein, ammonia channel (AmtB) from Escherichia coli. Free of ensemble effects, MS-IM-MS reveals that bound lipids are ejected as neutral species; however, no correlation was found between the lipid-induced stabilization of complex and their equilibrium binding constants. In comparison to data obtained by IM-MS, there are surprisingly limited differences in stability measurements from IM-MS and MS-IM-MS. The approach described here to isolate ions of membrane protein complexes will be useful for other MS methods, such as surface induced dissociation or collision induced dissociation to determine the stoichiometry of hetero-oligomeric membrane protein complexes.

  5. Characterization of Membrane Protein-Lipid Interactions by Mass Spectrometry Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Cong, Xiao; Liu, Wen; Laganowsky, Arthur

    2016-12-01

    Lipids in the biological membrane can modulate the structure and function of integral and peripheral membrane proteins. Distinguishing individual lipids that bind selectively to membrane protein complexes from an ensemble of lipid-bound species remains a daunting task. Recently, ion mobility mass spectrometry (IM-MS) has proven to be invaluable for interrogating the interactions between protein and individual lipids, where the complex undergoes collision induced unfolding followed by quantification of the unfolding pathway to assess the effect of these interactions. However, gas-phase unfolding experiments for membrane proteins are typically performed on the entire ensemble (apo and lipid bound species), raising uncertainty to the contribution of individual lipids and the species that are ejected in the unfolding process. Here, we describe the application of mass spectrometry ion mobility mass spectrometry (MS-IM-MS) for isolating ions corresponding to lipid-bound states of a model integral membrane protein, ammonia channel (AmtB) from Escherichia coli. Free of ensemble effects, MS-IM-MS reveals that bound lipids are ejected as neutral species; however, no correlation was found between the lipid-induced stabilization of complex and their equilibrium binding constants. In comparison to data obtained by IM-MS, there are surprisingly limited differences in stability measurements from IM-MS and MS-IM-MS. The approach described here to isolate ions of membrane protein complexes will be useful for other MS methods, such as surface induced dissociation or collision induced dissociation to determine the stoichiometry of hetero-oligomeric membrane protein complexes.

  6. Structure characterization of polyaromatic hydrocarbons in Arabian mix vacuum residue by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

    NASA Astrophysics Data System (ADS)

    Miyabayashi, Keiko; Naito, Yasuhide; Tsujimoto, Kazuo; Miyake, Mikio

    2004-06-01

    Molecular formulas of constituents in vacuum residue were characterized by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Evaluation of electrospray ionization (ESI) ability for hydrocarbons by using model compounds indicates that aromatic compounds having more than two fused rings without functional group are detectable as molecular ions, while that basic nitrogen-containing compounds produce protonated ions in the ESI solvent of methanol/chloroform. Thus, even peaks appear for both hydrocarbons and nitrogen-containing compounds in methanol/chloroform. Although basic nitrogen compound detected selectively in mixture of equal molar concentration of hydrocarbons, hydrocarbon could be observed almost the same intensity when the concentration of nitrogen compounds was adjusted as low as that of Arabian mix vacuum residue (AM-VR: N 0.4 wt.%). When ESI solvent of methanol/chloroform/trifluoroacetic acid (TFA) was used, protonated hydrocarbons produced predominantly as odd peaks. Thus, it was revealed that peaks originating from nitrogen-containing compounds and hydrocarbons can be clearly distinguished by changing composition of ESI solvents. In application to AM-VR, protonated nitrogen-containing compounds ([CnH2n+ZN + H]+ and [CnH2n+ZNS + H]+; even masses) were observed selectively in methanol/chloroform, and both protonated nitrogen-containing compounds and protonated or sodium-cationized hydrocarbons ([M + H]+ or [M + Na]+; odd masses) were observed simultaneously in the solvent composition of methanol/chloroform/TFA.

  7. Molecular mass spectrometry imaging in biomedical and life science research.

    PubMed

    Pól, Jaroslav; Strohalm, Martin; Havlíček, Vladimír; Volný, Michael

    2010-11-01

    This review describes the current state of mass spectrometry imaging (MSI) in life sciences. A brief overview of mass spectrometry principles is presented followed by a thorough introduction to the MSI workflows, principles and areas of application. Three major desorption-ionization techniques used in MSI, namely, secondary ion mass spectrometry (SIMS), matrix-assisted laser desorption ionization (MALDI), and desorption electrospray ionization (DESI) are described, and biomedical and life science imaging applications of each ionization technique are reviewed. A separate section is devoted to data handling and current challenges and future perspectives are briefly discussed at the end.

  8. imzML: Imaging Mass Spectrometry Markup Language: A common data format for mass spectrometry imaging.

    PubMed

    Römpp, Andreas; Schramm, Thorsten; Hester, Alfons; Klinkert, Ivo; Both, Jean-Pierre; Heeren, Ron M A; Stöckli, Markus; Spengler, Bernhard

    2011-01-01

    Imaging mass spectrometry is the method of scanning a sample of interest and generating an "image" of the intensity distribution of a specific analyte. The data sets consist of a large number of mass spectra which are usually acquired with identical settings. Existing data formats are not sufficient to describe an MS imaging experiment completely. The data format imzML was developed to allow the flexible and efficient exchange of MS imaging data between different instruments and data analysis software.For this purpose, the MS imaging data is divided in two separate files. The mass spectral data is stored in a binary file to ensure efficient storage. All metadata (e.g., instrumental parameters, sample details) are stored in an XML file which is based on the standard data format mzML developed by HUPO-PSI. The original mzML controlled vocabulary was extended to include specific parameters of imaging mass spectrometry (such as x/y position and spatial resolution). The two files (XML and binary) are connected by offset values in the XML file and are unambiguously linked by a universally unique identifier. The resulting datasets are comparable in size to the raw data and the separate metadata file allows flexible handling of large datasets.Several imaging MS software tools already support imzML. This allows choosing from a (growing) number of processing tools. One is no longer limited to proprietary software, but is able to use the processing software which is best suited for a specific question or application. On the other hand, measurements from different instruments can be compared within one software application using identical settings for data processing. All necessary information for evaluating and implementing imzML can be found at http://www.imzML.org .

  9. Application of Lithium Attachment Mass Spectrometry for Knudsen Evaporation and Chemical Ionisation Mass Spectrometry (KEMS, CIMS)

    NASA Astrophysics Data System (ADS)

    Bannan, T.; Booth, M.; Benyezzar, M.; Bacak, A.; Alfarra, M. R. R.; Topping, D. O.; Percival, C.

    2015-12-01

    Lithium ion attachment mass spectrometry provides a non-specific, non-fragmenting and sensitive method for detection of volatile species in the gas phase. The design, manufacture, and results from lithium ion attachment ionisation sources for two mass spectrometry systems are presented. Trace gas analysis is investigated using a modified Chemical Ionization Mass Spectrometer (CIMS) and vapour pressure (VP) measurements using a modified Knudsen Effusion Mass Spectrometer (KEMS) are presented. The Li+ modified CIMS provided limits of detection of 4 ppt for acetone, 0.2 ppt for formic acid, 15 ppt for nitric acid and 120 ppt from ammonia. Despite improvements, the problem of burnout remained persistent. The Li+ CIMS would unlikely be suitable for field or aircraft work, but could be appropriate for certain lab applications. The KEMS currently utilizes an electron impact (EI) ionisation source which provides a highly sensitive source, with the drawback of fragmentation of ionized molecules (Booth et al., 2009). Using Li+ KEMS the VP of samples can be measured without fragmentation and can therefore be used to identify VPs of individual components in mixtures. The validity of using Li+ for determining the VP of mixtures was tested by making single component VP measurements, which showed good agreement with EI measurements of Poly ethylene glycol (PEG) 3 and PEG 4, both when individually measured and when mixed. The Li+ KEMS was then used to investigate a system of atmospheric relevance, α-pinene secondary organic aerosol, generated in a reaction chamber (Alfarra et al., 2012). The VPs of the individual components from this generated sample are within the range we expect for compounds capable of partitioning between the particle and gas phase of an aerosol (0.1-10-5 Pa). Li+ source has a calculated sensitivity approximately 75 times less than that of EI, but the lack of fragmentation using the Li+ source is a significant advantage.

  10. Application of Lithium Attachment Mass Spectrometry for Knudsen Evaporation and Chemical Ionisation Mass Spectrometry (KEMS, CIMS)

    NASA Astrophysics Data System (ADS)

    Bannan, Thomas; Booth, A. Murray; Alfarra, Rami; Bacak, Asan; Pericval, Carl

    2016-04-01

    Lithium ion attachment mass spectrometry provides a non-specific, non-fragmenting and sensitive method for detection of volatile species in the gas phase. The design, manufacture, and results from lithium ion attachment ionisation sources for two mass spectrometry systems are presented. Trace gas analysis is investigated using a modified Chemical Ionization Mass Spectrometer (CIMS) and vapour pressure (VP) measurements using a modified Knudsen Effusion Mass Spectrometer (KEMS) are presented. The Li+ modified CIMS provided limits of detection of 4 ppt for acetone, 0.2 ppt for formic acid, 15 ppt for nitric acid and 120 ppt from ammonia. Despite improvements, the problem of burnout remained persistent. The Li+ CIMS would unlikely be suitable for field or aircraft work, but could be appropriate for certain lab applications. The KEMS currently utilizes an electron impact (EI) ionisation source which provides a highly sensitive source, with the drawback of fragmentation of ionized molecules (Booth et al., 2009). Using Li+ KEMS the VP of samples can be measured without fragmentation and can therefore be used to identify VPs of individual components in mixtures. The validity of using Li+ for determining the VP of mixtures was tested by making single component VP measurements, which showed good agreement with EI measurements of Poly ethylene glycol (PEG) 3 and PEG 4, both when individually measured and when mixed. The Li+ KEMS was then used to investigate a system of atmospheric relevance, α-pinene secondary organic aerosol, generated in a reaction chamber (Alfarra et al., 2012). The VPs of the individual components from this generated sample are within the range we expect for compounds capable of partitioning between the particle and gas phase of an aerosol (0.1-10-5 Pa). Li+ source has a calculated sensitivity approximately 75 times less than that of EI, but the lack of fragmentation using the Li+ source is a significant advantage.

