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

PubMed

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

2012-04-17

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

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

PubMed

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

2013-01-01

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

Nano-LC FTICR tandem mass spectrometry for top-down proteomics: routine baseline unit mass resolution of whole cell lysate proteins up to 72 kDa.

PubMed

Tipton, Jeremiah D; Tran, John C; Catherman, Adam D; Ahlf, Dorothy R; Durbin, Kenneth R; Lee, Ji Eun; Kellie, John F; Kelleher, Neil L; Hendrickson, Christopher L; Marshall, Alan G

2012-03-06

Current high-throughput top-down proteomic platforms provide routine identification of proteins less than 25 kDa with 4-D separations. This short communication reports the application of technological developments over the past few years that improve protein identification and characterization for masses greater than 25 kDa. Advances in separation science have allowed increased numbers of proteins to be identified, especially by nanoliquid chromatography (nLC) prior to mass spectrometry (MS) analysis. Further, a goal of high-throughput top-down proteomics is to extend the mass range for routine nLC MS analysis up to 80 kDa because gene sequence analysis predicts that ~70% of the human proteome is transcribed to be less than 80 kDa. Normally, large proteins greater than 50 kDa are identified and characterized by top-down proteomics through fraction collection and direct infusion at relatively low throughput. Further, other MS-based techniques provide top-down protein characterization, however at low resolution for intact mass measurement. Here, we present analysis of standard (up to 78 kDa) and whole cell lysate proteins by Fourier transform ion cyclotron resonance mass spectrometry (nLC electrospray ionization (ESI) FTICR MS). The separation platform reduced the complexity of the protein matrix so that, at 14.5 T, proteins from whole cell lysate up to 72 kDa are baseline mass resolved on a nano-LC chromatographic time scale. Further, the results document routine identification of proteins at improved throughput based on accurate mass measurement (less than 10 ppm mass error) of precursor and fragment ions for proteins up to 50 kDa.

Extracting biomolecule collision cross sections from the high-resolution FT-ICR mass spectral linewidths.

PubMed

Jiang, Ting; Chen, Yu; Mao, Lu; Marshall, Alan G; Xu, Wei

2016-01-14

It is known that the ion collision cross section (CCS) may be calculated from the linewidth of a Fourier transform ion cyclotron resonance (FT-ICR) mass spectral peak at elevated pressure (e.g., ∼10(-6) Torr). However, the high mass resolution of FT-ICR is sacrificed in those experiments due to high buffer gas pressure. In this study, we describe a linewidth correction method to eliminate the windowing-induced peak broadening effect. Together with the energetic ion-neutral collision model previously developed by our group, this method enables the extraction of CCSs of biomolecules from high-resolution FT-ICR mass spectral linewidths, obtained at a typical operating buffer gas pressure of modern FT-ICR instruments (∼10(-10) Torr). CCS values of peptides including MRFA, angiotensin I, and bradykinin measured by the proposed method agree well with ion mobility measurements, and the unfolding of protein ions (ubiquitin) at higher charge states is also observed.

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

NASA Astrophysics Data System (ADS)

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

2008-09-01

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

Improving mass measurement accuracy in mass spectrometry based proteomics by combining open source tools for chromatographic alignment and internal calibration.

PubMed

Palmblad, Magnus; van der Burgt, Yuri E M; Dalebout, Hans; Derks, Rico J E; Schoenmaker, Bart; Deelder, André M

2009-05-02

Accurate mass determination enhances peptide identification in mass spectrometry based proteomics. We here describe the combination of two previously published open source software tools to improve mass measurement accuracy in Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). The first program, msalign, aligns one MS/MS dataset with one FTICRMS dataset. The second software, recal2, uses peptides identified from the MS/MS data for automated internal calibration of the FTICR spectra, resulting in sub-ppm mass measurement errors.

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

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

PubMed

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

2011-05-15

This review focuses on recent applications of matrix-assisted laser desorption ionization-Fourier-transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) in qualitative and quantitative analysis of low molecular weight compounds. The scope of the work includes amino acids, small peptides, mono and oligosaccharides, lipids, metabolic compounds, small molecule phytochemicals from medicinal herbs and even the volatile organic compounds from tobacco. We discuss both direct analysis and analysis following derivatization. In addition we review sample preparation strategies to reduce interferences in the low m/z range and to improve sensitivities by derivatization with charge tags. We also present coupling of head space techniques with MALDI-FTICR-MS. Furthermore, omics analyses based on MALDI-FTICR-MS were also discussed, including proteomics, metabolomics and lipidomics, as well as the relative MS imaging for bio-active low molecular weight compounds. Finally, we discussed the investigations on dissociation/rearrangement processes of low molecular weight compounds by MALDI-FTICR-MS. Copyright © 2011 Elsevier B.V. All rights reserved.

Top-down mass spectrometry imaging of intact proteins by laser ablation ESI FT-ICR MS.

PubMed

Kiss, András; Smith, Donald F; Reschke, Brent R; Powell, Matthew J; Heeren, Ron M A

2014-05-01

Laser ablation ESI (LAESI) is a recent development in MS imaging. It has been shown that lipids and small metabolites can be imaged in various samples such as plant material, tissue sections or bacterial colonies without any sample pretreatment. Further, LAESI has been shown to produce multiply charged protein ions from liquids or solid surfaces. This presents a means to address one of the biggest challenges in MS imaging; the identification of proteins directly from biological tissue surfaces. Such identification is hindered by the lack of multiply charged proteins in common MALDI ion sources and the difficulty of performing tandem MS on such large, singly charged ions. We present here top-down identification of intact proteins from tissue with a LAESI ion source combined with a hybrid ion-trap FT-ICR mass spectrometer. The performance of the system was first tested with a standard protein with electron capture dissociation and infrared multiphoton dissociation fragmentation to prove the viability of LAESI FT-ICR for top-down proteomics. Finally, the imaging of a tissue section was performed, where a number of intact proteins were measured and the hemoglobin α chain was identified directly from tissue using CID and infrared multiphoton dissociation fragmentation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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.

High resolution mass spectrometric brain proteomics by MALDI-FTICR-MS combined with determination of P, S, Cu, Zn and Fe by LA-ICP-MS

NASA Astrophysics Data System (ADS)

Becker, J. Susanne; Zoriy, Miroslav; Przybylski, Michael; Becker, J. Sabine

2007-03-01

The combination of atomic and molecular mass spectrometric methods was applied for characterization and identification of several human proteins from Alzheimer's diseased brain. A brain protein mixture was separated by two-dimensional (2D) gel electrophoresis and the protein spots were fast screened by microlocal analysis using LA-ICP-MS (laser ablation inductively coupled plasma mass spectrometry) in respect to phosphorus, sulfur, copper, zinc and iron content. Five selected protein spots in 2D gel containing these elements were investigated after tryptic digestion by matrix assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS). Than element concentrations (P, Cu, Zn and Fe) were determined in three identified human brain proteins by LA-ICP-MS in the 2D gel. Results of structure analysis of human brain proteins by MALDI-FTICR-MS were combined with those of the direct determination of phosphorus, copper, zinc and iron concentrations in protein spots with LA-ICP-MS. From the results of atomic and molecular mass spectrometric techniques the human brain proteins were characterized in respect to their structure, sequence, phosphorylation state and metal content as well.

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

PubMed

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

2015-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2017-07-01

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

Structural characterization of arginine-vasopressin and lysine-vasopressin by Fourier- transform ion cyclotron resonance mass spectrometry and infrared multiphoton dissociation.

PubMed

Bianco, Giuliana; Battista, Fabio; Buchicchio, Alessandro; Amarena, Concetta G; Schmitt-Kopplin, Philippe; Guerrieri, Antonio

2015-01-01

Arginine-vasopressin (AVP) and lysine-vasopressin (LVP) were analyzed by reversed-phase liquid chromatography/mass spectrometry (LC-MS) using Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) electrospray ionization (ESI) in the positive ion mode. LVP and AVP exhibited the protonated adduct [M+H](+) as the predominant ion at m/z 1056.43965 and at m/z 1084.44561, respectively. Infrared multiphoton dissociation (IRMPD), using a CO(2) laser source at a wavelength of 10.6 μm, was applied to protonated vasopressin molecules. The IRMPD mass spectra presented abundant mass fragments essential for a complete structural information. Several fragment ions, shared between two target molecules, are discussed in detail. Some previously unpublished fragments were identified unambiguously utilizing the high resolution and accurate mass information provided by the FT-ICR mass spectrometer. The opening of the disulfide loop and the cleavage of the peptide bonds within the ring were observed even under low-energy fragmentation conditions. Coupling the high-performance FT-ICR mass spectrometer with IRMPD as a contemporary fragmentation technique proved to be very promising for the structural characterization of vasopressin.

High field FT-ICR mass spectrometry for molecular characterization of snow board from Moscow regions.

PubMed

Mazur, Dmitry M; Harir, Mourad; Schmitt-Kopplin, Philippe; Polyakova, Olga V; Lebedev, Albert T

2016-07-01

High field Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry analysis of eight snow samples from Moscow city allowed us to identify more than 2000 various elemental compositions corresponding to regional air pollutants. The hierarchical cluster analysis (HCA) of the data showed good concordance of three main groups of samples with the main wind directions. The North-West group (A1) is represented by several homologous CHOS series of aliphatic organic aerosols. They may form as a result of enhanced photochemical reactions including oxidation of hydrocarbons with sulfonations due to higher amount of SO2 emissions in the atmosphere in this region. Group A2, corresponding to the South-East part of Moscow, contains large amount of oxidized hydrocarbons of different sources that may form during oxidation in atmosphere. These hydrocarbons appear correlated to emissions from traffic, neighboring oil refinery, and power plants. Another family of compounds specific for this region involves CHNO substances formed during oxidation processes including NOx and NO3 radical since emissions of NOx are higher in this part of the city. Group A3 is rich in CHO type of compounds with high H/C and low O/C ratios, which is characteristic of oxidized hydrocarbon-like organic aerosol. CHNO types of compounds in A3 group are probably nitro derivatives of condensed hydrocarbons such as PAH. This non-targeted profiling revealed site specific distribution of pollutants and gives a chance to develop new strategies in air quality control and further studies of Moscow environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of a new qQq-FTICR mass spectrometer for post-translational modification analysis and top-down tandem mass spectrometry of whole proteins.

PubMed

Jebanathirajah, Judith A; Pittman, Jason L; Thomson, Bruce A; Budnik, Bogdan A; Kaur, Parminder; Rape, Michael; Kirschner, Marc; Costello, Catherine E; O'Connor, Peter B

2005-12-01

The use of a new electrospray qQq Fourier transform ion cyclotron mass spectrometer (qQq-FTICR MS) instrument for biologic applications is described. This qQq-FTICR mass spectrometer was designed for the study of post-translationally modified proteins and for top-down analysis of biologically relevant protein samples. The utility of the instrument for the analysis of phosphorylation, a common and important post-translational modification, was investigated. Phosphorylation was chosen as an example because it is ubiquitous and challenging to analyze. In addition, the use of the instrument for top-down sequencing of proteins was explored since this instrument offers particular advantages to this approach. Top-down sequencing was performed on different proteins, including commercially available proteins and biologically derived samples such as the human E2 ubiquitin conjugating enzyme, UbCH10. A good sequence tag was obtained for the human UbCH10, allowing the unambiguous identification of the protein. The instrument was built with a commercially produced front end: a focusing rf-only quadrupole (Q0), followed by a resolving quadrupole (Q1), and a LINAC quadrupole collision cell (Q2), in combination with an FTICR mass analyzer. It has utility in the analysis of samples found in substoichiometric concentrations, as ions can be isolated in the mass resolving Q1 and accumulated in Q2 before analysis in the ICR cell. The speed and efficacy of the Q2 cooling and fragmentation was demonstrated on an LCMS-compatible time scale, and detection limits for phosphopeptides in the 10 amol/muL range (pM) were demonstrated. The instrument was designed to make several fragmentation methods available, including nozzle-skimmer fragmentation, Q2 collisionally activated dissociation (Q2 CAD), multipole storage assisted dissociation (MSAD), electron capture dissociation (ECD), infrared multiphoton induced dissociation (IRMPD), and sustained off resonance irradiation (SORI) CAD, thus

RAPID AND AUTOMATED PROCESSING OF MALDI-FTICR/MS DATA FOR N-METABOLIC LABELING IN A SHOTGUN PROTEOMICS ANALYSIS.

PubMed

Jing, Li; Amster, I Jonathan

2009-10-15

Offline high performance liquid chromatography combined with matrix assisted laser desorption and Fourier transform ion cyclotron resonance mass spectrometry (HPLC-MALDI-FTICR/MS) provides the means to rapidly analyze complex mixtures of peptides, such as those produced by proteolytic digestion of a proteome. This method is particularly useful for making quantitative measurements of changes in protein expression by using (15)N-metabolic labeling. Proteolytic digestion of combined labeled and unlabeled proteomes produces complex mixtures that with many mass overlaps when analyzed by HPLC-MALDI-FTICR/MS. A significant challenge to data analysis is the matching of pairs of peaks which represent an unlabeled peptide and its labeled counterpart. We have developed an algorithm and incorporated it into a compute program which significantly accelerates the interpretation of (15)N metabolic labeling data by automating the process of identifying unlabeled/labeled peak pairs. The algorithm takes advantage of the high resolution and mass accuracy of FTICR mass spectrometry. The algorithm is shown to be able to successfully identify the (15)N/(14)N peptide pairs and calculate peptide relative abundance ratios in highly complex mixtures from the proteolytic digest of a whole organism protein extract.

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

PubMed Central

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

2016-01-01

Thousands of chemically distinct compounds are encountered in fossil oil samples that require rapid screening and accurate identification. In the present paper, we show for the first time, the advantages of gas chromatography (GC) separation in combination with atmospheric-pressure laser ionization (APLI) and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for the screening of polyaromatic hydrocarbons (PAHs) in fossil oils. In particular, reference standards of organics in shale oil, petroleum crude oil, and heavy sweet crude oil were characterized by GC-APLI-FT-ICR MS and APLI-FT-ICR MS. Results showed that, while APLI increases the ionization efficiency of PAHs, when compared to other ionization sources, the complexity of the fossil oils reduces the probability of ionizing lower-concentration compounds during direct infusion. When gas chromatography precedes APLI-FT-ICR MS, an increase (more than 2-fold) in the ionization efficiency and an increase in the signal-to-noise ratio of lower-concentration fractions are observed, giving better molecular coverage in the m/z 100–450 range. That is, the use of GC prior to APLI-FT-ICR MS resulted in higher molecular coverage, higher sensitivity, and the ability to separate and characterize molecular isomers, while maintaining the ultrahigh resolution and mass accuracy of the FT-ICR MS separation. PMID:27212790

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

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

NASA Astrophysics Data System (ADS)

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

2006-12-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

From Supercomputer Modeling to Highest Mass Resolution in FT-ICR.

PubMed

N Nikolaev, Evgene; N Vladimirov, Gleb; Jertz, Roland; Baykut, Gökhan

2013-01-01

Understanding of behavior of ion ensembles inside FT-ICR cell based on the computer simulation of ion motion gives rise to the new ideas of cell designs. The recently introduced novel FT-ICR cell based on a Penning ion trap with specially shaped excitation and detection electrodes prevents distortion of ion cyclotron motion phases (normally caused by non-ideal electric trapping fields) by averaging the trapping DC electric field during the ion motion in the ICR cell. Detection times of 5 min resulting in resolving power close to 40,000,000 have been reached for reserpine at m/z 609 at a magnetic field of only 7 Tesla. Fine structures of resolved 13Cn isotopic cluster groups could be measured for molecular masses up to 5.7 kDa (insulin) with resolving power of 4,000,000 at 7 Tesla. Based on resolved fine structure patterns atomic compositions can be directly determined using a new developed algorithm for fine structure processing. Mass spectra of proteins and multimers of proteins reaching masses up to 186 kDa (enolase tetramer) could be measured with isotopic resolution. For instance, at 7 Tesla resolving power of 800,000 was achieved for enolase dimer (96 kDa) and 500,000 for molecular masses above 100 kDa. Experimental data indicate that there is practically no limit for the resolving power of this ICR cell except by collisional damping in the ultrahigh vacuum chamber.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderton, Christopher R.; Gamble, Lara J.

2016-03-01

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

Online quench-flow electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry for elucidating kinetic and chemical enzymatic reaction mechanisms.

PubMed

Clarke, David J; Stokes, Adam A; Langridge-Smith, Pat; Mackay, C Logan

2010-03-01

We have developed an automated quench-flow microreactor which interfaces directly to an electrospray ionization (ESI) mass spectrometer. We have used this device in conjunction with ESI Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) to demonstrate the potential of this approach for studying the mechanistic details of enzyme reactions. For the model system chosen to test this device, namely, the pre-steady-state hydrolysis of p-nitrophenyl acetate by the enzyme chymotrypsin, the kinetic parameters obtained are in good agreement with those in the literature. To our knowledge, this is the first reported use of online quench-flow coupled with FTICR MS. Furthermore, we have exploited the power of FTICR MS to interrogate the quenched covalently bound enzyme intermediate using top-down fragmentation. The accurate mass capabilities of FTICR MS permitted the nature of the intermediate to be assigned with high confidence. Electron capture dissociation (ECD) fragmentation allowed us to locate the intermediate to a five amino acid section of the protein--which includes the known catalytic residue, Ser(195). This experimental approach, which uniquely can provide both kinetic and chemical details of enzyme mechanisms, is a potentially powerful tool for studies of enzyme catalysis.

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

USGS Publications Warehouse

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

2017-01-01

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

Rapid Trace Detection and Isomer Quantitation of Pesticide Residues via Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

PubMed

Wu, Xinzhou; Li, Weifeng; Guo, Pengran; Zhang, Zhixiang; Xu, Hanhong

2018-04-18

Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) has been applied for rapid, sensitive, undisputed, and quantitative detection of pesticide residues on fresh leaves with little sample pretreatment. Various pesticides (insecticides, bactericides, herbicides, and acaricides) are detected directly in the complex matrix with excellent limits of detection down to 4 μg/L. FTICR-MS could unambiguously identify pesticides with tiny mass differences (∼0.017 75 Da), thereby avoiding false-positive results. Remarkably, pesticide isomers can be totally discriminated by use of diagnostic fragments, and quantitative analysis of pesticide isomers is demonstrated. The present results expand the horizons of the MALDI-FTICR-MS platform in the reliable determination of pesticides, with integrated advantages of ultrahigh mass resolution and accuracy. This method provides growing evidence for the resultant detrimental effects of pesticides, expediting the identification and evaluation of innovative pesticides.

