Science.gov

Sample records for mass spectrometry generated

  1. Electrochemical generation of selegiline metabolites coupled to mass spectrometry.

    PubMed

    Mielczarek, Przemyslaw; Smoluch, Marek; Kotlinska, Jolanta H; Labuz, Krzysztof; Gotszalk, Teodor; Babij, Michal; Suder, Piotr; Silberring, Jerzy

    2015-04-10

    The metabolic pathways of selegiline (a drug used for the treatment of early-stage Parkinson's disease) were analyzed by electrochemical oxidation with application of the flow electrochemical cell consisting of three electrodes (ROXY™, Antec, the Netherlands). Two types of working electrodes were applied: glassy carbon (GC) and boron-doped diamond (BDD). The potential applied at working electrode and composition of the solvent were optimized for the best conditions for oxidation and identification processes. All products were directly analyzed on-line by mass spectrometry. For further characterization of electrochemical oxidation products, the novel approach involving reversed phase chromatography linked to mass spectrometry with dielectric barrier discharge ionization (DBDI-MS) was used. In this manuscript, we report a novel technique for simulation of drug metabolism by electrochemical system (EC) connected to liquid chromatography (LC) and dielectric barrier discharge ionization (DBDI) mass spectrometry (MS) for direct on-line detection of electrochemical oxidation products. Here, we linked LC/DBDI-MS system with an electrochemical flow cell in order to study metabolic pathways via identification of drug metabolites generated electrochemically. The DBDI source has never been used before for identification of psychoactive metabolites generated in an electrochemical flow cell. Our knowledge on the biological background of xenobiotics metabolism and its influence on human body is constantly increasing, but still many mechanisms are not explained. Nowadays, metabolism of pharmaceuticals is mainly studied using liver cells prepared from animals or humans. Cytochrome P450, present in microsomes, is primarily responsible for oxidative metabolism of xenobiotics. It was also shown, that breakdown of popular medicines may be successfully simulated by electrochemistry under appropriate conditions. The presented experiments allow for comparison of these two entirely

  2. 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.

  3. 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.

  4. Analysis of electrocautery generated smoke by chromatographic-mass spectrometry.

    PubMed

    Kalil, Jefferson; Pessine, Francisco B T; Fidelis, Carlos H V; Menezes, Fabio H; Palma, Paulo Cesar Rodrigues

    2016-01-01

    to analyze the chemical components of the smoke from electrocautery from coagulating muscle and liver tissues of pigs. we collected smoke produced by electrocautery applied to porcine tissue in previously evacuated bottles, with qualitative and quantitative analysis of the compounds present through the hyphenated technique gas chromatography / mass spectrometry. there was a majority of decanal aldehyde in the fumes from the subcutaneous, muscle and liver tissues. Fumes of subcutaneous and muscular tissues also showed the presence of hexanal and phenol. In the fumes of subcutaneous and liver tissues we also found toluene and limonene and, finally, nonanal smoke was present in the muscle and liver tissues. there is increasing evidence showing that smoke from electrocautery used in subcutaneous, muscle and liver tissue is harmful to human health. Thus, there is need to reduce exposure to it or wear masks with filters capable of retaining these particles. analisar quimicamente os componentes da fumaça do eletrocautério, provenientes da coagulação de tecidos, muscular e hepático de suino. coleta de fumaça produzida por eletrocauterização de tecido porcino em frascos previamente evacuados com análise qualitativa e quantitativa dos compostos presentes, através de técnica hifenada, cromatografia a gás/espectrometria de massas. houve presença majoritária do aldeído decanal nas fumaças provenientes dos tecidos subcutâneo, muscular e hepático. Fumaças dos tecidos subcutâneo e muscular mostraram também a presença de hexanal e fenol. Nas fumaças dos tecidos subcutâneo e hepático foram encontrados ainda tolueno e limoneno e, por fim, nonanal estava presente nas fumaças dos tecidos muscular e hepático. há número crescente de evidências mostrando que fumaça proveniente de eletrocauterização de tecidos subcutâneo, muscular e hepático é nociva à saúde de seres humanos. Portanto, há necessidade de reduzir a exposição a ela ou usar máscara com

  5. INVESTIGATION OF ARSINE-GENERATING REACTIONS USING DEUTERIUM-LABELED REAGENTS AND MASS SPECTROMETRY

    EPA Science Inventory

    Mass spectrometry was used to detect transfer of deuterium from labeled reagents to arsines following hydride-generation reactions. The arsine gases liberated from the reactions of arsenite, arsenate, methylarsonic acid, and dimethylarsinic acid with HC1 and NaBD4 in H2O, or with...

  6. Ion trap mass spectrometry of externally generated ions

    SciTech Connect

    McLuckey, S.A.; Van Berkel, G.J.; Georinger, D.E. ); Glish, G.L.

    1994-07-01

    This discussion provides background for consideration of the merits of ion trap MS in conjunction with an external ion source relative to a scanning beam-type form of mass analysis. Emphasis has been placed primarily on efficiency. However, a variety of other factors can be major considerations, depending upon the application. For example, the ion trap has clear advantages over most other forms of MS in terms of size, weight, and pumping requirements. These advantages make the ion trap attractive for field applications, particularly because the performance characteristics of the ion trap need not be compromised in a compact system. One of the most significant advantages is the high efficiency obtainable with tandem MS experiments by using collisional activation via resonance excitation. Under favorable conditions, the conversion of 100% of the parent ions to product ions can be achieved, although 10-50% conversions are more typical. The analogous conversion in most beam-type tendem MS experiments is typically 1-3 orders of magnitude lower; thus, significant reductions in detection limits by use of the ion trap can be anticipated in analyses requiring two or more stages of MS. 61 refs., 3 figs.

  7. Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation

    NASA Astrophysics Data System (ADS)

    Sheynkman, Gloria M.; Shortreed, Michael R.; Cesnik, Anthony J.; Smith, Lloyd M.

    2016-06-01

    Mass spectrometry-based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications.

  8. Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation.

    PubMed

    Sheynkman, Gloria M; Shortreed, Michael R; Cesnik, Anthony J; Smith, Lloyd M

    2016-06-12

    Mass spectrometry-based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications.

  9. Generation of CsI cluster ions for mass calibration in matrix-assisted laser desorption/ionization mass spectrometry.

    PubMed

    Lou, Xianwen; van Dongen, Joost L J; Meijer, E W

    2010-07-01

    A simple method was developed for the generation of cesium iodide (CsI) cluster ions up to m/z over 20,000 in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Calibration ions in both positive and negative ion modes can readily be generated from a single MALDI spot of CsI(3) with 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene] malononitrile (DCTB) matrix. The major cluster ion series observed in the positive ion mode is [(CsI)(n)Cs](+), and in the negative ion mode is [(CsI)(n)I](-). In both cluster series, ions spread evenly every 259.81 units. The easy method described here for the production of CsI cluster ions should be useful for MALDI MS calibrations. Copyright 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. Nanoelectrospray ion generation for high-throughput mass spectrometry using a micromachined ultrasonic ejector array

    NASA Astrophysics Data System (ADS)

    Aderogba, S.; Meacham, J. M.; Degertekin, F. L.; Fedorov, A. G.; Fernandez, F. M.

    2005-05-01

    Ultrasonic electrospray ionization (ESI) for high-throughput mass spectrometry is demonstrated using a silicon micromachined microarray. The device uses a micromachined ultrasonic atomizer operating in the 900kHz-2.5MHz range for droplet generation and a metal electrode in the fluid cavity for ionization. Since the atomization and ionization processes are separated, the ultrasonic ESI source shows the potential for operation at low voltages with a wide range of solvents in contrast with conventional capillary ESI technology. This is demonstrated using the ultrasonic ESI microarray to obtain the mass spectrum of a 10μM reserpine sample on a time of flight mass spectrometer with 197:1 signal-to-noise ratio at an ionization potential of 200V.

  12. 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)

  13. Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation

    PubMed Central

    Sheynkman, Gloria M.; Shortreed, Michael R.; Cesnik, Anthony J.; Smith, Lloyd M.

    2016-01-01

    Mass spectrometry–based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications. PMID:27049631

  14. Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems

    NASA Astrophysics Data System (ADS)

    Hook, Vivian; Bandeira, Nuno

    2015-12-01

    Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human

  15. Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems.

    PubMed

    Hook, Vivian; Bandeira, Nuno

    2015-12-01

    Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human

  16. New-generation mass spectrometry expands the toolbox of cell and developmental biology.

    PubMed

    Lombard-Banek, Camille; Portero, Erika P; Onjiko, Rosemary M; Nemes, Peter

    2017-01-01

    Systems cell biology understanding of development requires characterization of all the molecules produced in the biological system. Decades of research and new-generation sequencing provided functional information on key genes and transcripts. However, there is less information available on how differential gene expression translates into the domains of functionally important proteins, peptides, and metabolites, and how changes in these molecules impact development. Mass spectrometry (MS) is the current technology of choice for the detection and quantification of large numbers of proteins and metabolites, because it requires no use of antibodies, functional probes, or a priori knowledge of molecules produced in the system. This review focuses on recent technologies that have improved MS sensitivity for proteins and metabolites and enabled new functionalities to assess their temporal and spatial changes during vertebrate embryonic development. This review highlights case studies, in which new-generation MS tools have enabled the study of hundreds-to-thousands of proteins and metabolites in tissues, cell populations, and single cells in model systems of vertebrate development, particularly the frog (Xenopus), zebrafish, and mouse. New-generation MS expands the toolbox of cell and developmental studies, raising exciting potentials to advance basic and translational research in the life sciences. © 2017 Wiley Periodicals, Inc.

  17. Testing for Multivariate Normality in Mass Spectrometry Imaging Data: A Robust Statistical Approach for Clustering Evaluation and the Generation of Synthetic Mass Spectrometry Imaging Data Sets.

    PubMed

    Dexter, Alex; Race, Alan M; Styles, Iain B; Bunch, Josephine

    2016-11-15

    Spatial clustering is a powerful tool in mass spectrometry imaging (MSI) and has been demonstrated to be capable of differentiating tumor types, visualizing intratumor heterogeneity, and segmenting anatomical structures. Several clustering methods have been applied to mass spectrometry imaging data, but a principled comparison and evaluation of different clustering techniques presents a significant challenge. We propose that testing whether the data has a multivariate normal distribution within clusters can be used to evaluate the performance when using algorithms that assume normality in the data, such as k-means clustering. In cases where clustering has been performed using the cosine distance, conversion of the data to polar coordinates prior to normality testing should be performed to ensure normality is tested in the correct coordinate system. In addition to these evaluations of internal consistency, we demonstrate that the multivariate normal distribution can then be used as a basis for statistical modeling of MSI data. This allows the generation of synthetic MSI data sets with known ground truth, providing a means of external clustering evaluation. To demonstrate this, reference data from seven anatomical regions of an MSI image of a coronal section of mouse brain were modeled. From this, a set of synthetic data based on this model was generated. Results of r(2) fitting of the chi-squared quantile-quantile plots on the seven anatomical regions confirmed that the data acquired from each spatial region was found to be closer to normally distributed in polar space than in Euclidean. Finally, principal component analysis was applied to a single data set that included synthetic and real data. No significant differences were found between the two data types, indicating the suitability of these methods for generating realistic synthetic data.

  18. Correction of the data generated by mass spectrometry analyses of biological tissues: application to food authentication.

    PubMed

    Engel, Erwan; Ratel, Jérémy

    2007-06-22

    The objective of the work was to assess the relevance for the authentication of food of a novel chemometric method developed to correct mass spectrometry (MS) data from instrumental drifts, namely, the comprehensive combinatory standard correction (CCSC). Applied to gas chromatography (GC)-MS data, the method consists in analyzing a liquid sample with a mixture of n internal standards and in using the best combination of standards to correct the MS signal provided by each compound. The paper focuses on the authentication of the type of feeding in farm animals based on the composition in volatile constituents of their adipose tissues. The first step of the work enabled on one hand to ensure the feasibility of the conversion of the adipose tissue sample into a liquid phase required for the use of the CCSC method and on the other hand, to determine the key parameters of the extraction of the volatile fraction from this liquid phase by dynamic headspace. The second step showed the relevance of the CCSC pre-processing of the MS fingerprints generated by dynamic headspace-MS analysis of lamb tissues, for the discrimination of animals fed exclusively with pasture (n=8) or concentrate (n=8). When compared with filtering of raw data, internal normalization and correction by a single standard, the CCSC method increased by 17.1-, 3.3- and 1.3-fold, respectively, the number of mass fragments which discriminated the type of feeding. The final step confirmed the advantage of the CCSC pre-processing of dynamic headspace-gas chromatography-MS data for revealing molecular tracers of the type of feeding those number (n=72) was greater when compared to the number of tracers obtained with raw data (n=42), internal normalization (n=63) and correction by a single standard (n=57). The relevance of the information gained by using the CCSC method is discussed.

  19. 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)

  20. High Precision Osmium Isotope Measurements Using New Generation Thermal Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Brandon, A.

    2006-12-01

    The technique for measuring Os isotopes to high precision (e.g. +/-30-50 ppm on the 186/188 ratio, 2 sigma) via negative thermal ionization mass spectrometry (NTIMS) was established a decade ago at the University of Maryland. Recent technical advances have resulted in the production of a new generation of TIMS that allows isotopic measurements with substantial improvement in accuracy and precision. Because of the improved capability, the new generation TIMS holds great potential to examine a variety of problems in geochemistry and cosmochemistry. Over the past 5 years, I have refined the technique for higher precision measurements of Os isotopes using the Triton TIMS from Thermo Electron. The measurements are made in static mode using 7 Faraday collectors. 70 or more nanograms of Os is loaded onto a Pt filament with barium hydroxide, the latter is an electron emitter that promotes efficient production of Os trioxide. Oxygen is bled into the source at constant pressures. Signal intensities of 120-180 mV 186Os trioxide are generated and measured as negative ions. Oxygen corrections to the raw data are made using the oxygen isotopic composition obtained for 2 ng loads of Re tetroxide measured on the Faraday cups. Multiple runs over the course of 3 years for the same lecture bottle used to bleed in oxygen to the source showed no change in the oxygen isotopic composition. Oxygen corrections are followed by instrumental mass fractionation corrections using 189/188, 192/189, or 192/188 using the exponential law. Both the internal and external precision for standard and unknown data are best when using 192/188, by a factor of 1.4 over 189/188, and 1.8 over 192/189. Replicate runs on 100 ng standard loads of a single filament shows no change in corrected values within external precision for all Os isotopic ratios over a wide range of fractionation, confirming adherence to the exponential law during emission. 39 runs for a standard solution gave +/-14 ppm (2 sigma) on the

  1. 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…

  2. 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…

  3. 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.

  4. 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.

  5. Verification of the sputter-generated 32SFn- (n = 1-6) anions by accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Mane, R. G.; Surendran, P.; Kumar, Sanjay; Nair, J. P.; Yadav, M. L.; Hemalatha, M.; Thomas, R. G.; Mahata, K.; Kailas, S.; Gupta, A. K.

    2016-01-01

    Recently, we have performed systematic Secondary Ion Mass Spectrometry (SIMS) measurements at our ion source test set up and have demonstrated that gas phase 32SFn- (n = 1-6) anions for all size 'n' can be readily generated from a variety of surfaces undergoing Cs+ ion sputtering in the presence of high purity SF6 gas by employing the gas spray-cesium sputter technique. In our SIMS measurements, the isotopic yield ratio 34SFn-/32SFn- (n = 1-6) was found to be close to its natural abundance but not for all size 'n'. In order to gain further insight into the constituents of these molecular anions, ultra sensitive Accelerator Mass Spectrometry (AMS) measurements were conducted with the most abundant 32SFn- (n = 1-6) anions, at BARC-TIFR 14 UD Pelletron accelerator. The results from these measurements are discussed in this paper.

  6. 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.

  7. 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

  8. Annotator: Post-processing Software for generating function-based signatures from quantitative mass spectrometry

    PubMed Central

    Sylvester, Juliesta E.; Bray, Tyler S.; Kron, Stephen J.

    2012-01-01

    Mass spectrometry is used to investigate global changes in protein abundance in cell lysates. Increasingly powerful methods of data collection have emerged over the past decade, but this has left researchers with the task of sifting through mountains of data for biologically significant results. Often, the end result is a list of proteins with no obvious quantitative relationships to define the larger context of changes in cell behavior. Researchers are often forced to perform a manual analysis from this list or to fall back on a range of disparate tools, which can hinder the communication of results and their reproducibility. To address these methodological problems we developed Annotator, an application that filters validated mass spectrometry data and applies a battery of standardized heuristic and statistical tests to determine significance. To address systems-level interpretations we incorporated UniProt and Gene Ontology keywords as statistical units of analysis, yielding quantitative information about changes in abundance for an entire functional category. This provides a consistent and quantitative method for formulating conclusions about cellular behavior, independent of network models or standard enrichment analyses. Annotator allows for “bottom-up” annotations that are based on experimental data and not inferred by comparison to external or hypothetical models. Annotator was developed as an independent post-processing platform that runs on all common operating systems, thereby providing a useful tool for establishing the inherently dynamic nature of functional annotations, which depend on results from on-going proteomic experiments. Annotator is available for download at http://people.cs.uchicago.edu/~tyler/annotator/annotator_desktop_0.1.tar.gz. PMID:22224429

  9. 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)

  10. 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)

  11. Identification of methylene diphenyl diisocyanate thermal degradation products in a generation chamber by liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Gagne, Sébastien; Cloutier, Yves

    2016-01-01

    Isocyanate thermal degradation characterization by liquid chromatography coupled with electrospray tandem mass spectrometry has been performed to elucidate the methylene diphenyl diisocyanate (MDI) thermal degradation structure emitted in a generation chamber using a temperature between 50°C and 180°C to produce MDI vapors. [M+H](+) ions containing an isocyanate functional group were studied by tandem mass spectrometry. The [M+H](+) ion analyses based on the combination of full scans and precursor ion scans were useful for identifying all structures. The compounds emitted were identified and validated as a mixture of compounds containing amine and isocyanate functions. Residual MDI, methylene diphenyl amino-isocyanate, and methylene diphenyl diamine were identified. Polymerized forms of these structures were also observed because amine and isocyanate chemical functions react rapidly to polymerize. These results must be used with special care by scientists establishing sensitization diagnostics and developing sampling devices using generation chambers as they must be related to MDI behavior in workplaces. Even if pure MDI is introduced in the generation chamber, several different compounds are generated when the MDI is heated at a high temperature. This can result in some misleading interpretations for non-specific isocyanate sampling device development and sensitization diagnostics as MDI is present in the chamber with other compounds with known adverse effects.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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...

  18. 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.

  19. SILEC: a protocol for generating and using isotopically labeled coenzyme A mass spectrometry standards.

    PubMed

    Basu, Sankha S; Blair, Ian A

    2011-12-08

    Stable isotope labeling by essential nutrients in cell culture (SILEC) was recently developed to generate isotopically labeled coenzyme A (CoA) and short-chain acyl-CoA thioesters. This was accomplished by modifying the widely used technique of stable isotope labeling by amino acids in cell culture to include [(13)C(3)(15)N]-pantothenate (vitamin B(5)), a CoA precursor, instead of the isotopically labeled amino acids. The lack of a de novo pantothenate synthesis pathway allowed for efficient and near-complete labeling of the measured CoA species. This protocol provides a step-by-step approach for generating stable isotope-labeled short-chain acyl-CoA internal standards in mammalian and insect cells as well as instructions on how to use them in stable isotope dilution mass spectrometric-based analyses. Troubleshooting guidelines, as well as a list of unlabeled and labeled CoA species, are also included. This protocol represents a prototype for generating stable isotope internal standards from labeled essential nutrients such as pantothenate. The generation and use of SILEC standards takes approximately 2-3 weeks.

  20. SILEC: a protocol for generating and using isotopically labeled coenzyme A mass spectrometry standards

    PubMed Central

    Basu, Sankha S; Blair, Ian A

    2013-01-01

    Stable isotope labeling by essential nutrients in cell culture (SILEC) was recently developed to generate isotopically labeled coenzyme A (CoA) and short-chain acyl-CoA thioesters. This was accomplished by modifying the widely used technique of stable isotope labeling by amino acids in cell culture to include [13C315N]-pantothenate (vitamin B5), a CoA precursor, instead of the isotopically labeled amino acids. The lack of a de novo pantothenate synthesis pathway allowed for efficient and near-complete labeling of the measured CoA species. This protocol provides a step-by-step approach for generating stable isotope-labeled short-chain acyl-CoA internal standards in mammalian and insect cells as well as instructions on how to use them in stable isotope dilution mass spectrometric-based analyses. Troubleshooting guidelines, as well as a list of unlabeled and labeled CoA species, are also included. This protocol represents a prototype for generating stable isotope internal standards from labeled essential nutrients such as pantothenate. The generation and use of SILEC standards takes approximately 2–3 weeks. PMID:22157971

  1. INFRARED SPECTRUM OF POTASSIUM-CATIONIZED TRIETHYLPHOSPHATE GENERATED USING TANDEM MASS SPECTROMETRY AND INFRARED MULTIPLE PHOTON DISSOCIATION

    SciTech Connect

    Gary S. Groenewold; Christopher M. Leavitt; Ryan P. Dain; Jos Oomens; Jeff Steill; van Stipdonk, Michael J.

    2009-09-01

    Tandem mass spectrometry and wavelength selective infrared photodissociation was used to generate an infrared spectrum of gas-phase triethylphosphate cationized by attachment of K+. Prominent absorptions were observed in the region of 900 to 1300 cm-1 that are characteristic of phosphate P=O and P-O-R stretches. The relative positions and intensities of the IR absorptions were reproduced well by density functional theory (DFT) calculations performed using the B3LYP functional and the 6-31+g(d), 6-311+g(d,p) and 6-311++G(3df,2pd) basis sets. Because of good correspondence between experiment and theory for the cation, DFT was then used to generate a theoretical spectrum for neutral triethylphosphate, which in turn accurately reproduces the IR spectrum of the neat liquid when solvent effects are included in the calculations.

  2. Infrared spectrum of potassium-cationized triethylphosphate generated using tandem mass spectrometry and infrared multiple photon dissociation.

    PubMed

    Groenewold, Gary S; Leavitt, Christopher M; Dain, Ryan P; Oomens, Jos; Steill, Jeffrey D; van Stipdonk, Michael J

    2009-09-01

    Tandem mass spectrometry and wavelength-selective infrared photodissociation were used to generate an infrared spectrum of gas-phase triethylphosphate cationized by attachment of K(+). Prominent absorptions were observed in the region of 900 to 1300 cm(-1) that are characteristic of phosphate P=O and P-O-R stretches. The relative positions and intensities of the IR absorptions were reproduced well by density functional theory (DFT) calculations performed using the B3LYP functional and the 6-31+G(d), 6-311+G(d,p) and 6-311++G(3df,2pd) basis sets. Because of good correspondence between experiment and theory for the cation, DFT was then used to generate a theoretical spectrum for neutral triethylphosphate, which in turn accurately reproduces the IR spectrum of the neat liquid when solvent effects are included in the calculations.

  3. "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.

  4. "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.

  5. Recommendations for the Generation, Quantification, Storage, and Handling of Peptides Used for Mass Spectrometry-Based Assays.

    PubMed

    Hoofnagle, Andrew N; Whiteaker, Jeffrey R; Carr, Steven A; Kuhn, Eric; Liu, Tao; Massoni, Sam A; Thomas, Stefani N; Townsend, R Reid; Zimmerman, Lisa J; Boja, Emily; Chen, Jing; Crimmins, Daniel L; Davies, Sherri R; Gao, Yuqian; Hiltke, Tara R; Ketchum, Karen A; Kinsinger, Christopher R; Mesri, Mehdi; Meyer, Matthew R; Qian, Wei-Jun; Schoenherr, Regine M; Scott, Mitchell G; Shi, Tujin; Whiteley, Gordon R; Wrobel, John A; Wu, Chaochao; Ackermann, Brad L; Aebersold, Ruedi; Barnidge, David R; Bunk, David M; Clarke, Nigel; Fishman, Jordan B; Grant, Russ P; Kusebauch, Ulrike; Kushnir, Mark M; Lowenthal, Mark S; Moritz, Robert L; Neubert, Hendrik; Patterson, Scott D; Rockwood, Alan L; Rogers, John; Singh, Ravinder J; Van Eyk, Jennifer E; Wong, Steven H; Zhang, Shucha; Chan, Daniel W; Chen, Xian; Ellis, Matthew J; Liebler, Daniel C; Rodland, Karin D; Rodriguez, Henry; Smith, Richard D; Zhang, Zhen; Zhang, Hui; Paulovich, Amanda G

    2016-01-01

    For many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope-labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays. The Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials-in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry-is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care. © 2015 American Association for Clinical Chemistry.

  6. Relative Stability of Peptide Sequence Ions Generated by Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bythell, Benjamin J.; Hendrickson, Christopher L.; Marshall, Alan G.

    2012-04-01

    We report the use of unimolecular dissociation by infrared radiation for gaseous multiphoton energy transfer to determine relative activation energy (Ea,laser) for dissociation of peptide sequence ions. The sequence ions of interest are mass-isolated; the entire ion cloud is then irradiated with a continuous wave CO2 laser, and the first order rate constant, kd, is determined for each of a series of laser powers. Provided these conditions are met, a plot of the natural logarithm of kd versus the natural logarithm of laser power yields a straight line, whose slope provides a measure of Ea,laser. This method reproduces the Ea values from blackbody radiative dissociation (BIRD) for the comparatively large, singly and doubly protonated bradykinin ions (nominally y 9 and y 9 2+ ). The comparatively small sequence ion systems produce Ea,laser values that are systematic underestimates of theoretical barriers calculated with density functional theory (DFT). However, the relative Ea,laser values are in qualitative agreement with the mobile proton model and available theory. Additionally, novel protonated cyclic-dipeptide (diketopiperazine) fragmentation reactions are analyzed with DFT. FT-ICR MS provides access to sequence ions generated by electron capture dissociation, infrared multiphoton dissociation, and collisional activation methods (i.e., b n , y m , c n , z m • ions).

  7. Development of a new method for sulfide determination by vapor generator inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Colon, Mireia; Iglesias, Mònica; Hidalgo, Manuela

    2007-05-01

    A new sensitive methodology for the determination of total reduced sulfur species in natural waters and acid volatile sulfides in sediments at low levels (μg L - 1 ) is described. Reduced sulfur species were separated from the water matrix in the form of H 2S after reaction with hydrochloric acid in a commercial vapor generator coupled to an inductively coupled plasma quadrupole mass spectrometer (VG-ICP-QMS) equipped with a reaction cell. The method avoided the effect of polyatomic isobaric interferences at m/z 32 caused by 16O 16O + and 14N 18O + through the elimination of the aqueous matrix, a source of oxygen. By introducing a mixture of helium and hydrogen gases into the octopole reaction cell, a series of ion-molecule reactions were induced to reduce the interfering polyatomic species. Operating conditions of the octopole reaction cell system and the analyzer were optimized to get the best signal to background ratio for 32S; a full factorial 2 3 experimental design was developed in order to evaluate which variables had a significant effect and a simplex methodology was applied to find the optimum conditions for the variables. The new method was evaluated by comparison to the standard potentiometric method. The analytical methodology developed was applied to the analysis of reduced sulfur species in natural waters and acid volatile sulfides in sea sediments.

  8. 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.

  9. 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.

  10. 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

  11. Multivariate optimization of photochemical vapor generation for direct determination of arsenic in seawater by inductively coupled plasma mass spectrometry.

    PubMed

    Gao, Ying; Sturgeon, Ralph E; Mester, Zoltán; Hou, Xiandeng; Yang, Lu

    2015-12-11

    Photochemical vapor generation (PVG) sample introduction coupled to inductively coupled plasma mass spectrometry (ICPMS) is described for the determination of As in seawater. A Plackett-Burman design (PBD) and central composite design (CCD) were employed to evaluate the significance of experimental variables relevant to the optimization of PVG-ICPMS detection. The impact of the saline matrix on the suppression of analyte signal was eliminated by use of a mixture of 20% (v/v) formic and 20% acetic acid (v/v) as the photochemical reductants. Optimized conditions yielded equivalent PVG generation efficiencies for As(III), As(V), monomethylarsonic acids (MMAs) and dimethylarsinic acids (DMAs), permitting direct and rapid determination of total arsenic in seawater without any other sample pre-treatment. Quantitation was accomplished using one point gravimetric standard addition along with a spike of (82)Se internal standard to compensate for signal drift and fluctuation during analysis. The resulting method detection limit of 3 pg g(-1) (3σ) provided a 15-fold improvement over that obtained using direct solution nebulization, and is comparable to that for conventional chemical hydride generation (HG)-ICPMS. Accuracy was demonstrated by analysis of two Certified Reference Materials (NASS-6 and CASS-5 seawater) with satisfying results characterized by precisions of 3.5% and 3.2% RSD for CASS-5 and NASS-6, respectively. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  12. Complex mixtures of antibodies generated from a single production qualitatively and quantitatively evaluated by native Orbitrap mass spectrometry.

    PubMed

    Thompson, Natalie J; Hendriks, Linda J A; de Kruif, John; Throsby, Mark; Heck, Albert J R

    2014-01-01

    Composite antibody mixtures designed to combat diseases present a new, rapidly emerging technology in the field of biopharmaceuticals. The combination of multiple antibodies can lead to increased effector response and limit the effect of escape variants that can propagate the disease. However, parallel development of analytical technologies is required to provide fast, thorough, accurate, and robust characterization of these mixtures. Here, we evaluate the utility of native mass spectrometry on an Orbitrap platform with high mass resolving power to characterize composite mixtures of up to 15 separate antibodies. With this technique, unambiguous identification of each antibody in the mixtures was achieved. Mass measurements of the intact antibodies varied 7 ppm on average, allowing highly reproducible identification and quantitation of each compound in these complex mixtures. We show that with the high mass-resolving power and robustness of this technology, high-resolution native mass spectrometry can be used efficiently even for batch-to batch characterization.

  13. 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.

  14. REAL TIME, ON-LINE CHARACTERIZATION OF DIESEL GENERATOR AIR TOXIC EMISSIONS BY RESONANCE ENHANCED MULTI-PHOTON IONIZATION TIME OF FLIGHT MASS SPECTROMETRY

    EPA Science Inventory

    The laser based resonance, enhanced multi-photon ionization time-of-flight mass spectrometry (REMPI-TOFMS) technique has been applied to the exhaust gas stream of a diesel generator to measure, in real time, concentration levels of aromatic air toxics. Volatile organic compounds ...

  15. REAL TIME, ON-LINE CHARACTERIZATION OF DIESEL GENERATOR AIR TOXIC EMISSIONS BY RESONANCE ENHANCED MULTI-PHOTON IONIZATION TIME OF FLIGHT MASS SPECTROMETRY

    EPA Science Inventory

    The laser based resonance, enhanced multi-photon ionization time-of-flight mass spectrometry (REMPI-TOFMS) technique has been applied to the exhaust gas stream of a diesel generator to measure, in real time, concentration levels of aromatic air toxics. Volatile organic compounds ...

  16. 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

  17. Tunable VUV light generation for resonance ionization mass spectrometry of Krypton

    NASA Astrophysics Data System (ADS)

    Strashnov, I.; Blagburn, D. J.; Thonnard, N.; Gilmour, J. D.

    2009-03-01

    Tunable coherent VUV radiation from 115.8 to 116.9 nm has been produced by non-linear four-wave sum frequency mixing in a xenon-argon mixture. 116.5 nm light generated by this means has been used as the first step in a three color, doubly resonant ionization scheme for Kr. In the process of validating the system the xenon refractive index per atom (STP) at 116.5 nm has been determined to be (n(Xe) - 1)/NXe = -6.8(±0.8) × 10-23 cm3.

  18. A toolbox for validation of mass spectrometry peptides identification and generation of database: IRMa.

    PubMed

    Dupierris, Véronique; Masselon, Christophe; Court, Magali; Kieffer-Jaquinod, Sylvie; Bruley, Christophe

    2009-08-01

    The IRMa toolbox provides an interactive application to assist in the validation of Mascot search results. It allows automatic filtering of Mascot identification results as well as manual confirmation or rejection of individual PSM (a match between a fragmentation mass spectrum and a peptide). Dynamic grouping and coherence of information are maintained by the software in real time. Validated results can be exported under various forms, including an identification database (MSIdb). This allows biologists to compile search results from a whole study in a unique repository in order to provide a summarized view of their project. IRMa also features a fully automated version that can be used in a high-throughput pipeline. Given filter parameters, it can delete hits with no significant PSM, regroup hits identified by the same peptide(s) and export the result to the specified format without user intervention. http://biodev.extra.cea.fr/docs/irma (java 1.5 or higher needed).

  19. 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.

  20. Highly sensitive protein detection by combination of atomic force microscopy fishing with charge generation and mass spectrometry analysis.