  11. The allure of mass spectrometry: From an earlyday chemist's perspective.

    PubMed

    Tőkés, László

    2017-07-01

    This reminiscing review article is an account of the author's fascination and involvements with mass spectrometry from the perspective of an organic chemist with an interest in natural product chemistry. It covers a period from 1961 through the mid 1990s as mass spectrometry evolved form a novelty technique to become a most widely used analytical technique. Following a brief synopsis of my pathway to mass spectrometry, my research efforts in this field are presented with a focus mainly on evolving principles and technologies which I had personal involvements with. To provide historical perspectives, discussions of these developments are accompanied by brief outlines of the relevant state-of-the-art, shedding light on the technical and conceptual challenges encountered during those early days in mass spectrometry. Examples are presented of my involvements with basic and applied research in mass spectrometry during graduate studies at Stanford University and close to three decade tenure in pharmaceutical research at Syntex Research. My basic research interests focused mainly on principles of electron ionization induced fragmentation mechanisms, with an emphasis on steroids and other model compounds. Extensive deuterium labeling evidence was used to determine the fragmentation mechanisms of the diagnostically significant ions in the spectra of numerous model compounds, uncovering examples of wide-ranging hydrogen transfers, skeletal rearrangements, methyl and phenyl migrations, stereoselective fragmentations and low and high energy fragmentation processes. Depiction of the industrial research phase of my career includes comments on the pivotal role mass spectrometry played on advancing modern pharmaceutical research. Examples are presented of involvements with instrumental developments and a few select cases of applied research, including studies of bile mechanisms in vertebrates, identification of bisphenol-A leaching from sterilized polycarbonate containers, high

  12. Advanced Mass Spectrometric Methods for the Rapid and Quantitative Characterization of Proteomes

    DOE PAGES

    Smith, Richard D.

    2002-01-01

    Progress is reviewedmore » towards the development of a global strategy that aims to extend the sensitivity, dynamic range, comprehensiveness and throughput of proteomic measurements based upon the use of high performance separations and mass spectrometry. The approach uses high accuracy mass measurements from Fourier transform ion cyclotron resonance mass spectrometry (FTICR) to validate peptide ‘accurate mass tags’ (AMTs) produced by global protein enzymatic digestions for a specific organism, tissue or cell type from ‘potential mass tags’ tentatively identified using conventional tandem mass spectrometry (MS/MS). This provides the basis for subsequent measurements without the need for MS/ MS. High resolution capillary liquid chromatography separations combined with high sensitivity, and high resolution accurate FTICR measurements are shown to be capable of characterizing peptide mixtures of more than 10 5 components. The strategy has been initially demonstrated using the microorganisms Saccharomyces cerevisiae and Deinococcus radiodurans. Advantages of the approach include the high confidence of protein identification, its broad proteome coverage, high sensitivity, and the capability for stableisotope labeling methods for precise relative protein abundance measurements. Abbreviations : LC, liquid chromatography; FTICR, Fourier transform ion cyclotron resonance; AMT, accurate mass tag; PMT, potential mass tag; MMA, mass measurement accuracy; MS, mass spectrometry; MS/MS, tandem mass spectrometry; ppm, parts per million.« less

  13. Protein Quantitation of the Developing Cochlea Using Mass Spectrometry.

    PubMed

    Darville, Lancia N F; Sokolowski, Bernd H A

    2016-01-01

    Mass spectrometry-based proteomics allows for the measurement of hundreds to thousands of proteins in a biological system. Additionally, mass spectrometry can also be used to quantify proteins and peptides. However, observing quantitative differences between biological systems using mass spectrometry-based proteomics can be challenging because it is critical to have a method that is fast, reproducible, and accurate. Therefore, to study differential protein expression in biological samples labeling or label-free quantitative methods can be used. Labeling methods have been widely used in quantitative proteomics, however label-free methods have become equally as popular and more preferred because they produce faster, cleaner, and simpler results. Here, we describe the methods by which proteins are isolated and identified from cochlear sensory epithelia tissues at different ages and quantitatively differentiated using label-free mass spectrometry.

  14. Molecular Beam Mass Spectrometry (MBMS) (Revised) (Fact Sheet)

    SciTech Connect

    Not Available

    2011-07-01

    This fact sheet provides information about Molecular Beam Mass Spectrometry (MBMS) capabilities and applications at NREL's National Bioenergy Center. NREL has six MBMS systems that researchers and industry partners can use to understand thermochemical biomass conversion and biomass composition recalcitrance.

  15. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    NASA Astrophysics Data System (ADS)

    Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Chung, C. N.; Allman, S. L.

    1997-05-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, we recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Sanger's enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. Our preliminary results indicate laser mass spectrometry can possible be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, we applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  16. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    SciTech Connect

    Winston Chen, C.H.; Taranenko, N.I.; Zhu, Y.F.; Chung, C.N.; Allman, S.L.

    1997-03-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, the authors recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Snager`s enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. The preliminary results indicate laser mass spectrometry can possibly be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, the authors applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  17. Challenges and developments in tandem mass spectrometry based clinical metabolomics.

    PubMed

    Ceglarek, Uta; Leichtle, Alexander; Brügel, Mathias; Kortz, Linda; Brauer, Romy; Bresler, Kristin; Thiery, Joachim; Fiedler, Georg Martin

    2009-03-25

    'Clinical metabolomics' aims at evaluating and predicting health and disease risk in an individual by investigating metabolic signatures in body fluids or tissues, which are influenced by genetics, epigenetics, environmental exposures, diet, and behaviour. Powerful analytical techniques like liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) offers a rapid, effective and economical way to analyze metabolic alterations of pre-defined target metabolites in biological samples. Novel hyphenated technical approaches like the combination of tandem mass spectrometry combined with linear ion trap (QTrap mass spectrometry) combines both identification and quantification of known and unknown metabolic targets. We describe new concepts and developments of mass spectrometry based multi-target metabolome profiling in the field of clinical diagnostics and research. Particularly, the experiences from newborn screening provided important insights about the diagnostic potential of metabolite profiling arrays and directs to the clinical aim of predictive, preventive and personalized medicine by metabolomics.

  18. Environmental Mass Spectrometry: Emerging Contaminants and Current Issues (2010 Review)

    EPA Science Inventory

    This biennial review covers developments in environmental mass spectrometry for emerging environmental contaminants over the period of 2008-2009. A few significant references that appeared between January and February 2010 are also included. Analytical Chemistry’s current polic...

  19. Environmental Mass Spectrometry: Emerging Contaminants and Current Issues, 2008 Review

    EPA Science Inventory

    This biennial review covers developments in Environmental Mass Spectrometry for Emerging Environmental Contaminants over the period of 2006-2007. A few significant references that appeared between January and February 2008 are also included. Analytical Chemistry’s current polic...

  20. Mass Spectrometry of Membrane Proteins: A Focus on Aquaporins

    PubMed Central

    Schey, Kevin L.; Grey, Angus C.; Nicklay, Joshua J.

    2015-01-01

    Membrane proteins are abundant, critically important biomolecules that conduct essential functions in all cells and are the targets of a significant number of therapeutic drugs. However, the analysis of their expression, modification, protein–protein interactions, and structure by mass spectrometry has lagged behind similar studies of soluble proteins. Here we review the limitations to analysis of integral membrane and membrane-associated proteins and highlight advances in sample preparation and mass spectrometry methods that have led to the successful analysis of this protein class. Advances in the analysis of membrane protein posttranslational modification, protein–protein interaction, protein structure, and tissue distributions by imaging mass spectrometry are discussed. Furthermore, we focus our discussion on the application of mass spectrometry for the analysis of aquaporins as a prototypical integral membrane protein and how advances in analytical methods have revealed new biological insights into the structure and function of this family of proteins. PMID:23394619

  1. Environmental Mass Spectrometry: Emerging Contaminants and Current Issues (2010 Review)

    EPA Science Inventory

    This biennial review covers developments in environmental mass spectrometry for emerging environmental contaminants over the period of 2008-2009. A few significant references that appeared between January and February 2010 are also included. Analytical Chemistry’s current polic...

  2. Recent applications of mass spectrometry in forensic toxicology

    NASA Astrophysics Data System (ADS)

    Foltz, Rodger L.

    1992-09-01

    This review encompasses applications of mass spectrometry reported during the years 1989, 1990 and 1991 for the analysis of cannabinoids, cocaine, opiates, amphetamines, lysergic acid diethylamide (LSD), and their metabolites in physiological specimens.

  3. Mass spectrometry of membrane proteins: a focus on aquaporins.

    PubMed

    Schey, Kevin L; Grey, Angus C; Nicklay, Joshua J

    2013-06-04

    Membrane proteins are abundant, critically important biomolecules that conduct essential functions in all cells and are the targets of a significant number of therapeutic drugs. However, the analysis of their expression, modification, protein-protein interactions, and structure by mass spectrometry has lagged behind similar studies of soluble proteins. Here we review the limitations to analysis of integral membrane and membrane-associated proteins and highlight advances in sample preparation and mass spectrometry methods that have led to the successful analysis of this protein class. Advances in the analysis of membrane protein posttranslational modification, protein-protein interaction, protein structure, and tissue distributions by imaging mass spectrometry are discussed. Furthermore, we focus our discussion on the application of mass spectrometry for the analysis of aquaporins as a prototypical integral membrane protein and how advances in analytical methods have revealed new biological insights into the structure and function of this family of proteins.

  4. Photodissociation mass spectrometry: New tools for characterization of biological molecules

    PubMed Central

    Brodbelt, Jennifer S.

    2014-01-01

    Photodissociation mass spectrometry combines the ability to activate and fragment ions using photons with the sensitive detection of the resulting product ions by mass spectrometry. The resulting combination affords a versatile tool for characterization of biological molecules. The scope and breadth of photodissociation mass spectrometry have increased substantially over the past decade as new research groups have entered the field and developed a number of innovative applications that illustrate the ability of photodissociation to produce rich fragmentation patterns, to cleave bonds selectively, and to target specific molecules based on incorporation of chromophores. This review focuses on many of the key developments in photodissociation mass spectrometry over the past decade with a particular emphasis on its applications to biological molecules. PMID:24481009

  5. Dynamically harmonized FT-ICR cell with specially shaped electrodes for compensation of inhomogeneity of the magnetic field. Computer simulations of the electric field and ion motion dynamics.

    PubMed

    Kostyukevich, Yury I; Vladimirov, Gleb N; Nikolaev, Eugene N

    2012-12-01

    The recently introduced ion trap for FT-ICR mass spectrometers with dynamic harmonization showed the highest resolving power ever achieved both for ions with moderate masses 500-1000 Da (peptides) as well as ions with very high masses of up to 200 kDa (proteins). Such results were obtained for superconducting magnets of very high homogeneity of the magnetic field. For magnets with lower homogeneity, the time of transient duration would be smaller. In superconducting magnets used in FT-ICR mass spectrometry the inhomogeneity of the magnetic field in its axial direction prevails over the inhomogeneity in other directions and should be considered as the main factor influencing the synchronic motion of the ion cloud. The inhomogeneity leads to a dependence of the cyclotron frequency from the amplitude of axial oscillation in the potential well of the ion trap. As a consequence, ions in an ion cloud become dephased, which leads to signal attenuation and decrease in the resolving power. Ion cyclotron frequency is also affected by the radial component of the electric field. Hence, by appropriately adjusting the electric field one can compensate the inhomogeneity of the magnetic field and align the cyclotron frequency in the whole range of amplitudes of z-oscillations. A method of magnetic field inhomogeneity compensation in a dynamically harmonized FT-ICR cell is presented, based on adding of extra electrodes into the cell shaped in such a way that the averaged electric field created by these electrodes produces a counter force to the forces caused by the inhomogeneous magnetic field.