Fragmentation studies of fulvic acids using collision induced dissociation fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Witt, Matthias; Fuchser, Jens; Koch, Boris P

2009-04-01

The complex natural organic matter standard Suwannee river fulvic acid (SRFA) was analyzed by negative ion mode electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS) using on-resonance collision induced dissociation (CID) of single ultrahigh resolved mass peaks in the ICR cell. Molecular formula assignment of precursor masses resulted in exactly one molecular formula for each of the peaks. Analyses of the corresponding fragment spectra and comparison to different standard substances revealed specific neutral losses and fragmentation patterns which result in structures consisting of a high degree of carboxyl- and fewer hydroxyl groups. The comparison of fragmented mass peaks within different pseudohomologous series (CH(2)-series, and CH(4) vs O exchange) suggested structurally based differences between these series. CID FTICR MS allowed isolating single mass peaks in a very complex natural organic matter spectrum. Subsequently, fragmentation gave structural insights into this material. Our results suggest that the structural diversity in complex humic substances is not as high as expected.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aizikov, Konstantin; Lin, Tzu-Yung; Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215

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

Advanced Mass Spectrometric Methods for the Rapid and Quantitative Characterization of Proteomes

DOE PAGES

Smith, Richard D.

2002-01-01

Progress is reviewedmore » towards the development of a global strategy that aims to extend the sensitivity, dynamic range, comprehensiveness and throughput of proteomic measurements based upon the use of high performance separations and mass spectrometry. The approach uses high accuracy mass measurements from Fourier transform ion cyclotron resonance mass spectrometry (FTICR) to validate peptide ‘accurate mass tags’ (AMTs) produced by global protein enzymatic digestions for a specific organism, tissue or cell type from ‘potential mass tags’ tentatively identified using conventional tandem mass spectrometry (MS/MS). This provides the basis for subsequent measurements without the need for MS/ MS. High resolution capillary liquid chromatography separations combined with high sensitivity, and high resolution accurate FTICR measurements are shown to be capable of characterizing peptide mixtures of more than 10 5 components. The strategy has been initially demonstrated using the microorganisms Saccharomyces cerevisiae and Deinococcus radiodurans. Advantages of the approach include the high confidence of protein identification, its broad proteome coverage, high sensitivity, and the capability for stableisotope labeling methods for precise relative protein abundance measurements. Abbreviations : LC, liquid chromatography; FTICR, Fourier transform ion cyclotron resonance; AMT, accurate mass tag; PMT, potential mass tag; MMA, mass measurement accuracy; MS, mass spectrometry; MS/MS, tandem mass spectrometry; ppm, parts per million.« less

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

PubMed

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

2014-10-07

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

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

PubMed

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

2017-04-01

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

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

PubMed Central

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

2014-01-01

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

High Speed Intact Protein Characterization Using 4X Frequency Multiplication, Ion Trap Harmonization, and 21 Tesla FTICR-MS.

PubMed

Shaw, Jared B; Gorshkov, Mikhail V; Wu, Qinghao; Paša-Tolić, Ljiljana

2018-05-01

Mass spectrometric characterization of large biomolecules, such as intact proteins, requires the specificity afforded by ultrahigh resolution mass measurements performed at both the intact mass and product ion levels. Although the performance of time-of-flight mass analyzers is steadily increasing, the choice of mass analyzer for large biomolecules (e.g., proteins >50 kDa) is generally limited to the Fourier transform family of mass analyzers such as Orbitrap and ion cyclotron resonance (FTICR-MS), with the latter providing unmatched mass resolving power and measurement accuracy. Yet, protein analyses using FTMS are largely hindered by the low acquisition rates of spectra with ultrahigh resolving power. Frequency multiple detection schemes enable FTICR-MS to overcome this fundamental barrier and achieve resolving powers and acquisition speeds 4× greater than the limits imposed by magnetic field strength. Here we expand upon earlier work on the implementation of this technique for biomolecular characterization. We report the coupling of 21T FTICR-MS, 4X frequency multiplication, ion trapping field harmonization technology, and spectral data processing methods to achieve unprecedented acquisition rates and resolving power in mass spectrometry of large intact proteins. Isotopically resolved spectra of multiply charged ubiquitin ions were acquired using detection periods as short as 12 ms. Large proteins such as apo-transferrin (MW = 78 kDa) and monoclonal antibody (MW = 150 kDa) were isotopically resolved with detection periods of 384 and 768 ms, respectively. These results illustrate the future capability of accurate characterization of large proteins on time scales compatible with online separations.

Collision cross section (CCS) measurement by ion cyclotron resonance mass spectrometry with short-time Fourier transform.

PubMed

Hu, Miao; Zhang, Linzhou; He, Shan; Xu, Chunming; Shi, Quan

2018-05-15

The collision cross section (CCS) is an important shape parameter which is often used in molecular structure investigation. In Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), the CCS affects the ion signal damping shape due to the effect of ion-neutral collisions. It is potential to obtain ion CCS values from FTICR-MS with the help of a proper ion-collision model. We have developed a rapid method to obtain the ion damping profile and CCS for mixtures by only one FTICR-MS measurement. The method utilizes short-time Fourier transform (STFT) to process FTICR-MS time domain signals. The STFT-processed result is a three-dimensional (3D) spectrum which has an additional time axis in addition to the conventional mass-to-charge ratio and intensity domains. The damping profile of each ion can be recognized from the 3D spectrum. After extracting the decay profile of a specified ion, all the three ion-neutral collision models were tested in curve fitting. The hard-sphere model was proven to be suitable for our experimental setup. A linear relationship was observed between the CCS value and hard-sphere model parameters. Therefore, the CCS values of all the peaks were obtained through the addition of internal model compounds and linear calibration. The proposed method was successfully applied to determine the CCSs of fatty acids and polyalanines in a petroleum gas oil matrix. This technique can be used for simultaneous measurement of cross sections for many ions in congested spectra. Copyright © 2018 John Wiley & Sons, Ltd.

Functional Groups and Structural Insights of Water-Soluble Organic Carbon using Ultrahigh Resolution FT-ICR Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Mazzoleni, L. R.; Habib, D.; Zhao, Y.; Dalbec, M.; Samburova, V.; Hallar, G.; Zielinska, B.; Lowenthal, D.

2013-12-01

Water-soluble organic carbon (WSOC) is a complex mixture of thousands of organic compounds which may have significant influence on the climate-relevant properties of atmospheric aerosols. An improved understanding of the molecular composition of WSOC is needed to evaluate the effect of aerosol composition upon aerosol physical properties. Products of gas phase, aqueous phase and particle phase reactions contribute to pre-existing aerosol organic mass or nucleate new aerosol particles. Thus, ambient aerosols carry a complex array of WSOC components with variable chemical signatures depending upon its origin and aerosol life-cycle processes. In this work, ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to characterize aerosol WSOC collected during the summer of 2010 at the Storm Peak Laboratory (3210 m a.s.l.) near Steamboat Springs, CO. Approximately 4000 molecular formulas were assigned in the mass range of m/z 100-800 after negative-ion electrospray ionization. The observed trends indicate significant non-oxidative accretion reaction pathways for the formation of high molecular weight WSOC components closely associated with terpene ozonolysis secondary organic aerosol (SOA). The aerosol WSOC was further characterized using ultrahigh resolution tandem MS analysis with infrared multiphoton dissociation to determine the functional groups and structural properties of 1700 WSOC species up to m/z 600. Due to the complex nature of the WSOC, multiple precursor ions were simultaneously fragmented. The exact mass measurements of the precursor and product ions facilitated molecular formula assignments and matching of neutral losses. The most important neutral losses are CO2, H2O, CH3OH, HNO3, CH3NO3, SO3 and SO4. The presence and frequency of these losses indicate the type of functional groups contained in the precursor structures. Consistent with the acidic nature of WSOC compounds, the most frequently observed losses

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

PubMed

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

2016-02-01

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

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

NASA Astrophysics Data System (ADS)

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

2011-04-01

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

A Robust Two-Dimensional Separation for Top-Down Tandem Mass Spectrometry of the Low-Mass Proteome

PubMed Central

Lee, Ji Eun; Kellie, John F.; Tran, John C.; Tipton, Jeremiah D.; Catherman, Adam D.; Thomas, Haylee M.; Ahlf, Dorothy R.; Durbin, Kenneth R.; Vellaichamy, Adaikkalam; Ntai, Ioanna; Marshall, Alan G.; Kelleher, Neil L.

2010-01-01

For fractionation of intact proteins by molecular weight (MW), a sharply improved two-dimensional (2D) separation is presented to drive reproducible and robust fractionation before top-down mass spectrometry of complex mixtures. The “GELFrEE” (i.e., gel-eluted liquid fraction entrapment electrophoresis) approach is implemented by use of Tris-glycine and Tris-tricine gel systems applied to human cytosolic and nuclear extracts from HeLa S3 cells, to achieve a MW-based fractionation of proteins from 5 to >100 kDa in 1 h. For top-down tandem mass spectroscopy (MS/MS) of the low-mass proteome (5–25 kDa), between 5 and 8 gel-elution (GE) fractions are sampled by nanocapillary-LC-MS/MS with 12 or 14.5 tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. Single injections give about 40 detectable proteins, about half of which yield automated ProSight identifications. Reproducibility metrics of the system are presented, along with comparative analysis of protein targets in mitotic versus asynchronous cells. We forward this basic 2D approach to facilitate wider implementation of top-down mass spectrometry and a variety of other protein separation and/or characterization approaches. PMID:19747844

Application of phase correction to improve the interpretation of crude oil spectra obtained using 7 T Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Cho, Yunju; Qi, Yulin; O'Connor, Peter B; Barrow, Mark P; Kim, Sunghwan

2014-01-01

In this study, a phase-correction technique was applied to the study of crude oil spectra obtained using a 7 T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). 7 T FT-ICR MS had not been widely used for oil analysis due to the lower resolving power compared with high field FT-ICR MS. For low field instruments, usage of data that has not been phase-corrected results in an inability to resolve critical mass splits of C3 and SH4 (3.4 mDa), and (13)C and CH (4.5 mDa). This results in incorrect assignments of molecular formulae, and discontinuous double bond equivalents (DBE) and carbon number distributions of S1, S2, and hydrocarbon classes are obtained. Application of phase correction to the same data, however, improves the reliability of assignments and produces continuous DBE and carbon number distributions. Therefore, this study clearly demonstrates that phase correction improves data analysis and the reliability of assignments of molecular formulae in crude oil anlayses.

Rapid Analysis of Microalgal Triacylglycerols with Direct-Infusion Mass Spectrometry

DOE PAGES

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

2015-09-01

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

Electrochemistry coupled online to liquid chromatography-mass spectrometry for fast simulation of biotransformation reactions of the insecticide chlorpyrifos.

PubMed

Mekonnen, Tessema F; Panne, Ulrich; Koch, Matthias

2017-05-01

An automated method is presented for fast simulation of (bio)transformation products (TPs) of the organophosphate insecticide chlorpyrifos (CPF) based on electrochemistry coupled online to liquid chromatography-mass spectrometry (EC-LC-MS). Oxidative TPs were produced by a boron doped diamond (BDD) electrode, separated by reversed phase HPLC and online detected by electrospray ionization-mass spectrometry (ESI-MS). Furthermore, EC oxidative TPs were investigated by HPLC-tandem mass spectrometry (LC-MS/MS) and FT-ICR high resolution mass spectrometry (HRMS) and compared to in vitro assay metabolites (rat and human liver microsomes). Main phase I metabolites of CPF: chlorpyrifos oxon (CPF oxon), trichloropyridinol (TCP), diethylthiophosphate (DETP), diethylphosphate (DEP), desethyl chlorpyrifos (De-CPF), and desethyl chlorpyrifos oxon (De-CPF oxon), were successfully identified by the developed EC-LC-MS method. The EC-LC-MS method showed similar metabolites compared to the in vitro assay with possibilities of determining reactive species. Our results reveal that online EC-(LC)-MS brings an advantage on time of analysis by eliminating sample preparation steps and matrix complexity compared to conventional in vivo or in vitro methods.

Application of Tandem Two-Dimensional Mass Spectrometry for Top-Down Deep Sequencing of Calmodulin.

PubMed

Floris, Federico; Chiron, Lionel; Lynch, Alice M; Barrow, Mark P; Delsuc, Marc-André; O'Connor, Peter B

2018-06-04

Two-dimensional mass spectrometry (2DMS) involves simultaneous acquisition of the fragmentation patterns of all the analytes in a mixture by correlating their precursor and fragment ions by modulating precursor ions systematically through a fragmentation zone. Tandem two-dimensional mass spectrometry (MS/2DMS) unites the ultra-high accuracy of Fourier transform ion cyclotron resonance (FT-ICR) MS/MS and the simultaneous data-independent fragmentation of 2DMS to achieve extensive inter-residue fragmentation of entire proteins. 2DMS was recently developed for top-down proteomics (TDP), and applied to the analysis of calmodulin (CaM), reporting a cleavage coverage of about ~23% using infrared multiphoton dissociation (IRMPD) as fragmentation technique. The goal of this work is to expand the utility of top-down protein analysis using MS/2DMS in order to extend the cleavage coverage in top-down proteomics further into the interior regions of the protein. In this case, using MS/2DMS, the cleavage coverage of CaM increased from ~23% to ~42%. Graphical Abstract Two-dimensional mass spectrometry, when applied to primary fragment ions from the source, allows deep-sequencing of the protein calmodulin.

Structural analysis of an intact monoclonal antibody by online electrochemical reduction of disulfide bonds and Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

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

2014-06-03

Structural confirmation and quality control of recombinant monoclonal antibodies (mAbs) by top-down mass spectrometry is still challenging due to the size of the proteins, disulfide content, and post-translational modifications such as glycosylation. In this study we have applied electrochemistry (EC) to overcome disulfide bridge complexity in top-down analysis of mAbs. To this end, an electrochemical cell was coupled directly to an electrospray ionization (ESI) source and a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer (MS) equipped with a 15 T magnet. By performing online EC-assisted reduction of interchain disulfide bonds in an intact mAb, the released light chains could be selected for tandem mass spectrometry (MS/MS) analysis without interference from heavy-chain fragments. Moreover, the acquisition of full MS scans under denaturing conditions allowed profiling of all abundant mAb glycoforms. Ultrahigh-resolution FTICR-MS measurements provided fully resolved isotopic distributions of intact mAb and enabled the identification of the most abundant adducts and other interfering species. Furthermore, it was found that reduction of interchain disulfide bonds occurs in the ESI source dependent on capillary voltage and solvent composition. This phenomenon was systematically evaluated and compared with the results obtained from reduction in the electrochemical cell.

Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

NASA Astrophysics Data System (ADS)

Zhou, Mowei; Yan, Jing; Romano, Christine A.; Tebo, Bradley M.; Wysocki, Vicki H.; Paša-Tolić, Ljiljana

2018-01-01

Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase, Mnx, from Bacillus sp. PL-12 has been successfully overexpressed in active form as a protein complex with a molecular mass of 211 kDa. We have recently used surface induced dissociation (SID) and ion mobility-mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data from the native mass spectrometry experiments led to a plausible structural model of this multicopper oxidase, which has been difficult to study by conventional structural biology methods. It was also revealed that each Mnx subunit binds a variable number of copper ions. Becasue of the heterogeneity of the protein and limited mass resolution, ambiguities in assigning some of the observed peaks remained as a barrier to fully understanding the role of metals and potential unknown ligands in Mnx. In this study, we performed SID in a modified Fourier transform-ion cyclotron resonance (FTICR) mass spectrometer. The high mass accuracy and resolution offered by FTICR unveiled unexpected artificial modifications on the protein that had been previously thought to be iron bound species based on lower resolution spectra. Additionally, isotopically resolved spectra of the released subcomplexes revealed the metal binding stoichiometry at different structural levels. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes. [Figure not available: see fulltext.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain

2015-03-01

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

Application of Tandem Two-Dimensional Mass Spectrometry for Top-Down Deep Sequencing of Calmodulin

NASA Astrophysics Data System (ADS)

Floris, Federico; Chiron, Lionel; Lynch, Alice M.; Barrow, Mark P.; Delsuc, Marc-André; O'Connor, Peter B.

2018-06-01

Two-dimensional mass spectrometry (2DMS) involves simultaneous acquisition of the fragmentation patterns of all the analytes in a mixture by correlating their precursor and fragment ions by modulating precursor ions systematically through a fragmentation zone. Tandem two-dimensional mass spectrometry (MS/2DMS) unites the ultra-high accuracy of Fourier transform ion cyclotron resonance (FT-ICR) MS/MS and the simultaneous data-independent fragmentation of 2DMS to achieve extensive inter-residue fragmentation of entire proteins. 2DMS was recently developed for top-down proteomics (TDP), and applied to the analysis of calmodulin (CaM), reporting a cleavage coverage of about 23% using infrared multiphoton dissociation (IRMPD) as fragmentation technique. The goal of this work is to expand the utility of top-down protein analysis using MS/2DMS in order to extend the cleavage coverage in top-down proteomics further into the interior regions of the protein. In this case, using MS/2DMS, the cleavage coverage of CaM increased from 23% to 42%.

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

PubMed

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

2016-10-01

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

Automatic Gain Control in Mass Spectrometry using a Jet Disrupter Electrode in an Electrodynamic Ion Funnel

PubMed Central

Page, Jason S.; Bogdanov, Bogdan; Vilkov, Andrey N.; Prior, David C.; Buschbach, Michael A.; Tang, Keqi; Smith, Richard D.

2007-01-01

We report on the use of a jet disrupter electrode in an electrodynamic ion funnel as an electronic valve to regulate the intensity of the ion beam transmitted through the interface of a mass spectrometer in order to perform automatic gain control (AGC). The ion flux is determined by either directly detecting the ion current on the conductance limiting orifice of the ion funnel or using a short mass spectrometry acquisition. Based upon the ion flux intensity, the voltage of the jet disrupter is adjusted to alter the transmission efficiency of the ion funnel to provide a desired ion population to the mass analyzer. Ion beam regulation by an ion funnel is shown to provide control to within a few percent of a targeted ion intensity or abundance. The utility of ion funnel AGC was evaluated using a protein tryptic digest analyzed with liquid chromatography Fourier transform ion cyclotron resonance (LC-FTICR) mass spectrometry. The ion population in the ICR cell was accurately controlled to selected levels, which improved data quality and provided better mass measurement accuracy. PMID:15694774

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callister, Stephen J.; Barry, Richard C.; Adkins, Joshua N.

2006-02-01

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

Qualitative metabolome analysis of human cerebrospinal fluid by 13C-/12C-isotope dansylation labeling combined with liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Guo, Kevin; Bamforth, Fiona; Li, Liang

2011-02-01

Metabolome analysis of human cerebrospinal fluid (CSF) is challenging because of low abundance of metabolites present in a small volume of sample. We describe and apply a sensitive isotope labeling LC-MS technique for qualitative analysis of the CSF metabolome. After a CSF sample is divided into two aliquots, they are labeled by (13)C-dansyl and (12)C-dansyl chloride, respectively. The differentially labeled aliquots are then mixed and subjected to LC-MS using Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS). Dansylation offers significant improvement in the performance of chromatography separation and detection sensitivity. Moreover, peaks detected in the mass spectra can be readily analyzed for ion pair recognition and database search based on accurate mass and/or retention time information. It is shown that about 14,000 features can be detected in a 25-min LC-FTICR MS run of a dansyl-labeled CSF sample, from which about 500 metabolites can be profiled. Results from four CSF samples are compared to gauge the detectability of metabolites by this method. About 261 metabolites are commonly detected in replicate runs of four samples. In total, 1132 unique metabolite ion pairs are detected and 347 pairs (31%) matched with at least one metabolite in the Human Metabolome Database. We also report a dansylation library of 220 standard compounds and, using this library, about 85 metabolites can be positively identified. Among them, 21 metabolites have never been reported to be associated with CSF. These results illustrate that the dansylation LC-FTICR MS method can be used to analyze the CSF metabolome in a more comprehensive manner. © American Society for Mass Spectrometry, 2011

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.