    PubMed

    Ivanov, Yuri D; Pleshakova, Tatyana; Malsagova, Krystina; Kozlov, Andrey; Kaysheva, Anna; Kopylov, Arthur; Izotov, Alexander; Andreeva, Elena; Kanashenko, Sergey; Usanov, Sergey; Archakov, Alexander

    2014-10-01

    An approach combining atomic force microscopy (AFM) fishing and mass spectrometry (MS) analysis to detect proteins at ultra-low concentrations is proposed. Fishing out protein molecules onto a highly oriented pyrolytic graphite surface coated with polytetrafluoroethylene film was carried out with and without application of an external electric field. After that they were visualized by AFM and identified by MS. It was found that injection of solution leads to charge generation in the solution, and an electric potential within the measuring cell is induced. It was demonstrated that without an external electric field in the rapid injection input of diluted protein solution the fishing is efficient, as opposed to slow fluid input. The high sensitivity of this method was demonstrated by detection of human serum albumin and human cytochrome b5 in 10(-17) -10(-18) m water solutions. It was shown that an external negative voltage applied to highly oriented pyrolytic graphite hinders the protein fishing. The efficiency of fishing with an external positive voltage was similar to that obtained without applying any voltage. © 2014 FEBS.

  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. 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.

  4. 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

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. Analysis of indandione anticoagulant rodenticides in animal liver by eluent generator reagent free ion chromatography coupled with electrospray mass spectrometry.

    PubMed

    Jin, Mi-cong; Chen, Xiao-hong; Ye, Ming-li; Zhu, Yan

    2008-12-05

    A novel analytical method has been developed for simultaneous determination of four indandione anticoagulant rodenticides (diphacinone, chlorophacinone, pindone and valone) in animal liver tissues by eluent generator reagent free ion chromatography coupled with electrospray ionization mass spectrometry (RFIC-ESI-MS). After the rodenticides were extracted from homogenized animal liver tissues with methanol-acetonitrile (10/90, v/v), the extracts were subjected to a solid-phase extraction (SPE) process using Oasis HLB cartridges. The IC separation was carried out on an IonPac AS11 analytical column (250 mm x 4.0 mm) using 10% methanol in a gradient of KOH solution at a constant flow rate of 1.0 mL/min. The objective compounds were ionized by negative ion pneumatically assisted electrospray and detected in the selected ion monitoring (SIM) mode. Warfarin was applied as an internal standard (IS) for the compensation of the losses in the course of sample processing and the sensitivity drift of the detector, linear calibration functions were calculated for all analytes. The relative average recoveries of the objective compounds spiked in animal liver tissues were between 83.4 and 104.9%. The limits of quantification (LOQs) were 0.2-1.0 ng/g for them. Within-day and day-to-day relative standard deviations (RSDs) were less than 10.4 and 13.3%, respectively. It was confirmed that this method could be used in a toxicological analysis. The coupling of IC to MS provided a new analytical tool to the analysts faced with the requirement of separating and analyzing indandione rodenticides in animal livers.

  10. Integrating Next-Generation Genomic Sequencing and Mass Spectrometry To Estimate Allele-Specific Protein Abundance in Human Brain.

    PubMed

    Wingo, Thomas S; Duong, Duc M; Zhou, Maotian; Dammer, Eric B; Wu, Hao; Cutler, David J; Lah, James J; Levey, Allan I; Seyfried, Nicholas T

    2017-09-01

    Gene expression contributes to phenotypic traits and human disease. To date, comparatively less is known about regulators of protein abundance, which is also under genetic control and likely influences clinical phenotypes. However, identifying and quantifying allele-specific protein abundance by bottom-up proteomics is challenging since single nucleotide variants (SNVs) that alter protein sequence are not considered in standard human protein databases. To address this, we developed the GenPro software and used it to create personalized protein databases (PPDs) to identify single amino acid variants (SAAVs) at the protein level from whole exome sequencing. In silico assessment of PPDs generated by GenPro revealed only a 1% increase in tryptic search space compared to a direct translation of all human transcripts and an equivalent search space compared to the UniProtKB reference database. To identify a large unbiased number of SAAV peptides, we performed high-resolution mass spectrometry-based proteomics for two human post-mortem brain samples and searched the collected MS/MS spectra against their respective PPD. We found an average of ∼117 000 unique peptides mapping to ∼9300 protein groups for each sample, and of these, 977 were unique variant peptides. We found that over 400 reference and SAAV peptide pairs were, on average, equally abundant in human brain by label-free ion intensity measurements and confirmed the absolute levels of three reference and SAAV peptide pairs using heavy labeled peptides standards coupled with parallel reaction monitoring (PRM). Our results highlight the utility of integrating genomic and proteomic sequencing data to identify sample-specific SAAV peptides and support the hypothesis that most alleles are equally expressed in human brain.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Recommendations for the generation, quantification, storage and handling of peptides used for mass spectrometry-based assays

    SciTech Connect

    Hoofnagle, Andrew N.; Whiteaker, Jeffrey R.; Carr, Steven A.; Kuhn, Eric; Liu, Tao; Massoni, Sam A.; Thomas, Stefani N.; Townsend, Reid; Zimmerman, Lisa J.; Boja, Emily; Chen, Jing; Crimmins, Daniel L.; Davies, Sherri; Gao, Yuqian; Hiltke, Tara R.; Ketchum, Karen; Kinsinger, Christopher; Mesri, Mehdi; Meyer, Matthew R.; Qian, Weijun; Schoenherr, Regine M.; Scott, Mitchell; Shi, Tujin; Whiteley, Gordon; Wrobel, John; Wu, Chaochao; Ackermann, Bradley L.; Aebersold, Ruedi; Barnidge, David R.; Bunk, David M.; Clarke, Nigel; Fishman, Jordan B.; Grant, Russ P.; Kusebauch, Ulrike; Kushnir, Mark M.; Lowenthal, Mark S.; Moritz, Robert; Neubert, Hendrik; Patterson, Scott D.; Rockwood, Alan L.; Rogers, John; Singh, Ravinder J.; Van Eyk, Jennifer; Wong, Steven H.; Zhang, Shucha; Chan, Daniel W.; Chen, Xian; Ellis, Matthew J.; Liebler, Daniel; Rodland, Karin D.; Rodriguez, Henry; Smith, Richard D.; Zhang, Zhen; Zhang, Hui; Paulovich, Amanda G.

    2015-12-30

    The Clinical Proteomic Tumor Analysis Consortium (1) (CPTAC) of the National Cancer Institute (NCI) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of robust technologies and workflows for the quantitative measurements of proteins. The Assay Development Working Group of the CPTAC Program aims to foster broad uptake of targeted mass spectrometry-based assays employing isotopically labeled peptides for confident assignment and quantification, including multiple reaction monitoring (MRM; also referred to as Selected Reaction Monitoring), parallel reaction monitoring (PRM), and other targeted methods.

  16. Propagation of structural deviations of poly(amidoamine) fan-shape dendrimers (generations 0-3) characterized by MALDI and electrospray mass spectrometry

    NASA Astrophysics Data System (ADS)

    Giordanengo, Rémi; Mazarin, Michaël; Wu, Jiangyu; Peng, Ling; Charles, Laurence

    2007-10-01

    Fan-shape PAMAM dendrimers, from generations 0 to 3, were analyzed by mass spectrometry, using both MALDI and electrospray ionization techniques, to identify any structural deviations present in each sample. First, it could be concluded that all detected molecules were present in the samples as they were detected in MALDI as well as in electrospray mass spectra. Apart from commonly reported dendrimer defects ("missing arm" and "molecular loop"), new impurities were found to arise from propagation of these defects during the synthesis of upper generations. These assignments were based on both compound molecular weight and, when ions were detected with sufficient abundance, deviations from perfect structure behaviour during MS/MS experiments. Since new impurities could be created, either from perfect or defective molecules, during each new generation dendrimer synthesis, models were built to predict the molecular weight of a compound as a function of its synthesis history and efficiently guide mass spectral interpretation.

  17. Determination of mercury in fish otoliths by cold vapor generation inductively coupled plasma mass spectrometry (CVG-ICP-MS)†

    PubMed Central

    Kenduzler, Erdal; Ates, Mehmet; Arslan, Zikri; McHenry, Melanie; Tchounwou, Paul B.

    2012-01-01

    A method based on cold vapor generation inductively coupled plasma mass spectrometry (CVG-ICP-MS) has been developed for determination of inorganic mercury, Hg(II), and total mercury in fish otoliths. Sodium borohydride (NaBH4) was used as the only reducing agent and its concentration was optimized across an acidity gradient to selectively reduce Hg(II) without affecting methylmercury, CH3Hg(I). Inorganic Hg was quantitatively reduced to elemental mercury (Hg0) with 1×10−4% (m/v) NaBH4. CH3Hg(I) required a minimum of 0.5% (m/v) NaBH4 for complete reduction. Increasing the HCl concentration of solution to 5% (v/v) improved the selectivity toward Hg(II) as it decreased the signals from CH3Hg(I) to baseline levels. Potassium ferricyanide solution was the most effective in eliminating the memory effects of Hg compared with a number of chelating and oxidizing agents, including EDTA, gold chloride, thiourea, cerium ammonium nitrate and 2-mercaptoethylamine chloride. The relative standard deviation (RSD) was less than 5% for 1.0 μg L−1 Hg(II) solution. The detection limits were 4.2 and 6.4 ng L−1 (ppt) for Hg(II) and total Hg, respectively. Sample dissolution conditions and recoveries were examined with ultra-pure CaCO3 (99.99%) spiked with Hg(II) and CH3HgCl. Methylmercury was stable when dissolution was performed with up to 20% (v/v) HCl at 100 oC. Recoveries from spiked solutions were higher than 95% for both Hg(II) and CH3Hg(I). The method was applied to the determination of Hg(II) and total Hg concentrations in the otoliths of red emperor (CRM 22) and Pacific halibut. Total Hg concentration in the otoliths was 0.038 ± 0.004 μg g−1 for the red emperor and 0.021 ± 0.003 μg g−1 for the Pacific halibut. Inorganic Hg accounted for about 25% of total Hg indicating that Hg in the otoliths was predominantly organic mercury (e.g., methylmercury). However, as opposed to the bioaccumulation in tissues, methylmercury levels in otoliths was very low suggesting a

  18. Determination of mercury in fish otoliths by cold vapor generation inductively coupled plasma mass spectrometry (CVG-ICP-MS).

    PubMed

    Kenduzler, Erdal; Ates, Mehmet; Arslan, Zikri; McHenry, Melanie; Tchounwou, Paul B

    2012-05-15

    A method based on cold vapor generation inductively coupled plasma mass spectrometry (CVG-ICP-MS) has been developed for determination of inorganic mercury, Hg(II), and total mercury in fish otoliths. Sodium borohydride (NaBH(4)) was used as the only reducing agent and its concentration was optimized across an acidity gradient to selectively reduce Hg(II) without affecting methylmercury, CH(3)Hg(I). Inorganic Hg was quantitatively reduced to elemental mercury (Hg(0)) with 1 × 10(-4)% (m/v) NaBH(4). CH(3)Hg(I) required a minimum of 0.5% (m/v) NaBH(4) for complete reduction. Increasing the HCl concentration of solution to 5% (v/v) improved the selectivity toward Hg(II) as it decreased the signals from CH(3)Hg(I) to baseline levels. Potassium ferricyanide solution was the most effective in eliminating the memory effects of Hg compared with a number of chelating and oxidizing agents, including EDTA, gold chloride, thiourea, cerium ammonium nitrate and 2-mercaptoethylamine chloride. The relative standard deviation (RSD) was less than 5% for 1.0 μg L(-1) Hg(II) solution. The detection limits were 4.2 and 6.4 ng L(-1) (ppt) for Hg(II) and total Hg, respectively. Sample dissolution conditions and recoveries were examined with ultra-pure CaCO(3) (99.99%) spiked with Hg(II) and CH(3)HgCl. Methylmercury was stable when dissolution was performed with up to 20% (v/v) HCl at 100°C. Recoveries from spiked solutions were higher than 95% for both Hg(II) and CH(3)Hg(I). The method was applied to the determination of Hg(II) and total Hg concentrations in the otoliths of red emperor (CRM 22) and Pacific halibut. Total Hg concentration in the otoliths was 0.038 ± 0.004 μg g(-1) for the red emperor and 0.021 ± 0.003 μg g(-1) for the Pacific halibut. Inorganic Hg accounted for about 25% of total Hg indicating that Hg in the otoliths was predominantly organic mercury (e.g., methylmercury). However, as opposed to the bioaccumulation in tissues, methylmercury levels in otoliths was

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. "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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Evaluation of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Second-Generation Lignin Analysis

    PubMed Central

    Richel, Aurore; Vanderghem, Caroline; Simon, Mathilde; Wathelet, Bernard; Paquot, Michel

    2012-01-01

    Matrix-Assisted Laser Desorption/Ionization time-of-flight (MALDI-TOF) mass spectrometry is evaluated as an elucidation tool for structural features and molecular weights estimation of some extracted herbaceous lignins. Optimization of analysis conditions, using a typical organic matrix, namely α-cyano-4-hydroxycinnamic acid (CHCA), in combination with α-cyclodextrin, allows efficient ionization of poorly soluble lignin materials and suppression of matrix-related ions background. Analysis of low-mass fragments ions (m/z 100–600) in the positive ion mode offers a “fingerprint” of starting lignins that could be a fine strategy to qualitatively identify principal inter-unit linkages between phenylpropanoid units. The molecular weights of lignins are estimated using size exclusion chromatography and compared to MALDI-TOF-MS profiles. Miscanthus (Miscanthus x giganteus) and Switchgrass (Panicum Virgatum L.) lignins, recovered after a formic acid/acetic acid/water process or aqueous ammonia soaking, are selected as benchmarks for this study. PMID:23300342

  12. High-Speed MALDI-TOF Imaging Mass Spectrometry: Rapid Ion Image Acquisition and Considerations for Next Generation Instrumentation

    PubMed Central

    Spraggins, Jeffrey M.; Caprioli, Richard M.

    2012-01-01

    A prototype matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer has been used for high-speed ion image acquisition. The instrument incorporates a Nd:YLF solid state laser capable of pulse repetition rates up to 5 kHz and continuous laser raster sampling for high-throughput data collection. Lipid ion images of a sagittal rat brain tissue section were collected in 10 min with an effective acquisition rate of roughly 30 pixels/s. These results represent more than a 10-fold increase in throughput compared with current commercially available instrumentation. Experiments aimed at improving conditions for continuous laser raster sampling for imaging are reported, highlighting proper laser repetition rates and stage velocities to avoid signal degradation from significant oversampling. As new high spatial resolution and large sample area applications present themselves, the development of high-speed microprobe MALDI imaging mass spectrometry is essential to meet the needs of those seeking new technologies for rapid molecular imaging. PMID:21953043

  13. 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

  14. 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

  15. 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

  16. Photodegradation of secondary organic aerosol generated from limonene oxidation by ozone studied with chemical ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pan, X.; Underwood, J. S.; Xing, J.-H.; Mang, S. A.; Nizkorodov, S. A.

    2009-06-01

    Photodegradation of secondary organic aerosol (SOA) prepared by ozone-initiated oxidation of D-limonene is studied with an action spectroscopy approach, which relies on detection of volatile photoproducts with chemical ionization mass-spectrometry as a function of the UV irradiation wavelength. Efficient photodegradation is observed for a broad range of ozone (0.1-300 ppm) and D-limonene (0.02-3 ppm) concentrations used in the preparation of SOA. The observed photoproducts are dominated by oxygenated C1-C3 compounds such as methanol, formic acid, acetaldehyde, acetic acid, and acetone. The irradiation wavelength dependence of the combined yield of the photoproducts closely tracks the absorption spectrum of the SOA material suggesting that photodegradation is not limited to the UV wavelengths. Kinetic simulations suggest that RO2+HO2/RO2 reactions represent the dominant route to photochemically active carbonyl and peroxide species in the limonene SOA prepared in these experiments. Similar photodegradation processes are likely to occur in realistic SOA produced by OH- or O3-initiated oxidation of biogenic volatile organic compounds in clean air.

  17. Photodegradation of secondary organic aerosol generated from limonene oxidation by ozone studied with chemical ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pan, X.; Underwood, J. S.; Xing, J.-H.; Mang, S. A.; Nizkorodov, S. A.

    2009-02-01

    Photodegradation of secondary organic aerosol (SOA) prepared by ozone-initiated oxidation of D-limonene is studied with an action spectroscopy approach, which relies on detection of volatile photoproducts with chemical ionization mass-spectrometry as a function of the UV irradiation wavelength. Efficient photodegradation is observed for a broad range of ozone and D-limonene concentrations (0.1-300 ppm) used in the preparation of SOA. The observed photoproducts are dominated by oxygenated C1-C3 compounds such as methanol, formic acid, acetaldehyde, acetic acid, and acetone. The irradiation wavelength dependence of the combined yield of the photoproducts closely tracks the absorption spectrum of the SOA material suggesting that photodegradation is not limited to the UV wavelengths. Kinetic simulations suggest that RO2+HO2/RO2 reactions represent the dominant route to photochemically active carbonyl and peroxide species in the limonene SOA material. Similar photodegradation processes are likely to occur in realistic SOA produced by OH- or O3-initiated oxidation of biogenic volatile organic compounds in clean air.

  18. Generation and detection of gaseous W12O41-* and other tungstate anions by laser desorption ionization mass spectrometry.

    PubMed

    Pavlov, Julius; Braida, Washington; Ogundipe, Adebayo; O'Connor, Gregory; Attygalle, Athula B

    2009-10-01

    The presence of a peak centered near m/z 2862, observed for the first time for the caged dodecatungstate radical-anion, [W12O41]-*, enables distinguishing WO2 from WO3 by Laser Desorption Ionization mass spectrometry (LDI-MS). In addition to WO2, laser irradiation of dry deposits made from aqueous ammonium paratungstate, and calcium and lead orthotungstate also produce the [W12O41]-. In contrast, spectra recorded from deposits made from aqueous Na2WO4, sodium metatungstate, and WO3, or non-aqueous calcium and lead orthotungstate, and ammonium paratungstate, failed to show the m/z 2862 peak cluster. These observations support the hypothesis that polycondensation reactions to form [W12O41]-* occur solely in the presence of water. Although dry spots are irradiated for ionization, the solvent used for sample preparation plays an important role on the chemical composition endowed to ions detected. For example, the m/z 2862 peak seen from deposits made from aqueous ammonium paratungstate, and calcium and lead orthotungstate, is absent in the spectra recorded either from pristine deposits or those derived from solutions made with organic solvents such as acetonitrile or ethanol.

  19. Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections

    PubMed Central

    2015-01-01

    Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data. PMID:25360896

  20. Distance geometry protocol to generate conformations of natural products to structurally interpret ion mobility-mass spectrometry collision cross sections.

    PubMed

    Stow, Sarah M; Goodwin, Cody R; Kliman, Michal; Bachmann, Brian O; McLean, John A; Lybrand, Terry P

    2014-12-04

    Ion mobility-mass spectrometry (IM-MS) allows the separation of ionized molecules based on their charge-to-surface area (IM) and mass-to-charge ratio (MS), respectively. The IM drift time data that is obtained is used to calculate the ion-neutral collision cross section (CCS) of the ionized molecule with the neutral drift gas, which is directly related to the ion conformation and hence molecular size and shape. Studying the conformational landscape of these ionized molecules computationally provides interpretation to delineate the potential structures that these CCS values could represent, or conversely, structural motifs not consistent with the IM data. A challenge in the IM-MS community is the ability to rapidly compute conformations to interpret natural product data, a class of molecules exhibiting a broad range of biological activity. The diversity of biological activity is, in part, related to the unique structural characteristics often observed for natural products. Contemporary approaches to structurally interpret IM-MS data for peptides and proteins typically utilize molecular dynamics (MD) simulations to sample conformational space. However, MD calculations are computationally expensive, they require a force field that accurately describes the molecule of interest, and there is no simple metric that indicates when sufficient conformational sampling has been achieved. Distance geometry is a computationally inexpensive approach that creates conformations based on sampling different pairwise distances between the atoms within the molecule and therefore does not require a force field. Progressively larger distance bounds can be used in distance geometry calculations, providing in principle a strategy to assess when all plausible conformations have been sampled. Our results suggest that distance geometry is a computationally efficient and potentially superior strategy for conformational analysis of natural products to interpret gas-phase CCS data.

  1. 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.

  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. 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.

  4. 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

  5. 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

  6. 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

  7. Photoionization-Generated Dibromomethane Cation Chemical Ionization Source for Time-of-Flight Mass Spectrometry and Its Application on Sensitive Detection of Volatile Sulfur Compounds.

    PubMed

    Jiang, Jichun; Wang, Yan; Hou, Keyong; Hua, Lei; Chen, Ping; Liu, Wei; Xie, Yuanyuan; Li, Haiyang

    2016-05-17

    Soft ionization mass spectrometry is one of the key techniques for rapid detection of trace volatile organic compounds. In this work, a novel photoionization-generated dibromomethane cation chemical ionization (PDCI) source has been developed for time-of-flight mass spectrometry (TOFMS). Using a commercial VUV lamp, a stable flux of CH2Br2(+) was generated with 1000 ppmv dibromomethane (CH2Br2) as the reagent gas, and the analytes were further ionized by reaction with CH2Br2(+) cation via charge transfer and ion association. Five typical volatile sulfur compounds (VSCs) were chosen to evaluate the performance of the new ion source. The limits of detection (LOD), 0.01 ppbv for dimethyl sulfide and allyl methyl sulfide, 0.05 ppbv for carbon disulfide and methanthiol, and 0.2 ppbv for hydrogen sulfide were obtained. Compared to direct single photon ionization (SPI), the PDCI has two distinctive advantages: first, the signal intensities were greatly enhanced, for example more than 10-fold for CH3SH and CS2; second, H2S could be measured in PDCI by formation [H2S + CH2Br2](+) adduct ion and easy to recognize. Moreover, the rapid analytical capacity of this ion source was demonstrated by analysis of trace VSCs in breath gases of healthy volunteers and sewer gases.

  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. Determination of mercury in coal by isotope dilution cold-vapor generation inductively coupled plasma mass spectrometry.

    PubMed

    Long, Stephen E; Kelly, W Robert

    2002-04-01

    A method based on isotope dilution cold-vapor inductively coupled plasma mass spectrometry (ID-CV-ICPMS) has been developed for high-accuracy determinations of mercury in bituminous and sub-bituminous coals. A closed-system digestion process employing a Carius tube is used to completely oxidize the coal matrix and chemically equilibrate the mercury in the sample with a 201Hg isotopic spike. The digestates are diluted with high-purity quartz-distilled water, and the mercury is released as a vapor by reduction with tin(II) chloride. Measurements of 201Hg/202Hg isotope ratios are made using a quadrupole ICPMS system in time-resolved analysis mode. The new method has some significant advantages over existing methods. The instrument detection limit is less than 1 pg/mL. The average blank (n = 17) is 30 pg, which is roughly 1 order of magnitude lower than the equivalent microwave digestion procedure. The detection limit in coal is blank limited and is approximately 40 pg/g. Memory effects are very low. The relative reproducibility of the analytical measurements is approximately 0.5% for mercury concentrations in the range 10-150 ng/g. The method has been used to measure mercury concentrations in six coal reference materials, SRM 1632b (77.4 ng/g), SRM 1632c (94.3 ng/g), BCR 40 (433.2 ng/g), BCR 180 (125.0 ng/g), BCR 181 (135.8 ng/g), and SARM 20 (252.6 ng/g), as well as a coal fly ash, SRM 1633b (143.1 ng/g). The method is equally applicable to other types of fossil fuels including both crude and refined oils.

  10. An in-depth evaluation of accuracy and precision in Hg isotopic analysis via pneumatic nebulization and cold vapor generation multi-collector ICP-mass spectrometry.

    PubMed

    Rua-Ibarz, Ana; Bolea-Fernandez, Eduardo; Vanhaecke, Frank

    2016-01-01

    Mercury (Hg) isotopic analysis via multi-collector inductively coupled plasma (ICP)-mass spectrometry (MC-ICP-MS) can provide relevant biogeochemical information by revealing sources, pathways, and sinks of this highly toxic metal. In this work, the capabilities and limitations of two different sample introduction systems, based on pneumatic nebulization (PN) and cold vapor generation (CVG), respectively, were evaluated in the context of Hg isotopic analysis via MC-ICP-MS. The effect of (i) instrument settings and acquisition parameters, (ii) concentration of analyte element (Hg), and internal standard (Tl)-used for mass discrimination correction purposes-and (iii) different mass bias correction approaches on the accuracy and precision of Hg isotope ratio results was evaluated. The extent and stability of mass bias were assessed in a long-term study (18 months, n = 250), demonstrating a precision ≤0.006% relative standard deviation (RSD). CVG-MC-ICP-MS showed an approximately 20-fold enhancement in Hg signal intensity compared with PN-MC-ICP-MS. For CVG-MC-ICP-MS, the mass bias induced by instrumental mass discrimination was accurately corrected for by using either external correction in a sample-standard bracketing approach (SSB) or double correction, consisting of the use of Tl as internal standard in a revised version of the Russell law (Baxter approach), followed by SSB. Concomitant matrix elements did not affect CVG-ICP-MS results. Neither with PN, nor with CVG, any evidence for mass-independent discrimination effects in the instrument was observed within the experimental precision obtained. CVG-MC-ICP-MS was finally used for Hg isotopic analysis of reference materials (RMs) of relevant environmental origin. The isotopic composition of Hg in RMs of marine biological origin testified of mass-independent fractionation that affected the odd-numbered Hg isotopes. While older RMs were used for validation purposes, novel Hg isotopic data are provided for the

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Generation of highly charged peptide and protein ions by atmospheric pressure matrix-assisted infrared laser desorption/ionization ion trap mass spectrometry.

    PubMed

    König, Simone; Kollas, Oliver; Dreisewerd, Klaus

    2007-07-15

    We show that highly charged ions can be generated if a pulsed infrared laser and a glycerol matrix are employed for atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry with a quadrupole ion trap. Already for small peptides like bradykinin, doubly protonated ions form the most abundant analyte signal in the mass spectra. The center of the charge-state distribution increases with the size of the analyte. For example, insulin is detected with a most abundant ion signal corresponding to a charge state of four, whereas for cytochrome c, the 10 times protonated ion species produces the most intense signal. Myoglobin is observed with up to 13 charges. The high m/z ratios allow us to use the Paul trap for the detection of MALDI-generated protein ions that are, owing to their high molecular weight, not amenable in their singly protonated charge state. Formation of multiple charges critically depends on the addition of diluted acid to the analyte-matrix solution. Tandem mass spectra generated by collision-induced dissociation of doubly charged peptides are also presented. The findings allow speculations about the involvement of electrospray ionization processes in these MALDI experiments.

  16. 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

  17. 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.

  18. Using ProtMAX to create high-mass-accuracy precursor alignments from label-free quantitative mass spectrometry data generated in shotgun proteomics experiments.

    PubMed

    Egelhofer, Volker; Hoehenwarter, Wolfgang; Lyon, David; Weckwerth, Wolfram; Wienkoop, Stefanie

    2013-03-01

    Recently, new software tools have been developed for improved protein quantification using mass spectrometry (MS) data. However, there are still limitations especially in high-sample-throughput quantification methods, and most of these relate to extensive computational calculations. The mass accuracy precursor alignment (MAPA) strategy has been shown to be a robust method for relative protein quantification. Its major advantages are high resolution, sensitivity and sample throughput. Its accuracy is data dependent and thus best suited for precursor mass-to-charge precision of ∼1 p.p.m. This protocol describes how to use a software tool (ProtMAX) that allows for the automated alignment of precursors from up to several hundred MS runs within minutes without computational restrictions. It comprises features for 'ion intensity count' and 'target search' of a distinct set of peptides. This procedure also includes the recommended MS settings for complex quantitative MAPA analysis using ProtMAX (http://www.univie.ac.at/mosys/software.html).

  19. Online Monitoring Oxidative Products and Metabolites of Nicotine by Free Radicals Generation with Fenton Reaction in Tandem Mass Spectrometry

    PubMed Central

    Liang, Shih-Shin; Shiue, Yow-Ling; Kuo, Chao-Jen; Liao, Wei-Ting; Tsai, Eing-Mei

    2013-01-01

    In general, over 70% absorbed nicotine is metabolized to cotinine and trans-3′-hydroxycotinine by cytochrome oxidase P450, and nicotine is also a major addictive and the psychoactive component in cigarettes. As a xenobiotic metabolism, hydrophobic compounds are usually converted into more hydrophilic products through enzyme systems such as cytochrome oxidase P450, sulfotransferases, and UDP-glucuronosyltransferases to deliver drug metabolites out of the cell during the drug metabolic process. In this study, an electrodeless electrochemical oxidation (EEO) reaction via Fenton reaction by producing free radical to react with nicotine to immediately monitor the oxidative products and metabolic derivatives of nicotine by tandem mass spectrometer (MS) is done. Fenton reaction generates free radicals via ferrous ion (Fe2+) and hydrogen peroxide (H2O2) to oxidize DNA and to degrade proteins in cells. In the EEO method, the oxidative products of nicotine including cotinine, cotinine-N-oxide, trans-3′-hydroxycotinine, nornicotine, norcotinine, 4-oxo-4-(3-pyridyl)-butanoic acid, 4-hydroxy-4-(3-pyridyl)-butanoic acid, and nicotine-N′-oxide were detected by tandem mass spectrometer to simulate the changes of nicotine and its derivatives in a time-dependent manner. PMID:23983622

  20. Online monitoring oxidative products and metabolites of nicotine by free radicals generation with Fenton reaction in tandem mass spectrometry.

    PubMed

    Liang, Shih-Shin; Shiue, Yow-Ling; Kuo, Chao-Jen; Guo, Su-Er; Liao, Wei-Ting; Tsai, Eing-Mei

    2013-01-01

    In general, over 70% absorbed nicotine is metabolized to cotinine and trans-3'-hydroxycotinine by cytochrome oxidase P450, and nicotine is also a major addictive and the psychoactive component in cigarettes. As a xenobiotic metabolism, hydrophobic compounds are usually converted into more hydrophilic products through enzyme systems such as cytochrome oxidase P450, sulfotransferases, and UDP-glucuronosyltransferases to deliver drug metabolites out of the cell during the drug metabolic process. In this study, an electrodeless electrochemical oxidation (EEO) reaction via Fenton reaction by producing free radical to react with nicotine to immediately monitor the oxidative products and metabolic derivatives of nicotine by tandem mass spectrometer (MS) is done. Fenton reaction generates free radicals via ferrous ion (Fe(2+)) and hydrogen peroxide (H2O2) to oxidize DNA and to degrade proteins in cells. In the EEO method, the oxidative products of nicotine including cotinine, cotinine-N-oxide, trans-3'-hydroxycotinine, nornicotine, norcotinine, 4-oxo-4-(3-pyridyl)-butanoic acid, 4-hydroxy-4-(3-pyridyl)-butanoic acid, and nicotine-N'-oxide were detected by tandem mass spectrometer to simulate the changes of nicotine and its derivatives in a time-dependent manner.

  1. A Novel Phase-Coherent Programmable Clock for High-Precision Arbitrary Waveform Generation Applied to Digital Ion Trap Mass Spectrometry

    SciTech Connect

    Koizumi, Hideya; Jatko, William Bruce; Andrews Jr, William H; Whitten, William B; Reilly, Pete

    2010-01-01

    Digital ion trap (DIT) mass spectrometry requires the ability to precisely and accurately produce waveforms. The quality of the mass spectra produced in terms of resolution and mass accuracy depend on the resolution and precision of the applied waveforms. This publication reveals a novel method for the production of arbitrary waveforms in general and then applies the method to the production of DIT waveforms. Arbitrary waveforms can be created by varying the clock frequency input to a programmable read only memory that is then input to a digital-to-analog converter (DAC). The arbitrary waveform is composed of a defined number of points that are triggered to be written after programmed numbers of clock cycles to define the arbitrary waveform. The novelty introduced here is that the direct digital synthesis (DDS) generated clock frequency can be precisely changed as the arbitrary waveform is written because we have developed a method to rapidly switch the DDS frequency exactly at the end of the output clock cycle allowing exact timing of multiple transitions to produce precise and temporally complex waveforms. Changing the frequency only at the end of the output clock cycle is a phase coherent process that permits precise timing between each point in the arbitrary waveform. The waveform generation technique was demonstrated by creating a prototype that was used to operate a digital ion trap mass spectrometer. The jitter in the phase-coherent DDS TTL output that was used as the frequency variable clock was 20 ps. This jitter represents the realizable limit of precision for waveform generation. The rectangular waveforms used to operate the mass spectrometer were created with counters that increased the jitter to 100 ps. The mass resolution achieved was 5000 at m/z = 414. This resolution corresponds to a jitter of 275 ps assuming DC fluctuations and overshoots in the waveform are insignificant. Resolution should improve with increasing mass because the waveforms have

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Generation of new Agm Ten clusters via laser ablation synthesis using Ag-Te nano-composite as precursor. Quadrupole ion trap time-of-flight mass spectrometry.