  6. THE APPLICATION OF MASS SPECTROMETRY TO THE STUDY OF MICROORGANISMS

    EPA Science Inventory

    The purpose of this research project is to use state-of-the-art mass spectrometric techniques, such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS), to provide "protein mass fingerprinting" and protein sequencing i...

  7. THE APPLICATION OF MASS SPECTROMETRY TO THE STUDY OF MICROORGANISMS

    EPA Science Inventory

    The purpose of this research project is to use state-of-the-art mass spectrometric techniques, such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS), to provide "protein mass fingerprinting" and protein sequencing i...

  8. Subcellular analysis by laser ablation electrospray ionization mass spectrometry

    DOEpatents

    Vertes, Akos; Stolee, Jessica A; Shrestha, Bindesh

    2014-12-02

    In various embodiments, a method of laser ablation electrospray ionization mass spectrometry (LAESI-MS) may generally comprise micro-dissecting a cell comprising at least one of a cell wall and a cell membrane to expose at least one subcellular component therein, ablating the at least one subcellular component by an infrared laser pulse to form an ablation plume, intercepting the ablation plume by an electrospray plume to form ions, and detecting the ions by mass spectrometry.

  9. Analysis of chirality by femtosecond laser ionization mass spectrometry.

    PubMed

    Horsch, Philipp; Urbasch, Gunter; Weitzel, Karl-Michael

    2012-09-01

    Recent progress in the field of chirality analysis employing laser ionization mass spectrometry is reviewed. Emphasis is given to femtosecond (fs) laser ionization work from the author's group. We begin by reviewing fundamental aspects of determining circular dichroism (CD) in fs-laser ionization mass spectrometry (fs-LIMS) discussing an example from the literature (resonant fs-LIMS of 3-methylcyclopentanone). Second, we present new data indicating CD in non-resonant fs-LIMS of propylene oxide.

  10. Determination of nitrofuran and chloramphenicol residues by high resolution mass spectrometry versus tandem quadrupole mass spectrometry.

    PubMed

    Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M

    2015-03-03

    An ultra-high performance liquid chromatography based method, coupled to high resolution mass spectrometry (UHPLC-HRMS), was developed to permit the detection and quantification of various nitrofuran and chloramphenicol residues in a number of animal based food products. This method is based on the hydrolysis of covalently bound metabolites and derivatization with 2-nitrobenzaldehyde. Clean-up is achieved by a liquid/liquid and a reversed phase/solid phase extraction. Not only are the four conventional nitrofurans (nitrofurantoin, furazolidone, nitrofurazone and furaltadone) detected, but also nifursol, nitrovin and nifuroxazide. Furthermore, an underivatizable nitrofuran (nifurpirinol) and another banned drug (chloramphenicol) can be quantified as well. The compounds are detected in the form of their precursor ions, [M+H](+) and [M-H](-), respectively. The mass resolving power of 70,000 FWHM, and the applied mass window ensure sufficient selectivity and sensitivity. Confirmation is obtained by monitoring the HRMS resolved product ions which were derived from the unit-mass resolved precursor ions. The multiplexing capability of the utilized Orbitrap instrument provides not only highly selective, but also sensitive confirmatory signals. This method has been validated according to the CD 2002/657/EC for the following matrices: muscle, liver, kidney, fish, honey, eggs and milk.

  11. Mass Spectrometry Imaging of Complex Microbial Communities

    PubMed Central

    2016-01-01

    Conspectus In the two decades since mass spectrometry imaging (MSI) was first applied to visualize the distribution of peptides across biological tissues and cells, the technique has become increasingly effective and reliable. MSI excels at providing complementary information to existing methods for molecular analysis—such as genomics, transcriptomics, and metabolomics—and stands apart from other chemical imaging modalities through its capability to generate information that is simultaneously multiplexed and chemically specific. Today a diverse family of MSI approaches are applied throughout the scientific community to study the distribution of proteins, peptides, and small-molecule metabolites across many biological models. The inherent strengths of MSI make the technique valuable for studying microbial systems. Many microbes reside in surface-attached multicellular and multispecies communities, such as biofilms and motile colonies, where they work together to harness surrounding nutrients, fend off hostile organisms, and shield one another from adverse environmental conditions. These processes, as well as many others essential for microbial survival, are mediated through the production and utilization of a diverse assortment of chemicals. Although bacterial cells are generally only a few microns in diameter, the ecologies they influence can encompass entire ecosystems, and the chemical changes that they bring about can occur over time scales ranging from milliseconds to decades. Because of their incredible complexity, our understanding of and influence over microbial systems requires detailed scientific evaluations that yield both chemical and spatial information. MSI is well-positioned to fulfill these requirements. With small adaptations to existing methods, the technique can be applied to study a wide variety of chemical interactions, including those that occur inside single-species microbial communities, between cohabitating microbes, and between microbes

  12. Calculating Measurement Uncertainties for Mass Spectrometry Data

    NASA Astrophysics Data System (ADS)

    Essex, R. M.; Goldberg, S. A.

    2006-12-01

    A complete and transparent characterization of measurement uncertainty is fundamentally important to the interpretation of analytical results. We have observed that the calculation and reporting of uncertainty estimates for isotopic measurement from a variety of analytical facilities are inconsistent, making it difficult to compare and evaluate data. Therefore, we recommend an approach to uncertainty estimation that has been adopted by both US national metrology facilities and is becoming widely accepted within the analytical community. This approach is outlined in the ISO "Guide to the Expression of Uncertainty in Measurement" (GUM). The GUM approach to uncertainty estimation includes four major steps: 1) Specify the measurand; 2) Identify uncertainty sources; 3) Quantify components by determining the standard uncertainty (u) for each component; and 4) Calculate combined standard uncertainty (u_c) by using established propagation laws to combine the various components. To obtain a desired confidence level, the combined standard uncertainty is multiplied by a coverage factor (k) to yield an expanded uncertainty (U). To be consistent with the GUM principles, it is also necessary create an uncertainty budget, which is a listing of all the components comprising the uncertainty and their relative contribution to the combined standard uncertainty. In mass spectrometry, Step 1 is normally the determination of an isotopic ratio for a particular element. Step 2 requires the identification of the many potential sources of measurement variability and bias including: gain, baseline, cup efficiency, Schottky noise, counting statistics, CRM uncertainties, yield calibrations, linearity calibrations, run conditions, and filament geometry. Then an equation expressing the relationship of all of the components to the measurement value must be written. To complete Step 3, these potential sources of uncertainty must be characterized (Type A or Type B) and quantified. This information

  13. Detection of Non-aromatic Organic Compounds in Meteorites using Imaging Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Scott, J. R.; Hinman, N. W.; Richardson, C. D.; Mahon, R. C.; McJunkin, T. R.

    2009-12-01

    Our most extensive understanding of extraterrestrial organic matter is based on what has been learned from meteorites that have been delivered naturally to Earth. Meteorites have been analyzed by a variety of techniques ranging from extensive sample preparation with extraction and subsequent chromatography to direct laser desorption mass spectrometry (LDMS). While extraction studies have reported a variety of organics (e.g., aliphatic and aromatic hydrocarbons, ketones, aldehydes, and amino acids), LDMS studies have only reported polycyclic aromatic hydrocarbons (PAHs). This is rather surprising considering that Yan et al. (Talanta 2007, 72, 634-641) reported that even a small amount of PAH enables the detection of organics that are not otherwise ionized during the desorption event from minerals. Therefore, we have begun re-investigating meteorites because, regardless of the source of the organic compounds, the presences of PAHs should allow other organic molecules to be observed using imaging laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (LD-FTICR-MS). Indeed, we have mapped meteorites (e.g., EETA 79001) and found many mass-to-charge peaks that are non-aromatic as determined by analysis of their mass defects. Mapping also revealed that the distribution of organics is heterogeneous, which necessitates the collection of a mass spectrum from a single laser shot so that minor peaks of interest are not lost in signal averaging. These studies have implications for analyzing future returned samples from Mars or elsewhere with minimal preparation or damage.

  14. The allure of mass spectrometry: From an earlyday chemist's perspective

    PubMed Central

    2016-01-01

    1 This reminiscing review article is an account of the author's fascination and involvements with mass spectrometry from the perspective of an organic chemist with an interest in natural product chemistry. It covers a period from 1961 through the mid 1990s as mass spectrometry evolved form a novelty technique to become a most widely used analytical technique. Following a brief synopsis of my pathway to mass spectrometry, my research efforts in this field are presented with a focus mainly on evolving principles and technologies which I had personal involvements with. To provide historical perspectives, discussions of these developments are accompanied by brief outlines of the relevant state‐of‐the‐art, shedding light on the technical and conceptual challenges encountered during those early days in mass spectrometry. Examples are presented of my involvements with basic and applied research in mass spectrometry during graduate studies at Stanford University and close to three decade tenure in pharmaceutical research at Syntex Research. My basic research interests focused mainly on principles of electron ionization induced fragmentation mechanisms, with an emphasis on steroids and other model compounds. Extensive deuterium labeling evidence was used to determine the fragmentation mechanisms of the diagnostically significant ions in the spectra of numerous model compounds, uncovering examples of wide‐ranging hydrogen transfers, skeletal rearrangements, methyl and phenyl migrations, stereoselective fragmentations and low and high energy fragmentation processes. Depiction of the industrial research phase of my career includes comments on the pivotal role mass spectrometry played on advancing modern pharmaceutical research. Examples are presented of involvements with instrumental developments and a few select cases of applied research, including studies of bile mechanisms in vertebrates, identification of bisphenol‐A leaching from sterilized polycarbonate

  15. NCBI Peptidome: a new repository for mass spectrometry proteomics data.

    PubMed

    Ji, Li; Barrett, Tanya; Ayanbule, Oluwabukunmi; Troup, Dennis B; Rudnev, Dmitry; Muertter, Rolf N; Tomashevsky, Maxim; Soboleva, Alexandra; Slotta, Douglas J

    2010-01-01

    Peptidome is a public repository that archives and freely distributes tandem mass spectrometry peptide and protein identification data generated by the scientific community. Data from all stages of a mass spectrometry experiment are captured, including original mass spectra files, experimental metadata and conclusion-level results. The submission process is facilitated through acceptance of data in commonly used open formats, and all submissions undergo syntactic validation and curation in an effort to uphold data integrity and quality. Peptidome is not restricted to specific organisms, instruments or experiment types; data from any tandem mass spectrometry experiment from any species are accepted. In addition to data storage, web-based interfaces are available to help users query, browse and explore individual peptides, proteins or entire Samples and Studies. Results are integrated and linked with other NCBI resources to ensure dissemination of the information beyond the mass spectroscopy proteomics community. Peptidome is freely accessible at http://www.ncbi.nlm.nih.gov/peptidome.