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

PubMed

Ghaste, Manoj; Mistrik, Robert; Shulaev, Vladimir

2016-05-25

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

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

PubMed Central

Ghaste, Manoj; Mistrik, Robert; Shulaev, Vladimir

2016-01-01

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

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

USGS Publications Warehouse

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

2013-01-01

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

Surface-Induced Dissociation of Protein Complexes in a Hybrid Fourier Transform Ion Cyclotron Resonance Mass Spectrometer.

PubMed

Yan, Jing; Zhou, Mowei; Gilbert, Joshua D; Wolff, Jeremy J; Somogyi, Árpád; Pedder, Randall E; Quintyn, Royston S; Morrison, Lindsay J; Easterling, Michael L; Paša-Tolić, Ljiljana; Wysocki, Vicki H

2017-01-03

Mass spectrometry continues to develop as a valuable tool in the analysis of proteins and protein complexes. In protein complex mass spectrometry studies, surface-induced dissociation (SID) has been successfully applied in quadrupole time-of-flight (Q-TOF) instruments. SID provides structural information on noncovalent protein complexes that is complementary to other techniques. However, the mass resolution of Q-TOF instruments can limit the information that can be obtained for protein complexes by SID. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) provides ultrahigh resolution and ultrahigh mass accuracy measurements. In this study, an SID device was designed and successfully installed in a hybrid FT-ICR instrument in place of the standard gas collision cell. The SID-FT-ICR platform has been tested with several protein complex systems (homooligomers, a heterooligomer, and a protein-ligand complex, ranging from 53 to 85 kDa), and the results are consistent with data previously acquired on Q-TOF platforms, matching predictions from known protein interface information. SID fragments with the same m/z but different charge states are well-resolved based on distinct spacing between adjacent isotope peaks, and the addition of metal cations and ligands can also be isotopically resolved with the ultrahigh mass resolution available in FT-ICR.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Characterization of unknown brominated disinfection byproducts during chlorination using ultrahigh resolution mass spectrometry.

PubMed

Zhang, Haifeng; Zhang, Yahe; Shi, Quan; Zheng, Hongdie; Yang, Min

2014-03-18

Brominated disinfection byproducts (Br-DBPs), formed from the reaction of disinfectant(s) with natural organic matter in the presence of bromide in raw water, are generally more cytotoxic and genotoxic than their chlorinated analogues. To date, only a few Br-DBPs in drinking water have been identified, while a significant portion of Br-DBPs in drinking water is still unknown. In this study, negative ion electrospray ionization ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) was used to characterize unknown Br-DBPs in artificial drinking water. In total, 441 formulas for one-bromine-containing products and 37 formulas for two-bromine-containing products, most of which had not been previously reported, were detected in the chlorinated sample. Most Br-DBPs have corresponding chlorine-containing analogues with identical CHO composition. In addition, on-resonance collision-induced dissociation (CID) of single ultrahigh resolved bromine containing mass peaks was performed in the ICR cell to isolate single bromine-containing components in a very complex natural organic matter spectrum and provide structure information. Relatively abundant neutral loss of CO2 was observed in MS-MS spectra, indicating that the unknown Br-DBPs are rich in carboxyl groups. The results demonstrate that the ESI FT-ICR MS method could provide valuable molecular composition and structure information on unknown Br-DBPs.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-09-01

A novel single-transistor transimpedance preamplifier has been introduced for improving performance in Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry. A low noise junction field-effect transistor (JFET), BF862, is used as the main amplification stage of this trans-impedance preamplifier, and a T-shaped feedback network is introduced as both the feedback and the gate biasing solutions. The T feedback network has been studied using an operational amplifier (Op Amp), AD8099. Such a feedback system allows ~100-fold less feedback resistance at a given transimpedance, hence preserving bandwidth, which is beneficial to applications demanding high gain. The single-transistor preamplifier yields a tested transimpedance of ~10(4) Ω (80 dBΩ) in the frequency range between 1 kHz and 1 MHz (mass-to-charge ratio, m/z, of around 180-180k for a 12-T FT-ICR system), with a low power consumption of ~6 mW, which implies that this preamplifier is well suited to a 12-T FT-ICR mass spectrometer. In trading noise performance for higher trans-impedance, an alternative preamplifier design, an AD8099 preamplifier with the T feedback network, has also been studied with a capability of ~10(6) Ω (120 dBΩ) transimpedance in the same frequency range. The resistive components in the T feedback network reported here can be replaced by complex impedances, which allows adaptation of this feedback system to other frequency, transimpedance, and noise characteristics for applications not only in other mass spectrometers, such as Orbitrap, time-of-flight (TOF), and ion trap systems, but also in other charge/current detecting systems such as spectroscopy systems, microscopy systems, optical communication systems, or charge-coupled devices (CCDs).

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leach, Franklin E.; Norheim, Randolph V.; Anderson, Gordon A.

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

Ions generated from uranyl nitrate solutions by electrospray ionization (ESI) and detected with Fourier transform ion-cyclotron resonance (FT-ICR) mass spectrometry.

PubMed

Pasilis, Sofie; Somogyi, Arpád; Herrmann, Kristin; Pemberton, Jeanne E

2006-02-01

Electrospray ionization (ESI) of uranyl nitrate solutions generates a wide variety of positively and negatively charged ions, including complex adducts of uranyl ions with methoxy, hydroxy, and nitrate ligands. In the positive ion mode, ions detected by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry are sensitive to instrumental tuning parameters such as quadrupole operating frequency and trapping time. Positive ions correspond to oligomeric uranyl nitrate species that can be characterized as having a general formula of [(UO(2))(n)(A)(m)(CH(3)OH)(s)](+) or [(UO(2))(n)(O)(A)(m)(CH(3)OH)(s)](+) with n = 1-4, m = 1-7, s = 0 or 1, and A = OH, NO(3), CH(3)O or a combination of these, although the formation of NO(3)-containing species is preferred. In the negative ion mode, complexes of the form [(UO(2))(NO(3))(m)](-) (m = 1-3) are detected, although the formation of the oxo-containing ions [(UO(2))(O)(n)(NO(3))(m)](-) (n = 1-2, m = 1-2) and the hydroxy-containing ions [(UO(2))(OH)(n)(NO(3))(m)](-) (n = 1-2, m = 0-1) are also observed. The extent of coordinative unsaturation of both positive and negative ions can be determined by ligand association/exchange and H/D exchange experiments using D(2)O and CD(3)OD as neutral reaction partners in the gas-phase. Positive ions are of varying stability and reactivity and may fragment extensively upon collision with D(2)O, CD(3)OD and N(2) in sustained off-resonance irradiation/collision-induced dissociation (SORI-CID) experiments. Electron-transfer reactions, presumably occurring during electrospray ionization but also in SORI-CID, can result in reduction of U(VI) to U(V) and perhaps even U(IV).

Matrix-free mass spectrometric imaging using laser desorption ionisation Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Goodwin, Richard J A; Pitt, Andrew R; Harrison, David; Weidt, Stefan K; Langridge-Smith, Pat R R; Barrett, Michael P; Logan Mackay, C

2011-04-15

Mass spectrometry imaging (MSI) is a powerful tool in metabolomics and proteomics for the spatial localization and identification of pharmaceuticals, metabolites, lipids, peptides and proteins in biological tissues. However, sample preparation remains a crucial variable in obtaining the most accurate distributions. Common washing steps used to remove salts, and solvent-based matrix application, allow analyte spreading to occur. Solvent-free matrix applications can reduce this risk, but increase the possibility of ionisation bias due to matrix adhesion to tissue sections. We report here the use of matrix-free MSI using laser desorption ionisation performed on a 12 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. We used unprocessed tissue with no post-processing following thaw-mounting on matrix-assisted laser desorption ionisation (MALDI) indium-tin oxide (ITO) target plates. The identification and distribution of a range of phospholipids in mouse brain and kidney sections are presented and compared with previously published MALDI time-of-flight (TOF) MSI distributions. Copyright © 2011 John Wiley & Sons, Ltd.

Identification and characterization of complex bioactive oligosaccharides in white and red wine by a combination of mass spectrometry and gas chromatography.

PubMed

Bordiga, Matteo; Travaglia, Fabiano; Meyrand, Mickael; German, J Bruce; Lebrilla, Carlito B; Coïsson, Jean Daniel; Arlorio, Marco; Barile, Daniela

2012-04-11

Over forty-five complex free oligosaccharides (of which several are novel) have been isolated and chemically characterized by gas chromatography and high resolution and high mass accuracy matrix-assisted laser desorption/ionization mass spectrometry (MALDI-FTICR MS) in red and white wines, Grignolino and Chardonnay, respectively. Oligosaccharides with a degree of polymerization between 3 and 14 were separated from simple monosaccharides and disaccharides by solid-phase extraction. The concentrations of free oligosaccharides were over 100 mg/L in both red and white wines. The free oligosaccharides-characterized for the first time in the present study-include hexose-oligosaccharides, xyloglucans, and arabinogalactans and may be the natural byproduct of the degradation of cell wall polysaccharides. The coupled gas chromatography and accurate mass spectrometry approach revealed an effective method to characterize and quantify complex functional oligosaccharides in both red and white wine.

Identification and Characterization of Complex Bioactive Oligosaccharides in White and Red Wine by a Combination of Mass Spectrometry and Gas Chromatography

PubMed Central

Bordiga, Matteo; Travaglia, Fabiano; Meyrand, Mickael; German, J. Bruce; Lebrilla, Carlito B.; Coïsson, Jean Daniel; Arlorio, Marco; Barile, Daniela

2012-01-01

Over forty-five complex free oligosaccharides (of which several are novel) have been isolated and chemically characterized by gas chromatography and high resolution and high mass accuracy matrix-assisted laser desorption/ionization mass spectrometry (MALDI-FTICR MS) in red and white wines, Grignolino and Chardonnay, respectively. Oligosaccharides with a degree of polymerization between 3 and 14 were separated from simple monosaccharides and disaccharides by solid-phase extraction. The concentrations free oligosaccharides were over 100 mg/L in both red and white wines. The free oligosaccharides—characterized for the first time in the present study include hexose-oligosaccharides, xyloglucans and arabinogalactans, and may be the natural by-products of the degradation of cell wall polysaccharides. The coupled gas chromatography and accurate mass spectrometry approach revealed an effective method to characterize and quantify complex functional oligosaccharides in both red and white wine. PMID:22429017

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

PubMed

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

2016-09-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-08-01

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

Online Hydrophobic Interaction Chromatography-Mass Spectrometry for the Analysis of Intact Monoclonal Antibodies.

PubMed

Chen, Bifan; Lin, Ziqing; Alpert, Andrew J; Fu, Cexiong; Zhang, Qunying; Pritts, Wayne A; Ge, Ying

2018-06-19

Therapeutic monoclonal antibodies (mAbs) are an important class of drugs for a wide spectrum of human diseases. Liquid chromatography (LC) coupled to mass spectrometry (MS) is one of the techniques in the forefront for comprehensive characterization of analytical attributes of mAbs. Among various protein chromatography modes, hydrophobic interaction chromatography (HIC) is a popular offline nondenaturing separation technique utilized to purify and analyze mAbs, typically with the use of non-MS-compatible mobile phases. Herein we demonstrate for the first time, the application of direct HIC-MS and HIC-tandem MS (MS/MS) with electron capture dissociation (ECD) for analyzing intact mAbs on quadrupole-time-of-flight (Q-TOF) and Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, respectively. Our method allows for rapid determination of relative hydrophobicity, intact masses, and glycosylation profiles of mAbs as well as sequence and structural characterization of the complementarity-determining regions in an online configuration.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

The chemical speciation and bioavailability of mercury (Hg) is markedly influenced by its complexation with naturally dissolved organic matter (DOM) in aquatic environments. To date, however, analytical methodologies capable of identifying such complexes are scarce. Here in this paper, we utilize ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) coupled with electrospray ionization to identify individual Hg–DOM complexes. The measurements were performed by direct infusion of DOM in a 1:1 methanol:water solution at a Hg to dissolved organic carbon (DOC) molar ratio of 3 × 10 –4. Heteroatomic molecules, especially those containing multiple S and N atoms, weremore » found to be among the most important in forming strong complexes with Hg. Major Hg–DOM complexes of C 10H 21N 2S 4Hg + and C 8H 17N 2S 4Hg + were identified based on both the exact molecular mass and patterns of Hg stable isotope distributions detected by FTICR-MS. Density functional theory was used to predict the solution-phase structures of candidate molecules. Finally, these findings represent the first step to unambiguously identify specific DOM molecules in Hg binding, although future studies are warranted to further optimize and validate the methodology so as to explore detailed molecular compositions and structures of Hg–DOM complexes that affect biological uptake and transformation of Hg in the environment.« less

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

DOE PAGES

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

2016-12-22

The chemical speciation and bioavailability of mercury (Hg) is markedly influenced by its complexation with naturally dissolved organic matter (DOM) in aquatic environments. To date, however, analytical methodologies capable of identifying such complexes are scarce. Here in this paper, we utilize ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) coupled with electrospray ionization to identify individual Hg–DOM complexes. The measurements were performed by direct infusion of DOM in a 1:1 methanol:water solution at a Hg to dissolved organic carbon (DOC) molar ratio of 3 × 10 –4. Heteroatomic molecules, especially those containing multiple S and N atoms, weremore » found to be among the most important in forming strong complexes with Hg. Major Hg–DOM complexes of C 10H 21N 2S 4Hg + and C 8H 17N 2S 4Hg + were identified based on both the exact molecular mass and patterns of Hg stable isotope distributions detected by FTICR-MS. Density functional theory was used to predict the solution-phase structures of candidate molecules. Finally, these findings represent the first step to unambiguously identify specific DOM molecules in Hg binding, although future studies are warranted to further optimize and validate the methodology so as to explore detailed molecular compositions and structures of Hg–DOM complexes that affect biological uptake and transformation of Hg in the environment.« less

Combination of liquid chromatography-Fourier transform ion cyclotron resonance-mass spectrometry with 13C-labeling for chemical assignment of sulfur-containing metabolites in onion bulbs.

PubMed

Nakabayashi, Ryo; Sawada, Yuji; Yamada, Yutaka; Suzuki, Makoto; Hirai, Masami Yokota; Sakurai, Tetsuya; Saito, Kazuki

2013-02-05

Phytochemicals containing heteroatoms (N, O, S, and halogens) often have biological activities that are beneficial to humans. Although targeted profiling methods for such phytochemicals are expected to contribute to rapid chemical assignments, thus making phytochemical genomics and crop breeding much more efficient, there are few profiling methods for the metabolites. Here, as an ultrahigh performance approach, we propose a practical profiling method for S-containing metabolites (S-omics) using onions (Allium cepa) as a representative species and (12)C- and (13)C-based mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses by liquid chromatography-Fourier transform ion cyclotron resonance-mass spectrometry (LC-FTICR-MS). Use of the ultrahigh quality data from FTICR-MS enabled simplifying the previous methods to determine specific elemental compositions. MS analysis with a resolution of >250,000 full width at half-maximum and a mass accuracy of <1 ppm can distinguish S-containing monoisotopic ions from other ions on the basis of the natural abundance of (32)S and (34)S and the mass differences among the S isotopes. Comprehensive peak picking using the theoretical mass difference (1.99579 Da) between (32)S-containing monoisotopic ions and their (34)S-substituted counterparts led to the assignment of 67 S-containing monoisotopic ions from the (12)C-based MS spectra, which contained 4693 chromatographic ions. The unambiguous elemental composition of 22 ions was identified through comparative analysis of the (12)C- and (13)C-based MS spectra. Finally, of these, six ions were found to be derived from S-alk(en)ylcysteine sulfoxides and glutathione derivatives. This S-atom-driven approach afforded an efficient chemical assignment of S-containing metabolites, suggesting its potential application for screening not only S but also other heteroatom-containing metabolites in MS-based metabolomics.

Identification of low-abundance cancer biomarker candidate TIMP1 from serum with lectin fractionation and peptide affinity enrichment by ultrahigh-resolution mass spectrometry.

PubMed

Ahn, Yeong Hee; Kim, Kwang Hoe; Shin, Park Min; Ji, Eun Sun; Kim, Hoguen; Yoo, Jong Shin

2012-02-07

As investigating a proteolytic target peptide originating from the tissue inhibitor of metalloproteinase 1 (TIMP1) known to be aberrantly glycosylated in patients with colorectal cancer (CRC), we first confirmed that TIMP1 is to be a CRC biomarker candidate in human serum. For this, we utilized matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) showing ultrahigh-resolution and high mass accuracy. This investigation used phytohemagglutinin-L(4) (L-PHA) lectin, which shows binding affinity to the β-1,6-N-acetylglucosamine moiety of N-linked glycan on a protein, to compare fractionated aberrant protein glycoforms from both noncancerous control and CRC serum. Each lectin-captured fraction containing aberrant glycoforms of TIMP1 was digested by trypsin, resulting in the tryptic target peptide, representative of the serum glycoprotein TIMP1. The resulting target peptide was enriched using a stable isotope standard and capture by the antipeptide antibody (SISCAPA) technique and analyzed by a 15 T MALDI FTICR mass spectrometer with high mass accuracy (Δ < 0.5 ppm to the theoretical mass value of the target peptide). Since exact measurement of multiplex isotopic peaks of the target peptide could be accomplished by virtue of high mass resolution (Rs > 400,000), robust identification of the target peptide is only achievable with 15 T FTICR MS. Also, MALDI data obtained in this study showed that the L-PHA-captured glycoforms of TIMP1 were measured in the pooled CRC serum with about 5 times higher abundance than that in the noncancerous serum, and were further proved by MRM mass analysis. These results confirm that TIMP1 in human serum is a potent CRC biomarker candidate, demonstrating that ultrahigh-resolution MS can be a powerful tool toward identifying and verifying potential protein biomarker candidates. © 2011 American Chemical Society

An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes

NASA Astrophysics Data System (ADS)

Li, Huilin; Nguyen, Hong Hanh; Ogorzalek Loo, Rachel R.; Campuzano, Iain D. G.; Loo, Joseph A.

2018-02-01

Mass spectrometry (MS) has become a crucial technique for the analysis of protein complexes. Native MS has traditionally examined protein subunit arrangements, while proteomics MS has focused on sequence identification. These two techniques are usually performed separately without taking advantage of the synergies between them. Here we describe the development of an integrated native MS and top-down proteomics method using Fourier-transform ion cyclotron resonance (FTICR) to analyse macromolecular protein complexes in a single experiment. We address previous concerns of employing FTICR MS to measure large macromolecular complexes by demonstrating the detection of complexes up to 1.8 MDa, and we demonstrate the efficacy of this technique for direct acquirement of sequence to higher-order structural information with several large complexes. We then summarize the unique functionalities of different activation/dissociation techniques. The platform expands the ability of MS to integrate proteomics and structural biology to provide insights into protein structure, function and regulation.