    PubMed

    Mawale, Ravi Madhukar; Amato, Filippo; Alberti, Milan; Havel, Josef

    2014-12-30

    Silver tellurides find applications in the development of infrared detection, imaging, magnetics, sensors, memory devices, and optic materials. However, only a limited number of silver tellurides have been described to date. Laser ablation synthesis (LAS) was selected to generate new Ag-Te clusters. Isothermal adsorption was used to study the formation of silver nano-particles-tellurium aggregates. Laser desorption ionization quadrupole ion trap time-of-flight mass spectrometry (LDI-QIT-TOFMS) was used for the generation and analysis of Agm Ten clusters. Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to visualize the structure of materials. The stoichiometry of the generated clusters was determined by computer modeling of isotopic patterns. A simple, one-pot method for the preparation of Ag-Te nano-composite was developed and found suitable for LAS of silver tellurides. The LDI of Ag-Te nano-composite leads to the formation of 11 unary and 52 binary clusters. The stoichiometry of the 34 novel Agm Ten clusters is reported here for the first time. LAS with TOFMS detection was proven to be a powerful technique for the generation of silver telluride clusters. Knowledge of the stoichiometry of the generated clusters might facilitate the further development of novel high-tech silver tellurium nano-materials. Copyright © 2014 John Wiley & Sons, Ltd.

  7. 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

  8. 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

  9. Volatile generation in bell peppers during frozen storage and thawing using selected ion flow tube mass spectrometry (SIFT-MS).

    PubMed

    Wampler, Brendan; Barringer, Sheryl A

    2012-06-01

    To determine volatile formation during storage and thawing, whole, pureed, blanched, and raw green and red bell peppers (Capsicum annuum) were frozen quickly or slowly then stored at -18 °C for up to 7 mo, with and without SnCl(2) addition during thawing. Headspace analysis was performed by a Selected Ion Flow Tube Mass Spectrometer (SIFT-MS). After blanching, (Z)-3-hexenal had a large significant decrease in concentration since it is a heat labile compound while most other volatiles did not change in concentration. The freezing process increased volatile levels in the puree only. Slow freeze peppers had higher levels of some LOX generated volatiles during storage than quick freeze. During frozen storage of blanched samples (E)-2-hexenal, (Z and E)-hexen-1-ol, and (E)-2-pentenal increased likely because of nonenzymatic autoxidation of fatty acids while other volatiles remained constant. In Raw Whole peppers, (Z)-3-hexenal, hexanal, and 2-pentylfuran were generated during storage likely because the LOX enzyme is still active during frozen storage. However, blanched samples had higher concentrations of (E)-2-hexenal, (Z and E)-hexen-1-ol, 1-penten-3-one, and (E)-2-heptenal because of enzymatic destruction of these volatiles in the raw samples. The levels of many of the volatiles in the raw samples, including (Z)-3-hexenal, (E)-2-hexenal, (Z and E)-hexen-1-ol, hexanal, (E)-2-pentenal, and 2-pentylfuran, appeared to peak around 34 d after freezing. Pureed samples had significantly higher levels of volatiles than the whole samples, and volatiles peaked earlier. Green bell pepper volatile levels were always higher than red bell pepper. Significantly higher volatile formation occurred during thawing than it did during frozen storage. Studying and monitoring the headspace volatiles with a SIFT-MS can give information that will help manufacturers better understand how the volatiles in bell peppers change during frozen storage. This will give valuable information to

  10. Anti-Peptide Monoclonal Antibodies Generated for Immuno-Multiple Reaction Monitoring-Mass Spectrometry Assays Have a High Probability of Supporting Western blot and ELISA*

    PubMed Central

    Schoenherr, Regine M.; Saul, Richard G.; Whiteaker, Jeffrey R.; Yan, Ping; Whiteley, Gordon R.; Paulovich, Amanda G.

    2015-01-01

    Immunoaffinity enrichment of peptides coupled to targeted, multiple reaction monitoring-mass spectrometry (immuno-MRM) has recently been developed for quantitative analysis of peptide and protein expression. As part of this technology, antibodies are generated to short, linear, tryptic peptides that are well-suited for detection by mass spectrometry. Despite its favorable analytical performance, a major obstacle to widespread adoption of immuno-MRM is a lack of validated affinity reagents because commercial antibody suppliers are reluctant to commit resources to producing anti-peptide antibodies for immuno-MRM while the market is much larger for conventional technologies, especially Western blotting and ELISA. Part of this reluctance has been the concern that affinity reagents generated to short, linear, tryptic peptide sequences may not perform well in traditional assays that detect full-length proteins. In this study, we test the feasibility and success rates of generating immuno-MRM monoclonal antibodies (mAbs) (targeting tryptic peptide antigens) that are also compatible with conventional, protein-based immuno-affinity technologies. We generated 40 novel, peptide immuno-MRM assays and determined that the cross-over success rates for using immuno-MRM monoclonals for Western blotting is 58% and for ELISA is 43%, which compare favorably to cross-over success rates amongst conventional immunoassay technologies. These success rates could most likely be increased if conventional and immuno-MRM antigen design strategies were combined, and we suggest a workflow for such a comprehensive approach. Additionally, the 40 novel immuno-MRM assays underwent fit-for-purpose analytical validation, and all mAbs and assays have been made available as a resource to the community via the Clinical Proteomic Tumor Analysis Consortium's (CPTAC) Antibody (http://antibodies.cancer.gov) and Assay Portals (http://assays.cancer.gov), respectively. This study also represents the first

  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. Third-generation electrokinetically pumped sheath-flow nanospray interface with improved stability and sensitivity for automated capillary zone electrophoresis-mass spectrometry analysis of complex proteome digests.

    PubMed

    Sun, Liangliang; Zhu, Guijie; Zhang, Zhenbin; Mou, Si; Dovichi, Norman J

    2015-05-01

    We have reported a set of electrokinetically pumped sheath flow nanoelectrospray interfaces to couple capillary zone electrophoresis with mass spectrometry. A separation capillary is threaded through a cross into a glass emitter. A side arm provides fluidic contact with a sheath buffer reservoir that is connected to a power supply. The potential applied to the sheath buffer drives electro-osmosis in the emitter to pump the sheath fluid at nanoliter per minute rates. Our first-generation interface placed a flat-tipped capillary in the emitter. Sensitivity was inversely related to orifice size and to the distance from the capillary tip to the emitter orifice. A second-generation interface used a capillary with an etched tip that allowed the capillary exit to approach within a few hundred micrometers of the emitter orifice, resulting in a significant increase in sensitivity. In both the first- and second-generation interfaces, the emitter diameter was typically 8 μm; these narrow orifices were susceptible to plugging and tended to have limited lifetime. We now report a third-generation interface that employs a larger diameter emitter orifice with very short distance between the capillary tip and the emitter orifice. This modified interface is much more robust and produces much longer lifetime than our previous designs with no loss in sensitivity. We evaluated the third-generation interface for a 5000 min (127 runs, 3.5 days) repetitive analysis of bovine serum albumin digest using an uncoated capillary. We observed a 10% relative standard deviation in peak area, an average of 160,000 theoretical plates, and very low carry-over (much less than 1%). We employed a linear-polyacrylamide (LPA)-coated capillary for single-shot, bottom-up proteomic analysis of 300 ng of Xenopus laevis fertilized egg proteome digest and identified 1249 protein groups and 4038 peptides in a 110 min separation using an LTQ-Orbitrap Velos mass spectrometer; peak capacity was ∼330. The

  13. 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.

  14. Chemistry of α-pinene and naphthalene oxidation products generated in a Potential Aerosol Mass (PAM) chamber as measured by acetate chemical ionization mass spectrometry

    DOE PAGES

    Chhabra, P. S.; Lambe, A. T.; Canagaratna, M. R.; ...

    2014-07-01

    Recent developments in high resolution, time-of-flight chemical ionization mass spectrometry (HR-ToF-CIMS) have made possible the direct detection of atmospheric organic compounds in real-time with high sensitivity and with little or no fragmentation, including low volatility, highly oxygenated organic vapors that are precursors to secondary organic aerosol formation. Here, for the first time, we examine gas-phase O3 and OH oxidation products of α-pinene and naphthalene formed in the PAM flow reactor with an HR-ToF-CIMS using acetate reagent ion chemistry. Integrated OH exposures ranged from 1.2 × 1011 to 9.7 × 1011 molec cm−3 s, corresponding to approximately 1.0 to 7.5 daysmore » of equivalent atmospheric oxidation. Measured gas-phase organic acids are similar to those previously observed in environmental chamber studies. For both precursors, we find that acetate-CIMS spectra capture both functionalization (oxygen addition) and fragmentation (carbon loss) as a function of OH exposure. The level of fragmentation is observed to increase with increased oxidation. We present a method that estimates vapor pressures of organic molecules using the measured O/C ratio, H/C ratio, and carbon number for each compound detected by the CIMS. The predicted condensed-phase SOA average acid yields and O/C and H/C ratios agree within uncertainties with previous AMS measurements and ambient CIMS results. While acetate reagent ion chemistry is used to selectively measure organic acids, in principle this method can be applied to additional reagent ion chemistries depending on the application.« less

  15. Comparative oxidation state specific analysis of arsenic species by high-performance liquid chromatography-inductively coupled-mass spectrometry and hydride generation-cryotrapping-atomic absorption spectrometry

    EPA Science Inventory

    The formation of methylarsonous acid (MAsIII) and dimethylarsinous acid (DMAsIII) in the course of inorganic arsenic (iAs) metabolism plays an important role in the adverse effects of chronic exposure to iAs. High-performance liquid chromatography-inductively coupled plasma-mass ...

  16. Comparative oxidation state specific analysis of arsenic species by high-performance liquid chromatography-inductively coupled-mass spectrometry and hydride generation-cryotrapping-atomic absorption spectrometry

    EPA Science Inventory

    The formation of methylarsonous acid (MAsIII) and dimethylarsinous acid (DMAsIII) in the course of inorganic arsenic (iAs) metabolism plays an important role in the adverse effects of chronic exposure to iAs. High-performance liquid chromatography-inductively coupled plasma-mass ...

  17. Nano-objects emitted during maintenance of common particle generators: direct chemical characterization with aerosol mass spectrometry and implications for risk assessments

    NASA Astrophysics Data System (ADS)

    Nilsson, Patrik T.; Isaxon, Christina; Eriksson, Axel C.; Messing, Maria E.; Ludvigsson, Linus; Rissler, Jenny; Hedmer, Maria; Tinnerberg, Håkan; Gudmundsson, Anders; Deppert, Knut; Bohgard, Mats; Pagels, Joakim H.

    2013-11-01

    Nanotechnology gives us materials with enhanced or completely new properties. At the same time, inhalation of manufactured nano-objects has been related to an array of adverse biological effects. We characterized particle emissions, which occurred during maintenance of common metal nanoparticle generators and contrasted the properties of the emitted particles with those originally produced by the generators. A new approach using online aerosol mass spectrometry (AMS), for time- and size-resolved measurements of the particle chemical composition, was applied in combination with more conventional techniques for particle sampling and analysis, including electron microscopy. Emissions during maintenance work, in terms of mass and surface area concentration in the size range of 0.02-10 μm, were dominated by large agglomerates (1-5 μm). With AMS, we show that the particle composition depends on both generator type and maintenance task being performed and that the instrument can be used for highly time-resolved selective studies of metal nanoparticle emissions. The emitted agglomerates have a relatively high probability to be deposited in the lower respiratory tract, since the mean particle diameter coincided with a peak in the lung deposition curve. Each of these agglomerates consisted of a very high number (103-105/agglomerate) of nanometer-sized primary particles originating from the particle synthesis process. This made them possess large surface areas, one of the key properties in nanotoxicology. Similar agglomerates may be emitted in a wide range of processes when nanoparticles are manufactured or handled. The fate of such agglomerates, once deposited in the respiratory tract, is unknown and should therefore be considered in future particle toxicological studies. Our results highlight the importance of including micrometer-sized particles in exposure and emission assessments.

  18. Implementation of a semi-automated strategy for the annotation of metabolomic fingerprints generated by liquid chromatography-high resolution mass spectrometry from biological samples.

    PubMed

    Courant, Frédérique; Royer, Anne-Lise; Chéreau, Sylvain; Morvan, Marie-Line; Monteau, Fabrice; Antignac, Jean-Philippe; Le Bizec, Bruno

    2012-11-07

    Metabolomics aims at detecting and semi-quantifying small molecular weight metabolites in biological samples in order to characterise the metabolic changes resulting from one or more given factors and/or to develop models based on diagnostic biomarker candidates. Nevertheless, whatever the objective of a metabolomic study, one critical step consists in the structural identification of mass spectrometric features revealed by statistical analysis and this remains a real challenge. Indeed, this requires both an understanding of the studied biological system, the correct use of various analytical information (retention time, molecular weight experimentally measured, isotopic golden rules, MS/MS fragment pattern interpretation…), or querying online databases. In gas chromatography-electro-ionisation (EI)-mass spectrometry, EI leads to a very reproducible fragmentation allowing establishment of universal EI mass spectra databases (for example, the NIST database -National Institute of Standards and Technology) and thus facilitates the identification step. Unfortunately, the situation is different when working with liquid chromatography-mass spectrometry (LC-MS) since atmospheric pressure ionisation exhibits high inter-instrument variability regarding fragmentation. Therefore, the constitution of LC-MS "in-house" spectral databases appears relevant in this context. The present study describes the procedure developed and applied to increment 133 and 130 metabolites in databanks dedicated to analyses performed with LC-HRMS in positive and negative electrospray ionisation, and the use of these databanks for annotating quickly untargeted metabolomics fingerprints. This study also describes the optimization of the parameters controlling the automatic processing in order to obtain a fast and reliable annotation of a maximum of organic compounds. This strategy was applied to bovine kidney samples collected from control animals or animals treated with steroid hormones. Thirty

  19. 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.

  20. Determination of mercury compounds in fish by microwave-assisted extraction and liquid chromatography-vapor generation-inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Chiou, Chwei-Sheng; Jiang, Shiuh-Jen; Kumar Danadurai, K. Suresh

    2001-07-01

    A method employing a vapor generation system and LC combined with inductively coupled plasma mass spectrometry (LC-ICP-MS) is presented for the determination of mercury in biological tissues. An open vessel microwave digestion system was used to extract the mercury compounds from the sample matrix. The efficiency of the mobile phase, a mixture of L-cysteine and 2-mercaptoethanol, was evaluated for LC separation of inorganic mercury [Hg(II)], methylmercury (methyl-Hg) and ethylmercury (ethyl-Hg). The sensitivity, detection limits and repeatability of the liquid chromatography (LC) ICP-MS system with a vapor generator were comparable to, or better than, that of an LC-ICP-MS system with conventional pneumatic nebulization, or other sample introduction techniques. The experimental detection limits for various mercury species were in the range of 0.05-0.09 ng ml -1 Hg, based on peak height. The proposed method was successfully applied to the determination of mercury compounds in a swordfish sample purchased from the local market. The accuracy of the method was evaluated by analyzing a marine biological certified reference material (DORM-2, NRCC).

  1. 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.

  2. 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.

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

    PubMed

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

    2010-11-07

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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Slurry sampling flow injection chemical vapor generation inductively coupled plasma mass spectrometry for the determination of As, Cd, and Hg in cereals.

    PubMed

    Chen, Feng-Yi; Jiang, Shiuh-Jen

    2009-08-12

    A slurry sampling inductively coupled plasma mass spectrometry (ICP-MS) method has been developed for the determination of As, Cd, and Hg in cereals using flow injection chemical vapor generation (VG) as the sample introduction system. A slurry containing 6% m/v flour, 0.7% m/v thiourea, 0.4 microg mL(-1) Co(II), and 2.5% v/v HCl was injected into a VG-ICP-MS system for the determination of As, Cd, and Hg without dissolution and mineralization. Because the sensitivities of the elements studied in the slurry and that of aqueous solution were quite different, a standard addition method and an isotope dilution method were used for the determination of As, Cd, and Hg in selected cereal samples. The influences of vapor generation conditions and slurry preparation on the ion signals were reported. The effectiveness of the vapor generation sample introduction technique in alleviating various spectral interferences in ICP-MS analysis has been demonstrated. This method has been applied for the determination of As, Cd, and Hg in NIST SRM 1567a Wheat Flour reference material, NIST SRM 1568a Rice Flour reference material, and cereal samples obtained from local market. The As, Cd, and Hg analysis results of the reference materials agreed with the certified values. The method detection limits estimated from standard addition curves were about 0.10, 0.16, and 0.07 ng g(-1) for As, Cd, and Hg, respectively, in the original cereal samples.

  10. Liquid chromatography with tandem mass spectrometry method for the determination of nicotine and minor tobacco alkaloids in electronic cigarette refill liquids and second-hand generated aerosol.

    PubMed

    Famele, Marco; Palmisani, Jolanda; Ferranti, Carolina; Abenavoli, Carmelo; Palleschi, Luca; Mancinelli, Rosanna; Fidente, Rosanna Maria; de Gennaro, Gianluigi; Draisci, Rosa

    2017-03-01

    A liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nicotine and seven minor tobacco alkaloids in both refill liquids for electronic cigarettes and their generated aerosol was developed and validated. The limit of detection and limit of quantification values were 0.3-20.0 and 1.0-31.8 ng/mL, respectively. Within-laboratory reproducibility was 8.2-14.2% at limit of quantification values and 4.8-12.7% at other concentration levels. Interday recovery was 75.8-116.4%. The method was applied to evaluate the compliance of commercial liquids (n = 95) with their labels and to assess levels of minor alkaloids. Levels of nicotine and its corresponding compounds were also evaluated in generated aerosol. About 47% of samples showed differences above ±10 % of the stated nicotine concentration. About 78% of the "zero nicotine" liquids showed traces in the range of 1.3 ± 0.1-254.0 ± 14.6 μg/mL. Nicotine-N'-oxides, myosmine, and anatabine were the most common minor alkaloids in liquids containing nicotine. Nicotine and N'-oxides were detected in all air samples when aerosol was generated from liquids containing nicotine. Nicotine average emissions from electronic cigarette (2.7 ± 0.9 μg/m(3) ) were significantly lower (p < 0.01, t-test) with respect to conventional cigarette (30.2 ± 1.5 μg/m(3) ). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Bioactive compounds of fourth generation gamma-irradiated Typhoniumflagelliforme Lodd. mutants based on gas chromatography-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Sianipar, N. F.; Purnamaningsih, R.; Rosaria

    2016-08-01

    Rodent tuber (Typhonium flagelliforme Lodd.) is an Indonesian anticancer medicinal plant. The natural genetic diversity of rodent tuber is low due to vegetative propagation. Plant's genetic diversity has to be increased for obtaining clones which contain a high amount of anticancer compounds. In vitro calli were irradiated with 6 Gy of gamma ray to produce in vitro mutant plantlets. Mutant plantlets were acclimated and propagated in a greenhouse. This research was aimed to identify the chemical compounds in the leaves and tubers ofthe fourth generation of rodent tuber's vegetative mutant clones (MV4) and control plantsby using GC- MS method. Leaves and tubers of MV4 each contained 2 and 5 anticancer compounds which quantities were higher compared to control plants. MV4 leaves contained 5 new anticancer compounds while its tubers contained 3 new anticancer compounds which were not found in control. The new anticancer compounds in leaves were hexadecanoic acid, stigmast-5-en-3-ol, ergost-5-en-3-ol, farnesol isomer a, and oleic acid while the new anticancer compounds in tubers were alpha tocopherol, ergost-5-en-3-ol, and beta-elemene. Rodent tuber mutant clones are very potential to be developed into anticancer drugs.

  12. Ion Beam Generation from an Electrolyte Solution Containing Polyatomic Cations and Anions for Secondary Ion Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Fujiwara, Yukio; Watanabe, Kouji; Saito, Naoaki; Nonaka, Hidehiko; Suzuki, Atsushi; Nakanaga, Taisuke; Fujimoto, Toshiyuki; Kurokawa, Akira; Ichimura, Shingo; Tomita, Mitsuhiro

    2009-12-01

    A solution-type ion beam source was fabricated to utilize polyatomic anions as well as polyatomic cations that are stable in solutions. The ion source consists of an electrospray section at atmospheric pressure and a vacuum section with a differential pumping system. To demonstrate the beam generation of cations or anions, ethanol solution containing a room-temperature molten salt (i.e., an ionic liquid) was tested. The ionic liquid, N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide, consists of a polyatomic cation, [C8H20ON]+, and a polyatomic anion, [C2F6NO4S2]-. Ions produced at atmospheric pressure were passed through an aperture into a vacuum chamber and then transported to a target. The effects of the aperture dimensions were investigated in the range from 50 to 200 µm in diameter and 0.25 to 1 mm in thickness. The ratio of current passing through the aperture into the vacuum chamber to the total electrosprayed current was on the order of 10-3 to 10-5. The ratio increased with increasing aperture diameter. A reduction in the aperture thickness also improved the ratio. Beam current increased with applied voltage in both positive-ion and negative-ion modes. It was demonstrated that stable negative-ion beams as well as positive-ion beams on the order of pA were produced.

  13. Optimization of a single-drop microextraction method for multielemental determination by electrothermal vaporization inductively coupled plasma mass spectrometry following in situ vapor generation

    NASA Astrophysics Data System (ADS)

    Gil, Sandra; de Loos-Vollebregt, Margaretha T. C.; Bendicho, Carlos

    2009-03-01

    A headspace single-drop microextraction (HS-SDME) method has been developed in combination with electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICP-MS) for the simultaneous determination of As, Sb, Bi, Pb, Sn and Hg in aqueous solutions. Vapor generation is carried out in a 40 mL volume closed-vial containing a solution with the target analytes in hydrochloric acid and potassium ferricyanide medium. Hydrides (As, Sb, Bi, Pb, Sn) and Hg vapor are trapped onto an aqueous single drop (3 µL volume) containing Pd(II), followed by the subsequent injection in the ETV. Experimental variables such as medium composition, sodium tetrahydroborate (III) volume and concentration, stirring rate, extraction time, sample volume, ascorbic acid concentration and palladium amount in the drop were fully optimized. The limits of detection (LOD) (3 σ criterion) of the proposed method for As, Sb, Bi, Pb, Sn and Hg were 0.2, 0.04, 0.01, 0.07, 0.09 and 0.8 µg/L, respectively. Enrichment factors of 9, 85, 138, 130, 37 and 72 for As, Sb, Bi, Pb, Sn and Hg, respectively, were achieved in 210 s. The relative standard deviations ( N = 5) ranged from 4 to 8%. The proposed HS-SDME-ETV-ICP-MS method has been applied for the determination of As, Sb, Bi, Pb, Sn and Hg in NWRI TM-28.3 certified reference material.

  14. Monitoring variations of dimethyl sulfide and dimethylsulfoniopropionate in seawater and the atmosphere based on sequential vapor generation and ion molecule reaction mass spectrometry.

    PubMed

    Iyadomi, Satoshi; Ezoe, Kentaro; Ohira, Shin-Ichi; Toda, Kei

    2016-04-01

    To monitor the fluctuations of dimethyl sulfur compounds at the seawater/atmosphere interface, an automated system was developed based on sequential injection analysis coupled with vapor generation-ion molecule reaction mass spectrometry (SIA-VG-IMRMS). Using this analytical system, dissolved dimethyl sulfide (DMS(aq)) and dimethylsulfoniopropionate (DMSP), a precursor to DMS in seawater, were monitored together sequentially with atmospheric dimethyl sulfide (DMS(g)). A shift from the equilibrium point between DMS(aq) and DMS(g) results in the emission of DMS to the atmosphere. Atmospheric DMS emitted from seawater plays an important role as a source of cloud condensation nuclei, which influences the oceanic climate. Water samples were taken periodically and dissolved DMS(aq) was vaporized for analysis by IMRMS. After that, DMSP was hydrolyzed to DMS and acrylic acid, and analyzed in the same manner as DMS(aq). The vaporization behavior and hydrolysis of DMSP to DMS were investigated to optimize these conditions. Frequent (every 30 min) determination of the three components, DMS(aq)/DMSP (nanomolar) and DMS(g) (ppbv), was carried out by SIA-VG-IMRMS. Field analysis of the dimethyl sulfur compounds was undertaken at a coastal station, which succeeded in showing detailed variations of the compounds in a natural setting. Observed concentrations of the dimethyl sulfur compounds both in the atmosphere and seawater largely changed with time and similar variations were repeatedly observed over several days, suggesting diurnal variations in the DMS flux at the seawater/atmosphere interface.

  15. Identification of halogenated photoproducts generated after ultraviolet-irradiation of parabens and benzoates in water containing chlorine by solid-phase microextraction and gas chromatography-mass spectrometry.

    PubMed

    Alvarez-Rivera, Gerardo; Llompart, Maria; Garcia-Jares, Carmen; Lores, Marta

    2014-07-04

    This work presents a new solid-phase microextraction (SPME)-based approach to investigate the formation of halogenated by-products generated by the UV-induced photodegradation of parabens and their congener benzoates in water containing chlorine. Degradation of parent species, and further identification of their transformation by-products were monitored by gas chromatography coupled to mass spectrometry (GC/MS). In order to improve detectability, SPME was applied as a preconcentration step after UV-irradiation of target preservatives. Experiments performed with dechlorinated water, ultrapure water, and tap water showed that under UV-light, the presence of even low levels of free chlorine, increases the photodegradation rate of target preservatives, enhancing the formation of halogenated photoproducts. Monobrominated, dibrominated and bromochlorinated hydroxybenzoates were identified, and the transformation of benzoates into halogenated parabens was also confirmed. Bromination is expected to occur when free chlorine is present, due to the presence of traces of bromide in water samples. Five halogenated phenols (mainly brominated) were detected as breakdown photoproducts from both families of target preservatives. On the basis of the appearance of the aforementioned by-products, a tentative transformation pathway, consistent with the photoformation-photodecay kinetics of the by-products, is proposed herein for the first time.

  16. Probing Molecular Associations of Field-Collected and Laboratory-Generated SOA with Nano-DESI High-Resolution Mass Spectrometry

    SciTech Connect

    O'Brien, Rachel E.; Nguyen, Tran B.; Laskin, Alexander; Laskin, Julia; Hayes, Patrick L.; Liu, Shang; Jimenez, Jose L.; Russell, Lynn M.; Nizkorodov, Sergey; Goldstein, Allen H.

    2013-01-30

    Aerosol samples from the 2010 CalNex field study in Bakersfield (BF) and Los Angeles (LA) were analyzed using positive mode nanospray-desorption electrospray ionization mass spectrometry (nano-DESI-MS). Secondary organic aerosol (SOA) produced in a photochemical chamber by photooxidation of diesel (DSL) fuel and isoprene (ISO) under humid, high-NOx conditions, was analyzed for comparison. Three groups of organic compounds with zero, one, or two nitrogen atoms in their molecular formulas (0N, 1N, 2N) were compared in detail. The composition of ambient SOA exhibited greater overlap with DSL than with ISO. The overlap of the chamber experiments with the BF data was relatively consistent throughout the day while the overlap with LA data increased significantly in the noon-6pm sample, consistent with the SOA plume arriving from downtown Los Angeles. BF samples were more oxidized, contained more organic nitrogen, and had more overlap with the chamber data compared to LA samples. The addition of gaseous ammonia (NH3) to the DSL experiment was necessary to generate many of the 2N compounds observed in BF. This analysis demonstrates that DSL and ISO were important sources but cannot account for all of the observed ambient compounds indicating that other sources of organics were also likely important.

  17. Dispersive liquid-liquid microextraction for the determination of new generation pesticides in soils by liquid chromatography and tandem mass spectrometry.

    PubMed

    Pastor-Belda, Marta; Garrido, Isabel; Campillo, Natalia; Viñas, Pilar; Hellín, Pilar; Flores, Pilar; Fenoll, José

    2015-05-15

    A sensitive method for the determination of five new generation pesticides (chlorantraniliprole, spirotetramat, spiromesifen, spirodiclofen and flubendiamide) in soil samples has been developed using liquid chromatography and tandem mass spectrometry (LC-MS(2)) with a triple-quadrupole in the multiple reaction monitoring mode. The target analytes are released from the solid matrix by single-phase extraction in acetonitrile (SLE), this organic phase being used as dispersant solvent in the dispersive liquid-liquid microextraction (DLLME) step. The different parameters affecting the extraction efficiency in DLLME were carefully studied, being 1.5mL of acetonitrile extract (disperser solvent), 125μL carbon tetrachloride (extraction solvent) and 10mL aqueous solution, the selected conditions. The enriched organic phase was evaporated, reconstituted with 50μL acetonitrile and injected into a liquid chromatograph with a mobile phase composed of acetonitrile and 0.1% (v/v) formic acid under gradient elution and a C8 stationary phase. Detection limits in the 0.0015-0.0090ngg(-1) range were obtained. Insecticide concentrations ranging from 0.03 to 197ngg(-1), depending on the compound, were found in the soil samples analysed. The recovery values obtained by SLE-DLLME-LC-ESI-MS(2) for three spiked soils at three concentration levels varied between 87 and 114%, with RSDs of between 5.5 and 14%.

  18. Untargeted screening of unknown xenobiotics and potential toxins in plasma of poisoned patients using high-resolution mass spectrometry: Generation of xenobiotic fingerprint using background subtraction.

    PubMed

    Chen, Chang; Wohlfarth, Ariane; Xu, Hui; Su, Dan; Wang, Xin; Jiang, Hongliang; Feng, Yulin; Zhu, Mingshe

    2016-11-09

    A novel analytical workflow was developed and applied for the detection and identification of unknown xenobiotics in biological samples. High-resolution mass spectrometry (HRMS)-based data-independent MS(E) acquisition was employed to record full scan MS and fragment spectral datasets of test and control samples. Then, an untargeted data-mining technique, background subtraction, was utilized to find xenobiotics present only in test samples. Structural elucidation of the detected xenobiotics was accomplished by database search, spectral interpretation, and/or comparison with reference standards. Application of the workflow to analysis of unknown xenobiotics in plasma samples collected from four poisoned patients led to generation of xenobiotic profiles, which were regarded as xenobiotic fingerprints of the individual samples. Among 19 xenobiotics detected, 11 xenobiotics existed in a majority of the patients' plasma samples, thus were considered as potential toxins. The follow-up database search led to the tentative identification of azithromycin (X5), α-chaconine (X9) and penfluridol (X12). The identity of X12 was further confirmed with its reference standard. In addition, one xenobiotic component (Y5) was tentatively identified as a penfluridol metabolite. The remaining unidentified xenobiotics listed in the xenobiotic fingerprints can be further characterized or identified in retrospective analyses after their spectral data and/or reference compounds are available. This HRMS-based workflow may have broad applications in the detection and identification of unknown xenobiotics in individual biological samples, such as forensic and toxicological analysis and sport enhancement drug screening.

  19. Probing molecular associations of field-collected and laboratory-generated SOA with nano-DESI high-resolution mass spectrometry

    NASA Astrophysics Data System (ADS)

    O'Brien, Rachel E.; Nguyen, Tran B.; Laskin, Alexander; Laskin, Julia; Hayes, Patrick L.; Liu, Shang; Jimenez, Jose L.; Russell, Lynn M.; Nizkorodov, Sergey A.; Goldstein, Allen H.

    2013-01-01

    Aerosol samples from the 2010 CalNex field study in Bakersfield (BF) and Pasadena (LA) were analyzed using positive mode nanospray-desorption electrospray ionization mass spectrometry. Secondary organic aerosol (SOA) produced in a photochemical chamber by photooxidation of diesel (DSL) fuel and isoprene (ISO) under humid, high-NOx conditions, was analyzed for comparison. Three groups of organic compounds with zero, one, or two nitrogen atoms in their molecular formulas (0N, 1N, 2N) were compared in detail. The composition of ambient SOA exhibited greater overlap with DSL than with ISO. The overlap of the chamber experiments with the BF data was relatively consistent throughout the day while the overlap with LA data increased significantly in the noon to 6 P.M. sample, consistent with the SOA plume arriving from downtown Los Angeles. BF samples were more oxidized, contained more organic nitrogen, and had more overlap with the chamber data compared to LA samples. The addition of gaseous ammonia (NH3) to the DSL experiment was necessary to generate many of the 2N compounds observed in BF. This analysis demonstrates that DSL and ISO were important sources but cannot account for all of the observed ambient compounds indicating that other sources of organics were also likely important.

  20. Structural identification of SAR-943 metabolites generated by human liver microsomes in vitro using mass spectrometry in combination with analysis of fragmentation patterns.