  16. Revealing Novel Telomere Proteins Using in Vivo Cross-linking, Tandem Affinity Purification, and Label-free Quantitative LC-FTICR-MS*

    PubMed Central

    Nittis, Thalia; Guittat, Lionel; LeDuc, Richard D.; Dao, Ben; Duxin, Julien P.; Rohrs, Henry; Townsend, R. Reid; Stewart, Sheila A.

    2010-01-01

    Telomeres are DNA-protein structures that protect chromosome ends from the actions of the DNA repair machinery. When telomeric integrity is compromised, genomic instability ensues. Considerable effort has focused on identification of telomere-binding proteins and elucidation of their functions. To date, protein identification has relied on classical immunoprecipitation and mass spectrometric approaches, primarily under conditions that favor isolation of proteins with strong or long lived interactions that are present at sufficient quantities to visualize by SDS-PAGE. To facilitate identification of low abundance and transiently associated telomere-binding proteins, we developed a novel approach that combines in vivo protein-protein cross-linking, tandem affinity purification, and stringent sequential endoprotease digestion. Peptides were identified by label-free comparative nano-LC-FTICR-MS. Here, we expressed an epitope-tagged telomere-binding protein and utilized a modified chromatin immunoprecipitation approach to cross-link associated proteins. The resulting immunoprecipitant contained telomeric DNA, establishing that this approach captures bona fide telomere binding complexes. To identify proteins present in the immunocaptured complexes, samples were reduced, alkylated, and digested with sequential endoprotease treatment. The resulting peptides were purified using a microscale porous graphite stationary phase and analyzed using nano-LC-FTICR-MS. Proteins enriched in cells expressing HA-FLAG-TIN2 were identified by label-free quantitative analysis of the FTICR mass spectra from different samples and ion trap tandem mass spectrometry followed by database searching. We identified all of the proteins that constitute the telomeric shelterin complex, thus validating the robustness of this approach. We also identified 62 novel telomere-binding proteins. These results demonstrate that DNA-bound protein complexes, including those present at low molar ratios, can be

  17. Mass spectrometry imaging and profiling of single cells

    PubMed Central

    Lanni, Eric J.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-01-01

    Mass spectrometry imaging and profiling of individual cells and subcellular structures provide unique analytical capabilities for biological and biomedical research, including determination of the biochemical heterogeneity of cellular populations and intracellular localization of pharmaceuticals. Two mass spectrometry technologies—secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption ionization mass spectrometry (MALDI MS)—are most often used in micro-bioanalytical investigations. Recent advances in ion probe technologies have increased the dynamic range and sensitivity of analyte detection by SIMS, allowing two- and three-dimensional localization of analytes in a variety of cells. SIMS operating in the mass spectrometry imaging (MSI) mode can routinely reach spatial resolutions at the submicron level; therefore, it is frequently used in studies of the chemical composition of subcellular structures. MALDI MS offers a large mass range and high sensitivity of analyte detection. It has been successfully applied in a variety of single-cell and organelle profiling studies. Innovative instrumentation such as scanning microprobe MALDI and mass microscope spectrometers enable new subcellular MSI measurements. Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling. PMID:22498881

  18. Detection of Biosignatures using Geomatrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: Implications for the Search for Life in the Solar System

    NASA Astrophysics Data System (ADS)

    Richardson, C. D.; Kotler, J. M.; Hinman, N. W.; Scott, J. R.

    2008-12-01

    Detection of bio/organic signatures, defined as an organic structure produced by living organisms or derived from other biogenic organic compounds, is essential to investigating the origin and distribution of extant or extinct life in the solar system. In conjunction with mineralogical, inorganic, and isotopic data, the detection and identification of bio/organic signatures can assist in linking biochemical and geochemical processes. Geomatrix-assisted laser desorption/ionization (GALDI) in conjunction with a Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is a proven method of obtaining bio/organic signatures from a range of geological materials. Sulfate salts were studied because they are found on Mars and Jovian satellites. The goal here was to determine (1) which combinations of bio/organic compounds and sulfate salts produced distinctive spectral signatures, and (2) the detection limit of the method. In these experiments, thenardite (Na2SO4) was mixed with stearic acid to determine the detection limit of GALDI-FTICR-MS, previously estimated to be 3 ppt, which corresponds to approximately 7 zeptomoles (10-21) per laser shot. All spectra were collected with little to no sample preparation and were acquired using a single laser shot. Unlike conventional analytical practices, the signal-to-noise ratio increased as the concentration of bio/organic compounds decreased relative to the mineral host. In combination with thenardite, aromatic amino acids were observed to undergo simple cation attachment ([M+Na]+) due to the π-bonded aromatic ring. Subsequent cation substitution of the carboxyl group led to formation of peaks representing double cation attachment ([M-H+Na]Na+). Spectra from naturally occurring thenardite and jarosite (XFe3(OH)6(SO4)2) revealed the presence of high mass cluster ions; analysis of their isotopic distribution suggested the presence of bio/organic compounds. High mass cluster ions, both organic and inorganic, readily

  19. Differential mobility spectrometry/mass spectrometry history, theory, design optimization, simulations, and applications.

    PubMed

    Schneider, Bradley B; Nazarov, Erkinjon G; Londry, Frank; Vouros, Paul; Covey, Thomas R

    2016-10-01

    This review of differential mobility spectrometry focuses primarily on mass spectrometry coupling, starting with the history of the development of this technique in the Soviet Union. Fundamental principles of the separation process are covered, in addition to efforts related to design optimization and advancements in computer simulations. The flexibility of differential mobility spectrometry design features is explored in detail, particularly with regards to separation capability, speed, and ion transmission. 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:687-737, 2016. © 2015 Wiley Periodicals, Inc.

  20. Noncovalent Shiga-like toxin assemblies: characterization by means of mass spectrometry and tandem mass spectrometry.

    PubMed

    Williams, Jonathan P; Green, Brian N; Smith, Daniel C; Jennings, Keith R; Moore, Katherine A H; Slade, Susan E; Roberts, Lynne M; Scrivens, James H

    2005-06-14

    Shiga-like toxin 1 (SLTx), produced by enterohemorrhagic strains of Escherichia coli (EHEC), belongs to a family of structurally and functionally related AB(5) protein toxins that are associated with human disease. EHEC infection often gives rise to hemolytic colitis, while toxin-induced kidney damage is one of the major causes of hemolytic uremic syndrome (HUS) and acute renal failure in children. As such, an understanding and analysis of the noncovalent interactions that maintain the quaternary structure of this toxin are fundamentally important since such interactions have significant biochemical and medical implications. This paper reports on the analysis of the noncovalent homopentameric complex of Shiga-like toxin B chain (SLTx-B(5)) using electrospray ionization (ESI) triple-quadrupole (QqQ) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) and the analysis of the noncovalent hexameric holotoxin (SLTx-AB(5)) using ESI time-of-flight (TOF) MS. The triple-quadrupole analysis revealed highly charged monomer ions dissociate from the multiprotein complex to form dimer, trimer, and tetramer product ions, which were also seen to further dissociate. The ESI-TOFMS analysis of SLTx-AB(5) revealed the complex remained intact and was observed in the gas phase over a range of pHs. Theses findings demonstrate that the gas-phase structure observed for both the holotoxin and the isoloated B chains correlates well with the structures reported to exist in the solution phase for these proteins. Such analysis provides a rapid screening technique for assessing the noncovalent structure of this family of proteins and other structurally related toxins.

  1. DETERMINATION OF ELEMENTAL COMPOSITIONS BY HIGH RESOLUTION MASS SPECTROMETRY WITHOUT MASS CALIBRANTS

    EPA Science Inventory

    Widely applicable mass calibrants, including perfluorokerosene, are available for gas-phase introduction of analytes ionized by electron impact (EI) prior to analysis using high resolution mass spectrometry. Unfortunately, no all-purpose calibrants are available for recently dev...

  2. DETERMINATION OF ELEMENTAL COMPOSITIONS BY HIGH RESOLUTION MASS SPECTROMETRY WITHOUT MASS CALIBRANTS

    EPA Science Inventory

    Widely applicable mass calibrants, including perfluorokerosene, are available for gas-phase introduction of analytes ionized by electron impact (EI) prior to analysis using high resolution mass spectrometry. Unfortunately, no all-purpose calibrants are available for recently dev...

  3. Incorporating Biological Mass Spectrometry into Undergraduate Teaching Labs, Part 2: Peptide Identification via Molecular Mass Determination

    ERIC Educational Resources Information Center

    Arnquist, Isaac J.; Beussman, Douglas J.

    2009-01-01

    Mass spectrometry has become a routine analytical tool in the undergraduate curriculum in the form of GC-MS. While relatively few undergraduate programs have incorporated biological mass spectrometry into their programs, the importance of these techniques, as demonstrated by their recognition with the 2002 Nobel Prize, will hopefully lead to…

  4. Incorporating Biological Mass Spectrometry into Undergraduate Teaching Labs, Part 2: Peptide Identification via Molecular Mass Determination

    ERIC Educational Resources Information Center

    Arnquist, Isaac J.; Beussman, Douglas J.

    2009-01-01

    Mass spectrometry has become a routine analytical tool in the undergraduate curriculum in the form of GC-MS. While relatively few undergraduate programs have incorporated biological mass spectrometry into their programs, the importance of these techniques, as demonstrated by their recognition with the 2002 Nobel Prize, will hopefully lead to…

  5. mzML—a Community Standard for Mass Spectrometry Data*

    PubMed Central

    Martens, Lennart; Chambers, Matthew; Sturm, Marc; Kessner, Darren; Levander, Fredrik; Shofstahl, Jim; Tang, Wilfred H.; Römpp, Andreas; Neumann, Steffen; Pizarro, Angel D.; Montecchi-Palazzi, Luisa; Tasman, Natalie; Coleman, Mike; Reisinger, Florian; Souda, Puneet; Hermjakob, Henning; Binz, Pierre-Alain; Deutsch, Eric W.