Matrix-free mass spectrometric imaging using laser desorption ionisation Fourier transform ion cyclotron resonance mass spectrometry

PubMed Central

Goodwin, Richard J A; Pitt, Andrew R; Harrison, David; Weidt, Stefan K; Langridge-Smith, Pat R R; Barrett, Michael P; Logan Mackay, C

2011-01-01

Mass spectrometry imaging (MSI) is a powerful tool in metabolomics and proteomics for the spatial localization and identification of pharmaceuticals, metabolites, lipids, peptides and proteins in biological tissues. However, sample preparation remains a crucial variable in obtaining the most accurate distributions. Common washing steps used to remove salts, and solvent-based matrix application, allow analyte spreading to occur. Solvent-free matrix applications can reduce this risk, but increase the possibility of ionisation bias due to matrix adhesion to tissue sections. We report here the use of matrix-free MSI using laser desorption ionisation performed on a 12 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. We used unprocessed tissue with no post-processing following thaw-mounting on matrix-assisted laser desorption ionisation (MALDI) indium-tin oxide (ITO) target plates. The identification and distribution of a range of phospholipids in mouse brain and kidney sections are presented and compared with previously published MALDI time-of-flight (TOF) MSI distributions. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21416534

Isotope-labeled cross-linkers and Fourier transform ion cyclotron resonance mass spectrometry for structural analysis of a protein/peptide complex.

PubMed

Ihling, Christian; Schmidt, Andreas; Kalkhof, Stefan; Schulz, Daniela M; Stingl, Christoph; Mechtler, Karl; Haack, Michael; Beck-Sickinger, Annette G; Cooper, Dermot M F; Sinz, Andrea

2006-08-01

For structural studies of proteins and their complexes, chemical cross-linking combined with mass spectrometry presents a promising strategy to obtain structural data of protein interfaces from low quantities of proteins within a short time. We explore the use of isotope-labeled cross-linkers in combination with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry for a more efficient identification of cross-linker containing species. For our studies, we chose the calcium-independent complex between calmodulin and a 25-amino acid peptide from the C-terminal region of adenylyl cyclase 8 containing an "IQ-like motif." Cross-linking reactions between calmodulin and the peptide were performed in the absence of calcium using the amine-reactive, isotope-labeled (d0 and d4) cross-linkers BS3 (bis[sulfosuccinimidyl]suberate) and BS2G (bis[sulfosuccinimidyl]glutarate). Tryptic in-gel digestion of excised gel bands from covalently cross-linked complexes resulted in complicated peptide mixtures, which were analyzed by nano-HPLC/nano-ESI-FTICR mass spectrometry. In cases where more than one reactive functional group, e.g., amine groups of lysine residues, is present in a sequence stretch, MS/MS analysis is a prerequisite for unambiguously identifying the modified residues. MS/MS experiments revealed two lysine residues in the central alpha-helix of calmodulin as well as three lysine residues both in the C-terminal and N-terminal lobes of calmodulin to be cross-linked with one single lysine residue of the adenylyl cyclase 8 peptide. Further cross-linking studies will have to be conducted to propose a structural model for the calmodulin/peptide complex, which is formed in the absence of calcium. The combination of using isotope-labeled cross-linkers, determining the accurate mass of intact cross-linked products, and verifying the amino acid sequences of cross-linked species by MS/MS presents a convenient approach that offers the perspective to obtain structural

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…

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

NASA Astrophysics Data System (ADS)

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

2011-01-01

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

Advanced solvent based methods for molecular characterization of soil organic matter by high-resolution mass spectrometry.

PubMed

Tfaily, Malak M; Chu, Rosalie K; Tolić, Nikola; Roscioli, Kristyn M; Anderton, Christopher R; Paša-Tolić, Ljiljana; Robinson, Errol W; Hess, Nancy J

2015-01-01

Soil organic matter (SOM), a complex, heterogeneous mixture of above and belowground plant litter and animal and microbial residues at various degrees of decomposition, is a key reservoir for carbon (C) and nutrient biogeochemical cycling in soil based ecosystems. A limited understanding of the molecular composition of SOM limits the ability to routinely decipher chemical processes within soil and accurately predict how terrestrial carbon fluxes will respond to changing climatic conditions and land use. To elucidate the molecular-level structure of SOM, we selectively extracted a broad range of intact SOM compounds by a combination of different organic solvents from soils with a wide range of C content. Our use of electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and a suite of solvents with varying polarity significantly expands the inventory of the types of organic molecules present in soils. Specifically, we found that hexane is selective for lipid-like compounds with very low O/C ratios (<0.1); water (H2O) was selective for carbohydrates with high O/C ratios; acetonitrile (ACN) preferentially extracts lignin, condensed structures, and tannin polyphenolic compounds with O/C > 0.5; methanol (MeOH) has higher selectivity toward compounds characterized with low O/C < 0.5; and hexane, MeOH, ACN, and H2O solvents increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Our study of SOM molecules by ESI FTICR MS revealed new insight into the molecular-level complexity of organics contained in soils. We present the first comparative study of the molecular composition of SOM from different ecosystems using ultra high-resolution mass spectrometry.

High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids

NASA Astrophysics Data System (ADS)

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

2014-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2011-08-01

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

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

PubMed

Schmidt; Fiorentino; Arkin; Laude

2000-08-01

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

Top-Down Analysis of Highly Post-Translationally Modified Peptides by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

NASA Astrophysics Data System (ADS)

Guerrero, Andres; Lerno, Larry; Barile, Daniela; Lebrilla, Carlito B.

2015-03-01

Bovine κ-caseinoglycomacropeptide (GMP) is a highly modified peptide from κ-casein produced during the cheese making process. The chemical nature of GMP makes analysis by traditional proteomic approaches difficult, as the peptide bears a strong net negative charge and a variety of post-translational modifications. In this work, we describe the use of electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) for the top-down analysis of GMP. The method allows the simultaneous detection of different GMP forms that result from the combination of amino acid genetic variations and post-translational modifications, specifically phosphorylation and O-glycosylation. The different GMP forms were identified by high resolution mass spectrometry in both negative and positive mode and confirmation was achieved by tandem MS. The results showed the predominance of two genetic variants of GMP that occur as either mono- or bi-phosphorylated species. Additionally, these four forms can be modified with up to two O-glycans generally sialylated. The results demonstrate the presence of glycosylated, bi-phosphorylated forms of GMP never described before.

Polymer architectures via mass spectrometry and hyphenated techniques: A review.

PubMed

Crotty, Sarah; Gerişlioğlu, Selim; Endres, Kevin J; Wesdemiotis, Chrys; Schubert, Ulrich S

2016-08-17

This review covers the application of mass spectrometry (MS) and its hyphenated techniques to synthetic polymers of varying architectural complexities. The synthetic polymers are discussed as according to their architectural complexity from linear homopolymers and copolymers to stars, dendrimers, cyclic copolymers and other polymers. MS and tandem MS (MS/MS) has been extensively used for the analysis of synthetic polymers. However, the increase in structural or architectural complexity can result in analytical challenges that MS or MS/MS cannot overcome alone. Hyphenation to MS with different chromatographic techniques (2D × LC, SEC, HPLC etc.), utilization of other ionization methods (APCI, DESI etc.) and various mass analyzers (FT-ICR, quadrupole, time-of-flight, ion trap etc.) are applied to overcome these challenges and achieve more detailed structural characterizations of complex polymeric systems. In addition, computational methods (software: MassChrom2D, COCONUT, 2D maps etc.) have also reached polymer science to facilitate and accelerate data interpretation. Developments in technology and the comprehension of different polymer classes with diverse architectures have significantly improved, which allow for smart polymer designs to be examined and advanced. We present specific examples covering diverse analytical aspects as well as forthcoming prospects in polymer science. Copyright © 2016 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

Molecular and structural characterization of dissolved organic matter from the deep ocean by FTICR-MS, including hydrophilic nitrogenous organic molecules

USGS Publications Warehouse

Reemtsma, T.; These, A.; Linscheid, M.; Leenheer, J.; Spitzy, A.

2008-01-01

Dissolved organic matter isolated from the deep Atlantic Ocean and fractionated into a so-called hydrophobic (HPO) fraction and a very hydrophilic (HPI) fraction was analyzed for the first time by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to resolve the molecular species, to determine their exact masses, and to calculate their molecular formulas. The elemental composition of about 300 molecules was identified. Those in the HPO fraction (14C age of 5100 year) are very similar to much younger freshwater fulvic acids, but less aromatic and more oxygenated molecules are more frequent. This trend continues toward the HPI fraction and may indicate biotic and abiotic aging processes that this material experienced since its primary production thousands of years ago. In the HPI fraction series of nitrogenous molecules containing one, two, or three nitrogens were identified by FTICR-MS. Product ion spectra of the nitrogenous molecules suggest that the nitrogen atoms in these molecules are included in the (alicyclic) backbone of these molecules, possibly in reduced form. These mass spectrometric data suggest that a large set of stable fulvic acids is ubiquitous in all aquatic compartments. Although sources may differ, their actual composition and structure appears to be quite similar and largely independent from their source, because they are the remainder of intensive oxidative degradation processes. ?? 2008 American Chemical Society.

Linear excitation and detection in Fourier transform ion cyclotron resonance mass spectrometry

NASA Astrophysics Data System (ADS)

Grosshans, Peter B.; Chen, Ruidan; Limbach, Patrick A.; Marshall, Alan G.

1994-11-01

We present the first Fourier transform ion cyclotron resonance (FT-ICR) ion trap designed to produce both a linear spatial variation of the excitation electric potential field and a linear response of the detection circuit to the motion of the confined ions. With this trap, the magnitude of the detected signal at a given ion cyclotron frequency varies linearly with both the number of ions of given mass-to-charge ratio and also with the magnitude-mode excitation signal at the ion cyclotron orbital frequency; the proportionality constant is mass independent. Interestingly, this linearization may be achieved with any ion trap geometry. The excitation/detection design consists of an array of capacitively coupled electrodes which provide a voltage-divider network that produces a nearly spatially homogeneous excitation electric field throughout the linearized trap; resistive coupling to the electrodes isolates the a.c. excitation (or detection) circuit from the d.c. (trapping) potential. The design is based on analytical expressions for the potential associated with each electrode, from which we are able to compute the deviation from linearity for a trap with a finite number of elements. Based on direct experimental comparisons to an unmodified cubic trap, the linearized trap demonstrates the following performance advantages at the cost of some additional mechanical complexity: (a) signal response linearly proportional to excitation electric field amplitude; (b) vastly reduced axial excitation/ejection for significantly improved ion relative abundance accuracy; (c) elimination of harmonics and sidebands of the fundamental frequencies of ion motion. As a result, FT-ICR mass spectra are now more reproducible. Moreover, the linearized trap should facilitate the characterization of other fundamental aspects of ion behavior in an ICR ion trap, e.g. effects of space charge, non-quadrupolar electrostatic trapping field, etc. Furthermore, this novel design should improve

Re-investigation of the fragmentation of protonated carotenoids by electrospray ionization and nanospray tandem mass spectrometry.

PubMed

Neto, Fausto Carnevale; Guaratini, Thais; Costa-Lotufo, Letícia; Colepicolo, Pio; Gates, Paul J; Lopes, Norberto Peporine

2016-07-15

Carotenoids are polyene isoprenoids with an important role in photosynthesis and photoprotection. Their characterization in biological matrices is a crucial subject for biochemical research. In this work we report the full fragmentation of 16 polyenes (carotenes and xanthophylls) by electrospray ionization tandem mass spectrometry (ESI-CID-MS/MS) and nanospray tandem mass spectrometry (nanoESI-CID-MS/MS). Analyses were carried out on a quadrupole time-of-flight (QTOF) mass spectrometer coupled with a nanoESI source and on a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer with an ESI source. The formulae of the product ions were determined by accurate-mass measurements. It is demonstrated that the fragmentation routes observed for the protonated carotenoids derive essentially from charge-remote fragmentations and pericyclic rearrangements, such as electrocyclic and retro-ene eliminations (assisted or not by a sigmatropic hydrogen shift). All mechanisms are dependent on cis-trans isomerization through the formation of several conjugated polyene carbocation intermediates. Some specific ions for the carotenoid epoxides were justified through formation of cyclic oxonium ions. Complete fragmentation pathways of protonated carotenoids by ESI- and nanoESI-CID-MS/MS provided structural information about functional groups, polyene chain and double bonds, and contribute to identification of carotenoids based on MS/MS fragmentation patterns. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Amyloid Hydrogen Bonding Polymorphism Evaluated by (15)N{(17)O}REAPDOR Solid-State NMR and Ultra-High Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

PubMed

Wei, Juan; Antzutkin, Oleg N; Filippov, Andrei V; Iuga, Dinu; Lam, Pui Yiu; Barrow, Mark P; Dupree, Ray; Brown, Steven P; O'Connor, Peter B

2016-04-12

A combined approach, using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and solid-state NMR (Nuclear Magnetic Resonance), shows a high degree of polymorphism exhibited by Aβ species in forming hydrogen-bonded networks. Two Alzheimer's Aβ peptides, Ac-Aβ(16-22)-NH2 and Aβ(11-25), selectively labeled with (17)O and (15)N at specific amino acid residues were investigated. The total amount of peptides labeled with (17)O as measured by FTICR-MS enabled the interpretation of dephasing observed in (15)N{(17)O}REAPDOR solid-state NMR experiments. Specifically, about one-third of the Aβ peptides were found to be involved in the formation of a specific >C═(17)O···H-(15)N hydrogen bond with their neighbor peptide molecules, and we hypothesize that the rest of the molecules undergo ± n off-registry shifts in their hydrogen bonding networks.

Laser Ablation-Aerosol Mass Spectrometry-Chemical Ionization Mass Spectrometry for Ambient Surface Imaging

DOE PAGES

Berry, Jennifer L.; Day, Douglas A.; Elseberg, Tim; ...

2018-02-20

Mass spectrometry imaging is becoming an increasingly common analytical technique due to its ability to provide spatially resolved chemical information. In this paper, we report a novel imaging approach combining laser ablation with two mass spectrometric techniques, aerosol mass spectrometry and chemical ionization mass spectrometry, separately and in parallel. Both mass spectrometric methods provide the fast response, rapid data acquisition, low detection limits, and high-resolution peak separation desirable for imaging complex samples. Additionally, the two techniques provide complementary information with aerosol mass spectrometry providing near universal detection of all aerosol molecules and chemical ionization mass spectrometry with a heated inletmore » providing molecular-level detail of both gases and aerosols. The two techniques operate with atmospheric pressure interfaces and require no matrix addition for ionization, allowing for samples to be investigated in their native state under ambient pressure conditions. We demonstrate the ability of laser ablation-aerosol mass spectrometry-chemical ionization mass spectrometry (LA-AMS-CIMS) to create 2D images of both standard compounds and complex mixtures. Finally, the results suggest that LA-AMS-CIMS, particularly when combined with advanced data analysis methods, could have broad applications in mass spectrometry imaging applications.« less

Laser Ablation-Aerosol Mass Spectrometry-Chemical Ionization Mass Spectrometry for Ambient Surface Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berry, Jennifer L.; Day, Douglas A.; Elseberg, Tim

Mass spectrometry imaging is becoming an increasingly common analytical technique due to its ability to provide spatially resolved chemical information. In this paper, we report a novel imaging approach combining laser ablation with two mass spectrometric techniques, aerosol mass spectrometry and chemical ionization mass spectrometry, separately and in parallel. Both mass spectrometric methods provide the fast response, rapid data acquisition, low detection limits, and high-resolution peak separation desirable for imaging complex samples. Additionally, the two techniques provide complementary information with aerosol mass spectrometry providing near universal detection of all aerosol molecules and chemical ionization mass spectrometry with a heated inletmore » providing molecular-level detail of both gases and aerosols. The two techniques operate with atmospheric pressure interfaces and require no matrix addition for ionization, allowing for samples to be investigated in their native state under ambient pressure conditions. We demonstrate the ability of laser ablation-aerosol mass spectrometry-chemical ionization mass spectrometry (LA-AMS-CIMS) to create 2D images of both standard compounds and complex mixtures. Finally, the results suggest that LA-AMS-CIMS, particularly when combined with advanced data analysis methods, could have broad applications in mass spectrometry imaging applications.« less

Chemical Assignment of Structural Isomers of Sulfur-Containing Metabolites in Garlic by Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spectrometry.

PubMed

Nakabayashi, Ryo; Sawada, Yuji; Aoyagi, Morihiro; Yamada, Yutaka; Hirai, Masami Yokota; Sakurai, Tetsuya; Kamoi, Takahiro; Rowan, Daryl D; Saito, Kazuki

2016-02-01

The chemical assignment of metabolites is crucial to understanding the relation between food composition and biological activity. This study was designed to detect and chemically assign sulfur-containing metabolites by using LC-Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS) in Allium plants. Ultrahigh resolution (>250,000 full width at half-maximum) and mass accuracy (<1 mDa) by FTICR-MS allowed us to distinguish ions containing sulfur isotopes ((32)S and (34)S). Putative 69 S-containing monoisotopic ions (S-ions) were extracted from the metabolome data of onion (Allium cepa), green onion (Allium fistulosum), and garlic (Allium sativum) on the basis of theoretical mass differences between (32)S-ions and their (34)S-substituted counterparts and on the natural abundance of (34)S. Eight S-ions were chemically assigned by using the reference data according to the guidelines of the Metabolomics Standards Initiative. Three ions detected in garlic were assigned as derived from the isomers γ-glutamyl-S-1-propenylcysteine and γ-glutamyl-S-2-propenylcysteine and as S-2-propenylmercaptoglutathione on the basis of differences in key product ions identified in reference tandem MS spectra. The ability to discriminate between such geometric isomers will be extremely useful for the chemical assignment of unknown metabolites in MS-based metabolomics. © 2016 American Society for Nutrition.

Deamidation and transamidation of substance P by tissue transglutaminase revealed by electron-capture dissociation fourier transform mass spectrometry.

PubMed

Fornelli, Luca; Schmid, Adrien W; Grasso, Luigino; Vogel, Horst; Tsybin, Yury O

2011-01-10

Tissue transglutaminase (tTGase) catalyzes both deamidation and transamidation of peptides and proteins by using a peptidyl glutamine as primary substrate. A precise consensus sequence for the enzyme is unknown and the ratio between deamidated and transamidated (or cross-linked) reaction products is highly substrate-dependent. Due to its overlapping body distribution with tTGase and ease of manipulation with tandem mass spectrometry, we used the neuropeptide substance P as a model to investigate the associated enzymatic kinetics and reaction products. Online liquid-chromatography Fourier-transform ion-cyclotron-resonance mass spectrometry (FT-ICR MS) combined with electron-capture dissociation (ECD) was employed to study the tTGase-induced modifications of substance P. A particular strength of ECD for peptide-enzyme reaction product monitoring is its ability to distinguish isomeric amino acids, for example, Glu and iso-Glu, by signature product ions. Our studies show that the primary reaction observed is deamidation, with the two consecutive glutamine residues converted sequentially into glutamate: first Gln(5) , and subsequently Gln(6) . We then applied ECD FT-ICR MS to identify the transamidation site on an enzymatically cross-linked peptide, which turned out to correspond to Gln(5) . Three populations of substance-P dimers were detected that differed by the number of deamidated Gln residues. The higher reactivity of Gln(5) over Gln(6) was further confirmed by cross-linking SP with monodansylcadaverine (MDC). Overall, our approach described herein is of a general importance for mapping both enzymatically induced post-translational protein modifications and cross-linking. Finally, in vitro Ca-signaling assays revealed that the main tTGase reaction product, the singly deamidated SP (RPKPEQFFGLM-NH(2) ), has increased agonist potency towards its natural receptor, thus confirming the biologically relevant role of deamidation. Copyright © 2011 WILEY-VCH Verlag

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

PubMed

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

2016-07-01

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

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.