    PubMed

    Strom, Tobin; Shokati, Touraj; Klawitter, Jost; Klawitter, Jelena; Hoffman, Keith; Schiebel, Hans-Martin; Christians, Uwe

    2011-07-01

    SAR-943 (32-deoxo rapamycin) is a proliferation signal inhibitor via interaction with the mammalian target of rapamycin (mTOR). Most importantly, SAR-943 has improved chemical stability compared to rapamycin (sirolimus) and is currently under investigation as a drug coated on coronary stents. It was the goal of this study to identify the SAR-943 metabolites generated after incubation with human liver microsomes using high-resolution mass spectrometry (MS) and MS/iontrap (MS(n)) and comparison of fragmentation patterns of the metabolites with those of SAR-943 and other known rapamycin derivatives. Our study showed that SAR-943 is mainly hydroxylated and/or demethylated by human liver microsomes. The structures of the following metabolites were identified: O-demethylated metabolites: 39-O-desmethyl, 16-O-desmethyl and 27-O-desmethyl SAR-943; hydroxylated metabolites: hydroxy piperidine SAR-943, 11-hydroxy, 12-hydroxy, 14-hydroxy, 23-hydroxy, 24-hydroxy, 25-hydroxy, 46-hydroxy and 49-hydroxy SAR-943; didemethylated metabolites: 16,39-O-didesmethyl and 27,39-O-didesmethyl SAR-943; demethylated-hydroxylated metabolites: 39-O-desmethyl, 23- or 24-hydroxy and 39-O-desmethyl, hydroxy piperidine SAR-943 and dihydroxylated metabolites: 12-,23- or 24-dihydroxy SAR-943. In addition, several other demethylated-hydroxylated and dihydroxylated metabolites were detected. However, their exact structures could not be identified. Copyright © 2011 John Wiley & Sons, Ltd.

  1. Determination of As, Hg and Pb in herbs using slurry sampling flow injection chemical vapor generation inductively coupled plasma mass spectrometry.

    PubMed

    Tai, Chia-Yi; Jiang, Shiuh-Jen; Sahayam, A C

    2016-02-01

    Analysis of herbs for As, Hg and Pb has been carried out using slurry sampling inductively coupled plasma mass spectrometry (ICP-MS) with flow injection vapor generation. Slurry containing 0.5% m/v herbal powder, 0.1% m/v citric acid and 2% v/v HCl was injected into the VG-ICP-MS system for the determination of As, Hg and Pb that obviate dissolution and mineralization. Standard addition and isotope dilution methods were used for quantifications in selected herbal powders. This method has been validated by the determination of As, Hg and Pb in NIST standard reference materials SRM 1547 Peach Leaves and SRM 1573a Tomato Leaves. The As, Hg and Pb analysis results of the reference materials agreed with the certified values. The precision obtained by the reported procedure was better than 7% for all determinations. The detection limit estimated from standard addition curve was 0.008, 0.003, and 0.007 ng mL(-1) for As, Hg and Pb, respectively.

  2. 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.

  3. 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.

  4. 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)

  5. 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)

  6. Direct and non-destructive proof of authenticity for the 2nd generation of Brazilian real banknotes via easy ambient sonic spray ionization mass spectrometry.

    PubMed

    Schmidt, Eduardo Morgado; Franco, Marcos Fernando; Regino, Karen Gomes; Lehmann, Eraldo Luiz; Arruda, Marco Aurélio Zezzi; de Carvalho Rocha, Werickson Fortunato; Borges, Rodrigo; de Souza, Wanderley; Eberlin, Marcos Nogueira; Correa, Deleon Nascimento

    2014-12-01

    Using a desorption/ionization technique, easy ambient sonic-spray ionization coupled to mass spectrometry (EASI-MS), documents related to the 2nd generation of Brazilian Real currency (R$) were screened in the positive ion mode for authenticity based on chemical profiles obtained directly from the banknote surface. Characteristic profiles were observed for authentic, seized suspect counterfeit and counterfeited homemade banknotes from inkjet and laserjet printers. The chemicals in the authentic banknotes' surface were detected via a few minor sets of ions, namely from the plasticizers bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP), most likely related to the official offset printing process, and other common quaternary ammonium cations, presenting a similar chemical profile to 1st-generation R$. The seized suspect counterfeit banknotes, however, displayed abundant diagnostic ions in the m/z 400-800 range due to the presence of oligomers. High-accuracy FT-ICR MS analysis enabled molecular formula assignment for each ion. The ions were separated by 44 m/z, which enabled their characterization as Surfynol® 4XX (S4XX, XX=40, 65, and 85), wherein increasing XX values indicate increasing amounts of ethoxylation on a backbone of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (Surfynol® 104). Sodiated triethylene glycol monobutyl ether (TBG) of m/z 229 (C10H22O4Na) was also identified in the seized counterfeit banknotes via EASI(+) FT-ICR MS. Surfynol® and TBG are constituents of inks used for inkjet printing.

  7. 1-Adamantylamine a simple urine marker for screening for third generation adamantyl-type synthetic cannabinoids by ultra-performance liquid chromatography tandem mass spectrometry.

    PubMed

    Ford, Loretta T; Berg, Jonathan D

    2016-11-01

    Background Synthetic cannabinoids (NOIDS) are novel psychotropic drugs (NPS) currently freely sold in the United Kingdom as 'research chemicals'. Detection of NOIDS use is not available in current routine methods. Here we describe a marker which helps determine which patients have used these substances. Methods In a test case, ultra-performance liquid chromatography mass spectrometry (UPLC-Tof) was used to screen the legal high Herbal Haze II, the contents of hand-rolled cigarettes and five patient samples for NOIDS and their metabolites. Results Analysis of legal high Herbal Haze II and cigarettes identified the third generation adamantyl-type NOIDS N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), 5F-AKB-48 and N-adamantyl-1-fluoropentylindole-3-carboxamide (STS-135). Out of 18 potential metabolites, 1-adamantylamine (C10H17N) was detected in all five urine samples. This adamantyl-type NOID marker was incorporated into our routine LC-MS/MS urine screen. Out of 14,436 random urine samples screened over eight months, 296 (2.05%) tested positive for the adamantyl-type NOID marker. Conclusion We have discovered a urine marker for identifying patients smoking legal high products containing the third generation adamantyl-type NOIDS such as AKB-48 and its fluoropentyl analogue 5F-AKB-48, which are among the most popular NOIDS currently available in legal high products sold in UK. This marker can be incorporated into routine LC-MS/MS drug screening alongside classic drugs of abuse. Positive detection rates for this new legal high marker are greater than for established classic drugs that are routinely screened such as amphetamine. This work highlights the need for a flexible toxicology screening service capable of adapting to changes in drug use such as the growing popularity of legal highs/NPS.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Slurry sampling flow injection chemical vapor generation inductively coupled plasma mass spectrometry for the determination of trace Ge, As, Cd, Sb, Hg and Bi in cosmetic lotions.

    PubMed

    Chen, Wei-Ni; Jiang, Shiuh-Jen; Chen, Yen-Ling; Sahayam, A C

    2015-02-20

    A slurry sampling inductively coupled plasma mass spectrometry (ICP-MS) method has been developed for the determination of Ge, As, Cd, Sb, Hg and Bi in cosmetic lotions using flow injection (FI) vapor generation (VG) as the sample introduction system. A slurry containing 2% m/v lotion, 2% m/v thiourea, 0.05% m/v L-cysteine, 0.5 μg mL(-1) Co(II), 0.1% m/v Triton X-100 and 1.2% v/v HCl was injected into a VG-ICP-MS system for the determination of Ge, As, Cd, Sb, Hg and Bi without dissolution and mineralization. Because the sensitivities of the analytes in the slurry and that of aqueous solution were quite different, an isotope dilution method and a standard addition method were used for the determination. This method has been validated by the determination of Ge, As, Cd, Sb, Hg and Bi in GBW09305 Cosmetic (Cream) reference material. The method was also applied for the determination of Ge, As, Cd, Sb, Hg and Bi in three cosmetic lotion samples obtained locally. The analysis results of the reference material agreed with the certified value and/or ETV-ICP-MS results. The detection limit estimated from the standard addition curve was 0.025, 0.1, 0.2, 0.1, 0.15, and 0.03 ng g(-1) for Ge, As, Cd, Sb, Hg and Bi, respectively, in original cosmetic lotion sample.

  16. Probing the orientation of electrostatically immobilized cytochrome C by time of flight secondary ion mass spectrometry and sum frequency generation spectroscopy

    PubMed Central

    Baio, Joe E; Weidner, Tobias; Ramey, Dennis; Pruzinsky, Leah; Castner, David G

    2013-01-01

    By taking advantage of the electron pathway through the heme group in cytochrome c (CytoC) electrochemists have built sensors based upon CytoC immobilized onto metal electrodes. Previous studies have shown that the electron transfer rate through the protein is a function of the position of this heme group with respect to the electrode surface. In this study a detailed examination of CytoC orientation when electrostatically immobilized onto both amine (NH3+) and carboxyl (COO-) functionalized gold is presented. Protein coverage, on both surfaces, was monitored by the change in the atomic % N, as determined by x-ray photoelectron spectroscopy. Spectral features within the in situ sum frequency generation vibrational spectra, acquired for the protein interacting with positively and negatively charged surfaces, indicates that these electrostatic interactions do induce the protein into a well ordered film. Time of flight secondary ion mass spectrometry data demonstrated a clear separation between the two samples based on the intensity differences of secondary ions stemming from amino acids located asymmetrically within CytoC (cysteine: C2H6NS+; glutamic acid: C4H6NO+ and C4H8NO2+; leucine: C5H12N+). For a more quantitative examination of orientation, we developed a ratio comparing the sum of the intensities of secondary-ions stemming from the amino acid residues at either end of the protein. The 50 % increase in this ratio, observed between the protein covered NH3+ and COO- substrates, indicates opposite orientations of the CytoC on the two different surfaces. PMID:24706131

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Determination of lead by hydride generation inductively coupled plasma mass spectrometry (HG-ICP-MS): on-line generation of plumbane using potassium hexacyanomanganate(III)

    PubMed Central

    Yilmaz, Vedat; Arslan, Zikri; Rose, LaKeysha

    2012-01-01

    A hydride generation (HG) procedure has been described for determination of Pb by ICP-MS using potassium hexacyanomanganate(III), K3Mn(CN)6, as an additive to facilitate the generation of plumbane (PbH4). Potassium hexacyanomanganate(III) was prepared in acidic medium as it was unstable in water. The stability of hexacyanomanganate(III) was examined in dilute solutions of HCl, HNO3 and H2SO4. The solutions prepared in 1% v/v/ H2SO4 were found to be stable for over a period of 24 h. The least suitable medium was 1% v/v HNO3. For generation of plumbane, acidic hexacyanomanganate(III) and sample solutions were mixed online along a 5-cm long tygon tubing (1.14 mm i.d.) and then reacted with 2% m/v sodium borohydride (NaBH4). A concentration of 0.5% m/v K3Mn(CN)6 facilitated the generation of PbH4 remarkably. In comparison to H2SO4, HCl provided broader working range for which optimum concentration was 1% v/v. No significant interferences were noted from transition metals and hydride forming elements, up to 0.5 μg mL−1 levels, except Cu which depressed the signals severely. The depressive effects in the presence of 0.1 μg mL−1 Cu were alleviated by increasing the concentration of K3Mn(CN)6 to 2% m/v. Under these conditions, the sensitivity was enhanced by a factor of at least 42 to 48. The detection limit (3s) was 0.008 μg L−1 for 208Pb isotope. Average signal-to-noise ratio (S/N) ranged between 18 and 20 for 1.0 μg mL−1 Pb solution. The accuracy of the method was verified by analysis of several certified reference materials, including Nearshore seawater (CASS-4), Bone ash (SRM 1400), and Mussel tissue (SRM 2976). The procedure was also successfully applied to the determination of Pb in coastal seawater samples by ICP-MS. PMID:23312310

  6. Determination of lead by hydride generation inductively coupled plasma mass spectrometry (HG-ICP-MS): on-line generation of plumbane using potassium hexacyanomanganate(III).

    PubMed

    Yilmaz, Vedat; Arslan, Zikri; Rose, LaKeysha

    2013-01-25

    A hydride generation (HG) procedure has been described for determination of Pb by ICP-MS using potassium hexacyanomanganate(III), K(3)Mn(CN)(6), as an additive to facilitate the generation of plumbane (PbH(4)). Potassium hexacyanomanganate(III) was prepared in acidic medium as it was unstable in water. The stability of hexacyanomanganate(III) was examined in dilute solutions of HCl, HNO(3) and H(2)SO(4). The solutions prepared in 1% v/v H(2)SO(4) were found to be stable for over a period of 24h. The least suitable medium was 1% v/v HNO(3). For generation of plumbane, acidic hexacyanomanganate(III) and sample solutions were mixed on-line along a 5-cm long tygon tubing (1.14 mm i.d.) and then reacted with 2% m/v sodium borohydride (NaBH(4)). A concentration of 0.5% m/v K(3)Mn(CN)(6) facilitated the generation of PbH(4) remarkably. In comparison to H(2)SO(4), HCl provided broader working range for which optimum concentration was 1% v/v. No significant interferences were noted from transition metals and hydride forming elements, up to 0.5 μg mL(-1) levels, except Cu which depressed the signals severely. The depressive effects in the presence of 0.1 μg mL(-1) Cu were alleviated by increasing the concentration of K(3)Mn(CN)(6) to 2% m/v. Under these conditions, the sensitivity was enhanced by a factor of at least 42 to 48. The detection limit (3s) was 0.008 μg L(-1) for (208)Pb isotope. Average signal-to-noise ratio (S/N) ranged between 18 and 20 for 1.0 μg mL(-1) Pb solution. The accuracy of the method was verified by analysis of several certified reference materials, including Nearshore seawater (CASS-4), Bone ash (SRM 1400), and Mussel tissue (SRM 2976). The procedure was also successfully applied to the determination of Pb in coastal seawater samples by ICP-MS.

  7. 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

  8. 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.

  9. 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.

  10. Comparative oxidation state specific analysis of arsenic species by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry and hydride generation-cryotrapping-atomic absorption spectrometry.

    PubMed

    Currier, Jenna; Saunders, R Jesse; Ding, Lan; Bodnar, Wanda; Cable, Peter; Matoušek, Tomáš; Creed, John T; Stýblo, Miroslav

    2013-06-01

    The formation of methylarsonous acid (MAs(III)) and dimethylarsinous acid (DMAs(III)) in the course of inorganic arsenic (iAs) metabolism plays an important role in the adverse effects of chronic exposure to iAs. High-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) and hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS) have been frequently used for the analysis of MAs(III) and DMAs(III) in biological samples. While HG-CT-AAS has consistently detected MAs(III) and DMAs(III), HPLC-ICP-MS analyses have provided inconsistent and contradictory results. This study compares the capacities of both methods to detect and quantify MAs(III) and DMAs(III) in an in vitro methylation system consisting of recombinant human arsenic (+3 oxidation state) methyltransferase (AS3MT), S-adenosylmethionine as a methyl donor, a non-thiol reductant tris(2-carboxyethyl)phosphine, and arsenite (iAs(III)) or MAs(III) as substrate. The results show that reversed-phase HPLC-ICP-MS can identify and quantify MAs(III) and DMAs(III) in aqueous mixtures of biologically relevant arsenical standards. However, HPLC separation of the in vitro methylation mixture resulted in significant losses of MAs(III), and particularly DMAs(III) with total arsenic recoveries below 25%. Further analyses showed that MAs(III) and DMAs(III) bind to AS3MT or interact with other components of the methylation mixture, forming complexes that do not elute from the column. Oxidation of the mixture with H2O2 which converted trivalent arsenicals to their pentavalent analogs prior to HPLC separation increased total arsenic recoveries to ~95%. In contrast, HG-CT-AAS analysis found large quantities of methylated trivalent arsenicals in mixtures incubated with either iAs(III) or MAs(III) and provided high (>72%) arsenic recoveries. These data suggest that an HPLC-based analysis of biological samples can underestimate MAs(III) and DMAs(III) concentrations and that

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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)

  16. 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)

  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. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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…

  3. 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…

  4. 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.

  5. 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.

  6. 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 .

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Mass Processing—An Improved Technique for Protein Identification with Mass Spectrometry Data

    PubMed Central

    Henkin, Josh A.; Jennings, Mark E.; Matthews, Dwight E.; Vigoreaux, Jim O.

    2004-01-01

    Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis following tryptic digestion of polyacrylamide gel pieces is a common technique used to identify proteins. This approach is rapid, sensitive, and user friendly, and is becoming widely available to scientists in a variety of biological fields. Here we introduce a simple and effective strategy called “mass processing” where the list of masses generated from a mass spectrometer undergoes two stages of data reduction before identification. Mass processing improves the ability to identify in-gel tryptic-digested proteins by reducing the number of nonsample masses submitted to protein identification database search engines. Our results demonstrate that mass processing improves the statistical score and rank of putative protein identifications, especially with low-quantity samples, thus increasing the ability to confidently identify proteins with mass spectrometry data. PMID:15585819

  13. Analysis of proteins and proteomes by mass spectrometry.

    PubMed

    Mann, M; Hendrickson, R C; Pandey, A

    2001-01-01

    A decade after the discovery of electrospray and matrix-assisted laser desorption ionization (MALDI), methods that finally allowed gentle ionization of large biomolecules, mass spectrometry has become a powerful tool in protein analysis and the key technology in the emerging field of proteomics. The success of mass spectrometry is driven both by innovative instrumentation designs, especially those operating on the time-of-flight or ion-trapping principles, and by large-scale biochemical strategies, which use mass spectrometry to detect the isolated proteins. Any human protein can now be identified directly from genome databases on the basis of minimal data derived by mass spectrometry. As has already happened in genomics, increased automation of sample handling, analysis, and the interpretation of results will generate an avalanche of qualitative and quantitative proteomic data. Protein-protein interactions can be analyzed directly by precipitation of a tagged bait followed by mass spectrometric identification of its binding partners. By these and similar strategies, entire protein complexes, signaling pathways, and whole organelles are being characterized. Posttranslational modifications remain difficult to analyze but are starting to yield to generic strategies.

  14. 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

  15. 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...

  16. 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...

  17. 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

  18. 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.

  19. Characterization of Bacteria by Particle Beam Mass Spectrometry

    PubMed Central

    Sinha, Mahadeva P.; Platz, Robert M.; Friedlander, Sheldon K.; Vilker, Vincent L.

    1985-01-01

    A technique is described for detecting and characterizing bacteria on a single-particle basis by mass spectrometry. The method involves generation of a particle beam of single whole cells which are rapidly volatilized and ionized in vacuum in the ion source of a quadrupole mass spectrometer. The particle beam can be generated, with minimal sample handling, from a naturally occurring aerosol or from a solution of bacteria that can be dispersed as an aerosol. The mass spectrum is generated by successively measuring the average intensities of different mass peaks. The average intensity is obtained by measuring the ion intensity distribution at the particular mass (m/e) for ion pulses from more than 1,000 bacteria particles. Bacillus cereus, Bacillus subtilis, and Pseudomonas putida samples were analyzed to test the capability of the instrument for differentiating among species of bacteria. Significant ion-intensity information was produced over the m/e range of 50 to 300, an improvement over previous pyrolysis-mass spectrometry results. The complex mass spectra contained a few unique peaks which could be used for the differentiation of the bacteria. A statistical analysis of the variations in peak intensities among the three bacteria provided a quantitative measure of the reproducibility of the instrument and its ability to differentiate among bacteria. The technique could lead to a new rapid method for the analysis of microorganisms and could be used for the detection of airborne pathogens on a continuous, real-time basis. Images PMID:16346802

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Prediction of acrylamide formation in biscuits based on fingerprint data generated by ambient ionization mass spectrometry employing direct analysis in real time (DART) ion source.

    PubMed

    Vaclavik, Lukas; Capuano, Edoardo; Gökmen, Vural; Hajslova, Jana

    2015-04-15

    The objective of this study is the evaluation of the potential of high-throughput direct analysis in real time-high resolution mass spectrometry (DART-HRMS) fingerprinting and multivariate regression analysis in prediction of the extent of acrylamide formation in biscuit samples prepared by various recipes and baking conditions. Information-rich mass spectral fingerprints were obtained by analysis of biscuit extracts for preparation of which aqueous methanol was used. The principal component analysis (PCA) of the acquired data revealed an apparent clustering of samples according to the extent of heat-treatment applied during the baking of the biscuits. The regression model for prediction of acrylamide in biscuits was obtained by partial least square regression (PLSR) analysis of the data matrix representing combined positive and negative ionization mode fingerprints. The model provided a least root mean square error of cross validation (RMSECV) equal to an acrylamide concentration of 5.4 μg kg(-1) and standard error of prediction (SEP) of 14.8 μg kg(-1). The results obtained indicate that this strategy can be used to accurately predict the amounts of acrylamide formed during baking of biscuits. Such rapid estimation of acrylamide concentration can become a useful tool in evaluation of the effectivity of processes aiming at mitigation of this food processing contaminant. However, the robustness this approach with respect to variability in the chemical composition of ingredients used for preparation of biscuits should be tested further. Copyright © 2014. Published by Elsevier Ltd.

  6. 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.

  7. 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.

  8. 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

  9. [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.

  10. [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.

  11. Characterizing Glycoproteins by Mass Spectrometry in Campylobacter jejuni.

    PubMed

    Scott, Nichollas E

    2017-01-01

    The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered archetypal examples of both N- and O-linked glycosylations in the field of bacterial glycosylation. The discovery and characterization of these systems both have revealed important biological insight into C. jejuni and have led to the refinement and enhancement of methodologies to characterize bacterial glycosylation. In general, mass spectrometry-based characterization has become the preferred methodology for the study of C. jejuni glycosylation because of its speed, sensitivity, and ability to enable both qualitative and quantitative assessments of glycosylation events. In these experiments the generation of insightful data requires the careful selection of experimental approaches and mass spectrometry (MS) instrumentation. As such, it is essential to have a deep understanding of the technologies and approaches used for characterization of glycosylation events. Here we describe protocols for the initial characterization of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss considerations that can enhance the generation of insightful data.

  12. 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

  13. 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.

  14. Quantitation of mycotoxins using direct analysis in real time (DART)-mass spectrometry (MS)

    USDA-ARS?s Scientific Manuscript database

    Ambient ionization represents a new generation of mass spectrometry ion sources which is used for rapid ionization of small molecules under ambient conditions. The combination of ambient ionization and mass spectrometry allows analyzing multiple food samples with simple or no sample treatment, or in...

  15. 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.

  16. 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.

  17. Charge Prediction of Lipid Fragments in Mass Spectrometry

    SciTech Connect

    Schrom, Brian T.; Kangas, Lars J.; Ginovska, Bojana; Metz, Thomas O.; Miller, John H.

    2011-12-18

    An artificial neural network is developed for predicting which fragment is charged and which fragment is neutral for lipid fragment pairs produced from a liquid chromatography tandem mass spectrometry simulation process. This charge predictor is integrated into software developed at PNNL for in silico spectra generation and identification of metabolites known as Met ISIS. To test the effect of including charge prediction in Met ISIS, 46 lipids are used which show a reduction in false positive identifications when the charge predictor is utilized.

  18. Triboelectric nanogenerators for sensitive nano-coulomb molecular mass spectrometry.

    PubMed

    Li, Anyin; Zi, Yunlong; Guo, Hengyu; Wang, Zhong Lin; Fernández, Facundo M

    2017-02-27

    Ion sources for molecular mass spectrometry are usually driven by direct current power supplies with no user control over the total charges generated. Here, we show that the output of triboelectric nanogenerators (TENGs) can quantitatively control the total ionization charges in mass spectrometry. The high output voltage of TENGs can generate single- or alternating-polarity ion pulses, and is ideal for inducing nanoelectrospray ionization (nanoESI) and plasma discharge ionization. For a given nanoESI emitter, accurately controlled ion pulses ranging from 1.0 to 5.5 nC were delivered with an onset charge of 1.0 nC. Spray pulses can be generated at a high frequency of 17 Hz (60 ms in period) and the pulse duration is adjustable on-demand between 60 ms and 5.5 s. Highly sensitive (∼0.6 zeptomole) mass spectrometry analysis using minimal sample (18 pl per pulse) was achieved with a 10 pg ml(-1) cocaine sample. We also show that native protein conformation is conserved in TENG-ESI, and that patterned ion deposition on conductive and insulating surfaces is possible.

  19. Triboelectric nanogenerators for sensitive nano-coulomb molecular mass spectrometry

    NASA Astrophysics Data System (ADS)

    Li, Anyin; Zi, Yunlong; Guo, Hengyu; Wang, Zhong Lin; Fernández, Facundo M.

    2017-05-01

    Ion sources for molecular mass spectrometry are usually driven by direct current power supplies with no user control over the total charges generated. Here, we show that the output of triboelectric nanogenerators (TENGs) can quantitatively control the total ionization charges in mass spectrometry. The high output voltage of TENGs can generate single- or alternating-polarity ion pulses, and is ideal for inducing nanoelectrospray ionization (nanoESI) and plasma discharge ionization. For a given nanoESI emitter, accurately controlled ion pulses ranging from 1.0 to 5.5 nC were delivered with an onset charge of 1.0 nC. Spray pulses can be generated at a high frequency of 17 Hz (60 ms in period) and the pulse duration is adjustable on-demand between 60 ms and 5.5 s. Highly sensitive (˜0.6 zeptomole) mass spectrometry analysis using minimal sample (18 pl per pulse) was achieved with a 10 pg ml-1 cocaine sample. We also show that native protein conformation is conserved in TENG-ESI, and that patterned ion deposition on conductive and insulating surfaces is possible.

  20. Method for Detection of Trace Metal and Metalloid Contaminants in Coal-Generated Fuel Gas Using Gas Chromatography/Ion Trap Mass Spectrometry

    SciTech Connect

    Rupp, Erik C.; Granite, Evan J.; Stanko, Dennis C.

    2010-07-15

    There exists an increasing need to develop a reliable method to detect trace contaminants in fuel gas derived from coal gasification. While Hg is subject to current and future regulations, As, Se, and P emissions may eventually be regulated. Sorbents are the most promising technology for the removal of contaminants from coal-derived fuel gas, and it will be important to develop a rapid analytical detection method to ensure complete removal and determine the ideal time for sorbent replacement/regeneration in order to reduce costs. This technical note explores the use of a commercial gas chromatography/ion trap mass spectrometry system for the detection of four gaseous trace contaminants in a simulated fuel gas. Quantitative, repeatable detection with limits at ppbv to ppmv levels were obtained for arsine (AsH3), phosphine (PH3), and hydrogen selenide (H2Se), while qualitative detection was observed for mercury. Decreased accuracy and response caused by the primary components of fuel gas were observed.

  1. Application of liquid chromatography with electrospray tandem mass spectrometry to the determination of a new generation of pesticides in processed fruits and vegetables.

    PubMed

    Sannino, Anna; Bolzoni, Luciana; Bandini, Mirella

    2004-05-21

    This paper describes a method for the sensitive and selective determination of 24 new pesticide residues (azoxystrobin, trifloxystrobin, kresoxim-methyl, fenazaquin, indoxacarb, fenothiocarb, furathiocarb, benfuracarb, imidachloprid, dimethomorph, fenpyroximate, hexythiazox, tebufenpyrad, tebufenozide, difeconazole, fenbuconazole, flusilazole, paclobutrazol, tebuconazole, tetraconazole, bromuconazole, etofenprox, fenhexamid, pyridaben) in apple puree, concentrated lemon juice and tomato puree. A miniaturized extraction-partition procedure requiring small amounts of non-chlorinated solvents was used. The extracts are analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) without any further clean-up step. The pesticides are separated on a reversed-phase polar column using a gradient elution. Fifty-five simultaneous MS-MS transitions of precursor ions were monitored (two or three for each pesticide). Studies at fortification levels of 0.001-0.020 and 0.010-0.200 mg/kg gave mean recoveries ranging from 76 to 106% for all compounds, except for imidacloprid, with (R.S.D.s) < or = 15%. The excellent sensitivity and selectivity of LC-MS-MS method allowed quantitation and identification at low levels also in difficult matrices with a run time of 20 min. With the developed method almost 100 samples of commercial fruit products (nectars, juices, purees) were analyzed. None of samples contained residues higher than 0.010 mg/kg.

  2. Method for detection of trace metal and metalloid contaminants in coal-generated fuel gas using gas chromatography/ion trap mass spectrometry.

    PubMed

    Rupp, Erik C; Granite, Evan J; Stanko, Dennis C

    2010-07-15

    There exists an increasing need to develop a reliable method to detect trace contaminants in fuel gas derived from coal gasification. While Hg is subject to current and future regulations, As, Se, and P emissions may eventually be regulated. Sorbents are the most promising technology for the removal of contaminants from coal-derived fuel gas, and it will be important to develop a rapid analytical detection method to ensure complete removal and determine the ideal time for sorbent replacement/regeneration in order to reduce costs. This technical note explores the use of a commercial gas chromatography/ion trap mass spectrometry system for the detection of four gaseous trace contaminants in a simulated fuel gas. Quantitative, repeatable detection with limits at ppbv to ppmv levels were obtained for arsine (AsH(3)), phosphine (PH(3)), and hydrogen selenide (H(2)Se), while qualitative detection was observed for mercury. Decreased accuracy and response caused by the primary components of fuel gas were observed.

  3. Offline coupling of high-speed counter-current chromatography and gas chromatography/mass spectrometry generates a two-dimensional plot of toxaphene components.

    PubMed

    Kapp, Thomas; Vetter, Walter

    2009-11-20

    High-speed counter-current chromatography (HSCCC), a separation technique based solely on the partitioning of solutes between two immiscible liquid phases, was applied for the fractionation of technical toxaphene, an organochlorine pesticide which consists of a complex mixture of structurally closely related compounds. A solvent system (n-hexane/methanol/water 34:24:1, v/v/v) was developed which allowed to separate compounds of technical toxaphene (CTTs) with excellent retention of the stationary phase (S(f) = 88%). Subsequent analysis of all HSCCC fractions by gas chromatography coupled to electron-capture negative ion mass spectrometry (GC/ECNI-MS) provided a wealth of information regarding separation characteristics of HSCCC and the composition of technical toxaphene. The visualization of the large amount of data obtained from the offline two-dimensional HSCCC-GC/ECNI-MS experiment was facilitated by the creation of a two-dimensional (2D) contour plot. The contour plot not only provided an excellent overview of the HSCCC separation progress, it also illustrated the differences in selectivity between HSCCC and GC. The results of this proof-of-concept study showed that the 2D chromatographic approach involving HSCCC facilitated the separation of CTTs that coelute in unidimensional GC. Furthermore, the creation of 2D contour plots may provide a useful means of enhancing data visualization for other offline two-dimensional separations.

  4. Estimating the Efficiency of Phosphopeptide Identification by Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hsu, Chuan-Chih; Xue, Liang; Arrington, Justine V.; Wang, Pengcheng; Paez Paez, Juan Sebastian; Zhou, Yuan; Zhu, Jian-Kang; Tao, W. Andy

    2017-03-01

    Mass spectrometry has played a significant role in the identification of unknown phosphoproteins and sites of phosphorylation in biological samples. Analyses of protein phosphorylation, particularly large scale phosphoproteomic experiments, have recently been enhanced by efficient enrichment, fast and accurate instrumentation, and better software, but challenges remain because of the low stoichiometry of phosphorylation and poor phosphopeptide ionization efficiency and fragmentation due to neutral loss. Phosphoproteomics has become an important dimension in systems biology studies, and it is essential to have efficient analytical tools to cover a broad range of signaling events. To evaluate current mass spectrometric performance, we present here a novel method to estimate the efficiency of phosphopeptide identification by tandem mass spectrometry. Phosphopeptides were directly isolated from whole plant cell extracts, dephosphorylated, and then incubated with one of three purified kinases—casein kinase II, mitogen-activated protein kinase 6, and SNF-related protein kinase 2.6—along with 16O4- and 18O4-ATP separately for in vitro kinase reactions. Phosphopeptides were enriched and analyzed by LC-MS. The phosphopeptide identification rate was estimated by comparing phosphopeptides identified by tandem mass spectrometry with phosphopeptide pairs generated by stable isotope labeled kinase reactions. Overall, we found that current high speed and high accuracy mass spectrometers can only identify 20%-40% of total phosphopeptides primarily due to relatively poor fragmentation, additional modifications, and low abundance, highlighting the urgent need for continuous efforts to improve phosphopeptide identification efficiency.