    2011-01-01

    Mass spectrometry is a fundamental tool for discovery and analysis in the life sciences. With the rapid advances in mass spectrometry technology and methods, it has become imperative to provide a standard output format for mass spectrometry data that will facilitate data sharing and analysis. Initially, the efforts to develop a standard format for mass spectrometry data resulted in multiple formats, each designed with a different underlying philosophy. To resolve the issues associated with having multiple formats, vendors, researchers, and software developers convened under the banner of the HUPO PSI to develop a single standard. The new data format incorporated many of the desirable technical attributes from the previous data formats, while adding a number of improvements, including features such as a controlled vocabulary with validation tools to ensure consistent usage of the format, improved support for selected reaction monitoring data, and immediately available implementations to facilitate rapid adoption by the community. The resulting standard data format, mzML, is a well tested open-source format for mass spectrometer output files that can be readily utilized by the community and easily adapted for incremental advances in mass spectrometry technology. PMID:20716697

  6. Characterization of mutant xylanases using fourier transform ion cyclotron resonance mass spectrometry: stabilizing contributions of disulfide bridges and N-terminal extensions.

    PubMed

    Jänis, Janne; Turunen, Ossi; Leisola, Matti; Derrick, Peter J; Rouvinen, Juha; Vainiotalo, Pirjo

    2004-07-27

    Structural properties and thermal stability of Trichoderma reesei endo-1,4-beta-xylanase II (TRX II) and its three recombinant mutants were characterized using electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR) mass spectrometry and hydrogen/deuterium (H/D) exchange reactions. TRX II has been previously stabilized by a disulfide bridge C110-C154 and other site-directed mutations (TRX II mutants DS2 and DS5). Very recently, a highly thermostable mutant was introduced by combining mutations of DS5 with an N-terminal disulfide bridge C2-C28 (mutant DB1). Accurate mass measurements of TRX II, DS2, DS5, and DB1 verified the expected DNA-encoded protein sequences (average mass error 1.3 ppm) and allowed unequivocal assignment of the disulfides without chemical reduction and subsequent alkylation of the expected cross-links. Moreover, H/D exchange reactions provided means for the detection of a major heat-induced conformational change comprising two interconverting conformers of very different H/D exchange rates as well as allowed the apparent melting temperatures (T(m)) to be determined (62.6, 65.1, 68.0, and 82.2 degrees C for TRX II, DS2, DS5, and DB1, respectively). Residual activity measurements verified that the enzymes inactivated at significantly lower temperatures than expected on the basis of the apparent T(m) values, strongly suggesting that the inactivation takes place through minor conformational change other than observed by H/D exchange. ESI FT-ICR analyses also revealed molecular heterogeneity in DS5 and DB1 due to the propeptide incorporation. Resulting unintentional N-terminal extensions were observed to further improve the stability of the DB1 mutant. The extension of six amino acid residues upstream from the protein N-terminus increased stability by approximately 5 degrees C.

  7. A Developmental History of Polymer Mass Spectrometry

    ERIC Educational Resources Information Center

    Vergne, Matthew J.; Hercules, David M.; Lattimer, Robert P.

    2007-01-01

    The history of the development of mass spectroscopic methods used to characterize polymers is discussed. The continued improvements in methods and instrumentation will offer new and better ways for the mass spectral characterization of polymers and mass spectroscopy (MS) should be recognized as a complementary polymer characterization method along…

  8. A Developmental History of Polymer Mass Spectrometry

    ERIC Educational Resources Information Center

    Vergne, Matthew J.; Hercules, David M.; Lattimer, Robert P.

    2007-01-01

    The history of the development of mass spectroscopic methods used to characterize polymers is discussed. The continued improvements in methods and instrumentation will offer new and better ways for the mass spectral characterization of polymers and mass spectroscopy (MS) should be recognized as a complementary polymer characterization method along…

  9. Decoding protein modifications using top-down mass spectrometry

    PubMed Central

    Siuti, Nertila; Kelleher, Neil L

    2008-01-01

    Top-down mass spectrometry is an emerging technology which strives to preserve the post-translationally modified forms of proteins present in vivo by measuring them intact, rather than measuring peptides produced from them by proteolysis. The top-down technology is beginning to capture the interest of biologists and mass spectrometrists alike, with a main goal of deciphering interaction networks operative in cellular pathways. Here we outline recent approaches and applications of top-down mass spectrometry as well as an outlook for its future. PMID:17901871

  10. Top-Down Mass Spectrometry: Proteomics to Proteoforms.

    PubMed

    Patrie, Steven M

    2016-01-01

    This chapter highlights many of the fundamental concepts and technologies in the field of top-down mass spectrometry (TDMS), and provides numerous examples of contributions that TD is making in biology, biophysics, and clinical investigations. TD workflows include variegated steps that may include non-specific or targeted preparative strategies, orthogonal liquid chromatography techniques, analyte ionization, mass analysis, tandem mass spectrometry (MS/MS) and informatics procedures. This diversity of experimental designs has evolved to manage the large dynamic range of protein expression and diverse physiochemical properties of proteins in proteome investigations, tackle proteoform microheterogeneity, as well as determine structure and composition of gas-phase proteins and protein assemblies.

  11. Phylogenetic classification and identification of bacteria by mass spectrometry.

    PubMed

    Freiwald, Anja; Sauer, Sascha

    2009-01-01

    Bacteria are a convenient source of intrinsic marker proteins, which can be detected efficiently by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The patterns of protein masses observed can be used for accurate classification and identification of bacteria. Key to the reliability of the method is a robust and standardized procedure for sample preparations, including bacterial culturing, chemical treatment for bacterial cell wall disruption and for protein extraction, and mass spectrometry analysis. The protocol is an excellent alternative to classical microbiological classification and identification procedures, requiring minimal sample preparation efforts and costs. Without cell culturing, the protocol takes in general <1 h.

  12. Desorption electrospray ionization mass spectrometry of intact bacteria

    USDA-ARS?s Scientific Manuscript database

    Desorption electrospray ionization (DESI) mass spectrometry (MS) was used to differentiate 7 bacterial species based on their measured DESI-mass spectral profile. Both Gram positive and Gram negative bacteria were tested and included Escherichia coli, Staphyloccocus aureus, Enterococcus sp., Bordete...

  13. NEGATIVE-ION MASS SPECTROMETRY OF SULFONYLUREA HERBICIDES

    EPA Science Inventory

    Sulfonylurea herbicides have been studied using neg-ion desorption chem.-ionization (DCI) mass spectrometry (MS) and DCI-MS/MS techniques. Both {M-H]- and M.- ions were obsd. in the DCI mass spectra. The collisonally activated dissocn. (CAD) spectra were characteristic of the str...

  14. NEGATIVE-ION MASS SPECTROMETRY OF SULFONYLUREA HERBICIDES

    EPA Science Inventory

    Sulfonylurea herbicides have been studied using neg-ion desorption chem.-ionization (DCI) mass spectrometry (MS) and DCI-MS/MS techniques. Both {M-H]- and M.- ions were obsd. in the DCI mass spectra. The collisonally activated dissocn. (CAD) spectra were characteristic of the str...

  15. Mass Spectrometry-Based Tissue Imaging of Small Molecules

    PubMed Central

    Ferguson, Carly N.; Fowler, Joseph W.M.; Waxer, Jonathan F.; Gatti, Richard A.; Loo, Joseph A.

    2014-01-01

    Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques, and provides accurate, histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from mass spectrometry imaging laboratories around the globe. PMID:24952187

  16. Applications of Mass Spectrometry to Structural Analysis of Marine Oligosaccharides

    PubMed Central

    Lang, Yinzhi; Zhao, Xia; Liu, Lili; Yu, Guangli

    2014-01-01

    Marine oligosaccharides have attracted increasing attention recently in developing potential drugs and biomaterials for their particular physical and chemical properties. However, the composition and sequence analysis of marine oligosaccharides are very challenging for their structural complexity and heterogeneity. Mass spectrometry (MS) has become an important technique for carbohydrate analysis by providing more detailed structural information, including molecular mass, sugar constituent, sequence, inter-residue linkage position and substitution pattern. This paper provides an overview of the structural analysis based on MS approaches in marine oligosaccharides, which are derived from some biologically important marine polysaccharides, including agaran, carrageenan, alginate, sulfated fucan, chitosan, glycosaminoglycan (GAG) and GAG-like polysaccharides. Applications of electrospray ionization mass spectrometry (ESI-MS) are mainly presented and the general applications of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) are also outlined. Some technical challenges in the structural analysis of marine oligosaccharides by MS have also been pointed out. PMID:24983643

  17. Use of mass spectrometry for imaging metabolites in plants

    SciTech Connect

    Lee, Young-Jin; Perdian, David; Song, Zhihong; Yeung, Edward; Nikolau, Basil

    2012-03-27

    We discuss and illustrate recent advances that have been made to image the distribution of metabolites among cells and tissues of plants using different mass spectrometry technologies. These technologies include matrix-assisted laser desorption ionization, desorption electrospray ionization, and secondary ion mass spectrometry. These are relatively new technological applications of mass spectrometry and they are providing highly spatially resolved data concerning the cellular distribution of metabolites. We discuss the advantages and limitations of each of these mass spectrometric methods, and provide a description of the technical barriers that are currently limiting the technology to the level of single-cell resolution. However, we anticipate that advances in the next few years will increase the resolving power of the technology to provide unprecedented data on the distribution of metabolites at the subcellular level, which will increase our ability to decipher new knowledge concerning the spatial organization of metabolic processes in plants.

  18. Use of Mass spectrometry for imaging metabolites in plants

    SciTech Connect

    Lee, Young Jin; Perdian, David C.; Song, Zhihong; Yeung, Edward S.; Nikolau, Basil

    2012-03-27

    We discuss and illustrate recent advances that have been made to image the distribution of metabolites among cells and tissues of plants using different mass spectrometry technologies. These technologies include matrix-assisted laser desorption ionization, desorption electrospray ionization, and secondary ion mass spectrometry. These are relatively new technological applications of mass spectrometry and they are providing highly spatially resolved data concerning the cellular distribution of metabolites. We discuss the advantages and limitations of each of these mass spectrometric methods, and provide a description of the technical barriers that are currently limiting the technology to the level of single-cell resolution. However, we anticipate that advances in the next few years will increase the resolving power of the technology to provide unprecedented data on the distribution of metabolites at the subcellular level, which will increase our ability to decipher new knowledge concerning the spatial organization of metabolic processes in plants.