Recent advances in secondary ion mass spectrometry of solid acid catalysts: large zeolite crystals under bombardment.

PubMed

Hofmann, Jan P; Rohnke, Marcus; Weckhuysen, Bert M

2014-03-28

This Perspective aims to inform the heterogeneous catalysis and materials science community about the recent advances in Time-of-Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) to characterize catalytic solids by taking large model H-ZSM-5 zeolite crystals as a showcase system. SIMS-based techniques have been explored in the 1980-1990's to study porous catalyst materials but, due to their limited spectral and spatiotemporal resolution, there was no real major breakthrough at that time. The technical advancements in SIMS instruments, namely improved ion gun design and new mass analyser concepts, nowadays allow for a much more detailed analysis of surface species relevant to catalytic action. Imaging with high mass and lateral resolution, determination of fragment ion patterns, novel sputter ion concepts as well as new mass analysers (e.g. ToF, FTICR) are just a few novelties, which will lead to new fundamental insight from SIMS analysis of heterogeneous catalysts. The Perspective article ends with an outlook on instrumental innovations and their potential use for catalytic systems other than zeolite crystals.

Software tool for mining liquid chromatography/multi-stage mass spectrometry data for comprehensive glycerophospholipid profiling.

PubMed

Hein, Eva-Maria; Bödeker, Bertram; Nolte, Jürgen; Hayen, Heiko

2010-07-30

Electrospray ionization mass spectrometry (ESI-MS) has emerged as an indispensable tool in the field of lipidomics. Despite the growing interest in lipid analysis, there are only a few software tools available for data evaluation, as compared for example to proteomics applications. This makes comprehensive lipid analysis a complex challenge. Thus, a computational tool for harnessing the raw data from liquid chromatography/mass spectrometry (LC/MS) experiments was developed in this study and is available from the authors on request. The Profiler-Merger-Viewer tool is a software package for automatic processing of raw-data from data-dependent experiments, measured by high-performance liquid chromatography hyphenated to electrospray ionization hybrid linear ion trap Fourier transform mass spectrometry (FTICR-MS and Orbitrap) in single and multi-stage mode. The software contains three parts: processing of the raw data by Profiler for lipid identification, summarizing of replicate measurements by Merger and visualization of all relevant data (chromatograms as well as mass spectra) for validation of the results by Viewer. The tool is easily accessible, since it is implemented in Java and uses Microsoft Excel (XLS) as output format. The motivation was to develop a tool which supports and accelerates the manual data evaluation (identification and relative quantification) significantly but does not make a complete data analysis within a black-box system. The software's mode of operation, usage and options will be demonstrated on the basis of a lipid extract of baker's yeast (S. cerevisiae). In this study, we focused on three important representatives of lipids: glycerophospholipids, lyso-glycerophospholipids and free fatty acids. Copyright 2010 John Wiley & Sons, Ltd.

Application of stored waveform ion modulation 2D-FTICR MS/MS to the analysis of complex mixtures.

PubMed

Ross, Charles W; Simonsick, William J; Aaserud, David J

2002-09-15

Component identification of complex mixtures, whether they are from polymeric formulations or combinatorial synthesis, by conventional MS/MS techniques generally requires component separation by chromatography or mass spectrometry. An automated means of acquiring simultaneous MS/MS data from a complex mixture without prior separation is obtained from stored waveform ion modulation (SWIM) two-dimensional FTICR MS/MS. The technique applies a series of SWIFT excitation waveforms whose frequency domain magnitude spectrum is a sinusoid increasing in frequency from one waveform to the next. The controlled dissociation of the precursor ions produces an associated modulation of the product ion abundances. Fourier transformation of these abundances reveals the encoded modulation frequency from which connectivities of precursor and product ions are observed. The final result is total assignment of product ions for each precursor ion in a mixture from one automated experiment. We demonstrated the applicability of SWIM 2D-FTICR MS/MS to two diverse samples of industrial importance. We characterized structured polyester oligomers and products derived from combinatorial synthesis. Fragmentation pathways identified in standard serial ion isolation MS/MS experiments were observed for trimethylolpropane/methyl hexahydrophthalic anhydride. A 20-component sample derived from combinatorial synthesis was fragmented, and the template ion along with another key fragment ion was identified for each of the 20 components.

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

NASA Astrophysics Data System (ADS)

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

2012-04-01

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

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.

Qualitative Metabolome Analysis of Human Cerebrospinal Fluid by 13C-/12C-Isotope Dansylation Labeling Combined with Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

NASA Astrophysics Data System (ADS)

Guo, Kevin; Bamforth, Fiona; Li, Liang

2011-02-01

Metabolome analysis of human cerebrospinal fluid (CSF) is challenging because of low abundance of metabolites present in a small volume of sample. We describe and apply a sensitive isotope labeling LC-MS technique for qualitative analysis of the CSF metabolome. After a CSF sample is divided into two aliquots, they are labeled by 13C-dansyl and 12C-dansyl chloride, respectively. The differentially labeled aliquots are then mixed and subjected to LC-MS using Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS). Dansylation offers significant improvement in the performance of chromatography separation and detection sensitivity. Moreover, peaks detected in the mass spectra can be readily analyzed for ion pair recognition and database search based on accurate mass and/or retention time information. It is shown that about 14,000 features can be detected in a 25-min LC-FTICR MS run of a dansyl-labeled CSF sample, from which about 500 metabolites can be profiled. Results from four CSF samples are compared to gauge the detectability of metabolites by this method. About 261 metabolites are commonly detected in replicate runs of four samples. In total, 1132 unique metabolite ion pairs are detected and 347 pairs (31%) matched with at least one metabolite in the Human Metabolome Database. We also report a dansylation library of 220 standard compounds and, using this library, about 85 metabolites can be positively identified. Among them, 21 metabolites have never been reported to be associated with CSF. These results illustrate that the dansylation LC-FTICR MS method can be used to analyze the CSF metabolome in a more comprehensive manner.

ESI-FTICR-MS Molecular Characterization of DOM Degradation under Warming in Tundra Soils from Barrow, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hongmei Chen; Ziming Yang; Rosalie Chu

This dataset provides the results of warming incubation of Arctic soils from trough areas of a high-center polygon at the Barrow Environmental Observatory (BEO) in northern Alaska, United States. The organic-rich soil (8-20 cm below ground surface) and the mineral-rich soil (22-45 cm below surface) were separated, and the thawed and homogenized subsamples from each soil were incubated at -2 degrees C or 8 degrees C for 122 days under anoxic conditions (headspace filled with N2). The extracted DOM from soil samples were analyzed by Fourier transform ion cyclotron resonance mass spectrometry coupled with electrospray ionization (ESI-FTICR-MS). Reported analytes includemore » soil water content, dissolved organic carbon, total organic carbon, MS peaks' m/z and intensities, and elemental composition of identified molecular formulas.« less

Rapid Profiling of Bovine and Human Milk Gangliosides by Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

PubMed Central

Lee, Hyeyoung; An, Hyun Joo; Lerno, Larry A.; German, J. Bruce; Lebrilla, Carlito B.

2010-01-01

Gangliosides are anionic glycosphingolipids widely distributed in vertebrate tissues and fluids. Their structural and quantitative expression patterns depend on phylogeny and are distinct down to the species level. In milk, gangliosides are exclusively associated with the milk fat globule membrane. They may participate in diverse biological processes but more specifically to host-pathogen interactions. However, due to the molecular complexities, the analysis needs extensive sample preparation, chromatographic separation, and even chemical reaction, which makes the process very complex and time-consuming. Here, we describe a rapid profiling method for bovine and human milk gangliosides employing matrix-assisted desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS). Prior to the analyses of biological samples, milk ganglioside standards GM3 and GD3 fractions were first analyzed in order to validate this method. High mass accuracy and high resolution obtained from MALDI FTICR MS allow for the confident assignment of chain length and degree of unsaturation of the ceramide. For the structural elucidation, tandem mass spectrometry (MS/MS), specifically as collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) were employed. Complex ganglioside mixtures from bovine and human milk were further analyzed with this method. The samples were prepared by two consecutive chloroform/methanol extraction and solid phase extraction. We observed a number of differences between bovine milk and human milk. The common gangliosides in bovine and human milk are NeuAc-NeuAc-Hex-Hex-Cer (GD3) and NeuAc-Hex-Hex-Cer (GM3); whereas, the ion intensities of ganglioside species are different between two milk samples. Kendrick mass defect plot yields grouping of ganglioside peaks according to their structural similarities. Gangliosides were further probed by tandem MS to confirm the compositional and structural assignments

Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry as a Platform for Characterizing Multimeric Membrane Protein Complexes

NASA Astrophysics Data System (ADS)

Lippens, Jennifer L.; Nshanian, Michael; Spahr, Chris; Egea, Pascal F.; Loo, Joseph A.; Campuzano, Iain D. G.

2018-01-01

Membrane protein characterization is consistently hampered by challenges with expression, purification, and solubilization. Among several biophysical techniques employed for their characterization, native-mass spectrometry (MS) has emerged as a powerful tool for the analysis of membrane proteins and complexes. Here, two MS platforms, the FT-ICR and Q-ToF, have been explored to analyze the homotetrameric water channel protein, AquaporinZ (AqpZ), under non-denaturing conditions. This 97 kDa membrane protein complex can be readily liberated from the octylglucoside (OG) detergent micelle under a range of instrument conditions on both MS platforms. Increasing the applied collision energy of the FT-ICR collision cell yielded varying degrees of tetramer (97 kDa) liberation from the OG micelles, as well as dissociation into the trimeric (72 kDa) and monomeric (24 kDa) substituents. Tandem-MS on the Q-ToF yielded higher intensity tetramer signal and, depending on the m/z region selected, the observed monomer signal varied in intensity. Precursor ion selection of an m/z range above the expected protein signal distribution, followed by mild collisional activation, is able to efficiently liberate AqpZ with a high S/N ratio. The tetrameric charge state distribution obtained on both instruments demonstrated superpositioning of multiple proteoforms due to varying degrees of N-terminal formylation. [Figure not available: see fulltext.

IR-MALDESI MASS SPECTROMETRY IMAGING OF BIOLOGICAL TISSUE SECTIONS USING ICE AS A MATRIX

PubMed Central

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

2014-01-01

Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry imaging of biological tissue sections using a layer of deposited ice as an energy absorbing matrix was investigated. Dynamics of plume ablation were first explored using a nanosecond exposure shadowgraphy system designed to simultaneously collect pictures of the plume with a camera and collect the FT-ICR mass spectrum corresponding to that same ablation event. Ablation of fresh tissue analyzed with and without using ice as a matrix were both compared using this technique. Effect of spot-to-spot distance, number of laser shots per pixel and tissue condition (matrix) on ion abundance was also investigated for 50 µm thick tissue sections. Finally, the statistical method called design of experiments was used to compare source parameters and determine the optimal conditions for IR-MALDESI of tissue sections using deposited ice as a matrix. With a better understanding of the fundamentals of ablation dynamics and a systematic approach to explore the experimental space, it was possible to improve ion abundance by nearly one order of magnitude. PMID:24385399

Imaging mass spectrometry statistical analysis.

PubMed

Jones, Emrys A; Deininger, Sören-Oliver; Hogendoorn, Pancras C W; Deelder, André M; McDonnell, Liam A

2012-08-30

Imaging mass spectrometry is increasingly used to identify new candidate biomarkers. This clinical application of imaging mass spectrometry is highly multidisciplinary: expertise in mass spectrometry is necessary to acquire high quality data, histology is required to accurately label the origin of each pixel's mass spectrum, disease biology is necessary to understand the potential meaning of the imaging mass spectrometry results, and statistics to assess the confidence of any findings. Imaging mass spectrometry data analysis is further complicated because of the unique nature of the data (within the mass spectrometry field); several of the assumptions implicit in the analysis of LC-MS/profiling datasets are not applicable to imaging. The very large size of imaging datasets and the reporting of many data analysis routines, combined with inadequate training and accessible reviews, have exacerbated this problem. In this paper we provide an accessible review of the nature of imaging data and the different strategies by which the data may be analyzed. Particular attention is paid to the assumptions of the data analysis routines to ensure that the reader is apprised of their correct usage in imaging mass spectrometry research. Copyright © 2012 Elsevier B.V. All rights reserved.

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...

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

PubMed

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

2014-12-16

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

Analysis of phenolic choline esters from seeds of Arabidopsis thaliana and Brassica napus by capillary liquid chromatography/electrospray- tandem mass spectrometry.

PubMed

Böttcher, Christoph; von Roepenack-Lahaye, Edda; Schmidt, Jürgen; Clemens, Stephan; Scheel, Dierk

2009-04-01

Total phenolic choline ester fractions prepared from seeds of Arabidopsis thaliana and Brassica napus were analyzed by capillary LC/ESI-QTOF-MS and direct infusion ESI-FTICR-MS. In addition to the dominating sinapoylcholine, 30 phenolic choline esters could be identified based on accurate mass measurements, interpretation of collision-induced dissociation (CID) mass spectra, and synthesis of selected representatives. The compounds identified so far include substituted hydroxycinnamoyl- and hydroxybenzoylcholines, respective monohexosides as well as oxidative coupling products of phenolic choline esters and monolignols. Phenolic choline esters are well separable by reversed-phase liquid chromatography and sensitively detectable using electrospray ionization mass spectrometry in positive ion mode. CID mass spectra obtained from molecular ions facilitate the characterization of both the type and substitution pattern of such compounds. Therefore, LC/ESI-MS/MS represents a valuable tool for comprehensive qualitative and quantitative analysis of this compound class. Copyright (c) 2009 John Wiley & Sons, Ltd.

Surface-Induced Dissociation of Protein Complexes in a Hybrid Fourier Transform Ion Cyclotron Resonance Mass Spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Jing; Zhou, Mowei; Gilbert, Joshua D.

Mass spectrometry continues to develop as a valuable tool in the analysis of proteins and protein complexes. In protein complex mass spectrometry studies, surface-induced dissociation (SID) has been successfully applied in quadrupole time-of-flight (Q-TOF) instruments. SID provides structural information on noncovalent protein complexes that is complementary to other techniques. However, the mass resolution of Q-TOF instruments can limit the information that can be obtained for protein complexes by SID. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) provides ultrahigh resolution and ultrahigh mass accuracy measurements. Here in this study, an SID device was designed and successfully installed in amore » hybrid FT-ICR instrument in place of the standard gas collision cell. The SID-FT-ICR platform has been tested with several protein complex systems (homooligomers, a heterooligomer, and a protein-ligand complex, ranging from 53 to 85 kDa), and the results are consistent with data previously acquired on Q-TOF platforms, matching predictions from known protein interface information. Lastly, SID fragments with the same m/z but different charge states are well-resolved based on distinct spacing between adjacent isotope peaks, and the addition of metal cations and ligands can also be isotopically resolved with the ultrahigh mass resolution available in FT-ICR.« less

Surface-Induced Dissociation of Protein Complexes in a Hybrid Fourier Transform Ion Cyclotron Resonance Mass Spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Jing; Zhou, Mowei; Gilbert, Joshua D.

Mass spectrometry continues to develop as a valuable tool in the analysis of proteins and protein complexes. In protein complex mass spectrometry studies, surface-induced dissociation (SID) has been successfully applied in quadrupole time-of-flight (Q-TOF) instruments. SID provides structural information on non-covalent protein complexes that is complementary to other techniques. However, the mass resolution of Q-TOF instruments can limit the information that can be obtained for protein complexes by SID. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) provides ultrahigh resolution and ultrahigh mass accuracy measurements. In this study, an SID device was designed and successfully installed in a hybridmore » FT-ICR instrument in place of the standard gas collision cell. The SID-FT-ICR platform has been tested with several protein complex systems (homooligomers, a heterooligomer, and a protein-ligand complex, ranging from 53 kDa to 85 kDa), and the results are consistent with data previously acquired on Q-TOF platforms, matching predictions from known protein interface information. SID fragments with the same m/z but different charge states are well-resolved based on distinct spacing between adjacent isotope peaks, and the addition of metal cations and ligands can also be isotopically resolved with the ultrahigh mass resolution available in FT-ICR.« less

Surface-Induced Dissociation of Protein Complexes in a Hybrid Fourier Transform Ion Cyclotron Resonance Mass Spectrometer

DOE PAGES

Yan, Jing; Zhou, Mowei; Gilbert, Joshua D.; ...

2016-12-02

Mass spectrometry continues to develop as a valuable tool in the analysis of proteins and protein complexes. In protein complex mass spectrometry studies, surface-induced dissociation (SID) has been successfully applied in quadrupole time-of-flight (Q-TOF) instruments. SID provides structural information on noncovalent protein complexes that is complementary to other techniques. However, the mass resolution of Q-TOF instruments can limit the information that can be obtained for protein complexes by SID. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) provides ultrahigh resolution and ultrahigh mass accuracy measurements. Here in this study, an SID device was designed and successfully installed in amore » hybrid FT-ICR instrument in place of the standard gas collision cell. The SID-FT-ICR platform has been tested with several protein complex systems (homooligomers, a heterooligomer, and a protein-ligand complex, ranging from 53 to 85 kDa), and the results are consistent with data previously acquired on Q-TOF platforms, matching predictions from known protein interface information. Lastly, SID fragments with the same m/z but different charge states are well-resolved based on distinct spacing between adjacent isotope peaks, and the addition of metal cations and ligands can also be isotopically resolved with the ultrahigh mass resolution available in FT-ICR.« less

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

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

NASA Astrophysics Data System (ADS)

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

2012-01-01

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

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

PubMed

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

2016-06-28

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

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.

Fourier transform mass spectrometry.

PubMed

Scigelova, Michaela; Hornshaw, Martin; Giannakopulos, Anastassios; Makarov, Alexander

2011-07-01

This article provides an introduction to Fourier transform-based mass spectrometry. The key performance characteristics of Fourier transform-based mass spectrometry, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of Fourier transform-based mass spectrometry technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for an application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook.

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

DOE PAGES

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

2015-06-09

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

Analysis of Monoclonal Antibodies in Human Serum as a Model for Clinical Monoclonal Gammopathy by Use of 21 Tesla FT-ICR Top-Down and Middle-Down MS/MS

NASA Astrophysics Data System (ADS)

He, Lidong; Anderson, Lissa C.; Barnidge, David R.; Murray, David L.; Hendrickson, Christopher L.; Marshall, Alan G.

2017-05-01

With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2-0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error 4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.