  5. Estimating the Efficiency of Phosphopeptide Identification by Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hsu, Chuan-Chih; Xue, Liang; Arrington, Justine V.; Wang, Pengcheng; Paez Paez, Juan Sebastian; Zhou, Yuan; Zhu, Jian-Kang; Tao, W. Andy

    2017-06-01

    Mass spectrometry has played a significant role in the identification of unknown phosphoproteins and sites of phosphorylation in biological samples. Analyses of protein phosphorylation, particularly large scale phosphoproteomic experiments, have recently been enhanced by efficient enrichment, fast and accurate instrumentation, and better software, but challenges remain because of the low stoichiometry of phosphorylation and poor phosphopeptide ionization efficiency and fragmentation due to neutral loss. Phosphoproteomics has become an important dimension in systems biology studies, and it is essential to have efficient analytical tools to cover a broad range of signaling events. To evaluate current mass spectrometric performance, we present here a novel method to estimate the efficiency of phosphopeptide identification by tandem mass spectrometry. Phosphopeptides were directly isolated from whole plant cell extracts, dephosphorylated, and then incubated with one of three purified kinases—casein kinase II, mitogen-activated protein kinase 6, and SNF-related protein kinase 2.6—along with 16O4- and 18O4-ATP separately for in vitro kinase reactions. Phosphopeptides were enriched and analyzed by LC-MS. The phosphopeptide identification rate was estimated by comparing phosphopeptides identified by tandem mass spectrometry with phosphopeptide pairs generated by stable isotope labeled kinase reactions. Overall, we found that current high speed and high accuracy mass spectrometers can only identify 20%-40% of total phosphopeptides primarily due to relatively poor fragmentation, additional modifications, and low abundance, highlighting the urgent need for continuous efforts to improve phosphopeptide identification efficiency. [Figure not available: see fulltext.

  6. 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

  7. 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

  8. 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.

  9. Advances in structure elucidation of small molecules using mass spectrometry

    PubMed Central

    Fiehn, Oliver

    2010-01-01

    The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules. Electronic supplementary material The online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users. PMID:21289855

  10. 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

  11. Mass spectrometry-based analysis of whole-grain phytochemicals.

    PubMed

    Koistinen, Ville Mikael; Hanhineva, Kati

    2017-05-24

    Whole grains are a rich source of several classes of phytochemicals, such as alkylresorcinols, benzoxazinoids, flavonoids, lignans, and phytosterols. A high intake of whole grains has been linked to a reduced risk of some major noncommunicable diseases, and it has been postulated that a complex mixture of phytochemicals works in synergy to generate beneficial health effects. Mass spectrometry, especially when coupled with liquid chromatography, is a widely used method for the analysis of phytochemicals owing to its high sensitivity and dynamic range. In this review, the current knowledge of the mass spectral properties of the most important classes of phytochemicals found in cereals of common wheat, barley, oats, and rye is discussed.

  12. 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.

  13. 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.

  14. 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.

  15. Macromolecule mass spectrometry: citation mining of user documents.

    PubMed

    Kostoff, Ronald N; Bedford, Clifford D; del Río, J Antonio; Cortes, Héctor D; Karypis, George

    2004-03-01

    Identifying research users, applications, and impact is important for research performers, managers, evaluators, and sponsors. Identification of the user audience and the research impact is complex and time consuming due to the many indirect pathways through which fundamental research can impact applications. This paper identified the literature pathways through which two highly-cited papers of 2002 Chemistry Nobel Laureates Fenn and Tanaka impacted research, technology development, and applications. Citation Mining, an integration of citation bibliometrics and text mining, was applied to the >1600 first generation Science Citation Index (SCI) citing papers to Fenn's 1989 Science paper on Electrospray Ionization for Mass Spectrometry, and to the >400 first generation SCI citing papers to Tanaka's 1988 Rapid Communications in Mass Spectrometry paper on Laser Ionization Time-of-Flight Mass Spectrometry. Bibliometrics was performed on the citing papers to profile the user characteristics. Text mining was performed on the citing papers to identify the technical areas impacted by the research, and the relationships among these technical areas.

  16. 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.

  17. 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.

  18. 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

  19. Challenges ahead for mass spectrometry and proteomics applications in epigenetics.

    PubMed

    Kessler, Benedikt M

    2010-02-01

    Inheritance of biological information to future generations depends on the replication of DNA and the Mendelian principle of distribution of genes. In addition, external and environmental factors can influence traits that can be propagated to offspring, but the molecular details of this are only beginning to be understood. The discoveries of DNA methylation and post-translational modifications on chromatin and histones provided entry points for regulating gene expression, an area now defined as epigenetics and epigenomics. Mass spectrometry turned out to be instrumental in uncovering molecular details involved in these processes. The central role of histone post-translational modifications in epigenetics related biological processes has revitalized mass spectrometry based investigations. In this special report, current approaches and future challenges that lay ahead due to the enormous complexity are discussed.

  20. Protein identification using nano liquid chromatography-tandem mass spectrometry.

    PubMed

    Negroni, Luc

    2007-01-01

    Tandem mass spectrometry is an efficient technique for the identification of peptides on the basis of their fragmentation pattern (MS/MS scan). It can generate individual spectra for each peptide, thereby creating a powerful tool for protein identification on the basis of peptide characterization. This important advance in automatic data acquisition has allowed an efficient association between liquid chromatography and tandem mass spectrometry, and the use of nanocolumns and nanoelectrospray ionization has dramatically increased the efficiency of this method. Now large sets of peptides can be identified at a femtomole level. At the end of the process, batch processing of the MS/MS spectra produces peptide lists that identify purified proteins or protein mixtures with high confidence.

  1. Examining Histone Posttranslational Modification Patterns by High Resolution Mass Spectrometry

    PubMed Central

    Lin, Shu; Garcia, Benjamin A.

    2014-01-01

    Histone variants and posttranslational modifications (PTMs) are essential for epigenetic regulation of transcriptional expression. Single and/or combinatorial PTMs of histones play important roles in development and disease formation. Mass spectrometry (MS) has been a powerful tool to study histone variants and PTMs as it not only can identify novel PTMs but also can provide quantitative measurement of a spectrum of histone variants and PTMs in the same sample. In this chapter, we employ a combination of chemical derivation and high resolution mass spectrometry to identify and quantify multiple histone variants and PTMs. Histones are acid extracted and modified with propionyl groups, and subsequently produces suitable sizes of fragments for MS analysis by trypsin digestion. The newly generated N-termini of histone peptides can be differentially marked by stable isotope labeling in a second reaction of propionylation, which enables direct comparison between two different samples in the following MS analysis. PMID:22910200

  2. Peptide identification by tandem mass spectrometry with alternate fragmentation modes.

    PubMed

    Guthals, Adrian; Bandeira, Nuno

    2012-09-01

    The high-throughput nature of proteomics mass spectrometry is enabled by a productive combination of data acquisition protocols and the computational tools used to interpret the resulting spectra. One of the key components in mainstream protocols is the generation of tandem mass (MS/MS) spectra by peptide fragmentation using collision induced dissociation, the approach currently used in the large majority of proteomics experiments to routinely identify hundreds to thousands of proteins from single mass spectrometry runs. Complementary to these, alternative peptide fragmentation methods such as electron capture/transfer dissociation and higher-energy collision dissociation have consistently achieved significant improvements in the identification of certain classes of peptides, proteins, and post-translational modifications. Recognizing these advantages, mass spectrometry instruments now conveniently support fine-tuned methods that automatically alternate between peptide fragmentation modes for either different types of peptides or for acquisition of multiple MS/MS spectra from each peptide. But although these developments have the potential to substantially improve peptide identification, their routine application requires corresponding adjustments to the software tools and procedures used for automated downstream processing. This review discusses the computational implications of alternative and alternate modes of MS/MS peptide fragmentation and addresses some practical aspects of using such protocols for identification of peptides and post-translational modifications.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. 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.

  18. 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

  19. Elucidation of the mass fragmentation pathways of potato glycoalkaloids and aglycons using Orbitrap mass spectrometry.

    PubMed

    Cahill, Michael G; Caprioli, Giovanni; Vittori, Sauro; James, Kevin J

    2010-09-01

    The mass fragmentation of potato glycoalkaloids, α-solanine and α-chaconine, and the aglycons, demissidine and solasodine were studied using the Orbitrap Fourier transform (FT) mass spectrometer. Using the linear ion trap (LIT) mass spectrometry, multistage collisional-induced dissociation (CID) experiments (MS(n)) on the [M + H](+) precursor ions were performed to aid the elucidation of the mass fragmentation pathways. In addition, higher energy collisional-induced dissociation (HCD) mass spectra were generated for these toxins at a high resolution setting [100,000 FWHM (full width at half maximum)] using the Orbitrap. This hybrid mass spectrometry instrumentation was exploited to produce MS(3) spectra by selecting MS(2) product ions, generated using LIT MS, and fragmentation using HCD. The accurate mass data in the MS(3) spectra aided the confirmation of proposed product ion formulae. The precursor and product ions from glycoalkaloids lost up to four sugars from different regions during MS(n) experiments. Mass fragmentation of the six-ring aglycons were similar, generating major product ions that resulted from cleavages at the B-rings and E-rings.

  20. Ion sampling and transport in Inductively Coupled Plasma Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Farnsworth, Paul B.; Spencer, Ross L.

    2017-08-01

    Quantitative accuracy and high sensitivity in inductively coupled plasma mass spectrometry (ICP-MS) depend on consistent and efficient extraction and transport of analyte ions from an inductively coupled plasma to a mass analyzer, where they are sorted and detected. In this review we examine the fundamental physical processes that control ion sampling and transport in ICP-MS and compare the results of theory and computerized models with experimental efforts to characterize the flow of ions through plasma mass spectrometers' vacuum interfaces. We trace the flow of ions from their generation in the plasma, into the sampling cone, through the supersonic expansion in the first vacuum stage, through the skimmer, and into the ion optics that deliver the ions to the mass analyzer. At each stage we consider idealized behavior and departures from ideal behavior that affect the performance of ICP-MS as an analytical tool.

  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. Mass spectrometry theory and application to adrenal diseases.

    PubMed

    Wooding, Kerry M; Auchus, Richard J

    2013-05-22

    The diagnosis and management of adrenal diseases hinge upon accurate determination of hormone concentrations in blood and other body fluids. The advent of immunoassays for various steroid hormones has enabled the remarkable progress in adrenal disease over the last several decades, with some limitation. Sequential immunoassay of single analytes is a tedious process, which requires aliquots for each assay. In many complex adrenal diseases, including adrenal cancer and congenital adrenal hyperplasia, the patterns or ratios of multiple steroids rather than the value of any one steroid is more relevant. Although gas chromatography/mass spectrometry of urinary steroid metabolites has been employed to profile steroid production, throughput is slow, and availability is sparse. Recent generations of liquid chromatography-tandem mass spectrometry instruments (LC-MS/MS) provide the throughput and sensitivity required to measure many steroids simultaneously using small samples for commercial and research uses. Even in the best hands, however, LC-MS/MS suffers from limitations and requires diligent attention to detail during method development and implementation. This article reviews the theory, instrumentation principles and terminology, and practical application of mass spectrometry to clinical adrenal disorders.

  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. Clusters of Monoisotopic Elements for Calibration in (TOF) Mass Spectrometry.

    PubMed

    Kolářová, Lenka; Prokeš, Lubomír; Kučera, Lukáš; Hampl, Aleš; Peňa-Méndez, Eladia; Vaňhara, Petr; Havel, Josef

    2017-03-01

    Precise calibration in TOF MS requires suitable and reliable standards, which are not always available for high masses. We evaluated inorganic clusters of the monoisotopic elements gold and phosphorus (Au n(+)/Au n(-) and P n(+)/P n(-)) as an alternative to peptides or proteins for the external and internal calibration of mass spectra in various experimental and instrumental scenarios. Monoisotopic gold or phosphorus clusters can be easily generated in situ from suitable precursors by laser desorption/ionization (LDI) or matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Their use offers numerous advantages, including simplicity of preparation, biological inertness, and exact mass determination even at lower mass resolution. We used citrate-stabilized gold nanoparticles to generate gold calibration clusters, and red phosphorus powder to generate phosphorus clusters. Both elements can be added to samples to perform internal calibration up to mass-to-charge (m/z) 10-15,000 without significantly interfering with the analyte. We demonstrated the use of the gold and phosphorous clusters in the MS analysis of complex biological samples, including microbial standards and total extracts of mouse embryonic fibroblasts. We believe that clusters of monoisotopic elements could be used as generally applicable calibrants for complex biological samples. Graphical Abstract ᅟ.

  9. Clusters of Monoisotopic Elements for Calibration in (TOF) Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kolářová, Lenka; Prokeš, Lubomír; Kučera, Lukáš; Hampl, Aleš; Peňa-Méndez, Eladia; Vaňhara, Petr; Havel, Josef

    2016-12-01

    Precise calibration in TOF MS requires suitable and reliable standards, which are not always available for high masses. We evaluated inorganic clusters of the monoisotopic elements gold and phosphorus (Au n +/Au n - and P n +/P n -) as an alternative to peptides or proteins for the external and internal calibration of mass spectra in various experimental and instrumental scenarios. Monoisotopic gold or phosphorus clusters can be easily generated in situ from suitable precursors by laser desorption/ionization (LDI) or matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Their use offers numerous advantages, including simplicity of preparation, biological inertness, and exact mass determination even at lower mass resolution. We used citrate-stabilized gold nanoparticles to generate gold calibration clusters, and red phosphorus powder to generate phosphorus clusters. Both elements can be added to samples to perform internal calibration up to mass-to-charge (m/z) 10-15,000 without significantly interfering with the analyte. We demonstrated the use of the gold and phosphorous clusters in the MS analysis of complex biological samples, including microbial standards and total extracts of mouse embryonic fibroblasts. We believe that clusters of monoisotopic elements could be used as generally applicable calibrants for complex biological samples.

  10. Clusters of Monoisotopic Elements for Calibration in (TOF) Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Kolářová, Lenka; Prokeš, Lubomír; Kučera, Lukáš; Hampl, Aleš; Peňa-Méndez, Eladia; Vaňhara, Petr; Havel, Josef

    2017-03-01

    Precise calibration in TOF MS requires suitable and reliable standards, which are not always available for high masses. We evaluated inorganic clusters of the monoisotopic elements gold and phosphorus (Au n +/Au n - and P n +/P n -) as an alternative to peptides or proteins for the external and internal calibration of mass spectra in various experimental and instrumental scenarios. Monoisotopic gold or phosphorus clusters can be easily generated in situ from suitable precursors by laser desorption/ionization (LDI) or matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Their use offers numerous advantages, including simplicity of preparation, biological inertness, and exact mass determination even at lower mass resolution. We used citrate-stabilized gold nanoparticles to generate gold calibration clusters, and red phosphorus powder to generate phosphorus clusters. Both elements can be added to samples to perform internal calibration up to mass-to-charge ( m/z) 10-15,000 without significantly interfering with the analyte. We demonstrated the use of the gold and phosphorous clusters in the MS analysis of complex biological samples, including microbial standards and total extracts of mouse embryonic fibroblasts. We believe that clusters of monoisotopic elements could be used as generally applicable calibrants for complex biological samples.

  11. 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

  12. High Resolution Double-Focusing Isotope Ratio Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Radke, J.; Deerberg, M.; Hilkert, A.; Schlüter, H.-J.; Schwieters, J.

    2012-04-01

    In recent years isotope ratio mass spectrometry has extended to the capability of quantifying very small isotope signatures related with low abundances and simultaneously detecting molecular masses such as isotopomers and isotopologues containing clumped isotopes. Some of those applications are limited by molecular interferences like different gas molecules with the same nominal mass, e.g. Ar/O2, adducts of the same molecule or of different molecules, and very small isotope abundances. The Thermo Scientific MAT 253 ULTRA is the next generation of high precision gas isotope ratio mass spectrometry, which combines a 10 KV gas ionization source (Thermo Scientific MAT 253) with a double focusing multi-collector mass analyzer (Thermo Scientific Neptune) and reduces those limitations by measuring isotope ratios on a larger dynamic range with high precision. Small ion beam requirements and high sensitivity are achieved by signal-to-noise improvements through enhanced ion beam amplification in faraday cups and ion counters. Interfering backgrounds, e.g. interfering isotopologues or isobaric ions of contaminants, are dramatically decreased by a dynamic range increase combined with high evacuation leading to undisturbed ion transmission through the double-focusing analyser. Furthermore, automated gain calibration for mathematical baseline corrections, switchable detector arrays, ion source control, analyser focusing and full data export is controlled under Isodat data control. New reference/sample strategies are under investigation besides incorporation of the continuous-flow technique and its versatile inlet devices. We are presenting first results and applications of the MAT 253 Ultra.

  13. Characterization of a Distributed Plasma Ionization Source (DPIS) for Ion Mobility Spectrometry and Mass Spectrometry

    SciTech Connect

    Waltman, Melanie J.; Dwivedi, Prabha; Hill, Herbert; Blanchard, William C.; Ewing, Robert G.

    2008-10-15

    A recently developed atmospheric pressure ionization source, a distributed plasma ionization source (DPIS), was characterized and compared to commonly used atmospheric pressure ionization sources with both mass spectrometry and ion mobility spectrometry. The source consisted of two electrodes of different sizes separated by a thin dielectric. Application of a high RF voltage across the electrodes generated plasma in air yielding both positive and negative ions depending on the polarity of the applied potential. These reactant ions subsequently ionized the analyte vapors. The reactant ions generated were similar to those created in a conventional point-to-plane corona discharge ion source. The positive reactant ions generated by the source were mass identified as being solvated protons of general formula (H2O)nH+ with (H2O)2H+ as the most abundant reactant ion. The negative reactant ions produced were mass identified primarily as CO3-, NO3-, NO2-, O3- and O2- of various relative intensities. The predominant ion and relative ion ratios varied depending upon source construction and supporting gas flow rates. A few compounds including drugs, explosives and environmental pollutants were selected to evaluate the new ionization source. The source was operated continuously for several months and although deterioration was observed visually, the source continued to produce ions at a rate similar that of the initial conditions. The results indicated that the DPIS may have a longer operating life than a conventional corona discharge.

  14. Characterization of a distributed plasma ionization source (DPIS) for ion mobility spectrometry and mass spectrometry.

    PubMed

    Waltman, Melanie J; Dwivedi, Prabha; Hill, Herbert H; Blanchard, William C; Ewing, Robert G

    2008-10-19

    A recently developed atmospheric pressure ionization source, a distributed plasma ionization source (DPIS), was characterized and compared to commonly used atmospheric pressure ionization sources with both mass spectrometry (MS) and ion mobility spectrometry (IMS). The source consisted of two electrodes of different sizes separated by a thin dielectric. Application of a high RF voltage across the electrodes generated plasma in air yielding both positive and negative ions. These reactant ions subsequently ionized the analyte vapors. The reactant ions generated were similar to those created in a conventional point-to-plane corona discharge ion source. The positive reactant ions generated by the source were mass identified as being solvated protons of general formula (H(2)O)(n)H(+) with (H(2)O)(2)H(+) as the most abundant reactant ion. The negative reactant ions produced were mass identified primarily as CO(3)(-), NO(3)(-), NO(2)(-), O(3)(-) and O(2)(-) of various relative intensities. The predominant ion and relative ion ratios varied depending upon source construction and supporting gas flow rates. A few compounds including drugs, explosives and amines were selected to evaluate the new ionization source. The source was operated continuously for 3 months and although surface deterioration was observed visually, the source continued to produce ions at a rate similar that of the initial conditions.

  15. 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.

  16. 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

  17. [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.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Angular and internal state distributions of H2+ generated by (2 + 1) resonance enhanced multiphoton ionization of H2 using time-of-flight mass spectrometry

    NASA Astrophysics Data System (ADS)

    Perreault, William E.; Mukherjee, Nandini; Zare, Richard N.

    2016-06-01

    We report direct measurement of the anisotropy parameter β for the angular distribution of the photoelectron and photoion in (2 + 1) resonance enhanced multiphoton ionization process of H2 X 1 Σg + (v = 0, J = 0) molecules through the intermediate H2 E,F 1 Σg + (v' = 0, J' = 0) level (λ = 201.684 nm) using a time-of-flight mass spectrometer. The time-of-flight spectra were recorded as the direction of polarization of the ionizing laser was varied with respect to the flight axis of the H2 molecular beam and were fitted to an angular distribution in an appropriately rotated coordinate system with the z-axis oriented along the time-of-flight axis. The anisotropy parameter β was found to be 1.72 ± 0.13 by fitting the time-of-flight spectra and agreed with previous measurements. Using secondary ionization with a delayed laser pulse of different wavelength, we also determined the vibrational energy distribution of the ions, showing that 98% ± 4% of the ions are generated in their ground vibrational state, in agreement with the calculated Franck-Condon factors between the H2 E,F 1 Σg + (v' = 0) and H 2+ X 1 Σg + (v″) vibrational levels.

  14. Angular and internal state distributions of H2 (+) generated by (2 + 1) resonance enhanced multiphoton ionization of H2 using time-of-flight mass spectrometry.

    PubMed

    Perreault, William E; Mukherjee, Nandini; Zare, Richard N

    2016-06-07

    We report direct measurement of the anisotropy parameter β for the angular distribution of the photoelectron and photoion in (2 + 1) resonance enhanced multiphoton ionization process of H2 X (1)Σg (+) (v = 0, J = 0) molecules through the intermediate H2 E,F (1)Σg (+) (v' = 0, J' = 0) level (λ = 201.684 nm) using a time-of-flight mass spectrometer. The time-of-flight spectra were recorded as the direction of polarization of the ionizing laser was varied with respect to the flight axis of the H2 molecular beam and were fitted to an angular distribution in an appropriately rotated coordinate system with the z-axis oriented along the time-of-flight axis. The anisotropy parameter β was found to be 1.72 ± 0.13 by fitting the time-of-flight spectra and agreed with previous measurements. Using secondary ionization with a delayed laser pulse of different wavelength, we also determined the vibrational energy distribution of the ions, showing that 98% ± 4% of the ions are generated in their ground vibrational state, in agreement with the calculated Franck-Condon factors between the H2 E,F (1)Σg (+) (v' = 0) and H2 (+) X (1)Σg (+) (v″) vibrational levels.

  15. A practical method for the determination of total selenium in environmental samples using isotope dilution-hydride generation-inductively coupled plasma-mass spectrometry

    USGS Publications Warehouse

    Kleckner, Amy E.; Kakouros, Evangelos; Stewart, A. Robin

    2017-01-01

    A safe, practical, and accurate method for the determination of selenium (Se) in range of environmental samples was developed. Small sample masses, 5–20 mg, were amended with 82Se enriched isotope for the isotope dilution (ID), preceding a multi-step wet digestion with nitric acid (HNO3) and hydrogen peroxide (H2O2). Samples were incubated in an autoclave for 3 h at 20 psi and 126°C. Digestates were subsequently reduced with concentrated hydrochloric acid to Se(IV) the most favorable valence for hydride generation (HG). The solutions were then analyzed on an ICP-MS equipped with Flow Injection system (FIAS-400). Polyatomic, isobaric, and background interferences were removed through the use of HG and ID with an 82Se enriched isotope spike. Recoveries for certified reference materials were determined and averaged 96% for biological tissues (NRCC DOLT3, DOLT4, DORM2, TORT2, and TORT3, and NIST 2976) and 108% for estuarine sediment (NRCC PACS2) with an average coefficient of variation for replicate measurements of ∼ 3.5%. Limit of detection was 0.13 ng Se g−1 dry weight or 0.19 ng Se L−1. This method can be broadly applied to biological tissues, sediments, suspended particulates, and water samples with minimal modifications making this method highly useful for assessing the ecotoxicology of total Se in aquatic ecosystems.

  16. 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.

  17. 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.

  18. Accurate, Direct, and High-Throughput Analyses of a Broad Spectrum of Endogenously Generated DNA Base Modifications with Isotope-Dilution Two-Dimensional Ultraperformance Liquid Chromatography with Tandem Mass Spectrometry: Possible Clinical Implication.

    PubMed

    Gackowski, Daniel; Starczak, Marta; Zarakowska, Ewelina; Modrzejewska, Martyna; Szpila, Anna; Banaszkiewicz, Zbigniew; Olinski, Ryszard

    2016-12-20

    Our hereby presented methodology is suitable for reliable assessment of the most common unavoidable DNA modifications which arise as a product of fundamental metabolic processes. 8-Oxoguanine, one of the oxidatively modified DNA bases, is a typical biomarker of oxidative stress. A noncanonical base, uracil, may be also present in small quantities in DNA. A set of ten-eleven translocation (TET) proteins are involved in oxidation of 5-methylcytosine to 5-hydroxymethylcytosine which can be further oxidized to 5-formylcytosine and 5-carboxycytosine. 5-Hydroxymethyluracil may be formed in deamination reaction of 5-hydroxymethylcytosine or can be also generated by TET enzymes. All of the aforementioned modifications seem to play some regulatory roles. We applied isotope-dilution automated online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS) for direct measurement of the 5-methyl-2'-deoxycytidine, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine, 5-carboxy-2'-deoxycytidine, 5-(hydroxymethyl)-2'-deoxyuridine, 2'-deoxyuridine, and 8-oxo-2'-deoxyguanosine. Analyses of DNA extracted from matched human samples showed that the 5-(hydroxymethyl)-2'-deoxycytidine level was 5-fold lower in colorectal carcinoma tumor in comparison with the normal one from the tumor's margin; also 5-formyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine were lower in colorectal carcinoma tissue (ca. 2.5- and 3.5-fold, respectively). No such differences was found for 2'-deoxyuridine and 5-(hydroxymethyl)-2'-deoxyuridine. The presented methodology is suitable for fast, accurate, and complex evaluation of an array of endogenously generated DNA deoxynucleosides modifications. This novel technique could be used for monitoring of cancer and other diseases related to oxidative stress, aberrant metabolism, and environmental exposure. Furthermore, the fully automated two-dimensional separation is extremely useful for analysis of material

  19. Web Resources for Mass Spectrometry-based Proteomics

    PubMed Central

    Chen, Tao; Zhao, Jie; Ma, Jie; Zhu, Yunping

    2015-01-01

    With the development of high-resolution and high-throughput mass spectrometry (MS) technology, a large quantum of proteomic data is continually being generated. Collecting and sharing these data are a challenge that requires immense and sustained human effort. In this report, we provide a classification of important web resources for MS-based proteomics and present rating of these web resources, based on whether raw data are stored, whether data submission is supported, and whether data analysis pipelines are provided. These web resources are important for biologists involved in proteomics research. PMID:25721607

  20. Laser desorption mass spectrometry for point mutation detection

    SciTech Connect

    Taranenko, N.I.; Chung, C.N.; Zhu, Y.F.

    1996-10-01

    A point mutation can be associated with the pathogenesis of inherited or acquired diseases. Laser desorption mass spectrometry coupled with allele specific polymerase chain reaction (PCR) was first used for point mutation detection. G551D is one of several mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene present in 1-3% of the mutant CFTR alleles in most European populations. In this work, two different approaches were pursued to detect G551D point mutation in the cystic fibrosis gene. The strategy is to amplify the desired region of DNA template by PCR using two primers that overlap one base at the site of the point mutation and which vary in size. If the two primers based on the normal sequence match the target DNA sequence, a normal PCR product will be produced. However, if the alternately sized primers that match the mutant sequence recognize the target DNA, an abnormal PCR product will be produced. Thus, the mass spectrometer can be used to identify patients that are homozygous normal, heterozygous for a mutation or homozygous abnormal at a mutation site. Another approach to identify similar mutations is the use of sequence specific restriction enzymes which respond to changes in the DNA sequence. Mass spectrometry is used to detect the length of the restriction fragments generated by digestion of a PCR generated target fragment. 21 refs., 10 figs., 2 tabs.

  1. 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.

  2. 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

  3. 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

  4. Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry.

    PubMed

    Collins, Ben C; Hunter, Christie L; Liu, Yansheng; Schilling, Birgit; Rosenberger, George; Bader, Samuel L; Chan, Daniel W; Gibson, Bradford W; Gingras, Anne-Claude; Held, Jason M; Hirayama-Kurogi, Mio; Hou, Guixue; Krisp, Christoph; Larsen, Brett; Lin, Liang; Liu, Siqi; Molloy, Mark P; Moritz, Robert L; Ohtsuki, Sumio; Schlapbach, Ralph; Selevsek, Nathalie; Thomas, Stefani N; Tzeng, Shin-Cheng; Zhang, Hui; Aebersold, Ruedi

    2017-08-21

    Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently detect and reproducibly quantify >4000 proteins from HEK293 cells. Using synthetic peptide dilution series, we show that the sensitivity, dynamic range and reproducibility established with SWATH-mass spectrometry are uniformly achieved. This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification.SWATH-mass spectrometry consists of a data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics on the scale of thousands of proteins. Here, using data generated by eleven groups worldwide, the authors show that SWATH-MS is capable of generating highly reproducible data across different laboratories.

  5. Uncovering Biologically Significant Lipid Isomers with Liquid Chromatography, Ion Mobility Spectrometry and Mass Spectrometry

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2016-01-01

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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Laser ablation generation of clusters from As-Te mixtures, As-Te glass nano-layers and from Au-As-Te nano-composites. Quadrupole ion trap time-of-flight mass spectrometry.

    PubMed

    Štěpánová, Vlasta; Prokeš, Lubomír; Slavíček, Pavel; Alberti, Milan; Havel, Josef

    2015-06-15

    Arsenic tellurides have found important applications in various fields of science, but only a few gold-arsenic tellurides have been reported. Laser ablation synthesis (LAS), a suitable method for the generation of new compounds, has been used to generate clusters from As-Te mixtures, an As-Te glass and Au-As-Te nano-composites. Chalcogenide glass nano-layers prepared via Physical Vapour Deposition - thermal evaporation were characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). LAS with laser desorption ionisation quadrupole ion trap time-of-flight mass spectrometry (LDI QIT TOFMS) was used for the generation and analysis of new AuxAsmTen clusters. The stoichiometry of the clusters was determined via isotopic envelope modelling. A simple procedure for the preparation of the Au-As-Te nano-composite was developed. From As-Te mixtures only five binary AsmTen clusters were generated, while from a glass layer 10 binary AsmTen clusters were identified, because during the deposition of the glass the elements reacted with each other to form a complex three-dimensional (3D) structure. Using LAS on the Au-As-Te nano-composite leads to the formation of six unary Ten (n = 1-6), 16 binary (AsmTen and AuxTen), and 31 ternary AuxAsmTen clusters. LAS was demonstrated to be a useful technique for the generation of AuxAsmTen clusters in the gas phase. More AsmTen clusters were generated from the deposited glass layers than from As-Te mixtures. Most of the ternary AuxAsmTen clusters generated from the nano-composite are reported here for the first time. Copyright © 2015 John Wiley & Sons, Ltd.

  16. 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

  17. 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

  18. 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.

  19. Ion-molecule adduct formation in tandem mass spectrometry.

    PubMed

    Alechaga, Élida; Moyano, Encarnación; Galceran, Maria Teresa

    2016-02-01

    Nowadays most LC-MS methods rely on tandem mass spectrometry not only for quantitation and confirmation of compounds by multiple reaction monitoring (MRM), but also for the identification of unknowns from their product ion spectra. However, gas-phase reactions between charged and neutral species inside the mass analyzer can occur, yielding product ions at m/z values higher than that of the precursor ion, or at m/z values difficult to explain by logical losses, which complicate mass spectral interpretation. In this work, the formation of adduct ions in the mass analyzer was studied using several mass spectrometers with different mass analyzers (ion trap, triple quadrupole, and quadrupole-Orbitrap). Heterocyclic amines (AαC, MeAαC, Trp-P-1, and Trp-P-2), photo-initiators (BP and THBP), and pharmaceuticals (phenacetin and levamisole) were selected as model compounds and infused in LCQ Classic, TSQ Quantum Ultra AM, and Q-Exactive Orbitrap (ThermoFisher Scientific) mass spectrometers using electrospray as ionization method. The generation of ion-molecule adducts depended on the compound and also on the instrument employed. Adducts with neutral organic solvents (methanol and acetonitrile) were only observed in the ion trap instrument (LCQ Classic), because of the ionization source on-axis configuration and the lack of gas-phase barriers, which allowed inertial entrance of the neutrals into the analyzer. Adduct formation (only with water) in the triple quadrupole instruments was less abundant than in the ion trap and quadrupole-Orbitrap mass spectrometers, because of the lower residence time of the reactive product ions in the mass analyzer. The moisture level of the CID and/or damper gas had a great effect in beam-like mass analyzers such as triple quadrupole, but not in trap-like mass analyzers, probably because of the long residence time that allowed adduct formation even with very low concentrations of water inside the mass spectrometer.

  20. A third-generation electro-kinetically pumped sheath flow nanospray interface with improved stability and sensitivity for automated capillary zone electrophoresis-mass spectrometry analysis of complex proteome digests

    PubMed Central

    Sun, Liangliang; Zhu, Guijie; Zhang, Zhenbin; Mou, Si; Dovichi, Norman J.