  19. Applications of mass spectrometry to structural analysis of marine oligosaccharides.

    PubMed

    Lang, Yinzhi; Zhao, Xia; Liu, Lili; Yu, Guangli

    2014-06-30

    Marine oligosaccharides have attracted increasing attention recently in developing potential drugs and biomaterials for their particular physical and chemical properties. However, the composition and sequence analysis of marine oligosaccharides are very challenging for their structural complexity and heterogeneity. Mass spectrometry (MS) has become an important technique for carbohydrate analysis by providing more detailed structural information, including molecular mass, sugar constituent, sequence, inter-residue linkage position and substitution pattern. This paper provides an overview of the structural analysis based on MS approaches in marine oligosaccharides, which are derived from some biologically important marine polysaccharides, including agaran, carrageenan, alginate, sulfated fucan, chitosan, glycosaminoglycan (GAG) and GAG-like polysaccharides. Applications of electrospray ionization mass spectrometry (ESI-MS) are mainly presented and the general applications of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) are also outlined. Some technical challenges in the structural analysis of marine oligosaccharides by MS have also been pointed out.

  20. Molecular and structural characterization of dissolved organic matter from the deep ocean by FTICR-MS, including hydrophilic nitrogenous organic molecules

    USGS Publications Warehouse

    Reemtsma, T.; These, A.; Linscheid, M.; Leenheer, J.; Spitzy, A.

    2008-01-01

    Dissolved organic matter isolated from the deep Atlantic Ocean and fractionated into a so-called hydrophobic (HPO) fraction and a very hydrophilic (HPI) fraction was analyzed for the first time by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to resolve the molecular species, to determine their exact masses, and to calculate their molecular formulas. The elemental composition of about 300 molecules was identified. Those in the HPO fraction (14C age of 5100 year) are very similar to much younger freshwater fulvic acids, but less aromatic and more oxygenated molecules are more frequent. This trend continues toward the HPI fraction and may indicate biotic and abiotic aging processes that this material experienced since its primary production thousands of years ago. In the HPI fraction series of nitrogenous molecules containing one, two, or three nitrogens were identified by FTICR-MS. Product ion spectra of the nitrogenous molecules suggest that the nitrogen atoms in these molecules are included in the (alicyclic) backbone of these molecules, possibly in reduced form. These mass spectrometric data suggest that a large set of stable fulvic acids is ubiquitous in all aquatic compartments. Although sources may differ, their actual composition and structure appears to be quite similar and largely independent from their source, because they are the remainder of intensive oxidative degradation processes. ?? 2008 American Chemical Society.

  1. Exact masses and chemical formulas of individual Suwannee River fulvic acids from ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectra.

    PubMed

    Stenson, Alexandra C; Marshall, Alan G; Cooper, William T

    2003-03-15

    Molecular formulas have been assigned for 4626 individual Suwannee River fulvic acids based on accurate mass measurements from ions generated by electrospray ionization and observed by ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). Formula assignments were possible because of the mass accuracy of FTICR MS at high field (9.4 T) and the regular mass spacing patterns found in fulvic acid mixtures. Sorting the 4626 individually observed ions according to Kendrick mass defect and nominal mass series (z* score) revealed that all could be assigned to 1 of 266 distinct homologous series that differ in oxygen content and double bond equivalence. Tandem mass spectrometry based on infrared multiphoton dissociation identified labile fragments of fulvic acid molecules, whose chemical formulas led to plausible structures consistent with degraded lignin as a source of Suwannee River fulvic acids.

  2. Characterization of Thiolate-Protected Gold Nanoparticles by Mass Spectrometry

    PubMed Central

    Harkness, Kellen M.; Cliffel, David E.; McLean, John A.

    2014-01-01

    Thiolate-protected gold nanoparticles (AuNPs) are a highly versatile nanomaterial, with wide-ranging physical properties dependent upon the protecting thiolate ligands and gold core size. These nanoparticles serve as a scaffold for a diverse and rapidly increasing number of applications, extending from molecular electronics to vaccine development. Key to the development of such applications is the ability to quickly and precisely characterize synthesized AuNPs. While a unique set of challenges have inhibited the potential of mass spectrometry in this area, recent improvements have made mass spectrometry a dominant technique in the characterization of small AuNPs, specifically those with discrete sizes and structures referred to as monolayer-protected gold clusters (MPCs). The unique ability of mass spectrometry to analyze the protecting monolayer of the AuNP may cause it to become a major technique in the characterization of larger AuNPs. The development of mass spectrometry techniques for AuNP characterization has begun to reveal interesting new areas of research. This report is a discussion of the historical challenges in this field, the emerging techniques which aim to meet those challenges, and the future role of mass spectrometry in the growing field of thiolate-protected AuNPs. PMID:20419232

  3. de novo Sequencing and Disulfide Mapping of a Bromotryptophan-Containing Conotoxin by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    PubMed Central

    Nair, Sudarslal Sadasivan; Nilsson, Carol L.; Emmett, Mark R.; Schaub, Tanner M.; Gowd, Konkallu Hanumae; Thakur, Suman S.; Krishnan, K. S.; Balaram, Padmanabhan; Marshall, Alan G.

    2008-01-01

    T-1-family conotoxins belong to the T-superfamily and are composed of 10−17 amino acids. They share a common cysteine framework and disulfide connectivity, and exhibit unusual posttranslational modifications, such as tryptophan bromination, glutamic acid carboxylation and threonine glycosylation. We have isolated and characterized a novel peptide, Mo1274, containing 11 amino acids, that shows the same cysteine pattern, -CC-CC, and disulfide linkage as those of the T-1-family members. The complete sequence, GNWCCSARVCC, in which W denotes bromotryptophan, was derived from MS-based de novo sequencing. The FT-ICR MS/MS techniques of electron capture dissociation (ECD), infrared multiphoton dissociation (IRMPD), and collision-induced dissociation (CID) served to detect and localize the tryptophan bromination. The bromine contributes a distinctive isotopic distribution in all fragments that contain bromotryptophan. ECD fragmentation results in the loss of bromine and return to the normal isotopic distribution. Disulfide connectivity of Mo1274, between cysteine pairs 1−3 and 2−4, was determined by mass spectrometry in combination with chemical derivatization employing tris(2-carboxyethyl) phosphine, followed by differential alkylation with N-ethylmaleimide and iodoacetamide. The ECD spectra of the native and partially modified peptide reveal a loss of bromine in a process that requires the presence of a disulfide bond. PMID:17134143

  4. MEASURING OF PROTEIN SYNTHESIS USING METABOLIC 2H-LABELING, HIGH-RESOLUTION MASS SPECTROMETRY AND AN ALGORITHM

    PubMed Central

    Kasumov, Takhar; Ilchenko, Sergey; Li, Ling; Rachdaoui, Nadia; Sadigov, Rovshan; Willard, Belinda; McCullough, Arthur J.; Previs, Stephen

    2013-01-01

    We recently developed a method for estimating protin dynamics in vivo with 2H2O using MALDI-TOF MS (Rachdaoui N. et al., MCP, 8, 2653-2662, 2009) and we confirmed that 2H-labeling of many hepatic free amino acids rapidly equilibrated with body water. Although this is a reliable method, it required modest sample purification and necessitated the determination of tissue-specific amino acid labeling. Another approach for quantifying protein kinetics is to measure the 2H-enrichments of body water (precursor) and protein-bound amino acid or proteolytic peptide (product) and to estimate how many copies of deuterium are incorporated into a product. In this study we have used nanospray LTQ-FTICR mass spectrometry to simultaneously measure the isotopic enrichment of peptides and protein-bound amino acids. A mathematical algorithm was developed to aid the data processing. The most notable improvement centers on the fact that the precursor:product labeling ratio can be obtained by measuring the labeling of water and a protein(s) (or peptides) of interest, therein minimizing the need to measure the amino acid labeling. As a proof of principle, we demonstrate that this approach can detect the effect of nutritional status on albumin synthesis in rats given 2H2O. PMID:21256107

  5. Specific electrochemical iodination of horse heart myoglobin at tyrosine 103 as determined by Fourier transform ion cyclotron resonance mass spectrometry

    PubMed Central

    Iniesta, Jesus; Cooper, Helen J.; Marshall, Alan G.; Heptinstall, John; Walton, David J.; Peterson, Ian R.

    2008-01-01

    The iodination of proteins remains a useful tool in biochemistry for radiolabelling. However, chemical or enzymatic iodination is difficult to control and can give deleterious polyiodination. Previously, we have shown that electrooxidation with nitrite is a rapid method for the selective nitration of tyrosine residues in proteins. In principle, it should be possible to substitute a number of electrooxidisable anions into the tyrosine phenol ring. Electrochemical iodination is more difficult to control than nitration because the rapid anodic oxidation of I− leads to persistent formation of the iodinating triiodide anion. However, application of pulsed electrooxidation and reduction cycles is shown to be an effective procedure for the selective mono and double-iodination of myoglobin, which may have general application to other proteins in controlling of the level of iodination. Mono- and double-iodination of myoglobin by this method was confirmed by electrospray FT-ICR mass spectrometry. Infrared multiphoton dissociation (IRMPD) enabled localization of the site of mono-iodination to be restricted to either His97 or Tyr103. More extensive sequence coverage was obtained with electron capture dissociation (ECD), allowing unambiguous assignment of the site of iodination to Tyr103. PMID:18348862

  6. An antibiotic linked to peptides and proteins is released by electron capture dissociation fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Fagerquist, Clifton K; Hudgins, Robert R; Emmett, Mark R; Håkansson, Kristina; Marshall, Alan G

    2003-04-01

    Desfuroylceftiofur (DFC) is a bioactive beta-lactam antibiotic metabolite that has a free thiol group. Previous experiments have shown release of DFC from plasma extracts after addition of a disulfide reducing agent, suggesting that DFC may be bound to plasma and tissue proteins through disulfide bonds. We have reacted DFC with [Arg(8)]-vasopressin (which has one disulfide bond) and bovine insulin (which has three disulfide bonds) and analyzed the reaction products by use of electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry (ECD FT-ICR MS), which has previously shown preferential cleavage of disulfide bonds. We observe cleavage of DFC from vasopressin and insulin during ECD, suggesting that DFC is indeed bound to peptides and proteins through disulfide bonds. Specifically, we observed dissociative loss of one, as well as two, DFC species during ECD of [vasopressin + 2(DFC-H) + 2H](2+) from a single electron capture event. Loss of two DFCs could arise from either consecutive or simultaneous loss, but in any case implies a gas phase disulfide exchange step. ECD of [insulin + DFC + 4H](4+) shows preferential dissociative loss of DFC. Combined with HPLC, ECD FT-ICR-MS may be an efficient screening method for detection of drug-biomolecule binding.