Fourier Transform Mass Spectrometry

PubMed Central

Scigelova, Michaela; Hornshaw, Martin; Giannakopulos, Anastassios; Makarov, Alexander

2011-01-01

This article provides an introduction to Fourier transform-based mass spectrometry. The key performance characteristics of Fourier transform-based mass spectrometry, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of Fourier transform-based mass spectrometry technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for an application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook. PMID:21742802

Fractionation and characterization of dissolved organic matter (DOM) in refinery wastewater by revised phase retention and ion-exchange adsorption solid phase extraction followed by ESI FT-ICR MS.

PubMed

Fang, Zhi; He, Chen; Li, Yongyong; Chung, Keng H; Xu, Chunming; Shi, Quan

2017-01-01

Although the progress of high resolution mass spectrometry in the past decade has enabled the molecular characterization of dissolved organic matter (DOM) in water as a whole, fractionation of DOM is necessary for a comprehensive characterization due to its super-complex nature. Here we proposed a method for the fractionation of DOM in a wastewater based on solubility and acidic-basic properties. Solid phase extraction (SPE) cartridges with reversed phase retention and ion-exchange adsorption capacities, namely MAX and MCX, were used in succession to fractionate a petroleum refinery wastewater into four fractions: hydrophobic acid (HOA), hydrophobic neutral (HON), hydrophobic base (HOB), and hydrophilic substance (HIS) fractions. According to the total organic carbon (TOC) analysis, 72.6% (in term of TOC) of DOM was extracted in hydrophobic fractions, in which HON was the most abundant. Hydrophobic extracts were characterized by negative and positive ion electrospray (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), respectively. Compounds with multiple oxygen atoms were predominant in the HOA, which were responded strongly in the negative ESI MS. Nitrogen containing compounds were the major detected species by positive ion ESI in all hydrophobic fractions. The molecular composition of the DOM were discussed based on the FT-ICR MS results. The fractionation provided salt free samples which enables the direct analysis of the fractions by ESI and a deep insight into the molecular composition of DOM in the wastewater. The method is potential for routine evaluation of DOM in industry wastewaters, as well as environmental water samples. Copyright © 2016. Published by Elsevier B.V.

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

Mass spectrometry of atmospheric aerosols--recent developments and applications. Part II: On-line mass spectrometry techniques.

PubMed

Pratt, Kerri A; Prather, Kimberly A

2012-01-01

Many of the significant advances in our understanding of atmospheric particles can be attributed to the application of mass spectrometry. Mass spectrometry provides high sensitivity with fast response time to probe chemically complex particles. This review focuses on recent developments and applications in the field of mass spectrometry of atmospheric aerosols. In Part II of this two-part review, we concentrate on real-time mass spectrometry techniques, which provide high time resolution for insight into brief events and diurnal changes while eliminating the potential artifacts acquired during long-term filter sampling. In particular, real-time mass spectrometry has been shown recently to provide the ability to probe the chemical composition of ambient individual particles <30 nm in diameter to further our understanding of how particles are formed through nucleation in the atmosphere. Further, transportable real-time mass spectrometry techniques are now used frequently on ground-, ship-, and aircraft-based studies around the globe to further our understanding of the spatial distribution of atmospheric aerosols. In addition, coupling aerosol mass spectrometry techniques with other measurements in series has allowed the in situ determination of chemically resolved particle effective density, refractive index, volatility, and cloud activation properties. Copyright © 2011 Wiley Periodicals, Inc.

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.

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

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

NASA Astrophysics Data System (ADS)

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

2015-07-01

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

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

PubMed

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

2012-09-04

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

Theory of peak coalescence in Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Boldin, Ivan A; Nikolaev, Eugene N

2009-10-01

Peak coalescence, i.e. the merging of two close peaks in a Fourier transform ion cyclotron resonance (FTICR) mass spectrum at a high number of ions, plays an important role in various FTICR experiments. In order to describe the coalescence phenomenon we would like to propose a new theory of motion for ion clouds with close mass-to-charge ratios, driven by a uniform magnetic field and Coulomb interactions between the clouds. We describe the motion of the ion clouds in terms of their averaged drift motion in crossed magnetic and electric fields. The ion clouds are considered to be of constant size and their motion is studied in two dimensions. The theory deals with the first-order approximation of the equations of motion in relation to dm/m, where dm is the mass difference and m is the mass of a single ion. The analysis was done for an arbitrary inter-cloud interaction potential, which makes it possible to analyze finite-size ion clouds of any shape. The final analytical expression for the condition of the onset of coalescence is found for the case of uniformly charged spheres. An algorithm for finding this condition for an arbitrary interaction potential is proposed. The critical number of ions for the peak coalescence to take place is shown to depend quadratically on the magnetic field strength and to be proportional to the cyclotron radius and inversely proportional to the ion masses. Copyright (c) 2009 John Wiley & Sons, Ltd.

Molecular evidence of heavy-oil weathering following the M/V Cosco Busan spill: insights from Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Lemkau, Karin L; McKenna, Amy M; Podgorski, David C; Rodgers, Ryan P; Reddy, Christopher M

2014-04-01

Recent studies have highlighted a critical need to investigate oil weathering beyond the analytical window afforded by conventional gas chromatography (GC). In particular, techniques capable of detecting polar and higher molecular weight (HMW; > 400 Da) components abundant in crude and heavy fuel oils (HFOs) as well as transformation products. Here, we used atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI FT-ICR MS) to identify molecular transformations in oil-residue samples from the 2007 M/V Cosco Busan HFO spill (San Francisco, CA). Over 617 days, the abundance and diversity of oxygen-containing compounds increased relative to the parent HFO, likely from bio- and photodegradation. HMW, highly aromatic, alkylated compounds decreased in relative abundance concurrent with increased relative abundance of less alkylated stable aromatic structures. Combining these results with GC-based data yielded a more comprehensive understanding of oil spill weathering. For example, dealkylation trends and the overall loss of HMW species observed by FT-ICR MS has not previously been documented and is counterintuitive given losses of lower molecular weight species observed by GC. These results suggest a region of relative stability at the interface of these techniques, which provides new indicators for studying long-term weathering and identifying sources.

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring.

PubMed

Darebna, Petra; Novak, Petr; Kucera, Radek; Topolcan, Ondrej; Sanda, Miloslav; Goldman, Radoslav; Pompach, Petr

2017-02-05

Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer. Haptoglobin, hemopexin and complement factor H were detected after albumin depletion and the N-linked glycopeptides with fucosylated glycans were compared with their non-fucosylated forms. In addition, sialylated forms of an O-linked glycopeptide of hemopexin were quantified in the same samples. We observe significant increase in fucosylation of all three proteins and increase in bi-sialylated O-glycopeptide of hemopexin in HCC of hepatitis C viral (HCV) etiology by both LC-MS methods. The results of the MRM and full-MS scan FT-ICR analyses provide comparable quantitative readouts in spite of chromatographic, mass spectrometric and data analysis differences. Our results suggest that both workflows allow adequate relative quantification of glycopeptides and suggest that HCC of HCV etiology differs in glycosylation from colorectal cancer and liver metastasis of colorectal cancer. The article compares N- and O-glycosylation of several serum proteins in different diseases by a fast and easy sample preparation procedure in combination with high resolution Fourier transform ion cyclotron resonance mass spectrometry. The results show successful glycopeptides relative quantification in a complex peptide mixture by the high resolution instrument and the detection of glycan differences between the different types of cancer diseases. The presented method is comparable to conventional targeted MRM approach but allows additional curation of the data. Copyright © 2016 Elsevier B

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring

PubMed Central

Darebna, Petra; Novak, Petr; Kucera, Radek; Topolcan, Ondrej; Sanda, Miloslav; Goldman, Radoslav; Pompach, Petr

2018-01-01

Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer. Haptoglobin, hemopexin and complement factor H were detected after albumin depletion and the N-linked glycopeptides with fucosylated glycans were compared with their non-fucosylated forms. In addition, sialylated forms of an O-linked glycopeptide of hemopexin were quantified in the same samples. We observe significant increase in fucosylation of all three proteins and increase in bisialylated O-glycopeptide of hemopexin in HCC of hepatitis C viral (HCV) etiology by both LC-MS methods. The results of the MRM and full-MS scan FT-ICR analyses provide comparable quantitative readouts in spite of chromatographic, mass spectrometric and data analysis differences. Our results suggest that both workflows allow adequate relative quantification of glycopeptides and suggest that HCC of HCV etiology differs in glycosylation from colorectal cancer and liver metastasis of colorectal cancer. Significance The article compares N- and O-glycosylation of several serum proteins in different diseases by a fast and easy sample preparation procedure in combination with high resolution Fourier transform ion cyclotron resonance mass spectrometry. The results show successful glycopeptides relative quantification in a complex peptide mixture by the high resolution instrument and the detection of glycan differences between the different types of cancer diseases. The presented method is comparable to conventional targeted MRM approach but allows additional curation of the data. PMID:27646713

Collision cross section measurements for biomolecules within a high-resolution FT-ICR cell: theory.

PubMed

Guo, Dan; Xin, Yi; Li, Dayu; Xu, Wei

2015-04-14

In this study, an energetic hard-sphere ion-neutral collision model was proposed to bridge-link ion collision cross section (CCS) with the image current collected from a high-resolution Fourier transform ion cyclotron resonance (FT-ICR) cell. By investigating the nonlinear effects induced by high-order electric fields and image charge forces, the energetic hard-sphere collision model was validated through experiments. Suitable application regions for the energetic hard-sphere collision model, as well as for the conventional Langevin and hard-sphere collision models, were also discussed. The energetic hard-sphere collision model was applied in the extraction of ion CCSs from high-resolution FT-ICR mass spectra. Discussions in the present study also apply to FT-Orbitraps and FT-quadrupole ion traps.

Advanced solvent based methods for molecular characterization of soil organic matter by high-resolution mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tfaily, Malak M.; Chu, Rosalie K.; Tolic, Nikola

2015-05-19

Soil organic matter (SOM) a complex, heterogeneous mixture of above and belowground plant litter and animal and microbial residues at various degrees of decomposition, is a key reservoir for carbon (C) and nutrient biogeochemical cycling in soil based ecosystems. A limited understanding of the molecular composition of SOM limits the ability to routinely decipher chemical processes within soil and predict accurately how terrestrial carbon fluxes will response to changing climatic conditions and land use. To elucidate the molecular-level structure of SOM, we selectively extracted a broad range of intact SOM compounds by a combination of different organic solvents from soilsmore » with a wide range of C content. Our use of Electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and a suite of solvents with varying polarity significantly expands the inventory of the types of organic molecules present in soils. Specifically, we found that hexane is selective for lipid-like compounds with very low O:C ratios; water was selective for carbohydrates with high O:C ratios; acetonitrile preferentially extracts lignin, condensed structures, and tannin poly phenolic compounds with O:C > 0.5; methanol has higher selectivity towards compounds characterized with low O:C < 0.5; and hexane, MeOH, ACN and water solvents increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Our study of SOM molecules by ESI-FTICR MS revealed new insight into the molecular-level complexity of organics contained in soils.« less

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.

Molecular Characterization of Organosulfates in Urban Aerosols during the Spring Festival by FT-ICR Mass Spectrometry

NASA Astrophysics Data System (ADS)

Xie, Q.; Fu, P.

2017-12-01

Aerosol particles collected at daytime and nighttime in Beijing during the spring festival, including the episodes of various gradient level pollution and short-term pollution raised by fireworks, were analyzed using 15T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS). Organosulfates (OSs), tracers for secondary organic aerosol formation, were identified through accurate mass measurements. Both the total number and the arbitrary abundance of OSs were consistent with the total OC concentrations of the aerosol samples. Nitrooxy-organosulfates were more abundant in the nighttime than those in the daytime due to high NOX concentrations at night. Although all subgroups OSs increased with the deterioration of air quality, especially for the relative abundance of aromatic OSs with high double bond equivalents, the percentage contributions of aliphatic OSs with low degree of unsaturation decreased. It was worth to note that aliphatic OSs with a wide range in carbon-chain length of C6-40 were identified in this study. The candidates for their potential precursors were alkanes and fatty acids. Moreover, a large number of aromatic OSs, about two thirds of OSs, were detected. The rapid formation of these compounds in New Year's Eve with plentiful aromatics from firework burning suggests that they may be derived from PAHs. The high carbon and oxygen contents of OSs may indicate the presence of dimmers, even polymers. Our results support the important contribution of anthropogenic precursors to OSs in ambient aerosols on the basis of aromatic and aliphatic OSs, which may have a significant impact on the hygroscopic properties of ambient aerosol particles.

Mass spectrometry of long-lived radionuclides

NASA Astrophysics Data System (ADS)

Becker, Johanna Sabine

2003-10-01

The capability of determining element concentrations at the trace and ultratrace level and isotope ratios is a main feature of inorganic mass spectrometry. The precise and accurate determination of isotope ratios of long-lived natural and artificial radionuclides is required, e.g. for their environmental monitoring and health control, for studying radionuclide migration, for age dating, for determining isotope ratios of radiogenic elements in the nuclear industry, for quality assurance and determination of the burn-up of fuel material in a nuclear power plant, for reprocessing plants, nuclear material accounting and radioactive waste control. Inorganic mass spectrometry, especially inductively coupled plasma mass spectrometry (ICP-MS) as the most important inorganic mass spectrometric technique today, possesses excellent sensitivity, precision and good accuracy for isotope ratio measurements and practically no restriction with respect to the ionization potential of the element investigated—therefore, thermal ionization mass spectrometry (TIMS), which has been used as the dominant analytical technique for precise isotope ratio measurements of long-lived radionuclides for many decades, is being replaced increasingly by ICP-MS. In the last few years instrumental progress in improving figures of merit for the determination of isotope ratio measurements of long-lived radionuclides in ICP-MS has been achieved by the application of a multiple ion collector device (MC-ICP-MS) and the introduction of the collision cell interface in order to dissociate disturbing argon-based molecular ions, to reduce the kinetic energy of ions and neutralize the disturbing noble gas ions (e.g. of 129Xe + for the determination of 129I). The review describes the state of the art and the progress of different inorganic mass spectrometric techniques such as ICP-MS, laser ablation ICP-MS vs. TIMS, glow discharge mass spectrometry, secondary ion mass spectrometry, resonance ionization mass

Accurate mass measurement: terminology and treatment of data.

PubMed

Brenton, A Gareth; Godfrey, A Ruth

2010-11-01

High-resolution mass spectrometry has become ever more accessible with improvements in instrumentation, such as modern FT-ICR and Orbitrap mass spectrometers. This has resulted in an increase in the number of articles submitted for publication quoting accurate mass data. There is a plethora of terms related to accurate mass analysis that are in current usage, many employed incorrectly or inconsistently. This article is based on a set of notes prepared by the authors for research students and staff in our laboratories as a guide to the correct terminology and basic statistical procedures to apply in relation to mass measurement, particularly for accurate mass measurement. It elaborates on the editorial by Gross in 1994 regarding the use of accurate masses for structure confirmation. We have presented and defined the main terms in use with reference to the International Union of Pure and Applied Chemistry (IUPAC) recommendations for nomenclature and symbolism for mass spectrometry. The correct use of statistics and treatment of data is illustrated as a guide to new and existing mass spectrometry users with a series of examples as well as statistical methods to compare different experimental methods and datasets. Copyright © 2010. Published by Elsevier Inc.

On the isobaric space of 25-hydroxyvitamin D in human serum: potential for interferences in liquid chromatography/tandem mass spectrometry, systematic errors and accuracy issues.

PubMed

Qi, Yulin; Geib, Timon; Schorr, Pascal; Meier, Florian; Volmer, Dietrich A

2015-01-15

Isobaric interferences in human serum can potentially influence the measured concentration levels of 25-hydroxyvitamin D [25(OH)D], when low resolving power liquid chromatography/tandem mass spectrometry (LC/MS/MS) instruments and non-specific MS/MS product ions are employed for analysis. In this study, we provide a detailed characterization of these interferences and a technical solution to reduce the associated systematic errors. Detailed electrospray ionization Fourier transform ion cyclotron resonance (FTICR) high-resolution mass spectrometry (HRMS) experiments were used to characterize co-extracted isobaric components of 25(OH)D from human serum. Differential ion mobility spectrometry (DMS), as a gas-phase ion filter, was implemented on a triple quadrupole mass spectrometer for separation of the isobars. HRMS revealed the presence of multiple isobaric compounds in extracts of human serum for different sample preparation methods. Several of these isobars had the potential to increase the peak areas measured for 25(OH)D on low-resolution MS instruments. A major isobaric component was identified as pentaerythritol oleate, a technical lubricant, which was probably an artifact from the analytical instrumentation. DMS was able to remove several of these isobars prior to MS/MS, when implemented on the low-resolution triple quadrupole mass spectrometer. It was shown in this proof-of-concept study that DMS-MS has the potential to significantly decrease systematic errors, and thus improve accuracy of vitamin D measurements using LC/MS/MS. Copyright © 2014 John Wiley & Sons, Ltd.

Aquatic plant-derived changes in oil sands naphthenic acid signatures determined by low-, high- and ultrahigh-resolution mass spectrometry.

PubMed

Headley, John V; Peru, Kerry M; Armstrong, Sarah A; Han, Xiumei; Martin, Jonathan W; Mapolelo, Mmilili M; Smith, Donald F; Rogers, Ryan P; Marshall, Alan G

2009-02-01

Mass spectrometry is a common tool for studying the fate of complex organic compound mixtures in oil sands processed water (OSPW), but a comparison of low-, high- ( approximately 10 000), and ultrahigh-resolution ( approximately 400 000) instrumentation for this purpose has not previously been made. High-resolution quadrupole time-of-flight mass spectrometry (QTOF MS) and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), with negative-ion electrospray ionization, provided evidence for the selective dissipation of components in OSPW. Dissipation of oil sands naphthenic acids (NAs with general formula C(n)H(2n+z)O(2) where n is the number of carbon atoms, and Z is zero or a negative even number describing the number of rings) was masked (by components such as fatty acids, O(3), O(5), O(6), O(7), SO(2), SO(3), SO(4), SO(5), SO(6), and NO(4) species) at low resolution (1000) when using a triple quadrupole mass spectrometer. Changes observed in the relative composition of components in OSPW appear to be due primarily to the presence of plants, specifically cattails (Typha latifolia) and their associated microorganisms. The observed dissipation included a range of heteratomic species containing O(2), O(3), O(4), and O(5), present in Athabasca oil sands acid extracts. For the heteratomic O(2) species, namely naphthenic acids, an interesting structural relationship suggests that low and high carbon number NAs are dissipated by the plants preferentially, with a minimum around C(14)/C(15). Other heteratomic species containing O(6), O(7), SO(2), SO(3), SO(4), SO(5), SO(6), and NO(4) appear to be relatively recalcitrant to the cattails and were not dissipated to the same extent in planted systems. Copyright 2009 John Wiley & Sons, Ltd.

Separation of ion types in tandem mass spectrometry data interpretation -- a graph-theoretic approach.