    2015-01-01

    We have reported a set of electrokinetically pumped sheath flow nanoelectrospray interfaces to couple capillary zone electrophoresis with mass spectrometry. A separation capillary is threaded through a cross into a glass emitter. A side arm provides fluidic contact with a sheath buffer reservoir that is connected to a power-supply. The potential applied to the sheath buffer drives electro-osmosis in the emitter to pump the sheath fluid at nanoliter/minute rates. Our first generation interface placed a flat-tipped capillary in the emitter. Sensitivity was inversely related to orifice size and to the distance from the capillary tip to the emitter orifice. A second generation interface used a capillary with an etched tip that allowed the capillary exit to approach within a few hundred micrometers of the emitter orifice, resulting in a significant increase in sensitivity. In both the first and second-generation interfaces, the emitter diameter was typically 8-μm; these narrow orifices were susceptible to plugging and tended to have limited lifetime. We now report a third-generation interface that employs a larger diameter emitter orifice with very short distance between the capillary tip and the emitter orifice. This modified interface is much more robust and produces much longer lifetime than our earlier designs with no loss in sensitivity. We evaluated the third-generation interface for a 5,000-min (127 runs, 3.5 days) repetitive analysis of bovine serum albumin digest using an uncoated capillary. We observed a 10% relative standard deviation in peak area, an average of 160,000 theoretical plates, and very low carry-over (much less than 1%). We employed a linear-polyacrylamide (LPA) coated capillary for single-shot, bottom-up proteomic analysis of 300 ng of Xenopus laevis fertilized egg proteome digest, and identified 1,249 protein groups and 4,038 peptides in a 110 min separation using an LTQ-Orbitrap Velos mass spectrometer; peak capacity was ~330. The proteome

  1. 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…

  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. 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.

  4. Towards airborne nanoparticle mass spectrometry with nanomechanical string resonators

    NASA Astrophysics Data System (ADS)

    Schmid, Silvan; Kurek, Maksymilian; Boisen, Anja

    2013-06-01

    Airborne nanoparticles can cause severe harm when inhaled. Therefore, small and cheap portable airborne nanoparticle monitors are highly demanded by authorities and the nanoparticle producing industry. We propose to use nanomechanical resonators to build the next generation cheap and portable airborne nanoparticle sensors. Recently, nanomechanical mass spectrometry was established. One of the biggest challenges of nanomechanical sensors is the low efficiency of diffusion-based sampling. We developed an inertial-based sampling method that enables the efficient sampling of airborne nanoparticles on a nanomechanical sensor operating directly in air. We measured a sampling rate of over 1000 particles per second, for 28 nm silica nanoparticles with a concentration of 380000 #/cm3, collected on a 500 nm wide nanomechanical string resonator. We show that it is possible to reach a saturated sampling regime in which 100% of all nanoparticles are captured that are owing in the projection of the nanostring. We further show that it is possible to detect single airborne nanoparticles by detecting 50 nm Au particles with a 250 nm wide string resonator. Our resonators are currently operating in the first bending mode. Mass spectrometry of airborne nanoparticles requires the simultaneous operation in the first and second mode, which can be implemented in the transduction scheme of the resonator. The presented results lay the cornerstone for the realization of a portable airborne nanoparticle mass spectrometer.

  5. Laser desorption mass spectrometry for point mutation detection

    SciTech Connect

    Taranenko, N.I.; Chung, C.N.; Zhu, Y.F.

    1996-12-31

    A point mutation can be associated with the pathogenesis of inherited or acquired diseases. Laser desorption mass spectrometry coupled with allele specific polymerase chain reaction (PCR) was first used for point mutation detection. G551D is one of several mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene present in 1-3% of the mutant CFTR alleles in most European populations. In this work, two different approaches were pursued to detect G551D point mutation in the cystic fibrosis gene. The strategy is to amplify the desired region of DNA template by PCR using two primers that overlap one base at the site of the point mutation and which vary in size. If the two primers based on the normal sequence match the target DNA sequence, a normal PCR product will be produced. However, if the alternately sized primers that match the mutant sequence recognize the target DNA, an abnormal PCR product will be produced. Thus, the mass spectrometer can be used to identify patients that are homozygous normal, heterozygous for a mutation or homozygous abnormal at a mutation site. Another approach to identify similar mutations is the use of sequence specific restriction enzymes which respond to changes in the DNA sequence. Mass spectrometry is used to detect the length of the restriction fragments by digestion of a PCR generated target fragment. 21 refs., 10 figs., 2 tabs.

  6. 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.

  7. 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.

  8. [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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  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. A COMPARISON OF URINARY ARSENIC SPECIATION VIA DIRECT NEBULIZATION AND ON-LINE PHOTOOXIDATION-HYDRIDE GENERATION WITH DETECTION BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

    EPA Science Inventory

    Arsenic speciation continues to be important in assessing human and environmental exposure risk. Urinary arsenic analysis provides information on recent arsenic exposure. In this study, two sample introduction pathways: direct nebulization (DN) and hydride generation (HG) were ut...

  18. A COMPARISON OF URINARY ARSENIC SPECIATION VIA DIRECT NEBULIZATION AND ON-LINE PHOTOOXIDATION-HYDRIDE GENERATION WITH DETECTION BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

    EPA Science Inventory

    Arsenic speciation continues to be important in assessing human and environmental exposure risk. Urinary arsenic analysis provides information on recent arsenic exposure. In this study, two sample introduction pathways: direct nebulization (DN) and hydride generation (HG) were ut...

  19. Sequencing of Oligourea Foldamers by Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bathany, Katell; Owens, Neil W.; Guichard, Gilles; Schmitter, Jean-Marie

    2013-03-01

    This study is focused on sequence analysis of peptidomimetic helical oligoureas by means of tandem mass spectrometry, to build a basis for de novo sequencing for future high-throughput combinatorial library screening of oligourea foldamers. After the evaluation of MS/MS spectra obtained for model compounds with either MALDI or ESI sources, we found that the MALDI-TOF-TOF instrument gave more satisfactory results. MS/MS spectra of oligoureas generated by decay of singly charged precursor ions show major ion series corresponding to fragmentation across both CO-NH and N'H-CO urea bonds. Oligourea backbones fragment to produce a pattern of a, x, b, and y type fragment ions. De novo decoding of spectral information is facilitated by the occurrence of low mass reporter ions, representative of constitutive monomers, in an analogous manner to the use of immonium ions for peptide sequencing.

  20. Analysis of protein composition using multidimensional chromatography and mass spectrometry.

    PubMed

    Link, Andrew J; Washburn, Michael P

    2014-11-03

    Multidimensional liquid chromatography of peptides produced by protease digestion of complex protein mixtures followed by tandem mass spectrometry can be coupled with automated database searching to identify large numbers of proteins in complex samples. These methods avoid the limitations of gel electrophoresis and in-gel digestions by directly identifying protein mixtures in solution. One method used extensively is named Multidimensional Protein Identification Technology (MudPIT), where reversed-phase chromatography and strong cation-exchange chromatography are coupled directly in a microcapillary column. This column is then placed in line between an HPLC and a mass spectrometer for complex mixture analysis. MudPIT remains a powerful approach for analyzing complex mixtures like whole proteomes and protein complexes. MudPIT is used for quantitative proteomic analysis of complex mixtures to generate novel biological insights.

  1. 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

  2. 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.

  3. 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.

  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

    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.

  5. Charge Assisted Laser Desorption/Ionization Mass Spectrometry of Droplets

    PubMed Central

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

    2008-01-01

    We propose and evaluate a new mechanism to account for analyte ion signal enhancement in ultraviolet-laser desorption mass spectrometry of droplets in the presence of corona ions. Our new insights are based on timing control of corona ion production, laser desorption, and peptide ion extraction achieved by a novel pulsed corona apparatus. We demonstrate that droplet charging rather than gas-phase ion-neutral reactions is the major contributor to analyte ion generation from an electrically isolated droplet. Implications of the new mechanism, termed charge assisted laser desorption/ionization (CALDI), are discussed and contrasted to those of the laser desorption atmospheric pressure chemical ionization method (LD-APCI). It is also demonstrated that analyte ion generation in CALDI occurs with external electric fields about one order of magnitude lower than those needed for atmospheric pressure matrix assisted laser desorption/ionization or electrospray ionization of droplets. PMID:18387311

  6. Method for predicting peptide detection in mass spectrometry

    DOEpatents

    Kangas, Lars [West Richland, WA; Smith, Richard D [Richland, WA; Petritis, Konstantinos [Richland, WA

    2010-07-13

    A method of predicting whether a peptide present in a biological sample will be detected by analysis with a mass spectrometer. The method uses at least one mass spectrometer to perform repeated analysis of a sample containing peptides from proteins with known amino acids. The method then generates a data set of peptides identified as contained within the sample by the repeated analysis. The method then calculates the probability that a specific peptide in the data set was detected in the repeated analysis. The method then creates a plurality of vectors, where each vector has a plurality of dimensions, and each dimension represents a property of one or more of the amino acids present in each peptide and adjacent peptides in the data set. Using these vectors, the method then generates an algorithm from the plurality of vectors and the calculated probabilities that specific peptides in the data set were detected in the repeated analysis. The algorithm is thus capable of calculating the probability that a hypothetical peptide represented as a vector will be detected by a mass spectrometry based proteomic platform, given that the peptide is present in a sample introduced into a mass spectrometer.

  7. On-line chemical vapour generation of cadmium in the presence of hexacyanochromate(III) for determination by inductively coupled plasma mass spectrometry (ICP-MS).

    PubMed

    Yilmaz, Vedat; Rose, Lakeysha; Arslan, Zikri; Little, Maria D

    2012-11-01

    A vapour generation (VG) procedure has been described for determination of Cd by ICP-MS. Volatile species of Cd were generated on-line by interacting acidic sample solution containing potassium hexacyanochromate(III), K3Cr(CN)6, with sodium borohydride (NaBH4). The hexacyanochromate(III) complex was generated on-line by reacting 0.04 mol L(-1) chromium(III) nitrate and 0.16 mol L(-1) potassium cyanide (KCN) solutions in water. The resulting suspension of chromium(III) hydroxide, Cr(OH)3, was fed continuously to acidic stream of sample solution in the presence of excess KCN. The experimental conditions were optimized for effective generation of volatile species of Cd. Optimum signals were obtained from reaction of sample solutions in 4% v/v HCl with 2% m/v NaBH4 solution. Presence of K3Cr(CN)6 improved the efficiency of Cd vapour generation substantially affording 15-fold higher sensitivity. This phenomenon was thought to occur through formation of reactive intermediates evolved from interaction of [Cr(CN)6](3-) with NaBH4 that react with Cd(II) to increase the yield volatile Cd species. Under the optimum conditions, no significant interferences were observed from the transition metals, including Cu and Ni, up to 1.0 μg mL(-1) levels. Among the hydride forming elements, Bi, Pb, Sb and Sn depressed the signals above 0.1 μg mL(-1). The detection limits (3s) were 6.2 and 5.2 ng L(-1) for (110)Cd and (111)Cd isotopes, respectively. The method was successfully applied to determination of Cd by ICP-MS in several certified reference materials, including Nearshore seawater (CASS-4), Bone ash (SRM 1400), Dogfish liver (DOLT-4) and Mussel tissue (SRM 2976).

  8. On-line chemical vapour generation of cadmium in the presence of hexacyanochromate(III) for determination by inductively coupled plasma mass spectrometry (ICP-MS)

    PubMed Central

    Yilmaz, Vedat; Rose, LaKeysha; Little, Maria D.

    2012-01-01

    A vapour generation (VG) procedure has been described for determination of Cd by ICP-MS. Volatile species of Cd were generated on-line by interacting acidic sample solution containing potassium hexacyanochromate(III), K3Cr(CN)6, with sodium borohydride (NaBH4). The hexacyanochromate(III) complex was generated on-line by reacting 0.04 mol L−1 chromium(III) nitrate and 0.16 mol L−1 potassium cyanide (KCN) solutions in water. The resulting suspension of chromium(III) hydroxide, Cr(OH)3, was fed continuously to acidic stream of sample solution in the presence of excess KCN. The experimental conditions were optimized for effective generation of volatile species of Cd. Optimum signals were obtained from reaction of sample solutions in 4% v/v HCl with 2% m/v NaBH4 solution. Presence of K3Cr(CN)6 improved the efficiency of Cd vapour generation substantially affording 15-fold higher sensitivity. This phenomenon was thought to occur through formation of reactive intermediates evolved from interaction of [Cr(CN)6]3− with NaBH4 that react with Cd(II) to increase the yield volatile Cd species. Under the optimum conditions, no significant interferences were observed from the transition metals, including Cu and Ni, up to 1.0 μg mL−1 levels. Among the hydride forming elements, Bi, Pb, Sb and Sn depressed the signals above 0.1 μg mL−1. The detection limits (3s) were 6.2 and 5.2 ng L−1 for 110Cd and 111Cd isotopes, respectively. The method was successfully applied to determination of Cd by ICP-MS in several certified reference materials, including Nearshore seawater (CASS-4), Bone ash (SRM 1400), Dogfish liver (DOLT-4) and Mussel tissue (SRM 2976). PMID:23997384

  9. 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.

  10. Statistical design of mass spectrometry calibration procedures

    SciTech Connect

    Bayne, C.K.

    1996-11-01

    The main objective of this task was to agree on calibration procedures to estimate the system parameters (i.e., dead-time correction, ion-counting conversion efficiency, and detector efficiency factors) for SAL`s new Finnigan MAT-262 mass spectrometer. SAL will use this mass spectrometer in a clean-laboratory which was opened in December 1995 to measure uranium and plutonium isotopes on environmental samples. The Finnigan MAT-262 mass spectrometer has a multi-detector system with seven Faraday cup detectors and one ion- counter for the measurement of very small signals (e.g. 10{sup -17} Ampere range). ORNL has made preliminary estimates of the system parameters based on SAL`s experimental data measured in late 1994 when the Finnigan instrument was relatively new. SAL generated additional data in 1995 to verify the calibration procedures for estimating the dead-time correction factor, the ion-counting conversion factor and the Faraday cup detector efficiency factors. The system parameters estimated on the present data will have to be reestablished when the Finnigan MAT-262 is moved-to the new clean- laboratory. Different methods will be used to analyzed environmental samples than the current measurement methods being used. For example, the environmental samples will be electroplated on a single filament rather than using the current two filament system. An outline of the calibration standard operating procedure (SOP) is included.

  11. Generation of Au(p)Ag(q)Te(r) clusters via laser ablation synthesis using Au-Ag-Te nano-composite as precursor: quadrupole ion-trap time-of-flight mass spectrometry.

    PubMed

    Mawale, Ravi Madhukar; Amato, Filippo; Alberti, Milan; Havel, Josef

    2014-07-30

    Metal tellurides have applications in various fields of science and technology but only a few gold-silver tellurides have been reported. The laser ablation synthesis (LAS) method allows the preparation of nano-materials from solid substrates. Therefore, this method was selected to synthesise some gold-silver tellurides. Laser desorption ionisation quadrupole ion trap time-of-flight mass spectrometry (LDI QIT TOF MS) was used for the generation of new Au(p)Ag(q)Te(r) clusters. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to characterise the materials. The stoichiometry of the clusters generated was determined via collision-induced dissociation (CID) and modeling of isotopic patterns. Chemisorption of gold and silver nano-particles on tellurium powder led to the formation of a new kind of Au-Ag-Te nano-composite. The LDI of this nano-composite yielded nine unary (Ag(q), Te(r)), 40 binary (Au(p)Te(r) and Ag(p)Te(r)) and 78 ternary clusters. The stoichiometry of these novel Au(p)Ag(q)Te(r) clusters is reported here for the first time. The new Au-Ag-Te nano-composite was found to be a more suitable precursor for the generation of clusters than the mixtures of the elements. TOF MS was shown to be a useful technique for following the generation of gold-silver tellurides. Knowledge of the cluster stoichiometry could accelerate the further development of novel high-tech materials such as chalcogenide glasses. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Mass Spectrometry of Atmospheric Pressure Surface Wave Discharges

    NASA Astrophysics Data System (ADS)

    Ridenti, M. A.; Souza-Corrêa, J. A.; Amorim, J.

    2016-05-01

    By applying mass spectrometry techniques, we carried out measurements of ionic mass spectrum and their energy distribution in order to investigate an atmospheric argon discharge by using a surfatron surface-wave device. The mass and energy distribution measurements were performed with fixed flow rate (2.5 SLM) of pure argon gas (99.999%) and different Ar-O2 gas mixture compositions (99-1, 98-2 and 97-3). The mass spectra and energy distributions were recorded for Ar+, O+, O+ 2, N+ and N2 +. The axial distribution profiles of ionic mass and their energy were obtained for different experimental conditions as a function of the plasma length. The results showed that the peak of the positive ion energy distributions shifted to higher energies and also that the distribution width increased as the distance between the sampling orifice and the launcher gap was increased. It was also found that under certain experimental conditions the ion flux of atomic species were higher than the ion flux of their diatomic counterpart. The motivation of this study was to obtain a better understanding of a surface wave discharge in atmospheric pressure that may play a key role on new second generation biofuel technologies.

  13. High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

    NASA Astrophysics Data System (ADS)

    Dimzon, Ian Ken; Trier, Xenia; Frömel, Tobias; Helmus, Rick; Knepper, Thomas P.; de Voogt, Pim

    2016-02-01

    High resolution mass spectrometry (HRMS) was successfully applied to elucidate the structure of a polyfluorinated polyether (PFPE)-based formulation. The mass spectrum generated from direct injection into the MS was examined by identifying the different repeating units manually and with the aid of an instrument data processor. Highly accurate mass spectral data enabled the calculation of higher-order mass defects. The different plots of MW and the nth-order mass defects (up to n = 3) could aid in assessing the structure of the different repeating units and estimating their absolute and relative number per molecule. The three major repeating units were -C2H4O-, -C2F4O-, and -CF2O-. Tandem MS was used to identify the end groups that appeared to be phosphates, as well as the possible distribution of the repeating units. Reversed-phase HPLC separated of the polymer molecules on the basis of number of nonpolar repeating units. The elucidated structure resembles the structure in the published manufacturer technical data. This analytical approach to the characterization of a PFPE-based formulation can serve as a guide in analyzing not just other PFPE-based formulations but also other fluorinated and non-fluorinated polymers. The information from MS is essential in studying the physico-chemical properties of PFPEs and can help in assessing the risks they pose to the environment and to human health.

  14. Use of Tritium Accelerator Mass Spectrometry for Tree Ring Analysis

    PubMed Central

    LOVE, ADAM H.; HUNT, JAMES R.; ROBERTS, MARK L.; SOUTHON, JOHN R.; CHIARAPPA - ZUCCA, MARINA L.; DINGLEY, KAREN H.

    2010-01-01

    Public concerns over the health effects associated with low-level and long-term exposure to tritium released from industrial point sources have generated the demand for better methods to evaluate historical tritium exposure levels for these communities. The cellulose of trees accurately reflects the tritium concentration in the source water and may contain the only historical record of tritium exposure. The tritium activity in the annual rings of a tree was measured using accelerator mass spectrometry to reconstruct historical annual averages of tritium exposure. Milligram-sized samples of the annual tree rings from a Tamarix located at the Nevada Test Site are used for validation of this methodology. The salt cedar was chosen since it had a single source of tritiated water that was well-characterized as it varied over time. The decay-corrected tritium activity of the water in which the salt cedar grew closely agrees with the organically bound tritium activity in its annual rings. This demonstrates that the milligram-sized samples used in tritium accelerator mass spectrometry are suited for reconstructing anthropogenic tritium levels in the environment. PMID:12144257

  15. Photosensitized oxidation of phosphatidylethanolamines monitored by electrospray tandem mass spectrometry.

    PubMed

    Melo, Tânia; Santos, Nuno; Lopes, Diana; Alves, Eliana; Maciel, Elisabete; Faustino, Maria A F; Tomé, João P C; Neves, Maria G P M S; Almeida, Adelaide; Domingues, Pedro; Segundo, Marcela A; Domingues, M Rosário M

    2013-12-01

    Photodynamic therapy combines visible light and a photosensitizer (PS) in the presence of molecular oxygen to generate reactive oxygen species able to modify biological structures such as phospholipids. Phosphatidylethanolamines (PEs), being major phospholipid constituents of mammalian cells and membranes of Gram-negative bacteria, are potential targets of photosensitization. In this work, the oxidative modifications induced by white light in combination with cationic porphyrins (Tri-Py(+)-Me-PF and Tetra-Py(+)-Me) were evaluated on PE standards. Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) were used to identify and characterize the oxidative modifications induced in PEs (POPE: PE 16:0/18:1, PLPE: PE 16:0/18:2, PAPE: PE 16:0/20:4). Photo-oxidation products of POPE, PLPE and PAPE as hydroxy, hydroperoxy and keteno derivatives and products due to oxidation in ethanolamine polar head were identified. Hydroperoxy-PEs were found to be the major photo-oxidation products. Quantification of hydroperoxides (PE-OOH) allowed differentiating the potential effect in photodamage of the two porphyrins. The highest amounts of PE-OOH were notorious in the presence of Tri-Py(+)-Me-PF, a highly efficient PS against bacteria. The identification of these modifications in PEs is an important key point in the understanding cell damage processes underlying photodynamic therapy approaches. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Quantitation of DNA adducts by stable isotope dilution mass spectrometry

    PubMed Central

    Tretyakova, Natalia; Goggin, Melissa; Janis, Gregory

    2012-01-01

    Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations potentially contributing to the development of cancer. Due to their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples – including immunoassay, HPLC, and 32P-postlabeling – isotope dilution high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adducts concentrations in biological samples are between 0.01 – 10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry – especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS – have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke. PMID:22827593

  17. An efficient data format for mass spectrometry-based proteomics.

    PubMed

    Shah, Anuj R; Davidson, Jennifer; Monroe, Matthew E; Mayampurath, Anoop M; Danielson, William F; Shi, Yan; Robinson, Aaron C; Clowers, Brian H; Belov, Mikhail E; Anderson, Gordon A; Smith, Richard D

    2010-10-01

    The diverse range of mass spectrometry (MS) instrumentation along with corresponding proprietary and nonproprietary data formats has generated a proteomics community driven call for a standardized format to facilitate management, processing, storing, visualization, and exchange of both experimental and processed data. To date, significant efforts have been extended towards standardizing XML-based formats for mass spectrometry data representation, despite the recognized inefficiencies associated with storing large numeric datasets in XML. The proteomics community has periodically entertained alternate strategies for data exchange, e.g., using a common application programming interface or a database-derived format. However, these efforts have yet to gain significant attention, mostly because they have not demonstrated significant performance benefits over existing standards, but also due to issues such as extensibility to multidimensional separation systems, robustness of operation, and incomplete or mismatched vocabulary. Here, we describe a format based on standard database principles that offers multiple benefits over existing formats in terms of storage size, ease of processing, data retrieval times, and extensibility to accommodate multidimensional separation systems.

  18. An efficient data format for mass spectrometry based proteomics

    SciTech Connect

    Shah, Anuj R.; Davidson, Jennifer L.; Monroe, Matthew E.; Mayampurath, Anoop M.; Danielson, William F.; Shi, Yan; Robinson, Aaron C.; Clowers, Brian H.; Belov, Mikhail E.; Anderson, Gordon A.; Smith, Richard D.

    2010-10-01

    The diverse range of mass spectrometry (MS) instrumentation along with corresponding proprietary and non-proprietary data formats has generated a proteomics community driven call for a standardized format to facilitate management, processing, storing, visualization, and exchange of both experimental and processed data. To date, significant efforts have been extended towards standardizing XML-based formats for mass spectrometry data representation, despite the recognized inefficiencies associated with storing large numeric datasets in XML. The proteomics community has periodically entertained alternate strategies for data exchange, e.g., using a common application programming interface or a database-derived format. However these efforts have yet to garner significant attention, mostly because they haven’t illustrated significant performance benefits over existing standards, but also due to issues such as extensibility to multi-dimensional separation systems, robustness of operation, and incomplete or mismatched vocabulary. Here, we describe a format based on standard database principles that offers multiple benefits over existing formats in terms of storage size, ease of processing, data retrieval times and extensibility to accommodate multi-dimensional separation systems.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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

  8. 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...

  9. 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.

  10. 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.

  11. 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

  12. 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...

  13. 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...

  14. Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts.

    PubMed

    Bhasin, Shalender; Pencina, Michael; Jasuja, Guneet Kaur; Travison, Thomas G; Coviello, Andrea; Orwoll, Eric; Wang, Patty Y; Nielson, Carrie; Wu, Frederick; Tajar, Abdelouahid; Labrie, Fernand; Vesper, Hubert; Zhang, Anqi; Ulloor, Jagadish; Singh, Ravinder; D'Agostino, Ralph; Vasan, Ramachandran S

    2011-08-01

    Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

  15. An Effective Method to Detect Volatile Intermediates Generated in the Bioconversion of Coal to Methane by Gas Chromatography-Mass Spectrometry after In-Situ Extraction Using Headspace Solid-Phase Micro-Extraction under Strict Anaerobic Conditions.

    PubMed

    Liu, Jianmin; Wang, Baoyu; Tai, Chao; Wu, Li; Zhao, Han; Guan, Jiadong; Chen, Linyong

    2016-01-01

    Bioconversion of coal to methane has gained increased attention in recent decades because of its economic and environmental advantages. However, the mechanism of this process is difficult to study in depth, partly because of difficulties associated with the analysis of intermediates generated in coal bioconversion. In this investigation, we report on an effective method to analyze volatile intermediates generated in the bioconversion of coal under strict anaerobic conditions. We conduct in-situ extraction of intermediates using headspace solid-phase micro-extraction followed by detection by gas chromatography-mass spectrometry. Bioconversion simulation equipment was modified and combined with a solid-phase micro-extraction device. In-situ extraction could be achieved by using the combined units, to avoid a breakdown in anaerobic conditions and to maintain the experiment continuity. More than 30 intermediates were identified qualitatively in the conversion process, and the variation in trends of some typical intermediates has been discussed. Volatile organic acids (C2-C7) were chosen for a quantitative study of the intermediates because of their importance during coal bioconversion to methane. Fiber coating, extraction time, and solution acidity were optimized in the solid-phase micro-extraction procedure. The pressure was enhanced during the bioconversion process to investigate the influence of headspace pressure on analyte extraction. The detection limits of the method ranged from 0.0006 to 0.02 mmol/L for the volatile organic acids and the relative standard deviations were between 4.6% and 11.5%. The volatile organic acids (C2-C7) generated in the bioconversion process were 0.01-1.15 mmol/L with a recovery range from 80% to 105%. The developed method is useful for further in-depth research on the bioconversion of coal to methane.

  16. An Effective Method to Detect Volatile Intermediates Generated in the Bioconversion of Coal to Methane by Gas Chromatography-Mass Spectrometry after In-Situ Extraction Using Headspace Solid-Phase Micro-Extraction under Strict Anaerobic Conditions

    PubMed Central

    Liu, Jianmin; Wang, Baoyu; Tai, Chao; Wu, Li; Zhao, Han; Guan, Jiadong; Chen, Linyong

    2016-01-01

    Bioconversion of coal to methane has gained increased attention in recent decades because of its economic and environmental advantages. However, the mechanism of this process is difficult to study in depth, partly because of difficulties associated with the analysis of intermediates generated in coal bioconversion. In this investigation, we report on an effective method to analyze volatile intermediates generated in the bioconversion of coal under strict anaerobic conditions. We conduct in-situ extraction of intermediates using headspace solid-phase micro-extraction followed by detection by gas chromatography-mass spectrometry. Bioconversion simulation equipment was modified and combined with a solid-phase micro-extraction device. In-situ extraction could be achieved by using the combined units, to avoid a breakdown in anaerobic conditions and to maintain the experiment continuity. More than 30 intermediates were identified qualitatively in the conversion process, and the variation in trends of some typical intermediates has been discussed. Volatile organic acids (C2–C7) were chosen for a quantitative study of the intermediates because of their importance during coal bioconversion to methane. Fiber coating, extraction time, and solution acidity were optimized in the solid-phase micro-extraction procedure. The pressure was enhanced during the bioconversion process to investigate the influence of headspace pressure on analyte extraction. The detection limits of the method ranged from 0.0006 to 0.02 mmol/L for the volatile organic acids and the relative standard deviations were between 4.6% and 11.5%. The volatile organic acids (C2–C7) generated in the bioconversion process were 0.01–1.15 mmol/L with a recovery range from 80% to 105%. The developed method is useful for further in-depth research on the bioconversion of coal to methane. PMID:27695055

  17. 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.

  18. 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.

  19. 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.

  20. Charge detection mass spectrometry: Instrumentation & applications to viruses

    NASA Astrophysics Data System (ADS)

    Pierson, Elizabeth E.

    For over three decades, electrospray ionization (ESI) has been used to ionize non-covalent complexes and subsequently transfer the intact ion into the gas phase for mass spectrometry (MS) analysis. ESI generates a distribution of multiple charged ions, resulting in an m/z spectrum comprised of a series of peaks, known as a charge state envelope. To obtain mass information, the number of charges for each peak must be deduced. For smaller biological analytes like peptides, the charge states are sufficiently resolved and this process is straightforward. For macromolecular complexes exceeding ~100 kDa, this process is complicated by the broadening and shifting of charge states due to incomplete desolvation, salt adduction, and inherent mass heterogeneity. As the analyte mass approaches the MDa regime, the m/z spectrum is often comprised of a broad distribution of unresolved charge states. In such cases, mass determination is precluded. Charge detection mass spectrometry (CDMS) is an emerging MS technique for determining the masses of heterogeneous, macromolecular complexes. In CDMS, the m/z and z of single ions are measured concurrently so that mass is easily calculated. With this approach, deconvolution of an m/z spectrum is unnecessary. This measurement is carried out by passing macroions through a conductive cylinder. The induced image charge on the cylindrical detector provides information about m/z and z: the m/z is related to its time-of-flight through the detector, and the z is related to the intensity of the image charge. We have applied CDMS to study the self-assembly of virus capsids. Late-stage intermediates in the assembly of hepatitis B virus, a devastating human pathogen, have been identified. This is the first time that such intermediates have been detected and represent a significant advancement towards understanding virus capsid assembly. CDMS has also been used to identify oversized, non-icosahedral polymorphs in the assembly of woodchuck hepatitis

  1. A strategy for liquid chromatography/tandem mass spectrometry based quantitation of pegylated protein drugs in plasma using plasma protein precipitation with water-miscible organic solvents and subsequent trypsin digestion to generate surrogate peptides for detection.

    PubMed

    Wu, Steven T; Ouyang, Zheng; Olah, Timothy V; Jemal, Mohammed

    2011-01-30

    Recently, we have developed liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based methods for the quantitation of pegylated therapeutic proteins in plasma. The methods are based on the LC/MS/MS detection of a surrogate peptide generated from trypsin digestion of the therapeutic protein. Various parameters related to the bioanalytical methods were evaluated and optimized, including the preparation of calibration standards and quality control samples, sample extraction, internal standard selection and its stage of addition, trypsin digestion, and non-specific binding. In this paper, we report the development of a method for a specific pegylated therapeutic protein and detail the various optimization steps undertaken. Simple extraction of the pegylated therapeutic protein from plasma was achieved via the precipitation of the endogenous proteins in plasma using acidic isopropanol and the resulting supernatant extract was subjected to trypsin digestion. A unique tryptic peptide arising from the pegylated therapeutic protein was used for LC/MS/MS-based detection and quantitation. A protein and a peptide were used as internal standards, with the former added before the sample extraction and the latter after the sample extraction. The method developed is simple, sensitive, specific and rugged, and has been implemented in a high throughput 96-well format to analyze plasma samples from in vivo studies. A required lower limit of quantitation (LLOQ) of 10 ng/mL, expressed in terms of the concentration of the protein drug, was easily achieved.

  2. Extremely supercharged proteins in mass spectrometry: profiling the pH of electrospray generated droplets, narrowing charge state distributions, and increasing ion fragmentation.

    PubMed

    Zenaidee, Muhammad A; Donald, William A

    2015-03-21

    The effects of 12 acids, 4 solvents, and 8 low-volatility additives that increase analyte charging (i.e., superchargers) on the charge state distributions (CSDs) of protein ions in ESI-MS were investigated. We discovered that (i) relatively low concentrations [5% (v/v)] of 1,2-butylene carbonate (and 4-vinyl-1,3-dioxolan-2-one) can be added to ESI solutions to form higher charge states of cytochrome c and myoglobin ions than by using more traditional additives (e.g., propylene carbonate, sulfolane, or m-nitrobenzyl alcohol) under these conditions and (ii) the width of CSDs narrow as the effectiveness of superchargers increase, which concentrates protein ions into fewer detection channels. The use of strong acids (pKa values < 0) results in essentially no protein supercharging, higher adduction of acid molecules, and wider CSDs for many superchargers and proteins, whereas the use of weak acids (pKa > 0) results in significantly higher protein ion charging, less acid adduction, and narrower CSDs, indicating that protein ion supercharging in ESI can be significantly limited by the binding of conjugate base anions of acids that neutralize charge sites and broaden CSDs. The extent of protein charging as a function of acid identity (HA) does not strongly correlate with gas-phase proton transfer data (i.e., gas-phase basicity and proton affinity values for HA and A(-)), solution-phase protein secondary structures (as determined by circular dichroism spectroscopy), and/or acid molecule volatility data. For protein-denaturing solutions, these data were used to infer that the "effective" pH of ESI generated droplets near the moment of ion formation can be ∼0, which is ca. 1 to 3 pH units lower than the pH of the solutions prior to ESI. Electron capture dissociation (ECD) of [ubiquitin, 17H](17+) resulted in the identification of 223 cleavages, 74 of 75 inter-residue sites, and 92% ECD fragmentation efficiency, which correspond to highest of these values that have been

  3. Mass determination of megadalton-DNA Electrospray Ions usingCharge Detection Mass Spectrometry

    SciTech Connect

    Schultz, Jocelyn C.; Hack, Christopher; Benner, Henry W.