  7. Natural organic matter and the event horizon of mass spectrometry.

    PubMed

    Hertkorn, N; Frommberger, M; Witt, M; Koch, B P; Schmitt-Kopplin, Ph; Perdue, E M

    2008-12-01

    Soils, sediments, freshwaters, and marine waters contain natural organic matter (NOM), an exceedingly complex mixture of organic compounds that collectively exhibit a nearly continuous range of properties (size-reactivity continuum). NOM is composed mainly of carbon, hydrogen, and oxygen, with minor contributions from heteroatoms such as nitrogen, sulfur, and phosphorus. Suwannee River fulvic acid (SuwFA) is a fraction of NOM that is relatively depleted in heteroatoms. Ultrahigh resolution Fourier transform ion cyclotron (FTICR) mass spectra of SuwFA reveal several thousand molecular formulas, corresponding in turn to several hundred thousand distinct chemical environments of carbon even without accountancy of isomers. The mass difference deltam among adjoining C,H,O-molecules between and within clusters of nominal mass is inversely related to molecular dissimilarity: any decrease of deltam imposes an ever growing mandatory difference in molecular composition. Molecular formulas that are expected for likely biochemical precursor molecules are notably absent from these spectra, indicating that SuwFA is the product of diagenetic reactions that have altered the major components of biomass beyond the point of recognition. The degree of complexity of SuwFA can be brought into sharp focus through comparison with the theoretical limits of chemical complexity, as constrained and quantized by the fundamentals of chemical binding. The theoretical C,H,O-compositional space denotes the isomer-filtered complement of the entire, very vast space of molecular structures composed solely of carbon, hydrogen, and oxygen. The molecular formulas within SuwFA occupy a sizable proportion of the theoretical C,H,O-compositional space. A 100 percent coverage of the theoretically feasible C,H,O-compositional space by SuwFA molecules is attained throughout a sizable range of mass and H/C and O/C elemental ratios. The substantial differences between (and complementarity of) the SuwFA molecular

  8. Direct analysis of samples by mass spectrometry: From elements to bio-molecules using laser ablation inductively couple plasma mass spectrometry and laser desorption/ionization mass spectrometry

    SciTech Connect

    Perdian, David C.

    2009-01-01

    Mass spectrometric methods that are able to analyze solid samples or biological materials with little or no sample preparation are invaluable to science as well as society. Fundamental research that has discovered experimental and instrumental parameters that inhibit fractionation effects that occur during the quantification of elemental species in solid samples by laser ablation inductively coupled plasma mass spectrometry is described. Research that determines the effectiveness of novel laser desorption/ionization mass spectrometric methods for the molecular analysis of biological tissues at atmospheric pressure and at high spatial resolution is also described. A spatial resolution is achieved that is able to analyze samples at the single cell level.

  9. Characterization of 4-hydroxy-2-nonenal-modified peptides by liquid chromatography-tandem mass spectrometry using data-dependent acquisition: neutral loss-driven MS3 versus neutral loss-driven electron capture dissociation.

    PubMed

    Rauniyar, Navin; Stevens, Stanley M; Prokai-Tatrai, Katalin; Prokai, Laszlo

    2009-01-15

    Reactive oxygen species generated during oxidative stress can lead to unfavorable cellular consequences, predominantly due to formation of 4-hydroxy-2-nonenal (HNE) during lipid peroxidation. Data-dependent and neutral loss (NL)-driven MS(3) acquisition have been reported for the identification of HNE adducts by mass spectrometry-based proteomics. However, the limitation associated with this method is the ambiguity in correct assignment of the HNE modification site when more than one candidate site is present as MS(3) is triggered on the neutral loss ion. We introduce NL-triggered electron capture dissociation tandem mass spectrometry (NL-ECD-MS/MS) for the characterization of HNE-modification sites in peptides. With this method performed using a hybrid linear ion trap-Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, ECD in the FTICR unit of the instrument is initiated on precursor ions of peptides showing the neutral loss of 156 Da corresponding to an HNE molecule in the prescan acquired via collision-induced dissociation tandem mass spectrometry in the linear ion trap. In addition to manifold advantages associated with the ECD method of backbone fragmentation, including extensive sequence fragments, ECD tends to retain the HNE group during MS/MS of the precursor ion, facilitating the correct localization of the modification site. The results also suggest that predisposition of a peptide molecular ion to lose HNE during collision-induced dissociation-based fragmentation is independent of its charge state (2+ or 3+). In addition, we have demonstrated that coupling of solid-phase enrichment of HNE-modified peptides facilitates the detection of this posttranslational modification by NL-driven strategies for low-abundance proteins that are susceptible to substoichiometric carbonylation during oxidative stress.

  10. Identification of unknown surfactants using electrospray mass spectrometry and NMR spectroscopy preceded by liquid ionization mass spectrometry.

    PubMed

    Yokoyama, Yukio; Fukazawa, Yoshiyuki; Ito, Takashi; Sato, Hisakuni

    2002-05-01

    Commercially available but completely unknown surfactants used in the tin-lead plating industry were successfully identified by using electrospray mass spectrometry and NMR spectroscopy techniques, preceded by liquid ionization mass spectrometry used to obtain the preliminary information. The mass spectral data suggested that ethoxylated nonionic surfactants having a homologous distribution of molecular weights like 520, 564, 608, 652, 696, etc. were present. The NMR data suggested the presence of two aromatic rings and a quaternary carbon for the hydrophobe moiety instead of the well-known alkyl chains or alkylphenols. The unknown surfactants were finally concluded to be novel nonionic 4-(alpha,alpha-dimethylbenzyl)-phenol ethoxylates.

  11. Laser electrospray mass spectrometry of adsorbed molecules at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Brady, John J.; Judge, Elizabeth J.; Simon, Kuriakose; Levis, Robert J.

    2010-02-01

    Atmospheric pressure mass analysis of solid phase biomolecules is performed using laser electrospray mass spectrometry (LEMS). A non-resonant femtosecond duration laser pulse vaporizes native samples at atmospheric pressure for subsequent electrospray ionization and transfer into a mass spectrometer. LEMS was used to detect a complex molecule (irinotecan HCl), a complex mixture (cold medicine formulation with active ingredients: acetaminophen, dextromethorphan HBr and doxylamine succinate), and a biological building block (deoxyguanosine) deposited on steel surfaces without a matrix molecule.

  12. CITP ESI-FTICR for the study of X-irradiation damaged tetranucleotides

    SciTech Connect

    Hofstadler, S.A.; Zhao, Zhongxi; Smith, R.D.

    1995-12-31

    A unique advantage of capillary isotachophoresis (CITP) is the ability to pre-concentrate low-level analytes and subsequently perform high resolution separations starting with relatively large (and dilute) sample volumes. The inherent isoelectric focusing and purification common to CITP make it well suited for trace analysis. The coupling of this technique to a high performance mass spectrometric detection scheme provides an unprecedented opportunity to obtain molecular weight and structural information from analytes which are present in a concentration limited regime. The authors have recently combined CITP with electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry in order to analyze and identify low level DNA damage products which result from the X-irradiation of oligomeric DNA in N{sub 2}-saturated aqueous solutions. Damage to DNA is a critical event in mutagenesis, as well as for the initiation and possibly the promotion of carcinogenesis. The necessity of degrading polymeric DNA to the monomer level in order to carry out analyses has invariably complicated the study of DNA damage. Using short oligodeoxynucleotides of specific length and sequence, it is possible to isolate modified oligomers bearing specific lesions and to carry out analysis on the intact modified oligomers.

  13. Pharmaceutical metabolite profiling using quadrupole/ion mobility spectrometry/time-of-flight mass spectrometry.

    PubMed

    Chan, Eric C Y; New, Lee Sun; Yap, Chun Wei; Goh, Lin Tang

    2009-02-01

    The use of hybrid quadrupole ion mobility spectrometry time-of-flight mass spectrometry (Q/IMS/TOFMS) in the metabolite profiling of leflunomide (LEF) and acetaminophen (APAP) is presented. The IMS drift times (T(d)) of the drugs and their metabolites were determined in the IMS/TOFMS experiments and correlated with their exact monoisotopic masses and other in silico generated structural properties, such as connolly molecular area (CMA), connolly solvent-excluded volume (CSEV), principal moments of inertia along the X, Y and Z Cartesian coordinates (MI-X, MI-Y and MI-Z), inverse mobility and collision cross-section (CCS). The correlation of T(d) with these parameters is presented and discussed. IMS/TOF tandem mass spectrometry experiments (MS(2) and MS(3)) were successfully performed on the N-acetyl-p-benzoquinoneimine glutathione (NAPQI-GSH) adduct derived from the in vitro microsomal metabolism of APAP. As comparison, similar experiments were also performed using hybrid triple quadrupole linear ion trap mass spectrometry (QTRAPMS) and quadrupole time-of-flight mass spectrometry (QTOFMS). The abilities to resolve the product ions of the metabolite within the drift tube and fragment the ion mobility resolved product ions in the transfer travelling wave-enabled stacked ring ion guide (TWIG) demonstrated the potential applicability of the Q/IMS/TOFMS technique in pharmaceutical metabolite profiling.

  14. Candidate autoantigens identified by mass spectrometry in early rheumatoid arthritis are chaperones and citrullinated glycolytic enzymes

    PubMed Central

    Goëb, Vincent; Thomas-L'Otellier, Marlène; Daveau, Romain; Charlionet, Roland; Fardellone, Patrice; Le Loët, Xavier; Tron, François; Gilbert, Danièle; Vittecoq, Olivier

    2009-01-01

    Introduction The aim of our study was to identify new early rheumatoid arthritis (RA) autoantibodies. Methods Sera obtained from 110 early untreated RA patients (<6 months) were analyzed by western blot using HL-60 cell extract, separated on one-dimensional and two-dimensional gel electrophoresis (1-DE, 2-DE). Sera from 50 healthy blood donors and 20 patients with non-RA rheumatisms were used as controls for 1-DE and 2-DE, respectively. The immunoreactive proteins were identified by MALDI-TOF mass spectrometric analysis and the presence of potential sites of citrullination in each of these proteins was evaluated. FT-ICR mass spectrometry was used to verify experimentally the effect of citrullination upon the mass profile observed by MALDI-TOF analysis. Results The 110 1-DE patterns allowed detection of 10 recurrent immunoreactive bands of 33, 39, 43, 46, 51, 54, 58, 62, 67 and 70 kDa, which were further characterized by 2-DE and proteomic analysis. Six proteins were already described RA antigens: heterogeneous nuclear ribonucleoprotein A2/B1, aldolase, α-enolase, calreticulin, 60 kDa heat shock protein (HSP60) and BiP. Phosphoglycerate kinase 1 (PGK1), stress-induced phosphoprotein 1 and the far upstream element-binding proteins (FUSE-BP) 1 and 2 were identified as new antigens. Post-translational protein modifications were analyzed and potentially deiminated peptides were found on aldolase, α-enolase, PGK1, calreticulin, HSP60 and the FUSE-BPs. We compared the reactivity of RA sera with citrullinated and noncitrullinated α-enolase and FUSE-BP linear peptides, and showed that antigenicity of the FUSE-BP peptide was highly dependent on citrullination. Interestingly, the anti-cyclic citrullinated peptide antibody (anti-CCP2) status in RA serum at inclusion was not correlated to the reactivity directed against FUSE-BP citrullinated peptide. Conclusions Two categories of antigens, enzymes of the glycolytic family and molecular chaperones are also targeted by the