PubMed

Yan, Bo; Pan, Chongle; Olman, Victor N; Hettich, Robert L; Xu, Ying

2004-01-01

Mass spectrometry is one of the most popular analytical techniques for identification of individual proteins in a protein mixture, one of the basic problems in proteomics. It identifies a protein through identifying its unique mass spectral pattern. While the problem is theoretically solvable, it remains a challenging problem computationally. One of the key challenges comes from the difficulty in distinguishing the N- and C-terminus ions, mostly b- and y-ions respectively. In this paper, we present a graph algorithm for solving the problem of separating bfrom y-ions in a set of mass spectra. We represent each spectral peak as a node and consider two types of edges: a type-1 edge connects two peaks possibly of the same ion types and a type-2 edge connects two peaks possibly of different ion types, predicted based on local information. The ion-separation problem is then formulated and solved as a graph partition problem, which is to partition the graph into three subgraphs, namely b-, y-ions and others respectively, so to maximize the total weight of type-1 edges while minimizing the total weight of type-2 edges within each subgraph. We have developed a dynamic programming algorithm for rigorously solving this graph partition problem and implemented it as a computer program PRIME. We have tested PRIME on 18 data sets of high accurate FT-ICR tandem mass spectra and found that it achieved ~90% accuracy for separation of b- and y- ions.

Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Mowei; Yan, Jing; Romano, Christine A.

Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase Mnx from Bacillus sp. PL-12 has been successfully overexpressed in active form, unexpectedly, as a protein complex with a molecular weight of 211 kDa with no homology to known proteins in the database. We have recently used surface induced dissociation (SID) and ion mobility – mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data frommore » the native mass spectrometry experiment led to a plausible model of this unknown multicopper oxidase which has been difficult to study by conventional structural biology methods. However, because each subunit of Mnx binds copper ions as cofactor at varying ratios, there were remaining ambiguities in assigning some of the observed peaks to metal-binding species because of the sample heterogeneity and limited mass resolution. In this study, we performed SID in a modified Fourier transform – ion cyclotron resonance (FT-ICR) mass spectrometer for obtaining the ultimate resolution on the released subcomplexes of Mnx. The high mass accuracy and resolution unveiled unexpected artificial modifications in the protein that have been previously thought to be iron bound species based on lower resolution data. Additionally, most released subcomplexes were isotopically resolved for defining metal binding stoichiometry at each structural level. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes.« less

Deciphering the rhizosphere by liquid extraction surface analysis mass spectrometry (LESA-MS)

NASA Astrophysics Data System (ADS)

Chu, R. K.; Tfaily, M. M.; Handakumbura, P. P.; Paša-Tolić, L.; Anderton, C.

2016-12-01

Interactions of plants with their soil microenvironment and surrounding microbes are of major scientific importance for reasons ranging from understanding global carbon and nitrogen cycling to developing advanced crops. Gaining spatial information of the biochemical interactions that occur within the rhizosphere and other subsurface terrestrial ecosystems is an area of growing interest. Accordingly, development of analytical tools to probe and map molecular interactions in situ, and without intrusive and extensive sample preparation, would provide unique insights into the processes governing plant growth, nitrogen fixation and the metabolic exchange between the root and rhizobia, for example. Here, we will discuss the development of an application using LESA-MS—liquid extraction surface analysis mass spectrometry—that is capable of spatially characterizing molecular rhizospheric interactions in their native state and in a label-free manner. In LESA-MS, microextractions of a sample's surface are performed robotically, and we can either address points of interest (e.g., determined visually) or an entire area can be profiled in a serial fashion. Extracted molecules are then ionized by nanoelectrospray ionization (nano-ESI) and analyzed using high resolution and mass accuracy mass spectrometry (Fourier transform ion cyclotron resonance, FTICR MS). Because this analysis can be performed under ambient conditions, we are able to characterize the chemical distributions within the rhizosphere of a living plant. Here, we use Sorghum bicolor grown in a two-dimensional rhizobox that contains Turface clay as a model system, and used methanol-water as the solvent to characterize molecular distributions across the rhizosphere.

The life sciences mass spectrometry research unit.

PubMed

Hopfgartner, Gérard; Varesio, Emmanuel

2012-01-01

The Life Sciences Mass Spectrometry (LSMS) research unit focuses on the development of novel analytical workflows based on innovative mass spectrometric and software tools for the analysis of low molecular weight compounds, peptides and proteins in complex biological matrices. The present article summarizes some of the recent work of the unit: i) the application of matrix-assisted laser desorption/ionization (MALDI) for mass spectrometry imaging (MSI) of drug of abuse in hair, ii) the use of high resolution mass spectrometry for simultaneous qualitative/quantitative analysis in drug metabolism and metabolomics, and iii) the absolute quantitation of proteins by mass spectrometry using the selected reaction monitoring mode.

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)

Role of Mass Spectrometry in Clinical Endocrinology.

PubMed

Ketha, Siva S; Singh, Ravinder J; Ketha, Hemamalini

2017-09-01

The advent of mass spectrometry into the clinical laboratory has led to an improvement in clinical management of several endocrine diseases. Liquid chromatography tandem mass spectrometry found some of its first clinical applications in the diagnosis of inborn errors of metabolism, in quantitative steroid analysis, and in drug analysis laboratories. Mass spectrometry assays offer analytical sensitivity and specificity that is superior to immunoassays for many analytes. This article highlights several areas of clinical endocrinology that have witnessed the use of liquid chromatography tandem mass spectrometry to improve clinical outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

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

First signal from a broadband cryogenic preamplifier cooled by circulating liquid nitrogen in a 7 T Fourier transform ion cyclotron resonance mass spectrometer.

PubMed

Choi, Myoung Choul; Lee, Jeong Min; Lee, Se Gyu; Choi, Sang Hwan; Choi, Yeon Suk; Lee, Kyung Jae; Kim, SeungYong; Kim, Hyun Sik; Stahl, Stefan

2012-12-18

Despite the outstanding performance of Fourier transform ion cyclotron/mass spectrometry (FTICR/MS), the complexity of the cellular proteome or natural compounds presents considerable challenges. Sensitivity is a key performance parameter of a FTICR mass spectrometer. By improving this parameter, the dynamic range of the instrument can be increased to improve the detection signal of low-abundance compounds or fragment ion peaks. In order to improve sensitivity, a cryogenic detection system was developed by the KBSI (Korean Basic Science Institute) in collaboration with Stahl-Electronics (Mettenheim, Germany). A simple, efficient liquid circulation cooling system was designed and a cryogenic preamplifier implemented inside a FTICR mass spectrometer. This cooling system circulates a cryoliquid from a Dewar to the "liquid circulation unit" through a CF flange to cool a copper block and a cryopreamplifier; the cooling medium is subsequently exhausted into the air. The cryopreamplifier can be operated over a very wide temperature range, from room temperature to low temperature environments (4.2 K). First, ion signals detected by the cryopreamplifier using a circulating liquid nitrogen cooling system were observed and showed a signal-to-noise ratio (S/N) about 130% better than that obtained at room temperature.

Semi-Targeted Analysis of Complex Matrices by ESI FT-ICR MS or How an Experimental Bias may be Used as an Analytical Tool.

PubMed

Hertzog, Jasmine; Carré, Vincent; Dufour, Anthony; Aubriet, Frédéric

2018-03-01

Ammonia is well suited to favor deprotonation process in electrospray ionization mass spectrometry (ESI-MS) to increase the formation of [M - H] - . Nevertheless, NH 3 may react with carbonyl compounds (aldehyde, ketone) and bias the composition description of the investigated sample. This is of significant importance in the study of complex mixture such as oil or bio-oil. To assess the ability of primary amines to form imines with carbonyl compounds during the ESI-MS process, two aldehydes (vanillin and cinnamaldehyde) and two ketones (butyrophenone and trihydroxyacetophenone) have been infused in an ESI source with ammonia and two different amines (aniline and 3-chloronaniline). The (+) ESI-MS analyses have demonstrated the formation of imine whatever the considered carbonyl compound and the used primary amine, the structure of which was extensively studied by tandem mass spectrometry. Thus, it has been established that the addition of ammonia, in the solution infused in an ESI source, may alter the composition description of a complex mixture and leads to misinterpretations due to the formation of imines. Nevertheless, this experimental bias can be used to identify the carbonyl compounds in a pyrolysis bio-oil. As we demonstrated, infusion of the bio-oil with 3-chloroaniline in ESI source leads to specifically derivatized carbonyl compounds. Thanks to their chlorine isotopic pattern and the high mass measurement accuracy, (+) ESI Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) unambiguously highlighted them from the numerous C x H y O z bio-oil components. These results offer a new perspective into the detailed molecular structure of complex mixtures such as bio-oils. Graphical Abstract ᅟ.

Semi-Targeted Analysis of Complex Matrices by ESI FT-ICR MS or How an Experimental Bias may be Used as an Analytical Tool

NASA Astrophysics Data System (ADS)

Hertzog, Jasmine; Carré, Vincent; Dufour, Anthony; Aubriet, Frédéric

2018-03-01

Ammonia is well suited to favor deprotonation process in electrospray ionization mass spectrometry (ESI-MS) to increase the formation of [M - H]-. Nevertheless, NH3 may react with carbonyl compounds (aldehyde, ketone) and bias the composition description of the investigated sample. This is of significant importance in the study of complex mixture such as oil or bio-oil. To assess the ability of primary amines to form imines with carbonyl compounds during the ESI-MS process, two aldehydes (vanillin and cinnamaldehyde) and two ketones (butyrophenone and trihydroxyacetophenone) have been infused in an ESI source with ammonia and two different amines (aniline and 3-chloronaniline). The (+) ESI-MS analyses have demonstrated the formation of imine whatever the considered carbonyl compound and the used primary amine, the structure of which was extensively studied by tandem mass spectrometry. Thus, it has been established that the addition of ammonia, in the solution infused in an ESI source, may alter the composition description of a complex mixture and leads to misinterpretations due to the formation of imines. Nevertheless, this experimental bias can be used to identify the carbonyl compounds in a pyrolysis bio-oil. As we demonstrated, infusion of the bio-oil with 3-chloroaniline in ESI source leads to specifically derivatized carbonyl compounds. Thanks to their chlorine isotopic pattern and the high mass measurement accuracy, (+) ESI Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) unambiguously highlighted them from the numerous CxHyOz bio-oil components. These results offer a new perspective into the detailed molecular structure of complex mixtures such as bio-oils. [Figure not available: see fulltext.

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

Symposium on accelerator mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

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 themore » status of accelerator mass spectrometry. Individual papers were prepared separately for the data base.« less

Chemical cross-linking of the urease complex from Helicobacter pylori and analysis by Fourier transform ion cyclotron resonance mass spectrometry and molecular modeling

NASA Astrophysics Data System (ADS)

Carlsohn, Elisabet; Ångström, Jonas; Emmett, Mark R.; Marshall, Alan G.; Nilsson, Carol L.

2004-05-01

Chemical cross-linking of proteins is a well-established method for structural mapping of small protein complexes. When combined with mass spectrometry, cross-linking can reveal protein topology and identify contact sites between the peptide surfaces. When applied to surface-exposed proteins from pathogenic organisms, the method can reveal structural details that are useful in vaccine design. In order to investigate the possibilities of applying cross-linking on larger protein complexes, we selected the urease enzyme from Helicobacter pylori as a model. This membrane-associated protein complex consists of two subunits: [alpha] (26.5 kDa) and [beta] (61.7 kDa). Three ([alpha][beta]) heterodimers form a trimeric ([alpha][beta])3 assembly which further associates into a unique dodecameric 1.1 MDa complex composed of four ([alpha][beta])3 units. Cross-linked peptides from trypsin-digested urease complex were analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and molecular modeling. Two potential cross-linked peptides (present in the cross-linked sample but undetectable in [alpha], [beta], and native complex) were assigned. Molecular modeling of urease [alpha][beta] complex and trimeric urease units ([alpha][beta])3 revealed a linkage site between the [alpha]-subunit and the [beta]-subunit, and an internal cross-linkage in the [beta]-subunit.

A rapid method to assess a broad inventory of organic species in marine sediments using ultra-high resolution mass spectrometry.

PubMed

Radović, Jagoš R; Silva, Renzo C; Snowdon, Ryan W; Brown, Melisa; Larter, Steve; Oldenburg, Thomas B P

2016-06-15

A broad range of organic species in marine sediments is routinely used as biogeochemical proxies of Earth history. These species are typically analyzed using different analytical methods, targeting very specific components and often including time-intensive sample preparation. There is, therefore, a need for a more comprehensive, rapid and high-throughput approach to simultaneously analyze a broad range of known sedimentary polar species and also have a surveillance capability able to identify candidate new species classes. Whole solvent extracts from recently deposited Gulf of Mexico marine sediments were obtained after a simple, one-step extraction. They were analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), using atmospheric pressure photoionization in positive ion mode (APPI-P), over a broad mass range (m/z 150-1500). From 3000 to over 5000 peaks per sample were assigned molecular formulae, and the majority of assignments (90%) showed an absolute error lower than 200 ppb. The detected species belong to the NO1-7 , N4 O2-8 , O1-9 , HC, N and OS compound classes, including known biomarker species such as pigments (e.g. tetrapyrrole macrocycles and carotenoids) and lipids (e.g. glycerol dialkyl glycerol tetraethers, GDGTs), but also compounds of still unknown detailed molecular structure, but with clear potential geochemical relevance. The reported method enables rapid (12 min FTICR-MS analysis time) and simultaneous detection of a broad range of multi-heteroatom, polar organic species in whole sediment extracts. This allows for higher sample throughput, a more comprehensive investigation of sedimentary geochemistry, and potentially the discovery of new components and derivation of novel, multi-species proxies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annesley, Thomas M.; Cooks, Robert G.; Herold, David A.

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 onmore » Mass Spectrometry. The Q&A Transcript is attached« less

Silver nanostructures in laser desorption/ionization mass spectrometry and mass spectrometry imaging.

PubMed

Sekuła, Justyna; Nizioł, Joanna; Rode, Wojciech; Ruman, Tomasz

2015-09-21

Silver nanoparticles have been successfully applied as a matrix replacement for the laser desorption/ionization time-of-flight mass spectrometry (LDI-ToF-MS). Nanoparticles, producing spectra with highly reduced chemical background in the low m/z region, are perfectly suited for low-molecular weight compound analysis and imaging. Silver nanoparticles (AgNPs) can efficiently absorb ultraviolet laser radiation, transfer energy to the analyte and promote analyte desorption, but also constitute a source of silver ions suitable for analyte cationisation. This review provides an overview of the literature on silver nanomaterials as non-conventional desorption and ionization promoters in LDI-MS and mass spectrometry imaging.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Donald F.; Schulz, Carl; Konijnenburg, Marco

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

Imaging mass spectrometry in drug development and toxicology.

PubMed

Karlsson, Oskar; Hanrieder, Jörg

2017-06-01

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls

PubMed Central

Titulaer, Mark K; Siccama, Ivar; Dekker, Lennard J; van Rijswijk, Angelique LCT; Heeren, Ron MA; Sillevis Smitt, Peter A; Luider, Theo M

2006-01-01

Background Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest. Results A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups. Conclusion The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry

A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls.

PubMed

Titulaer, Mark K; Siccama, Ivar; Dekker, Lennard J; van Rijswijk, Angelique L C T; Heeren, Ron M A; Sillevis Smitt, Peter A; Luider, Theo M

2006-09-05

Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest. A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups. The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry experiments. It is expected that the

"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

Evaluation of the Orbitrap Mass Spectrometer for the Molecular Fingerprinting Analysis of Natural Dissolved Organic Matter.

PubMed

Hawkes, Jeffrey A; Dittmar, Thorsten; Patriarca, Claudia; Tranvik, Lars; Bergquist, Jonas

2016-08-02

We investigated the application of the LTQ-Orbitrap mass spectrometer (LTQ-Velos Pro, Thermo Fisher) for resolving complex mixtures of natural aquatic dissolved organic matter (DOM) and compared this technique to the more established state-of-the-art technique, Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS, Bruker Daltonics), in terms of the distribution of molecular masses detected and the reproducibility of the results collected. The Orbitrap was capable of excellent reproducibility: Bray-Curtis dissimilarity between duplicate measurements was 2.85 ± 0.42% (mean ± standard deviation). The Orbitrap was also capable of the detection of most major ionizable organic molecules in typical aquatic mixtures, with the exception of most sulfur and phosphorus containing masses. This result signifies that the Orbitrap is an appropriate technique for the investigation of very subtle biogeochemical processing of bulk DOM. The lower costs (purchase and maintenance) and wider availability of Orbitrap mass spectrometers in university departments means that the tools necessary for research into DOM processing at the molecular level should be accessible to a much wider group of scientists than before. The main disadvantage of the technique is that substantially fewer molecular formulas can be resolved from a complex mixture (roughly one third as many), meaning some loss of information. In balance, most biogeochemical studies that aim at molecularly fingerprinting the source of natural DOM could be satisfactorily carried out with Orbitrap mass spectrometry. For more targeted metabolomic studies where individual compounds are traced through natural systems, FTICR-MS remains advantageous.

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…

Revealing Ligand Binding Sites and Quantifying Subunit Variants of Noncovalent Protein Complexes in a Single Native Top-Down FTICR MS Experiment

NASA Astrophysics Data System (ADS)

Li, Huilin; Wongkongkathep, Piriya; Van Orden, Steve L.; Ogorzalek Loo, Rachel R.; Loo, Joseph A.

2014-12-01

"Native" mass spectrometry (MS) has been proven to be increasingly useful for structural biology studies of macromolecular assemblies. Using horse liver alcohol dehydrogenase (hADH) and yeast alcohol dehydrogenase (yADH) as examples, we demonstrate that rich information can be obtained in a single native top-down MS experiment using Fourier transform ion cyclotron mass spectrometry (FTICR MS). Beyond measuring the molecular weights of the protein complexes, isotopic mass resolution was achieved for yeast ADH tetramer (147 kDa) with an average resolving power of 412,700 at m/z 5466 in absorption mode, and the mass reflects that each subunit binds to two zinc atoms. The N-terminal 89 amino acid residues were sequenced in a top-down electron capture dissociation (ECD) experiment, along with the identifications of the zinc binding site at Cys46 and a point mutation (V58T). With the combination of various activation/dissociation techniques, including ECD, in-source dissociation (ISD), collisionally activated dissociation (CAD), and infrared multiphoton dissociation (IRMPD), 40% of the yADH sequence was derived directly from the native tetramer complex. For hADH, native top-down ECD-MS shows that both E and S subunits are present in the hADH sample, with a relative ratio of 4:1. Native top-down ISD of the hADH dimer shows that each subunit (E and S chains) binds not only to two zinc atoms, but also the NAD/NADH ligand, with a higher NAD/NADH binding preference for the S chain relative to the E chain. In total, 32% sequence coverage was achieved for both E and S chains.

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…

Mass Spectrometry Analyses of Multicellular Tumor Spheroids.