    1997-10-01

    Charge detection mass spectrometry (CD-MS) has been used to determine the mass of double-stranded, circular DNA and single-stranded, circular DNA in the range of 2500 to 8000 base pairs (1.5-5.0 MDa). Simultaneous measurement of the charge and velocity of an electrostatically accelerated ion allows a mass determination of the ion, with instrument calibration determined independently of samples. Positive ion mass spectra of electrosprayed commercial DNA samples supplied in tris(hydroxymethyl)ethylenediamine tetraacetic acid buffer, diluted in 50 vol. percent acetonitrile, were obtained without cleanup of the sample. ACD mass spectrum constructed from 3000 ion measurements takes 10 min to acquire and yields the DNA molecular mass directly (mass resolution = 6). The data collected represent progress toward a more automatable alternative to sizing of DNA by gel electrophoresis. In addition to the mass spectra, CD-MS generates charge versus mass plots, which provide another means to investigate the creation and fate of large electrospray ions.

  4. Matrix Factorization Techniques for Analysis of Imaging Mass Spectrometry Data

    PubMed Central

    Siy, Peter W.; Moffitt, Richard A.; Parry, R. Mitchell; Chen, Yanfeng; Liu, Ying; Sullards, M. Cameron; Merrill, Alfred H.; Wang, May D.

    2016-01-01

    Imaging mass spectrometry is a method for understanding the molecular distribution in a two-dimensional sample. This method is effective for a wide range of molecules, but generates a large amount of data. It is difficult to extract important information from these large datasets manually and automated methods for discovering important spatial and spectral features are needed. Independent component analysis and non-negative matrix factorization are explained and explored as tools for identifying underlying factors in the data. These techniques are compared and contrasted with principle component analysis, the more standard analysis tool. Independent component analysis and non-negative matrix factorization are found to be more effective analysis methods. A mouse cerebellum dataset is used for testing.

  5. Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

    PubMed Central

    Caron, Etienne; Kowalewski, Daniel J.; Chiek Koh, Ching; Sturm, Theo; Schuster, Heiko; Aebersold, Ruedi

    2015-01-01

    The myriad of peptides presented at the cell surface by class I and class II major histocompatibility complex (MHC) molecules are referred to as the immunopeptidome and are of great importance for basic and translational science. For basic science, the immunopeptidome is a critical component for understanding the immune system; for translational science, exact knowledge of the immunopeptidome can directly fuel and guide the development of next-generation vaccines and immunotherapies against autoimmunity, infectious diseases, and cancers. In this mini-review, we summarize established isolation techniques as well as emerging mass spectrometry-based platforms (i.e. SWATH-MS) to identify and quantify MHC-associated peptides. We also highlight selected biological applications and discuss important current technical limitations that need to be solved to accelerate the development of this field. PMID:26628741

  6. Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry.

    PubMed

    Caron, Etienne; Kowalewski, Daniel J; Chiek Koh, Ching; Sturm, Theo; Schuster, Heiko; Aebersold, Ruedi

    2015-12-01

    The myriad of peptides presented at the cell surface by class I and class II major histocompatibility complex (MHC) molecules are referred to as the immunopeptidome and are of great importance for basic and translational science. For basic science, the immunopeptidome is a critical component for understanding the immune system; for translational science, exact knowledge of the immunopeptidome can directly fuel and guide the development of next-generation vaccines and immunotherapies against autoimmunity, infectious diseases, and cancers. In this mini-review, we summarize established isolation techniques as well as emerging mass spectrometry-based platforms (i.e. SWATH-MS) to identify and quantify MHC-associated peptides. We also highlight selected biological applications and discuss important current technical limitations that need to be solved to accelerate the development of this field.

  7. 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

  8. 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

  9. 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.

  10. Study of Simvastatin Self-Association Using Electrospray-Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Vetrova, E. V.; Lekar, A. V.; Filonova, O. V.; Borisenko, S. N.; Maksimenko, E. V.; Borisenko, N. I.

    2015-07-01

    Self-association of simvastatin, which is widely used to treat coronary heart disease, was investigated using electrospray-ionization mass spectrometry. Formation of simvastatin self-associates in various solvents was demonstrated using mass spectrometry. Solvation effects were shown to play a special role in the formation of the self-associates. Self-associates containing from two to fi ve simvastatin molecules were detected in mass spectra of an aqueous MeOH (20%) solution of simvastatin. The formation of simvastatin self-associates could compete with the complexation of supramolecular structures during the synthesis of new generation drugs.

  11. 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.

  12. 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...

  13. 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...

  14. Small system for tritium accelerator mass spectrometry

    DOEpatents

    Roberts, M.L.; Davis, J.C.

    1993-02-23

    Apparatus for ionizing and accelerating a sample containing isotopes of hydrogen and detecting the ratios of hydrogen isotopes contained in the sample is disclosed. An ion source generates a substantially linear ion beam including ions of tritium from the sample. A radio-frequency quadrupole accelerator is directly coupled to and axially aligned with the source at an angle of substantially zero degrees. The accelerator accelerates species of the sample having different mass to different energy levels along the same axis as the ion beam. A spectrometer is used to detect the concentration of tritium ions in the sample. In one form of the invention, an energy loss spectrometer is used which includes a foil to block the passage of hydrogen, deuterium and [sup 3]He ions, and a surface barrier or scintillation detector to detect the concentration of tritium ions. In another form of the invention, a combined momentum/energy loss spectrometer is used which includes a magnet to separate the ion beams, with Faraday cups to measure the hydrogen and deuterium and a surface barrier or scintillation detector for the tritium ions.

  15. Small system for tritium accelerator mass spectrometry

    DOEpatents

    Roberts, Mark L.; Davis, Jay C.

    1993-01-01

    Apparatus for ionizing and accelerating a sample containing isotopes of hydrogen and detecting the ratios of hydrogen isotopes contained in the sample is disclosed. An ion source generates a substantially linear ion beam including ions of tritium from the sample. A radio-frequency quadrupole accelerator is directly coupled to and axially aligned with the source at an angle of substantially zero degrees. The accelerator accelerates species of the sample having different mass to different energy levels along the same axis as the ion beam. A spectrometer is used to detect the concentration of tritium ions in the sample. In one form of the invention, an energy loss spectrometer is used which includes a foil to block the passage of hydrogen, deuterium and .sup.3 He ions, and a surface barrier or scintillation detector to detect the concentration of tritium ions. In another form of the invention, a combined momentum/energy loss spectrometer is used which includes a magnet to separate the ion beams, with Faraday cups to measure the hydrogen and deuterium and a surface barrier or scintillation detector for the tritium ions.

  16. 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…

  17. 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…

  18. 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

  19. Electrospray Ionisation Mass Spectrometry: Principles and Clinical Applications

    PubMed Central

    Ho, CS; Lam, CWK; Chan, MHM; Cheung, RCK; Law, LK; Lit, LCW; Ng, KF; Suen, MWM; Tai, HL

    2003-01-01

    This mini-review provides a general understanding of electrospray ionisation mass spectrometry (ESI-MS) which has become an increasingly important technique in the clinical laboratory for structural study or quantitative measurement of metabolites in a complex biological sample. The first part of the review explains the electrospray ionisation process, design of mass spectrometers with separation capability, characteristics of the mass spectrum, and practical considerations in quantitative analysis. The second part then focuses on some clinical applications. The capability of ESI-tandem-MS in measuring bio-molecules sharing similar molecular structures makes it particularly useful in screening for inborn errors of amino acid, fatty acid, purine, pyrimidine metabolism and diagnosis of galactosaemia and peroxisomal disorders. Electrospray ionisation is also efficient in generating cluster ions for structural elucidation of macromolecules. This has fostered a new and improved approach (vs electrophoresis) for identification and quantification of haemoglobin variants. With the understanding of glycohaemoglobin structure, an IFCC reference method for glycohaemoglobin assay has been established using ESI-MS. It represents a significant advancement for the standardisation of HbA1c in diabetic monitoring. With its other applications such as in therapeutic drug monitoring, ESI-MS will continue to exert an important influence in the future development and organisation of the clinical laboratory service. PMID:18568044

  20. 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…

  1. 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…

  2. 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

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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...

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Screening for low molecular weight compounds in fish meal solubles by hydrophilic interaction liquid chromatography coupled to mass spectrometry

    USDA-ARS?s Scientific Manuscript database

    A simple analytical method using hydrophilic interaction liquid chromatography coupled with mass spectrometry was developed to screen for low molecular weight compounds in enzyme treated and untreated Alaskan pollock (Theragra chalcogramma) stickwater (SW) generated from processing fish meal with po...

  14. Microfluidic Chip Coupled with Thermal Desorption Atmospheric Pressure Ionization Mass Spectrometry

    PubMed Central

    Chang, Chia-Hsien; Chen, Tsung-Yi; Chen, Yu-Chie

    2014-01-01

    Microfluidic chips have been used as platforms for a diversity of research purposes such as for separation and micro-reaction. One of the suitable detectors for microfluidic chip is mass spectrometry. Because microfluidic chips are generally operated in an open air condition, mass spectrometry coupled with atmospheric pressure ion sources can suit the requirement with minimum compromise. In this study, we develop a new interface to couple a microfluidic chip with mass spectrometry. A capillary tip coated with a layer of graphite, capable of absorbing energy of near-infrared (NIR) light is used to interface microfluidic chip with mass spectrometry. An NIR laser diode (λ=808 nm) is used to irradiate the capillary tip for assisting the generation of spray from the eluent of the microfluidic chip. An electrospray is provided to fuse with the spray generated from the microfluidic chip for post-ionization. Transesterification is used as the example to demonstrate the feasibility of using this interface to couple microfluidic chip with mass spectrometry. PMID:26839753

  15. 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

  16. 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.

  17. Cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry for screening bioactive capilliposide C metabolites generated by rat intestinal microflora.

    PubMed

    Cheng, Zhongzhe; Huang, Meilin; Chen, Guiying; Yang, Guangjie; Zhou, Xin; Chen, Chang; Zhang, Yang; Xu, Yong; Feng, Yulin; Zhang, Lin; Jiang, Hongliang

    2016-02-05

    Many plant-derived glycosides are used as medications. It is common that these glycosides show poor intestinal absorption but their metabolites generated by intestinal microflora demonstrate strong bioactivity. Hence, it is crucial to develop a method for the identification and characterization of the metabolites, and consequently reveal the pathway in which the glycosides are processed in gut. In this study, cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) were developed for rapid discovery and evaluation of the metabolites of a glycoside compound, capilliposide C (LC-C). 92.7% of LC-C was biotransformed by rat intestinal microflora after 36-h incubation at 37°C. Human cancer cell lines HepG2, PC-3 and A549 was treated with metabolites pool, respectively, which was followed by cell viability assays and characterization of metabolites using UHPLC-QTOF-MS/MS. As a result, significant cytotoxicity was observed for the metabolites pool, from which six metabolites were identified. Based on the metabolites identified, deglycosylation and esterolysis were proposed as the major metabolic pathways of LC-C in rat intestinal microflora. In addition, M4, an esterolysis product of LC-C, was obtained and evaluated for its bioactivity in vitro. As a result, M4 exhibited a reduction in cell viability in HepG2 with an IC50 value of 17.46±1.55μg/mL.

  18. Probing the dynamic reversibility and generation of dynamic combinatorial libraries in the presence of bacterial model oligopeptides as templating guests of tetra-carbohydrazide macrocycles using electrospray mass spectrometry.

    PubMed

    Nour, Hany F; Islam, Tuhidul; Fernández-Lahore, Marcelo; Kuhnert, Nikolai

    2012-12-30

    Over the past few decades, bacterial resistance to antibiotics has emerged as a real threat to human health. Accordingly, there is an urgent demand for the development of innovative strategies for discovering new antibiotics. We present the first use of tetra-carbohydrazide cyclophane macrocycles in dynamic combinatorial chemistry (DCC) and molecular recognition as chiral hosts binding oligopeptides, which mimic bacterial cell wall. This study introduces an innovative application of electrospray ionisation time-of-flight mass spectrometry (ESI-TOF MS) to oligopeptides recognition using DCC. A small dynamic library composed of eight functionalised macrocycles has been generated in solution and all members were characterised by ESI-TOF MS. We also probed the dynamic reversibility and mechanism of formation of tetra-carbohydrazide cyclophanes in real-time using ESI-TOF MS. Dynamic reversibility of tetra-carbohydrazide cyclophanes is favored under thermodynamic control. The mechanism of formation of tetra-carbohydrazide cyclophanes involves key dialdehyde intermediates, which have been detected and assigned according to their high-resolution m/z values. Three members of the dynamic library bind efficiently in the gas phase to a selection of oligopeptides, unique to bacteria, allowing observation of host/guest complex ions in the gas phase. We probed the mechanism of the [2+2]-cyclocondensation reaction forming library members, proved dynamic reversibility of tetra-carbohydrazide cyclophanes and showed that complex ions formed between library members and hosts can be observed in the gas phase, allowing the solution of an important problem of biological interest. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Network generation enhances interpretation of proteomics data sets by a combination of two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

    PubMed

    Wang, Xijun; Zhang, Aihua; Sun, Hui; Wu, Gelin; Sun, Wenjun; Yan, Guangli

    2012-10-21

    Recent advances in proteomic technologies have enabled us to create detailed protein-protein interaction maps in diseases. As the size of the interaction dataset increases, powerful computational methods are required in order to effectively interpret network models from large scale interactome data. In this study, we carried out comparative proteomics to construct and identify the proteins networks associated with hepatic injury (HI) which are largely unknown, as a case study. All proteins expressed were separated and identified by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight-time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Protein-interacting networks and pathways were mapped using STRING analysis program. We have performed for the first time a comprehensive profiling of changes in protein expression of HI rats, to uncover the networks altered by treated with CCl(4). Identification of fifteen spots (seven over-expressed and eight under-expressed) were established by MALDI-TOF/TOF MS. These proteins were subjected to functional pathway analysis using STRING software for better understanding of the biological context of the identified proteins. It suggested that modulation of multiple vital physiological pathways including DNA repair process, cell apoptosis, oxidation reduction, signal transduction, metabolic process, intracellular signaling cascade, regulation of biological processes, cell communication, regulation of cellular process, and molecular transport. In summary, the present study provides the first protein-interacting network maps and novel insights into the biological responses and potential pathways of HI. The generation of protein interaction networks clearly enhances the interpretation of proteomic data, particularly in respect of understanding molecular mechanisms of panel protein biomarkers.

  20. 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.

  1. Distance-of-Flight Mass Spectrometry: A New Paradigm for Mass Separation and Detection

    SciTech Connect

    Enke, Chris; Ray, Steven J.; Graham, Alexander W.; Dennis, Elise; Hieftje, Gary M.; Carado, Anthony J.; Barinaga, Charles J.; Koppenaal, David W.

    2012-07-01

    Distance-of-flight mass spectrometry (DOFMS) offers the advantages of physical separation of ions, array-detection of ions, focusing of initial ion energy, great simplicity, and truly unlimited mass range. DOFMS instrumentation is similar to that of time-of-flight mass spectrometry (TOFMS) and shares its ion source versatility, batch analysis, and rapid spectral generation rate. With constant-momentum ion acceleration and an ion mirror, there is a time at which ions of all m/z values are energy-focused at their particular distance along the flight path. A pulsed field orthogonal to the flight path drives the ions to reach the detector array at this specific time. Results from a 0.31-m proof-of-principle instrument verify the theoretically predicted energy focus and demonstrate how the range of m/z values impinging on the detector array can be readily changed. DOFMS can potentially be combined sequentially with TOFMS to enable simultaneous scanless MS/MS.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Coupling of Ultrafast LC with Mass Spectrometry by DESI

    NASA Astrophysics Data System (ADS)

    Cai, Yi; Liu, Yong; Helmy, Roy; Chen, Hao

    2014-10-01

    Recently we reported a desorption electrospray ionization (DESI) interface to combine liquid chromatography (LC) with mass spectrometry (MS) using a new LC eluent splitting strategy through a tiny orifice on LC capillary tube [ J. Am. Soc. Mass Spectrom. 25, 286 (2014)]. The interface introduces negligible dead volume and back pressure, thereby allowing "near real-time" MS detection, fast LC elution, and online MS-directed purification. This study further evaluates the LC/DESI-MS performance with focus of using ultra-fast LC. Using a monolithic C18 column, metabolites in urine can be separated within 1.6 min and can be online collected for subsequent structure elucidation (e.g., by NMR, UV, IR) in a recovery yield up to 99%. Using a spray solvent with alkaline pH, negative ions could be directly generated for acidic analytes (e.g., ibuprofen) in acidic LC eluent by DESI, offering a novel protocol to realize "wrong-way around" ionization for LC/MS analysis. In addition, DESI-MS is found to be compatible with ultra-performance liquid chromatography (UPLC) for the first time.

  10. Quaternary diamines as mass spectrometry cleavable crosslinkers for protein interactions.

    PubMed

    Clifford-Nunn, Billy; Showalter, H D Hollis; Andrews, Philip C

    2012-02-01

    Mapping protein interactions and their dynamics is crucial to defining physiologic states, building effective models for understanding cell function, and to allow more effective targeting of new drugs. Crosslinking studies can estimate the proximity of proteins, determine sites of protein-protein interactions, and have the potential to provide a snapshot of dynamic interactions by covalently locking them in place for analysis. Several major challenges are associated with the use of crosslinkers in mass spectrometry, particularly in complex mixtures. We describe the synthesis and characterization of a MS-cleavable crosslinker containing cyclic amines, which address some of these challenges. The DC4 crosslinker contains two intrinsic positive charges, which allow crosslinked peptides to fragment into their component peptides by collision-induced dissociation (CID) or in-source decay. Initial fragmentation events result in cleavage on either side of the positive charges so crosslinked peptides are identified as pairs of ions separated by defined masses. The structures of the component peptides can then be robustly determined by MS(3) because their fragmentation products rearrange to generate a mobile proton. The DC4 crosslinking reagent is stable to storage, highly reactive, highly soluble (1 M solutions), quite labile to CID, and MS(3) results in productive backbone fragmentation.

  11. Quaternary Diamines as Mass Spectrometry Cleavable Crosslinkers for Protein Interactions

    NASA Astrophysics Data System (ADS)

    Clifford-Nunn, Billy; Showalter, H. D. Hollis; Andrews, Philip C.

    2012-02-01

    Mapping protein interactions and their dynamics is crucial to defining physiologic states, building effective models for understanding cell function, and to allow more effective targeting of new drugs. Crosslinking studies can estimate the proximity of proteins, determine sites of protein-protein interactions, and have the potential to provide a snapshot of dynamic interactions by covalently locking them in place for analysis. Several major challenges are associated with the use of crosslinkers in mass spectrometry, particularly in complex mixtures. We describe the synthesis and characterization of a MS-cleavable crosslinker containing cyclic amines, which address some of these challenges. The DC4 crosslinker contains two intrinsic positive charges, which allow crosslinked peptides to fragment into their component peptides by collision-induced dissociation (CID) or in-source decay. Initial fragmentation events result in cleavage on either side of the positive charges so crosslinked peptides are identified as pairs of ions separated by defined masses. The structures of the component peptides can then be robustly determined by MS3 because their fragmentation products rearrange to generate a mobile proton. The DC4 crosslinking reagent is stable to storage, highly reactive, highly soluble (1 M solutions), quite labile to CID, and MS3 results in productive backbone fragmentation.

  12. Quaternary Diamines as Mass Spectrometry Cleavable Crosslinkers for Protein Interactions

    PubMed Central

    Clifford-Nunn, Billy; Showalter, H. D. Hollis; Andrews, Philip C.

    2013-01-01

    Mapping protein interactions and their dynamics is crucial to defining physiologic states, building effective models for understanding cell function, and to allow more effective targeting of new drugs. Crosslinking studies can estimate the proximity of proteins, determine sites of protein–protein interactions, and have the potential to provide a snapshot of dynamic interactions by covalently locking them in place for analysis. Several major challenges are associated with the use of crosslinkers in mass spectrometry, particularly in complex mixtures. We describe the synthesis and characterization of a MS-cleavable crosslinker containing cyclic amines, which address some of these challenges. The DC4 crosslinker contains two intrinsic positive charges, which allow crosslinked peptides to fragment into their component peptides by collision-induced dissociation (CID) or in-source decay. Initial fragmentation events result in cleavage on either side of the positive charges so crosslinked peptides are identified as pairs of ions separated by defined masses. The structures of the component peptides can then be robustly determined by MS3 because their fragmentation products rearrange to generate a mobile proton. The DC4 crosslinking reagent is stable to storage, highly reactive, highly soluble (1 M solutions), quite labile to CID, and MS3 results in productive backbone fragmentation. PMID:22131227

  13. The Evolving Contribution of Mass Spectrometry to Integrative Structural Biology.

    PubMed

    Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-06-01

    Protein complexes are key catalysts and regulators for the majority of cellular processes. Unveiling their assembly and structure is essential to understanding their function and mechanism of action. Although conventional structural techniques such as X-ray crystallography and NMR have solved the structure of important protein complexes, they cannot consistently deal with dynamic and heterogeneous assemblies, limiting their applications to small scale experiments. A novel methodological paradigm, integrative structural biology, aims at overcoming such limitations by combining complementary data sources into a comprehensive structural model. Recent applications have shown that a range of mass spectrometry (MS) techniques are able to generate interaction and spatial restraints (cross-linking MS) information on native complexes or to study the stoichiometry and connectivity of entire assemblies (native MS) rapidly, reliably, and from small amounts of substrate. Although these techniques by themselves do not solve structures, they do provide invaluable structural information and are thus ideally suited to contribute to integrative modeling efforts. The group of Brian Chait has made seminal contributions in the use of mass spectrometric techniques to study protein complexes. In this perspective, we honor the contributions of the Chait group and discuss concepts and milestones of integrative structural biology. We also review recent examples of integration of structural MS techniques with an emphasis on cross-linking MS. We then speculate on future MS applications that would unravel the dynamic nature of protein complexes upon diverse cellular states. Graphical Abstract ᅟ.

  14. Laser desorption mass spectrometry for DNA analysis and sequencing

    SciTech Connect

    Chen, C.H.; Taranenko, N.I.; Tang, K.; Allman, S.L.

    1995-03-01

    Laser desorption mass spectrometry has been considered as a potential new method for fast DNA sequencing. Our approach is to use matrix-assisted laser desorption to produce parent ions of DNA segments and a time-of-flight mass spectrometer to identify the sizes of DNA segments. Thus, the approach is similar to gel electrophoresis sequencing using Sanger`s enzymatic method. However, gel, radioactive tagging, and dye labeling are not required. In addition, the sequencing process can possibly be finished within a few hundred microseconds instead of hours and days. In order to use mass spectrometry for fast DNA sequencing, the following three criteria need to be satisfied. They are (1) detection of large DNA segments, (2) sensitivity reaching the femtomole region, and (3) mass resolution good enough to separate DNA segments of a single nucleotide difference. It has been very difficult to detect large DNA segments by mass spectrometry before due to the fragile chemical properties of DNA and low detection sensitivity of DNA ions. We discovered several new matrices to increase the production of DNA ions. By innovative design of a mass spectrometer, we can increase the ion energy up to 45 KeV to enhance the detection sensitivity. Recently, we succeeded in detecting a DNA segment with 500 nucleotides. The sensitivity was 100 femtomole. Thus, we have fulfilled two key criteria for using mass spectrometry for fast DNA sequencing. The major effort in the near future is to improve the resolution. Different approaches are being pursued. When high resolution of mass spectrometry can be achieved and automation of sample preparation is developed, the sequencing speed to reach 500 megabases per year can be feasible.

  15. Mass spectrometry and inhomogeneous ion optics

    NASA Technical Reports Server (NTRS)

    White, F. A.

    1973-01-01

    Work done in several areas to advance the state of the art of magnetic mass spectrometers is described. The calculations and data necessary for the design of inhomogeneous field mass spectrometers, and the calculation of ion trajectories through such fields are presented. The development and testing of solid state ion detection devices providing the capability of counting single ions is discussed. New techniques in the preparation and operation of thermal-ionization ion sources are described. Data obtained on the concentrations of copper in rainfall and uranium in air samples using the improved thermal ionization techniques are presented. The design of a closed system static mass spectrometer for isotopic analyses is discussed. A summary of instrumental aspects of a four-stage mass spectrometer comprising two electrostatic and two 90 deg. magnetic lenses with a 122-cm radius used to study the interaction of ions with solids is presented.

  16. Determination of water content using mass spectrometry

    NASA Technical Reports Server (NTRS)

    Wood, G. M.; Upchurch, B. T.; Hughes, D. B.

    1975-01-01

    Mass spectrometer is used to measure small quantities of water present in different materials. System has been applied in measuring water and gases desorbed from microcircuitry insulation, can also be used with foods, polymeric materials, and organic solvents.

  17. Xenon purity analysis for EXO-200 via mass spectrometry

    NASA Astrophysics Data System (ADS)

    Dobi, A.; Hall, C.; Slutsky, S.; Yen, Y.-R.; Aharmin, B.; Auger, M.; Barbeau, P. S.; Benitez-Medina, C.; Breidenbach, M.; Cleveland, B.; Conley, R.; Cook, J.; Cook, S.; Counts, I.; Craddock, W.; Daniels, T.; Davis, C. G.; Davis, J.; deVoe, R.; Dixit, M.; Dolinski, M. J.; Donato, K.; Fairbank, W.; Farine, J.; Fierlinger, P.; Franco, D.; Giroux, G.; Gornea, R.; Graham, K.; Gratta, G.; Green, C.; Hagemann, C.; Hall, K.; Hallman, D.; Hargrove, C.; Herrin, S.; Hughes, M.; Hodgson, J.; Juget, F.; Karelin, A.; Kaufman, L. J.; Kuchenkov, A.; Kumar, K.; Leonard, D. S.; Lutter, G.; Mackay, D.; MacLellan, R.; Marino, M.; Mong, B.; Montero Díez, M.; Morgan, P.; Müller, A. R.; Neilson, R.; Odian, A.; O'Sullivan, K.; Piepke, A.; Pocar, A.; Prescott, C. Y.; Pushkin, K.; Rivas, A.; Rollin, E.; Rowson, P. C.; Sabourov, A.; Sinclair, D.; Skarpaas, K.; Stekhanov, V.; Strickland, V.; Swift, M.; Twelker, K.; Vuilleumier, J.-L.; Vuilleumier, J.-M.; Weber, M.; Wichoski, U.; Wodin, J.; Wright, J. D.; Yang, L.

    2012-05-01

    We describe purity measurements of the natural and enriched xenon stockpiles used by the EXO-200 double beta decay experiment based on a mass spectrometry technique. The sensitivity of the spectrometer is enhanced by several orders of magnitude by the presence of a liquid nitrogen cold trap, and many impurity species of interest can be detected at the level of one part-per-billion or better. We have used the technique to screen the EXO-200 xenon before, during, and after its use in our detector, and these measurements have proven useful. This is the first application of the cold trap mass spectrometry technique to an operating physics experiment.

  18. Major roles for minor bacterial lipids identified by mass spectrometry.

    PubMed

    Garrett, Teresa A

    2016-10-17

    Mass spectrometry of lipids, especially those isolated from bacteria, has ballooned over the past two decades, affirming in the process the complexity of the lipidome. With this has come the identification of new and interesting lipid structures. Here is an overview of several novel lipids, from both Gram-negative and Gram-positive bacteria with roles in health and disease, whose structural identification was facilitated using mass spectrometry. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.

  19. Issues and opportunities in accelerator mass spectrometry for stable isotopes.

    PubMed

    Matteson, Sam

    2008-01-01

    Accelerator mass spectrometry (AMS) has developed in the last 30 years many notable applications to the spectrometry of radioisotopes, particularly in radiocarbon dating. The instrumentation science of trace element AMS (TEAMS) that analyzes stable isotopes, also called Accelerator SIMS or MegaSIMS, while unique in many features, has also shared in many of these significant advances and has pushed TEAMS sensitivity to concentration levels surpassing many competing mass spectroscopic technologies. This review examines recent instrumentation developments, the capabilities of the new instrumentation and discernable trends for future development.

  20. Technical Challenges in Mass Spectrometry-Based Metabolomics

    PubMed Central

    Matsuda, Fumio

    2016-01-01

    Metabolomics is a strategy for analysis, and quantification of the complete collection of metabolites present in biological samples. Metabolomics is an emerging area of scientific research because there are many application areas including clinical, agricultural, and medical researches for the biomarker discovery and the metabolic system analysis by employing widely targeted analysis of a few hundred preselected metabolites from 10–100 biological samples. Further improvement in technologies of mass spectrometry in terms of experimental design for larger scale analysis, computational methods for tandem mass spectrometry-based elucidation of metabolites, and specific instrumentation for advanced bioanalysis will enable more comprehensive metabolome analysis for exploring the hidden secrets of metabolism. PMID:27900235

  1. Purifying protein complexes for mass spectrometry: applications to protein translation.

    PubMed

    Link, Andrew J; Fleischer, Tracey C; Weaver, Connie M; Gerbasi, Vincent R; Jennings, Jennifer L

    2005-03-01

    Proteins control and mediate most of the biological activities in the cell. In most cases, proteins either interact with regulatory proteins or function in large molecular assemblies to carryout biological processes. Understanding the functions of individual proteins requires the identification of these interacting proteins. With its speed and sensitivity, mass spectrometry has become the dominant method for identifying components of protein complexes. This article reviews and discusses various approaches to purify protein complexes and analyze the proteins using mass spectrometry. As examples, methods to isolate and analyze protein complexes responsible for the translation of messenger RNAs into polypeptides are described.

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

    PubMed

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

    2010-01-01

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

  3. Structure Determination of Natural Products by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Biemann, Klaus

    2015-07-01

    I review laboratory research on the development of mass spectrometric methodology for the determination of the structure of natural products of biological and medical interest, which I conducted from 1958 to the end of the twentieth century. The methodology was developed by converting small peptides to their corresponding polyamino alcohols to make them amenable to mass spectrometry, thereby making it applicable to whole proteins. The structures of alkaloids were determined by analyzing the fragmentation of a known alkaloid and then using the results to deduce the structures of related compounds. Heparin-like structures were investigated by determining their molecular weights from the mass of protonated molecular ions of complexes with highly basic, synthetic peptides. Mass spectrometry was also employed in the analysis of lunar material returned by the Apollo missions. A miniaturized gas chromatograph mass spectrometer was sent to Mars on board of the two Viking 1976 spacecrafts.

  4. Hydrogen exchange mass spectrometry of proteins at Langmuir monolayers

    PubMed Central

    Pirrone, Gregory F.; Vernon, Briana C.; Kent, Michael S.; Engen, John R.

    2015-01-01

    Hydrogen exchange (HX) mass spectrometry (MS) is valuable for providing conformational information for proteins/peptides that are very difficult to analyze with other methods such as peripheral membrane proteins and peptides that interact with membranes. We developed a new type of HX MS measurement that integrates Langmuir monolayers. A lipid monolayer was generated, a peptide or protein associated with it, and then the monolayer-associated peptide or protein was exposed to deuterium. The deuterated species was recovered from the monolayer, digested, and deuterium incorporation monitored by MS. Test peptides showed that deuterium recovery in an optimized protocol was equivalent to deuterium recovery in conventional solution HX MS. The reproducibility of the measurements was high despite the requirement of generating a new monolayer for each deuterium labeling time. We validated that known conformational changes in the presence of a monolayer/membrane could be observed with the peptide melittin and the myristoylated protein Arf-1. Results in an accompanying paper show that the method can reveal details of conformational changes in a protein (HIV-1 Nef) which adopts a different conformation depending on if it can insert into the lipid layer. Overall, the HX MS Langmuir monolayer method provided new and meaningful conformational information for proteins that associate with lipid layers. The combination of HX MS results with neutron or X-ray reflection of the same proteins in Langmuir monolayers can be more informative than isolated use of either method. PMID:26134943

  5. Solvent jet desorption capillary photoionization-mass spectrometry.

    PubMed

    Haapala, Markus; Teppo, Jaakko; Ollikainen, Elisa; Kiiski, Iiro; Vaikkinen, Anu; Kauppila, Tiina J; Kostiainen, Risto

    2015-03-17

    A new ambient mass spectrometry method, solvent jet desorption capillary photoionization (DCPI), is described. The method uses a solvent jet generated by a coaxial nebulizer operated at ambient conditions with nitrogen as nebulizer gas. The solvent jet is directed onto a sample surface, from which analytes are extracted into the solvent and ejected from the surface in secondary droplets formed in collisions between the jet and the sample surface. The secondary droplets are directed into the heated capillary photoionization (CPI) device, where the droplets are vaporized and the gaseous analytes are ionized by 10 eV photons generated by a vacuum ultraviolet (VUV) krypton discharge lamp. As the CPI device is directly connected to the extended capillary inlet of the MS, high ion transfer efficiency to the vacuum of MS is achieved. The solvent jet DCPI provides several advantages: high sensitivity for nonpolar and polar compounds with limit of detection down to low fmol levels, capability of analyzing small and large molecules, and good spatial resolution (250 μm). Two ionization mechanisms are involved in DCPI: atmospheric pressure photoionization, capable of ionizing polar and nonpolar compounds, and solvent assisted inlet ionization capable of ionizing larger molecules like peptides. The feasibility of DCPI was successfully tested in the analysis of polar and nonpolar compounds in sage leaves and chili pepper.