  15. Aberrant processing forms of lung surfactant proteins SP-B and SP-C revealed by high-resolution mass spectrometry.

    PubMed

    Galetskiy, Dmitry; Woischnik, Markus; Ripper, Jan; Griese, Matthias; Przybylski, Michael

    2008-01-01

    The mutation (g.1286T>C) of the pulmonary surfactant-associated protein C gene (SFTPC) leads to the I73T substitution in the precursor protein (pro-SP-C) and results in interstitial lung disease with the histological pattern of non-specific interstitial pneumonia and pulmonary alveolar proteinosis. Central for the disease is the abnormal processing of the SP-C pro-protein to mature SP-C; however little is known about the nature of intermediates and processing products. We report here the application of high resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry to the characterization of processing intermediates of hydrophobic pulmonary surfactant proteins SP-B and SP-C in intra- alveolar surfactant material of a patient with I73T mutation. SP-C and SP-B processing forms were separated from broncho-alveolar lavage fluid using chloroform/methanol extraction and sodium dodecyl sulfate poly acrylamide gel electrophoreis, detected by Western blot and identified by electrospray- and matrix-assisted laser desorption/ionization-FT-ICR mass spectrometry. The mass spectrometric and immuno-analytical results show the intra-alveolar accumulation of an aberrant C-terminal SP-C processing products in which the mature SP-C protein part is missing and aberrant processing intermediates of SP-B.

  16. Mass-spectrometry-based microbial metabolomics: recent developments and applications.

    PubMed

    Gao, Peng; Xu, Guowang

    2015-01-01

    Metabolomics is an omics technique aiming at qualitatively and quantitatively describing a metabolome by various analytical platforms. It is an indispensable component of modern systems biology. Microbial metabolomics can be roughly classified as metabolic footprint analysis and metabolic fingerprint analysis depending on the analyte origins. Both of them have been beneficial to microbiological research for different reasons. Mass spectrometry and nuclear magnetic resonance spectroscopy techniques are popular analytical strategies prevailing in the metabolomics field. In this review, chromatography-mass-spectrometry-based microbial metabolomic analysis steps are summarized, including sample collection, metabolite extraction, instrument analysis, and data analysis. Moreover, their applications in some representative fields are discussed as examples. The aim of this review is to present briefly recent technical advances in mass-spectrometry-based analysis, and to highlight the value of modern applications of microbial metabolomics.

  17. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated with Azithromycin

    NASA Astrophysics Data System (ADS)

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-06-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors, and natural products) are measured using phenotypic assays. However, advances in mass spectrometry-based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. Although previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reduce pathogenicity, we observed no clear decrease in specialized metabolite production.

  18. Ion mobility–mass spectrometry for structural proteomics

    PubMed Central

    Zhong, Yueyang; Hyung, Suk-Joon; Ruotolo, Brandon T

    2012-01-01

    Ion mobility coupled to mass spectrometry has been an important tool in the fields of chemical physics and analytical chemistry for decades, but its potential for interrogating the structure of proteins and multiprotein complexes has only recently begun to be realized. Today, ion mobility– mass spectrometry is often applied to the structural elucidation of protein assemblies that have failed high-throughput crystallization or NMR spectroscopy screens. Here, we highlight the technology, approaches and data that have led to this dramatic shift in use, including emerging trends such as the integration of ion mobility–mass spectrometry data with more classical (e.g., ‘bottom-up’) proteomics approaches for the rapid structural characterization of protein networks. PMID:22292823

  19. Laser desorption mass spectrometry for biomolecule detection and its applications

    NASA Astrophysics Data System (ADS)

    Winston Chen, C. H.; Sammartano, L. J.; Isola, N. R.; Allman, S. L.

    2001-08-01

    During the past few years, we developed and used laser desorption mass spectrometry for biomolecule detections. Matrix-assisted laser desorption/ionization (MALDI) was successfully used to detect DNA fragments with the size larger than 3000 base pairs. It was also successfully used to sequence DNA with both enzymatic and chemical degradation methods to produce DNA ladders. We also developed MALDI with fragmentation for direct DNA sequencing for short DNA probes. Since laser desorption mass spectrometry for DNA detection has the advantages of fast speed and no need of labeling, it has a great potential for molecular diagnosis for disease and person identification by DNA fingerprinting. We applied laser desorption mass spectrometry to succeed in the diagnosis of cystic fibrosis and several other nerve degenerative diseases such as Huntington's disease. We also succeeded in demonstrating DNA typing for forensic applications.

  20. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated With Azithromycin

    PubMed Central

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-01-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors and natural products) are measured using phenotypic assays. However, advances in mass spectrometry based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. While previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reducing pathogenicity, we observed no clear decrease in specialized metabolite production. PMID:25801585

  1. Determination of oxidative protein modifications using mass spectrometry.

    PubMed

    Raftery, Mark J

    2014-07-01

    Numerous oxidative modifications to proteins and amino acids have been identified with most susceptible, to varying degrees, of some form of oxidative modification. The consequence of oxidation on protein structure and function reveals that some of these modifications are functionally important. The discovery and accurate characterization/description of existing and new modifications requires modern instrumentation, great care, and attention to detail, especially if the modifications are present in low stoichiometric quantities or they only exist transiently. The focus of this brief review is on the use of mass spectrometry, protein chemistry, and proteomics methods and tools to identify oxidatively modified proteins and peptides along with the characterization of specific sites. Many of the specialized mass spectrometry technologies and techniques are becoming more widely available in research laboratories with mass spectrometry or proteomics facilities allowing even non-expert researchers in the field to accurately determine modifications. Illustrative examples of some approaches are provided from the author's work, collaborative research projects, and elsewhere.

  2. Mass spectrometry imaging for in situ kinetic histochemistry

    PubMed Central

    Louie, Katherine B.; Bowen, Benjamin P.; McAlhany, Stephanie; Huang, Yurong; Price, John C.; Mao, Jian-hua; Hellerstein, Marc; Northen, Trent R.

    2013-01-01

    Tissues are composed of diverse cell subpopulations each with distinct metabolic characteristics that influence overall behavior. Unfortunately, traditional histopathology imaging techniques are ‘blind’ to the spatially ordered metabolic dynamics within tissue. While mass spectrometry imaging enables spatial mapping of molecular composition, resulting images are only a static snapshot in time of molecules involved in highly dynamic processes; kinetic information of flux through metabolic pathways is lacking. To address this limitation, we developed kinetic mass spectrometry imaging (kMSI), a novel technique integrating soft desorption/ionization mass spectrometry with clinically accepted in vivo metabolic labeling of tissue with deuterium to generate images of kinetic information of biological processes. Applied to a tumor, kMSI revealed heterogeneous spatial distributions of newly synthesized versus pre-existing lipids, with altered lipid synthesis patterns distinguishing region-specific intratumor subpopulations. Images also enabled identification and correlation of metabolic activity of specific lipids found in tumor regions of varying grade. PMID:23584513

  3. Laser mass spectrometry at high vibrational excitation density

    NASA Astrophysics Data System (ADS)

    Haglund, R. F., Jr.; Baltz-Knorr, M.; Ermer, D. R.; Papantonakis, M. R.; Schriver, K. E.

    2003-06-01

    We describe a novel approach to infrared matrix-assisted laser desorption-ionization mass spectrometry using a tunable, picosecond pulse laser to selectively excite specific modes of a solid, thereby creating a high local density of vibrational quanta. The concept is based on recent results from our experiments employing a free-electron laser to explore 'matrix-less' mass spectrometry in which an infrared chromophore intrinsic to the sample, rather than an exogenous matrix, is excited by the laser. Examples from both environmental mass spectrometry and a proteomics-driven research project are presented, showing how the principle of selective vibrational excitation can be used to make possible novel and useful ion generation protocols. We conclude with an analysis of possible mechanisms for the phenomena of infrared desorption, ablation and ionization using very short laser pulses. Prospects for achieving similar results with more conventional laser sources are discussed.

  4. 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Greatly Expands Mass Spectrometry Toolbox

    NASA Astrophysics Data System (ADS)

    Shaw, Jared B.; Lin, Tzu-Yung; Leach, Franklin E.; Tolmachev, Aleksey V.; Tolić, Nikola; Robinson, Errol W.; Koppenaal, David W.; Paša-Tolić, Ljiljana

    2016-12-01

    We provide the initial performance evaluation of a 21 Tesla Fourier transform ion cyclotron resonance mass spectrometer operating at the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory. The spectrometer constructed for the 21T system employs a commercial dual linear ion trap mass spectrometer coupled to a FTICR spectrometer designed and built in-house. Performance gains from moving to higher magnetic field strength are exemplified by the measurement of peptide isotopic fine structure, complex natural organic matter mixtures, and large proteins. Accurate determination of isotopic fine structure was demonstrated for doubly charged Substance P with minimal spectral averaging, and 8158 molecular formulas assigned to Suwannee River Fulvic Acid standard with root-mean-square (RMS) error of 10 ppb. We also demonstrated superior performance for intact proteins; namely, broadband isotopic resolution of the entire charge state distribution of apo-transferrin (78 kDa) and facile isotopic resolution of monoclonal antibody under a variety of acquisition parameters (e.g., 6 s time-domains with absorption mode processing yielded resolution of approximately 1 M at m/z = 2700).

  5. 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Greatly Expands Mass Spectrometry Toolbox

    SciTech Connect

    Shaw, Jared B.; Lin, Tzu-Yung; Leach, Franklin E.; Tolmachev, Aleksey V.; Tolić, Nikola; Robinson, Errol W.; Koppenaal, David W.; Paša-Tolić, Ljiljana

    2016-10-12

    We provide the initial performance evaluation of a 21 Tesla Fourier transform ion cyclotron resonance mass spectrometer operating at the Environmental Molecular Sciences Laboratory at Pacific Northwest National Laboratory. The spectrometer constructed for the 21T system employs a commercial dual linear ion trap mass spectrometer coupled to a FTICR spectrometer designed and bui