  6. Exploiting the multiplexing capabilities of tandem mass tags for high-throughput estimation of cellular protein abundances by mass spectrometry.

    PubMed

    Ahrné, Erik; Martinez-Segura, Amalia; Syed, Afzal Pasha; Vina-Vilaseca, Arnau; Gruber, Andreas J; Marguerat, Samuel; Schmidt, Alexander

    2015-09-01

    The generation of dynamic models of biological processes critically depends on the determination of precise cellular concentrations of biomolecules. Measurements of system-wide absolute protein levels are particularly valuable information in systems biology. Recently, mass spectrometry based proteomics approaches have been developed to estimate protein concentrations on a proteome-wide scale. However, for very complex proteomes, fractionation steps are required, increasing samples number and instrument analysis time. As a result, the number of full proteomes that can be routinely analyzed is limited. Here we combined absolute quantification strategies with the multiplexing capabilities of isobaric tandem mass tags to determine cellular protein abundances in a high throughput and proteome-wide scale even for highly complex biological systems, such as a whole human cell line. We generated two independent data sets to demonstrate the power of the approach regarding sample throughput, dynamic range, quantitative precision and accuracy as well as proteome coverage in comparison to existing mass spectrometry based strategies.

  7. Evaluation of automated single mass spectrometry to tandem mass spectrometry function switching for comprehensive drug profiling analysis using a quadrupole time-of-flight mass spectrometer.

    PubMed

    Decaestecker, T N; Clauwaert, K M; Van Bocxlaer, J F; Lambert, W E; Van den Eeckhout, E G; Van Peteghem, C H; De Leenheer, A P

    2000-01-01

    A liquid chromatographic mass spectrometric strategy for systematic toxicological analysis (STA) is presented using the automatic 'on-the-fly' single mass spectrometry mode to tandem mass spectrometry mode (MS to MS/MS) switching abilities of a quadrupole time-of-flight (Q-TOF) instrument. During the chromatographic run, the quadrupole is initially set to transmit all masses until (an) ion(s) reaches a certain set threshold. Thereupon, the quadrupole automatically switches to the MS/MS mode, selecting the ion(s), which are subsequently fragmented in the high-efficiency hexapole collision cell, thus generating product ions that are further mass analyzed by the TOF. By limiting the TOF spectral accumulation time in the MS/MS mode to a statistically acceptable minimum, the quadrupole almost instantly switches back to the MS mode. Qualitative information, comprising the complementary MS ([M + H](+) ion mass) and MS/MS (informative product ion profile) data, as well as quantitative information obtained by integration of the MS extracted ion chromatogram(s), can be obtained in one single acquisition. Optimization of the automatic switching parameters, such as threshold, TOF spectral accumulation time, detection window and collision energy, was carried out by injection of a mix of 17 common drugs which were not necessarily baseline separated in the chromatographic system used. Indeed, the complete separation of the drugs is not deemed necessary since up to 8 different ions can 'simultaneously' be selected for MS/MS if they reach the preset criteria. In addition, the quantitative performance of the method was defined. In a second phase, the developed method was field-tested. To that end, the resulting data from extracts of urine samples were compared with and found to be in close concordance with those obtained by a standard toxicological analysis. This innovative approach clearly holds the potential for a substantial advance in the introduction of LC/MS in STA. Copyright

  8. Mass spectrometry imaging, an emerging technology in neuropsychopharmacology.

    PubMed

    Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

    2014-01-01

    Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience.

  9. Mass Spectrometry Imaging, an Emerging Technology in Neuropsychopharmacology

    PubMed Central

    Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

    2014-01-01

    Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience. PMID:23966069

  10. Gas-Phase Fragmentation Behavior of Oxidized Prenyl Peptides by CID and ETD Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bhawal, Ruchika P.; Shahinuzzaman, A. D. A.; Chowdhury, Saiful M.

    2017-04-01

    Farnesylation and geranylgeranylation are the two types of prenyl modification of proteins. Prenylated peptides are highly hydrophobic and their abundances in biological samples are low. In this report, we studied the oxidized prenylated peptides by electrospray ionization mass spectrometry and identified them by collision-induced dissociation (CID) and electron-transfer dissociation (ETD) tandem mass spectrometry. Modified prenyl peptides were generated utilizing strong and low strength oxidizing agents to selectively oxidize and epoxidize cysteine sulfur and prenyl side chain. We selected three peptides with prenyl motifs and synthesized their prenylated versions. The detailed characteristic fragmentations of oxidized and epoxidized farnesylated and geranylgeranylated peptides were studied side by side with two popular fragmentation techniques. CID and ETD mass spectrometry clearly distinguished the modified version of these peptides. ETD mass spectrometry provided sequence information of the highly labile modified prenyl peptides and showed different characteristic fragmentations compared with CID. A detailed fragmentation of modified geranylgeranylated peptides was compared by CID and ETD mass spectrometry for the first time.

  11. Gas-Phase Fragmentation Behavior of Oxidized Prenyl Peptides by CID and ETD Tandem Mass Spectrometry.

    PubMed

    Bhawal, Ruchika P; Shahinuzzaman, A D A; Chowdhury, Saiful M

    2017-04-01

    Farnesylation and geranylgeranylation are the two types of prenyl modification of proteins. Prenylated peptides are highly hydrophobic and their abundances in biological samples are low. In this report, we studied the oxidized prenylated peptides by electrospray ionization mass spectrometry and identified them by collision-induced dissociation (CID) and electron-transfer dissociation (ETD) tandem mass spectrometry. Modified prenyl peptides were generated utilizing strong and low strength oxidizing agents to selectively oxidize and epoxidize cysteine sulfur and prenyl side chain. We selected three peptides with prenyl motifs and synthesized their prenylated versions. The detailed characteristic fragmentations of oxidized and epoxidized farnesylated and geranylgeranylated peptides were studied side by side with two popular fragmentation techniques. CID and ETD mass spectrometry clearly distinguished the modified version of these peptides. ETD mass spectrometry provided sequence information of the highly labile modified prenyl peptides and showed different characteristic fragmentations compared with CID. A detailed fragmentation of modified geranylgeranylated peptides was compared by CID and ETD mass spectrometry for the first time. Graphical Abstract ᅟ.

  12. Gas-Phase Fragmentation Behavior of Oxidized Prenyl Peptides by CID and ETD Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bhawal, Ruchika P.; Shahinuzzaman, A. D. A.; Chowdhury, Saiful M.

    2016-10-01

    Farnesylation and geranylgeranylation are the two types of prenyl modification of proteins. Prenylated peptides are highly hydrophobic and their abundances in biological samples are low. In this report, we studied the oxidized prenylated peptides by electrospray ionization mass spectrometry and identified them by collision-induced dissociation (CID) and electron-transfer dissociation (ETD) tandem mass spectrometry. Modified prenyl peptides were generated utilizing strong and low strength oxidizing agents to selectively oxidize and epoxidize cysteine sulfur and prenyl side chain. We selected three peptides with prenyl motifs and synthesized their prenylated versions. The detailed characteristic fragmentations of oxidized and epoxidized farnesylated and geranylgeranylated peptides were studied side by side with two popular fragmentation techniques. CID and ETD mass spectrometry clearly distinguished the modified version of these peptides. ETD mass spectrometry provided sequence information of the highly labile modified prenyl peptides and showed different characteristic fragmentations compared with CID. A detailed fragmentation of modified geranylgeranylated peptides was compared by CID and ETD mass spectrometry for the first time.

  13. Mass spectrometry methods for the analysis of biodegradable hybrid materials

    NASA Astrophysics Data System (ADS)

    Alalwiat, Ahlam

    This dissertation focuses on the characterization of hybrid materials and surfactant blends by using mass spectrometry (MS), tandem mass spectrometry (MS/MS), liquid chromatography (LC), and ion mobility (IM) spectrometry combined with measurement and simulation of molecular collision cross sections. Chapter II describes the principles and the history of mass spectrometry (MS) and liquid chromatography (LC). Chapter III introduces the materials and instrumentation used to complete this dissertation. In chapter IV, two hybrid materials containing poly(t-butyl acrylate) (PtBA) or poly(acrylic acid) (PAA) blocks attached to a hydrophobic peptide rich in valine and glycine (VG2), as well as the poly(acrylic acid) (PAA) and VG2 peptide precursor materials, are characterized by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), electrospray ionization mass spectrometry (ESI-MS) and ion mobility mass spectrometry (IM-MS). Collision cross-sections and molecular modeling have been used to determine the final architecture of both hybrid materials. Chapter V investigates a different hybrid material, [BMP-2(HA)2 ], comprised of a dendron with two polyethylene glycol (PEG) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone morphogenic protein mimicking peptide (BMP-2). MALDI-MS, ESI-MS and IM-MS have been used to characterize the HA and BMP-2 peptides. Collisionally activated dissociation (CAD) and electron transfer dissociation (ETD) have been employed in double stage (i.e. tandem) mass spectrometry (MS/MS) experiments to confirm the sequences of the two peptides HA and BMP-2. The MALDI-MS, ESI-MS and IM-MS methods were also applied to characterize the [BMP-2(HA)2] hybrid material. Collision cross-section measurements and molecular modeling indicated that [BMP-2(HA)2] can attain folded or extended conformation, depending on its degree of protonation (charge state). Chapter VI focuses on the analysis of

  14. Electrospray and tandem mass spectrometry in biochemistry.

    PubMed Central

    Griffiths, W J; Jonsson, A P; Liu, S; Rai, D K; Wang, Y

    2001-01-01

    Over the last 20 years, biological MS has changed out of all recognition. This is primarily due to the development in the 1980s of 'soft ionization' methods that permit the ionization and vaporization of large, polar, and thermally labile biomolecules. These developments in ionization mode have driven the design and manufacture of smaller and cheaper mass analysers, making the mass spectrometer a routine instrument in the biochemistry laboratory today. In the present review the revolutionary 'soft ionization' methods will be discussed with particular reference to electrospray. The mass analysis of ions will be described, and the concept of tandem MS introduced. Where appropriate, examples of the application of MS in biochemistry will be provided. Although the present review will concentrate on the MS of peptides/proteins and lipids, all classes of biomolecules can be analysed, and much excellent work has been done in the fields of carbohydrate and nucleic acid biochemistry. PMID:11311115

  15. Electrospray and tandem mass spectrometry in biochemistry.

    PubMed

    Griffiths, W J; Jonsson, A P; Liu, S; Rai, D K; Wang, Y

    2001-05-01

    Over the last 20 years, biological MS has changed out of all recognition. This is primarily due to the development in the 1980s of 'soft ionization' methods that permit the ionization and vaporization of large, polar, and thermally labile biomolecules. These developments in ionization mode have driven the design and manufacture of smaller and cheaper mass analysers, making the mass spectrometer a routine instrument in the biochemistry laboratory today. In the present review the revolutionary 'soft ionization' methods will be discussed with particular reference to electrospray. The mass analysis of ions will be described, and the concept of tandem MS introduced. Where appropriate, examples of the application of MS in biochemistry will be provided. Although the present review will concentrate on the MS of peptides/proteins and lipids, all classes of biomolecules can be analysed, and much excellent work has been done in the fields of carbohydrate and nucleic acid biochemistry.

  16. Screening of drugs and toxic compounds with liquid chromatography-linear ion trap tandem mass spectrometry.

    PubMed

    Sauvage, François-Ludovic; Saint-Marcoux, Franck; Duretz, Bénédicte; Deporte, Didier; Lachatre, Gérard; Marquet, Pierre

    2006-09-01

    In clinical and forensic toxicology, general unknown screening is used to detect and identify exogenous compounds. In this study, we aimed to develop a comprehensive general unknown screening method based on liquid chromatography coupled with a hybrid triple-quadrupole linear ion trap mass spectrometer. After solid-phase extraction, separation was performed using gradient reversed-phase chromatography. The mass spectrometer was operated in the information-dependent acquisition mode, switching between a survey scan acquired in the Enhanced Mass Spectrometry mode with dynamic subtraction of background noise and a dependent scan obtained in the enhanced product ion scan mode. The complete cycle time was 1.36 s. A library of 1000 enhanced product ion-tandem mass spectrometry spectra in positive mode and 250 in negative mode, generated using 3 alternated collision tensions during each scan, was created by injecting pure solutions of drugs and toxic compounds. Comparison with HPLC-diode array detection and gas chromatography-mass spectrometry for the analysis of 36 clinical samples showed that linear ion trap tandem mass spectrometry could identify most of the compounds (94% of the total). Some compounds were detected only by 1 of the other 2 techniques. Specific clinical cases highlighted the advantages and limitations of the method. A unique combination of new operating modes provided by hybrid triple-quadrupole linear ion trap mass spectrometers and new software features allowed development of a comprehensive and efficient method for the general unknown screening of drugs and toxic compounds in blood or urine.

  17. Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques

    SciTech Connect

    Laskin, Julia; Lanekoff, Ingela

    2015-11-13

    Mass spectrometry imaging (MSI) is a powerful analytical technique that enables label-free spatial localization and identification of molecules in complex samples.1-4 MSI applications range from forensics5 to clinical research6 and from understanding microbial communication7-8 to imaging biomolecules in tissues.1, 9-10 Recently, MSI protocols have been reviewed.11 Ambient ionization techniques enable direct analysis of complex samples under atmospheric pressure without special sample pretreatment.3, 12-16 In fact, in ambient ionization mass spectrometry, sample processing (e.g., extraction, dilution, preconcentration, or desorption) occurs during the analysis.17 This substantially speeds up analysis and eliminates any possible effects of sample preparation on the localization of molecules in the sample.3, 8, 12-14, 18-20 Venter and co-workers have classified ambient ionization techniques into three major categories based on the sample processing steps involved: 1) liquid extraction techniques, in which analyte molecules are removed from the sample and extracted into a solvent prior to ionization; 2) desorption techniques capable of generating free ions directly from substrates; and 3) desorption techniques that produce larger particles subsequently captured by an electrospray plume and ionized.17 This review focuses on localized analysis and ambient imaging of complex samples using a subset of ambient ionization methods broadly defined as “liquid extraction techniques” based on the classification introduced by Venter and co-workers.17 Specifically, we include techniques where analyte molecules are desorbed from solid or liquid samples using charged droplet bombardment, liquid extraction, physisorption, chemisorption, mechanical force, laser ablation, or laser capture microdissection. Analyte extraction is followed by soft ionization that generates ions corresponding to intact species. Some of the key advantages of liquid extraction techniques include the ease

  18. A New Accelerator-Based Mass Spectrometry.

    ERIC Educational Resources Information Center

    Gove, H. E.

    1983-01-01

    Tandem electrostatic accelerators produce beams of positive ions which are used to penetrate atomic nuclei in a target, inducing nuclear reactions whose study elucidates varied properties of the nucleus. Uses of the system, which acts like a mass spectrometer, are discussed. These include radiocarbon dating measurements. (JN)

  19. A New Accelerator-Based Mass Spectrometry.

    ERIC Educational Resources Information Center

    Gove, H. E.

    1983-01-01

    Tandem electrostatic accelerators produce beams of positive ions which are used to penetrate atomic nuclei in a target, inducing nuclear reactions whose study elucidates varied properties of the nucleus. Uses of the system, which acts like a mass spectrometer, are discussed. These include radiocarbon dating measurements. (JN)

  20. Mass spectrometry on the surface of Mercury

    NASA Astrophysics Data System (ADS)

    Whitby, J.; Rohner, U.; Benz, W.; Wurz, P.

    2003-04-01

    The proposed Mercury Surface Element of the BepiColombo mission will place a lander on Mercury equipped with a geochemistry instrumentation package. We will discuss the utility of elemental and isotopic analyses of individual mineral grains in the hermean regolith, and present relevant results from a prototype laser-ablation time-of-flight mass spectrometer.

  1. Understanding ligand effects in gold clusters using mass spectrometry

    SciTech Connect

    Johnson, Grant E.; Laskin, Julia

    2016-01-01

    This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because “each-atom-counts” toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation of numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted that may be compared with the results of high-level theoretical calculations. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well

  2. Understanding ligand effects in gold clusters using mass spectrometry.

    PubMed

    Johnson, Grant E; Laskin, Julia

    2016-06-21

    This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because "each-atom-counts" toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation of numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well-defined surfaces may be explored using ion soft landing (SL) in a custom

  3. Mass spectrometry and metabolism of leukotriene B/sub 4/

    SciTech Connect

    Harper, T.W.

    1985-01-01

    Leukotriene B/sub 4/ (LTB/sub 4/) is a potent and powerful chemotactic factor for polymorphonuclear leukocytes and has been hypothesized to play a role as a mediator of the inflammatory response. A cell free system capable of generating leukotrienes from exogenous arachidonic acid was developed using both rat basophilic leukemia cells and murine mastocytoma cells. The cell free leukotriene generating system was used to prepare leukotrienes for mass spectral studies using electron impact (EI), chemical ionization (Cl), negative ion chemical ionization (NCl) and both positive and negative ion fast atom bombardment mass spectrometry (FAB-MS). Although all of the techniques examined yielded useful information, NCl was found to be the most useful for sensitive quantitation of leukotrienes, whereas Cl and El are more useful for unambiguous structural characterization of hydroxy fatty acid leukotrienes. Investigation of the in vivo metabolism of LTB/sub 4/ in the mouse and guinea pig indicated that less than 10% of the injected radiolabel from /sup 3/H-LTB/sub 4/ was excreted via the urine and feces. Approximately 30% of the urinary radioactivity was volatile, probably due to loss of the tritium label as water. In the monkey, approximately 10% of the injected radiolabel from /sup 14/C-LTB/sup 4/ was excreted in the urine within 5 1/2 hours. In this study, approximately 10% of the urinary radiolabel was volatile, with a large number of unidentified non-volatile products also observed. The isolated perfused rat lung was found to rapidly metabolize leukotriene C/sub 4/ to leukotrienes D/sub 4/ and E/sub 4/ and to leukotriene C/sub 4/ sulfoxide.

  4. Trace elements in coal by glow discharge mass spectrometry

    SciTech Connect

    Jacobs, M.L.; Wilson, C.R.; Pestovich, J. Jr.

    1995-08-01

    A need and a demand exist for determining trace elements in coal and coal related by-products, especially those elements which may potentially be a health hazard. The provisions of the 1990 clean air act require that the EPA evaluate the emissions of electric utilities for trace elements and other potentially hazardous organic compounds. The coal fired electric utility industry supplies roughly 60% of the total generating capacity of 2,882,525 million kilowatt hours (nearly 3 trillion kilowatt hours) generated in the U.S. This is accomplished by 414 power plants scattered across the country that burned 813,508,000 short tons of coal in 1993. The relative volatility of some inorganic constituents in coal makes them more prone to be emitted to the atmosphere following combustion. The production of analytical data for trace elements is known to be a difficult task in coal and by-products of coal combustion (fly ash, bottom ash, gas streams, etc.), in terms of both sample collection and analytical determinations. There are several common analytical methods available to the analyst to determine trace elements in coal and coal by-products. In general analytical germs, the material to be analyzed can be totally solubilized (or extracted), or the elements analytes can be determined in the material as a solid. A relatively new elemental technique, Glow Discharge Mass Spectrometry (GDMS) can be used with solids as well. This new analytical technique had never before been applied directly to coal. The radio frequency-glow discharge quadropole mass spectrometer was used to analyze coal directly for the first time ever by rf-GDMS. The rf-GDMS technique is described.

  5. Aerosol mass spectrometry systems and methods

    DOEpatents

    Fergenson, David P.; Gard, Eric E.

    2013-08-20

    A system according to one embodiment includes a particle accelerator that directs a succession of polydisperse aerosol particles along a predetermined particle path; multiple tracking lasers for generating beams of light across the particle path; an optical detector positioned adjacent the particle path for detecting impingement of the beams of light on individual particles; a desorption laser for generating a beam of desorbing light across the particle path about coaxial with a beam of light produced by one of the tracking lasers; and a controller, responsive to detection of a signal produced by the optical detector, that controls the desorption laser to generate the beam of desorbing light. Additional systems and methods are also disclosed.

  6. A new derivative for oxosteroid analysis by mass spectrometry

    PubMed Central

    Rigdova, K.; Wang, Y.; Ward, M.; Griffiths, W.J.

    2014-01-01

    Here we report a new method for oxosteroid identification utilizing “tandem mass tag hydrazine” (TMTH) carbonyl-reactive derivatisation reagent. TMTH is a reagent with a chargeable tertiary amino group attached through a linker to a carbonyl-reactive hydrazine group. Thirty oxosteroids were analysed after derivatisation with TMTH by electrospray ionization mass spectrometry (ESI-MS) and were found to give high ion-currents compared to underivatised molecules. ESI-tandem mass spectrometry (MS/MS) analysis of the derivatives yielded characteristic fragmentation patterns with specific mass reporter ions derived from the TMT group. A shotgun ESI-MS method incorporating TMTH derivatisation was applied to a urine sample. PMID:24525129

  7. A new derivative for oxosteroid analysis by mass spectrometry.

    PubMed

    Rigdova, K; Wang, Y; Ward, M; Griffiths, W J

    2014-04-11

    Here we report a new method for oxosteroid identification utilizing "tandem mass tag hydrazine" (TMTH) carbonyl-reactive derivatisation reagent. TMTH is a reagent with a chargeable tertiary amino group attached through a linker to a carbonyl-reactive hydrazine group. Thirty oxosteroids were analysed after derivatisation with TMTH by electrospray ionization mass spectrometry (ESI-MS) and were found to give high ion-currents compared to underivatised molecules. ESI-tandem mass spectrometry (MS/MS) analysis of the derivatives yielded characteristic fragmentation patterns with specific mass reporter ions derived from the TMT group. A shotgun ESI-MS method incorporating TMTH derivatisation was applied to a urine sample. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Universal collisional activation ion trap mass spectrometry

    DOEpatents

    McLuckey, S.A.; Goeringer, D.E.; Glish, G.L.

    1993-04-27

    A universal collisional activation ion trap comprises an ion trapping means containing a bath gas and having connected thereto a noise signal generator. A method of operating a universal collisional activation ion trap comprises the steps of: providing an ion trapping means; introducing into the ion trapping means a bath gas; and, generating a noise signal within the ion trapping means; introducing into the ion trapping means a substance that, when acted upon by the noise signal, undergoes collisional activation to form product ions.

  9. Universal collisional activation ion trap mass spectrometry

    DOEpatents

    McLuckey, Scott A.; Goeringer, Douglas E.; Glish, Gary L.

    1993-01-01

    A universal collisional activation ion trap comprises an ion trapping means containing a bath gas and having connected thereto a noise signal generator. A method of operating a universal collisional activation ion trap comprises the steps of: providing an ion trapping means; introducing into the ion trapping means a bath gas; and, generating a noise signal within the ion trapping means; introducing into the ion trapping means a substance that, when acted upon by the noise signal, undergoes collisional activation to form product ions.

  10. High-accuracy mass spectrometry for fundamental studies.

    PubMed

    Kluge, H-Jürgen

    2010-01-01

    Mass spectrometry for fundamental studies in metrology and atomic, nuclear and particle physics requires extreme sensitivity and efficiency as well as ultimate resolving power and accuracy. An overview will be given on the global status of high-accuracy mass spectrometry for fundamental physics and metrology. Three quite different examples of modern mass spectrometric experiments in physics are presented: (i) the retardation spectrometer KATRIN at the Forschungszentrum Karlsruhe, employing electrostatic filtering in combination with magnetic-adiabatic collimation-the biggest mass spectrometer for determining the smallest mass, i.e. the mass of the electron anti-neutrino, (ii) the Experimental Cooler-Storage Ring at GSI-a mass spectrometer of medium size, relative to other accelerators, for determining medium-heavy masses and (iii) the Penning trap facility, SHIPTRAP, at GSI-the smallest mass spectrometer for determining the heaviest masses, those of super-heavy elements. Finally, a short view into the future will address the GSI project HITRAP at GSI for fundamental studies with highly-charged ions.

  11. Plasma source mass spectrometry in experimental nutrition.

    PubMed

    Barnes, R M

    1998-01-01

    The development and commercial availability of plasma ion source, specifically inductively coupled plasma, mass spectrometers (ICP-MS) have significantly extended the potential application of stable isotopes for nutritional modeling. The status of research and commercial ICP-MS instruments, and their applications and limitations for stable isotopic studies are reviewed. The consequences of mass spectroscopic resolution and measurement sensitivity obtainable with quadrupole, sector, time-of-flight, and trap instruments on stable isotope analysis are examined. Requirements for reliable isotope measurements with practical biological samples including tissues and fluids are considered. The possibility for stable isotope analysis in chemically separated compounds (speciation) also is explored. On-line compound separations by chromatography or electrophoresis, for example, have been combined instrumentally with ICP-MS. Som possibilities and requirements are described for stable isotope speciation analysis.

  12. Laser Mass Spectrometry in Planetary Science

    SciTech Connect

    Wurz, P.; Whitby, J. A.; Managadze, G. G.

    2009-06-16

    Knowing the chemical, elemental, and isotopic composition of planetary objects allows the study of their origin and evolution within the context of our solar system. Exploration plans in planetary research of several space agencies consider landing spacecraft for future missions. Although there have been successful landers in the past, more landers are foreseen for Mars and its moons, Venus, the jovian moons, and asteroids. Furthermore, a mass spectrometer on a landed spacecraft can assist in the sample selection in a sample-return mission and provide mineralogical context, or identify possible toxic soils on Mars for manned Mars exploration. Given the resources available on landed spacecraft mass spectrometers, as well as any other instrument, have to be highly miniaturised.

  13. Laser Mass Spectrometry in Planetary Science

    NASA Astrophysics Data System (ADS)

    Wurz, P.; Whitby, J. A.; Managadze, G. G.

    2009-06-01

    Knowing the chemical, elemental, and isotopic composition of planetary objects allows the study of their origin and evolution within the context of our solar system. Exploration plans in planetary research of several space agencies consider landing spacecraft for future missions. Although there have been successful landers in the past, more landers are foreseen for Mars and its moons, Venus, the jovian moons, and asteroids. Furthermore, a mass spectrometer on a landed spacecraft can assist in the sample selection in a sample-return mission and provide mineralogical context, or identify possible toxic soils on Mars for manned Mars exploration. Given the resources available on landed spacecraft mass spectrometers, as well as any other instrument, have to be highly miniaturised.

  14. Calcium isotope analysis by mass spectrometry.

    PubMed

    Boulyga, Sergei F

    2010-01-01

    The variations in the isotopic composition of calcium caused by fractionation in heterogeneous systems and by nuclear reactions can provide insight into numerous biological, geological, and cosmic processes, and therefore isotopic analysis finds a wide spectrum of applications in cosmo- and geochemistry, paleoclimatic, nutritional, and biomedical studies. The measurement of calcium isotopic abundances in natural samples has challenged the analysts for more than three decades. Practically all Ca isotopes suffer from significant isobaric interferences, whereas low-abundant isotopes can be particularly affected by neighboring major isotopes. The extent of natural variations of stable isotopes appears to be relatively limited, and highly precise techniques are required to resolve isotopic effects. Isotope fractionation during sample preparation and measurements and instrumental mass bias can significantly exceed small isotope abundance variations in samples, which have to be investigated. Not surprisingly, a TIMS procedure developed by Russell et al. (Russell et al., 1978. Geochim Cosmochim Acta 42: 1075-1090) for Ca isotope measurements was considered as revolutionary for isotopic measurements in general, and that approach is used nowadays (with small modifications) for practically all isotopic systems and with different mass spectrometric techniques. Nevertheless, despite several decades of calcium research and corresponding development of mass spectrometers, the available precision and accuracy is still not always sufficient to achieve the challenging goals. The present article discusses figures of merits of presently used analytical methods and instrumentation, and attempts to critically assess their limitations. In Sections 2 and 3, mass spectrometric methods applied to precise stable isotope analysis and to the determination of (41)Ca are described. Section 4 contains a short summary of selected applications, and includes tracer experiments and the potential use

  15. Calcium Isotope Analysis by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Boulyga, S.; Richter, S.

    2010-12-01

    The variations in the isotopic composition of calcium caused by fractionation in heterogeneous systems and by nuclear reactions can provide insight into numerous biological, geological, and cosmic processes, and therefore isotopic analysis finds a wide spectrum of applications in cosmo- and geochemistry, paleoclimatic, nutritional, and biomedical studies. The measurement of calcium isotopic abundances in natural samples has challenged the analysts for more than three decades. Practically all Ca isotopes suffer from significant isobaric interferences, whereas low-abundant isotopes can be particularly affected by neighboring major isotopes. The extent of natural variations of stable isotopes appears to be relatively limited, and highly precise techniques are required to resolve isotopic effects. Isotope fractionation during sample preparation and measurements and instrumental mass bias can significantly exceed small isotope abundance variations in samples, which have to be investigated. Not surprisingly, a TIMS procedure developed by Russell et al. (Russell et al., 1978. Geochim Cosmochim Acta 42: 1075-1090) for Ca isotope measurements was considered as revolutionary for isotopic measurements in general, and that approach is used nowadays (with small modifications) for practically all isotopic systems and with different mass spectrometric techniques. Nevertheless, despite several decades of calcium research and corresponding development of mass spectrometers, the available precision and accuracy is still not always sufficient to achieve the challenging goals. This presentation discusses figures of merits of presently used analytical methods and instrumentation, and attempts to critically assess their limitations. Additionally, the availability of Ca isotope reference materials will be discussed.

  16. MICELLAR ELECTROKINETIC CHROMATOGRAPHY-MASS SPECTROMETRY (R823292)

    EPA Science Inventory

    The combination of micellar electrokinetic chromatography (MEKC) with mass spectrometry (MS) is very attractive for the direct identification of analyte molecules, for the possibility of selectivity enhancement, and for the structure confirmation and analysis in a MS-MS mode. The...

  17. Quantitative matrix-assisted laser desorption/ionization mass spectrometry

    PubMed Central

    Roder, Heinrich; Hunsucker, Stephen W.

    2008-01-01

    This review summarizes the essential characteristics of matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS), especially as they relate to its applications in quantitative analysis. Approaches to quantification by MALDI-TOF MS are presented and published applications are critically reviewed. PMID:19106161

  18. MICELLAR ELECTROKINETIC CHROMATOGRAPHY-MASS SPECTROMETRY (R823292)

    EPA Science Inventory

    The combination of micellar electrokinetic chromatography (MEKC) with mass spectrometry (MS) is very attractive for the direct identification of analyte molecules, for the possibility of selectivity enhancement, and for the structure confirmation and analysis in a MS-MS mode. The...

  19. Colloquium: 100 years of mass spectrometry: Perspectives and future trends

    NASA Astrophysics Data System (ADS)

    Maher, Simon; Jjunju, Fred P. M.; Taylor, Stephen

    2015-01-01

    Mass spectrometry (MS) is widely regarded as the most sensitive and specific general purpose analytical technique. More than a century has passed for MS since the ground-breaking work of Nobel laureate Sir Joseph John Thomson in 1913. This Colloquium aims to (1) give an historical overview of the major instrumentation achievements that have driven mass spectrometry forward in the past century, including those leading up to the initial work of Thomson, (2) provide the nonspecialist with an introduction to MS, and (3) highlight some key applications of MS and explore the current and future trends. Because of the vastness of the subject area and quality of the manifold research efforts that have been undertaken over the last 100 years, which have contributed to the foundations and subsequent advances in mass spectrometry, it should be understood that not all of the key contributions may have been included in this Colloquium. Mass spectrometry has embraced a multitude of scientific disciplines and to recognize all of the achievements is an impossible task, such has been the diverse impact of this invaluable technique. Scientific progress is usually made via the cumulative effort of a large number of researchers; the achievements reported herein are only a representation of that effort.

  20. Liquid Chromatography-Mass Spectrometry-based Quantitative Proteomics

    SciTech Connect

    Xie, Fang; Liu, Tao; Qian, Weijun; Petyuk, Vladislav A.; Smith, Richard D.

    2011-07-22

    Liquid chromatography-mass spectrometry (LC-MS)-based quantitative proteomics has become increasingly applied for a broad range of biological applications due to growing capabilities for broad proteome coverage and good accuracy in quantification. Herein, we review the current LC-MS-based quantification methods with respect to their advantages and limitations, and highlight their potential applications.