PubMed

Acland, Mitchell; Mittal, Parul; Lokman, Noor A; Klingler-Hoffmann, Manuela; Oehler, Martin K; Hoffmann, Peter

2018-05-01

Multicellular tumor spheroids (MCTS) are a powerful biological in vitro model, which closely mimics the 3D structure of primary avascularized tumors. Mass spectrometry (MS) has established itself as a powerful analytical tool, not only to better understand and describe the complex structure of MCTS, but also to monitor their response to cancer therapeutics. The first part of this review focuses on traditional mass spectrometry approaches with an emphasis on elucidating the molecular characteristics of these structures. Then the mass spectrometry imaging (MSI) approaches used to obtain spatially defined information from MCTS is described. Finally the analysis of primary spheroids, such as those present in ovarian cancer, and the great potential that mass spectrometry analysis of these structures has for improved understanding of cancer progression and for personalized in vitro therapeutic testing is discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zero voltage mass spectrometry probes and systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooks, Robert Graham; Wleklinski, Michael Stanley; Bag, Soumabha

The invention generally relates to zero volt mass spectrometry probes and systems. In certain embodiments, the invention provides a system including a mass spectrometry probe including a porous material, and a mass spectrometer (bench-top or miniature mass spectrometer). The system operates without an application of voltage to the probe. In certain embodiments, the probe is oriented such that a distal end faces an inlet of the mass spectrometer. In other embodiments, the distal end of the probe is 5 mm or less from an inlet of the mass spectrometer.

Chromatography - mass spectrometry in aerospace industry

NASA Astrophysics Data System (ADS)

Buryak, A. K.; Serdyuk, T. M.

2013-01-01

The applications of chromatography - mass spectrometry in aerospace industry are considered. The primary attention is devoted to the development of physicochemical grounds of the use of various chromatography - mass spectrometry procedures to solve topical problems of this industry. Various methods for investigation of the composition of rocket fuels, surfaces of structural materials and environmental media affected by aerospace activities are compared. The application of chromatography - mass spectrometry for the development and evaluation of processes for decontaminations of equipment, industrial wastes and soils from rocket fuel components is substantiated. The bibliography includes 135 references.

Mass spectrometry for biomarker development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chaochao; Liu, Tao; Baker, Erin Shammel

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.

Characterization of non-polar aromatic hydrocarbons in crude oil using atmospheric pressure laser ionization and Fourier transform ion cyclotron resonance mass spectrometry (APLI FT-ICR MS).

PubMed

Schrader, Wolfgang; Panda, Saroj K; Brockmann, Klaus J; Benter, Thorsten

2008-07-01

We report on the successful application of the recently introduced atmospheric pressure laser ionization (APLI) method as a novel tool for the analysis of crude oil and its components. Using Fourier transform ion cyclotron resonance mass spectrometry, unambiguous determination of key compounds in this complex matrix with unprecedented sensitivity is presented.

Unbiased and targeted mass spectrometry for the HDL proteome.

PubMed

Singh, Sasha A; Aikawa, Masanori

2017-02-01

Mass spectrometry is an ever evolving technology that is equipped with a variety of tools for protein research. Some lipoprotein studies, especially those pertaining to HDL biology, have been exploiting the versatility of mass spectrometry to understand HDL function through its proteome. Despite the role of mass spectrometry in advancing research as a whole, however, the technology remains obscure to those without hands on experience, but still wishing to understand it. In this review, we walk the reader through the coevolution of common mass spectrometry workflows and HDL research, starting from the basic unbiased mass spectrometry methods used to profile the HDL proteome to the most recent targeted methods that have enabled an unprecedented view of HDL metabolism. Unbiased global proteomics have demonstrated that the HDL proteome is organized into subgroups across the HDL size fractions providing further evidence that HDL functional heterogeneity is in part governed by its varying protein constituents. Parallel reaction monitoring, a novel targeted mass spectrometry method, was used to monitor the metabolism of HDL apolipoproteins in humans and revealed that apolipoproteins contained within the same HDL size fraction exhibit diverse metabolic properties. Mass spectrometry provides a variety of tools and strategies to facilitate understanding, through its proteins, the complex biology of HDL.

Ambient ionization mass spectrometry imaging for characterizing plant-microbe interactions using liquid extraction surface analysis (LESA)

NASA Astrophysics Data System (ADS)

Chu, R. K.; Anderton, C.; Weston, D. J.; Carrell, A. A.; Paša-Tolić, L.; Veličković, D.; Tfaily, M.

2017-12-01

The rhizosphere consists of a diverse community of plants, bacteria and fungi that are interacting with each other and with complex soil matrix they occupy. By studying the chemical signaling and processes that occur within this dynamic microenvironment, we will further our understanding of the symbiotic and competitive interaction within microbial communities. Field studies and bulk analyses shed light on the mechanisms by which environmental perturbations alter carbon and nitrogen cycling, but what is less clear are the intra- and interspecies molecular transformations and transactions between the different constituents within the rhizosphere. Chemical imaging by liquid extraction surface analysis mass spectrometry (LESA-MS) is a highly sensitive technique capable of providing both spatial and molecular information. Here, we examined the chemical interactions among a tripartite system of peat moss (Sphagnum fallax), cyanobacteria (Nostoc muscorium), and fungus (Trizdiaspa). We coupled LESA source to both a 15 Tesla Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS), for ultrahigh mass resolution and mass accuracy results, and a Thermo Velos-LTQ mass spectrometer, for tandem MS of selected molecules to increase confidence in molecular identifications. With LESA-MS approach we spatially probed the tripartite interactions and isolated cultures using a coordinate system that can be mapped back and overlaid onto the original image. Using this method, we mapped an array of metabolic distributions within the model sphagnum microbiome. For instance, we identified carbendazim, an anti-fungal agent, distributed within the interaction zone between the bacteria and fungi, while glyceropcholine and sucrose were localized within the sphagnum and fungus interaction zone. Further analysis will look into larger metabolites, lipids, and small proteins.

Peptide Analysis Using Tandem Mass Spectrometry

DTIC Science & Technology

1989-06-01

to give pyroglutamic acid during storage, eliminating ammonia. It is almost absent in the spectrum of a freshly-prepared sample and is not seen in...USING TANDEM MASS SPECTROMETRY INTRODUCTION S The objective of the project was to determine the complete amino acid sequence of the large polypeptide...Ubiquitin by use of fast atom bombardment (FAB) ionization and tandem mass spectrometry. The peptide containing 76 amino acid residues was available

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.

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

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

DOE PAGES

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

2017-03-29

A successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Furthermore, problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development ofmore » pregnancy related problems at the molecular level. Here, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy relatedmore » problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

A successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Furthermore, problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development ofmore » pregnancy related problems at the molecular level. Here, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less

Cyclotron Phase-Coherent Ion Spatial Dispersion in a Non-Quadratic Trapping Potential is Responsible for FT-ICR MS at the Cyclotron Frequency

NASA Astrophysics Data System (ADS)

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

2018-01-01

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) at the cyclotron frequency instead of the reduced cyclotron frequency has been experimentally demonstrated using narrow aperture detection electrode (NADEL) ICR cells. Here, based on the results of SIMION simulations, we provide the initial mechanistic insights into the cyclotron frequency regime generation in FT-ICR MS. The reason for cyclotron frequency regime is found to be a new type of a collective motion of ions with a certain dispersion in the initial characteristics, such as pre-excitation ion velocities, in a highly non-quadratic trapping potential as realized in NADEL ICR cells. During ion detection, ions of the same m/z move in phase for cyclotron ion motion but out of phase for magnetron (drift) ion motion destroying signals at the fundamental and high order harmonics that comprise reduced cyclotron frequency components. After an initial magnetron motion period, ion clouds distribute into a novel type of structures - ion slabs, elliptical cylinders, or star-like structures. These structures rotate at the Larmor (half-cyclotron) frequency on a plane orthogonal to the magnetic field, inducing signals at the true cyclotron frequency on each of the narrow aperture detection electrodes. To eliminate the reduced cyclotron frequency peak upon dipolar ion detection, a number of slabs or elliptical cylinders organizing a star-like configuration are formed. In a NADEL ICR cell with quadrupolar ion detection, a single slab or an elliptical cylinder is sufficient to minimize the intensity of the reduced cyclotron frequency components, particularly the second harmonic. [Figure not available: see fulltext.

Unambiguous identification and discovery of bacterial siderophores by direct injection 21 Tesla Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Walker, Lawrence R; Tfaily, Malak M; Shaw, Jared B; Hess, Nancy J; Paša-Tolić, Ljiljana; Koppenaal, David W

2017-01-25

Under iron-limiting conditions, bacteria produce low molecular mass Fe(iii) binding molecules known as siderophores to sequester the Fe(iii), along with other elements, increasing their bioavailability. Siderophores are thought to influence iron cycling and biogeochemistry in both marine and terrestrial ecosystems and hence the need for rapid, confident characterization of these compounds has increased. In this study, the type of siderophores produced by two marine bacterial species, Synechococcus sp. PCC 7002 and Vibrio cyclitrophicus 1F53, were characterized by use of a newly developed 21 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR MS) with direct injection electrospray ionization. This technique allowed for the rapid detection of synechobactins from Synechococcus sp. PCC 7002 as well as amphibactins from Vibrio cyclitrophicus 1F53 based on high mass accuracy and resolution allowing for observation of specific Fe isotopes and isotopic fine structure enabling highly confident identification of these siderophores. When combined with molecular network analysis two new amphibactins were discovered and verified by tandem MS. These results show that high-field FTICR MS is a powerful technique that will greatly improve the ability to rapidly identify and discover metal binding species in the environment.

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

High precision mass measurements for wine metabolomics

PubMed Central

Roullier-Gall, Chloé; Witting, Michael; Gougeon, Régis D.; Schmitt-Kopplin, Philippe

2014-01-01

An overview of the critical steps for the non-targeted Ultra-High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-ToF-MS) analysis of wine chemistry is given, ranging from the study design, data preprocessing and statistical analyses, to markers identification. UPLC-Q-ToF-MS data was enhanced by the alignment of exact mass data from FTICR-MS, and marker peaks were identified using UPLC-Q-ToF-MS2. In combination with multivariate statistical tools and the annotation of peaks with metabolites from relevant databases, this analytical process provides a fine description of the chemical complexity of wines, as exemplified in the case of red (Pinot noir) and white (Chardonnay) wines from various geographic origins in Burgundy. PMID:25431760

High precision mass measurements for wine metabolomics

NASA Astrophysics Data System (ADS)

Roullier-Gall, Chloé; Witting, Michael; Gougeon, Régis; Schmitt-Kopplin, Philippe

2014-11-01

An overview of the critical steps for the non-targeted Ultra-High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-ToF-MS) analysis of wine chemistry is given, ranging from the study design, data preprocessing and statistical analyses, to markers identification. UPLC-Q-ToF-MS data was enhanced by the alignment of exact mass data from FTICR-MS, and marker peaks were identified using UPLC-Q-ToF-MS². In combination with multivariate statistical tools and the annotation of peaks with metabolites from relevant databases, this analytical process provides a fine description of the chemical complexity of wines, as exemplified in the case of red (Pinot noir) and white (Chardonnay) wines from various geographic origins in Burgundy.

Mass spectrometry in life science research.

PubMed

Lehr, Stefan; Markgraf, Daniel

2016-12-01

Investigating complex signatures of biomolecules by mass spectrometry approaches has become indispensable in molecular life science research. Nowadays, various mass spectrometry-based omics technologies are available to monitor qualitative and quantitative changes within hundreds or thousands of biological active components, including proteins/peptides, lipids and metabolites. These comprehensive investigations have the potential to decipher the pathophysiology of disease development at a molecular level and to monitor the individual response of pharmacological treatment or lifestyle intervention.

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

Mass spectrometry-based proteomics for translational research: a technical overview.

PubMed

Paulo, Joao A; Kadiyala, Vivek; Banks, Peter A; Steen, Hanno; Conwell, Darwin L

2012-03-01

Mass spectrometry-based investigation of clinical samples enables the high-throughput identification of protein biomarkers. We provide an overview of mass spectrometry-based proteomic techniques that are applicable to the investigation of clinical samples. We address sample collection, protein extraction and fractionation, mass spectrometry modalities, and quantitative proteomics. Finally, we examine the limitations and further potential of such technologies. Liquid chromatography fractionation coupled with tandem mass spectrometry is well suited to handle mixtures of hundreds or thousands of proteins. Mass spectrometry-based proteome elucidation can reveal potential biomarkers and aid in the development of hypotheses for downstream investigation of the molecular mechanisms of disease.

Mass Spectrometry-Based Proteomics for Translational Research: A Technical Overview

PubMed Central

Paulo, Joao A.; Kadiyala, Vivek; Banks, Peter A.; Steen, Hanno; Conwell, Darwin L.

2012-01-01

Mass spectrometry-based investigation of clinical samples enables the high-throughput identification of protein biomarkers. We provide an overview of mass spectrometry-based proteomic techniques that are applicable to the investigation of clinical samples. We address sample collection, protein extraction and fractionation, mass spectrometry modalities, and quantitative proteomics. Finally, we examine the limitations and further potential of such technologies. Liquid chromatography fractionation coupled with tandem mass spectrometry is well suited to handle mixtures of hundreds or thousands of proteins. Mass spectrometry-based proteome elucidation can reveal potential biomarkers and aid in the development of hypotheses for downstream investigation of the molecular mechanisms of disease. PMID:22461744

Crux: Rapid Open Source Protein Tandem Mass Spectrometry Analysis

PubMed Central

2015-01-01

Efficiently and accurately analyzing big protein tandem mass spectrometry data sets requires robust software that incorporates state-of-the-art computational, machine learning, and statistical methods. The Crux mass spectrometry analysis software toolkit (http://cruxtoolkit.sourceforge.net) is an open source project that aims to provide users with a cross-platform suite of analysis tools for interpreting protein mass spectrometry data. PMID:25182276

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.

Advances in Proteomics Data Analysis and Display Using an Accurate Mass and Time Tag Approach

PubMed Central

Zimmer, Jennifer S.D.; Monroe, Matthew E.; Qian, Wei-Jun; Smith, Richard D.

2007-01-01

Proteomics has recently demonstrated utility in understanding cellular processes on the molecular level as a component of systems biology approaches and for identifying potential biomarkers of various disease states. The large amount of data generated by utilizing high efficiency (e.g., chromatographic) separations coupled to high mass accuracy mass spectrometry for high-throughput proteomics analyses presents challenges related to data processing, analysis, and display. This review focuses on recent advances in nanoLC-FTICR-MS-based proteomics approaches and the accompanying data processing tools that have been developed to display and interpret the large volumes of data being produced. PMID:16429408

Developments in Plasma-Source Mass Spectrometry

DTIC Science & Technology

1988-07-11

Spectrometry 12 PERSONAL AUTHOR(S) Gary M. Hieftje and George H. Vickers 13a. TYPE OF REPORT b.TMCOEE . TEO POTYerMohay 5.AGCUN Technical FROM TO 11 July...4134006 TECHNICAL REPORT NO. 41 DEVELOPMENTS IN PLASMA-SOURCE MASS SPECTROMETRY by Gary M. Hieftje and George H. Vickers Acessoo i or * NTIS GRMX Prepared...G. M. Hieftje , and A. T. Zander, Spectrochim. Acta 1987, 42B, 29 60 Determination of Lead Isotope Ratios by Inductively Coupled Plasma-Mass

Fast neutral beam ion source coupled to a Fourier transform ion cyclotron resonance mass spectrometer

NASA Astrophysics Data System (ADS)

Hill, Nicholas C.; Limbach, Patrick A.; Shomo, Ronald E., II; Marshall, Alan G.; Appelhans, Anthony D.; Delmore, James E.

1991-11-01

The coupling of an autoneutralizing SF-6 fast ion-beam gun to a Fourier transform ion cyclotron resonance (FT/ICR) mass spectrometer is described. The fast neutral beam provides for secondary-ion-type FT/ICR mass analysis [e.g., production of abundant pseudomolecular (M+H)+ ions] of involatile samples without the need for external ion injection, since ions are formed at the entrance to the ICR ion trap. The design, construction, and testing of the hybrid instrument are described. The feasibility of the experiment (for both broadband and high-resolution FT/ICR positive-ion mass spectra) is demonstrated with tetra-butylammonium bromide and a Tylenol■ sample. The ability to analyze high molecular weight polymers with high mass resolution is demonstrated for Teflon■. All of the advantages of the fast neutral beam ion source previously demonstrated with quadrupole mass analysis are preserved, and the additional advantages of FT/ICR mass analysis (e.g., high mass resolving power, ion trapping) are retained.

[Imaging Mass Spectrometry in Histopathologic Analysis].

PubMed

Yamazaki, Fumiyoshi; Seto, Mitsutoshi

2015-04-01

Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

High resolution laser mass spectrometry bioimaging.

PubMed

Murray, Kermit K; Seneviratne, Chinthaka A; Ghorai, Suman

2016-07-15

Mass spectrometry imaging (MSI) was introduced more than five decades ago with secondary ion mass spectrometry (SIMS) and a decade later with laser desorption/ionization (LDI) mass spectrometry (MS). Large biomolecule imaging by matrix-assisted laser desorption/ionization (MALDI) was developed in the 1990s and ambient laser MS a decade ago. Although SIMS has been capable of imaging with a moderate mass range at sub-micrometer lateral resolution from its inception, laser MS requires additional effort to achieve a lateral resolution of 10μm or below which is required to image at the size scale of single mammalian cells. This review covers untargeted large biomolecule MSI using lasers for desorption/ionization or laser desorption and post-ionization. These methods include laser microprobe (LDI) MSI, MALDI MSI, laser ambient and atmospheric pressure MSI, and near-field laser ablation MS. Novel approaches to improving lateral resolution are discussed, including oversampling, beam shaping, transmission geometry, reflective and through-hole objectives, microscope mode, and near-field optics. Copyright © 2016 Elsevier Inc. All rights reserved.

ENVIRONMENTAL MASS SPECTROMETRY: EMERGING CONTAMINANTS AND CURRENT ISSUES

EPA Science Inventory

This review covers developments in environmental mass spectrometry over the period of 2000-2001. A few significant references that appeared between January and February 2002 are also included. The previous Environmental Mass Spectrometry review was very comprehensive, including...

Comprehensive analysis of oil sands processed water by direct-infusion Fourier-transform ion cyclotron resonance mass spectrometry with and without offline UHPLC sample prefractionation.

PubMed

Nyakas, Adrien; Han, Jun; Peru, Kerry M; Headley, John V; Borchers, Christoph H

2013-05-07

Oil sands processed water (OSPW) is the main byproduct of the large-scale bitumen extraction activity in the Athabasca oil sands region (Alberta, Canada). We have investigated the acid-extractable fraction (AEF) of OSPW by extraction-only (EO) direct infusion (DI) negative-ion mode electrospray ionization (ESI) on a 12T-Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS), as well as by offline ultrahigh performance liquid chromatography (UHPLC) followed by DI-FTICR-MS. A preliminary offline UHPLC separation into 8 fractions using a reversed-phase C4 column led to approximately twice as many detected peaks and identified compounds (973 peaks versus 2231 peaks, of which 856 and 1734 peaks, respectively, could be assigned to chemical formulas based on accurate mass measurements). Conversion of these masses to the Kendrick mass scale allowed the straightforward recognition of homologues. Naphthenic (CnH2n+zO2) and oxy-naphthenic (CnH2n+zOx) acids represented the largest group of molecules with assigned formulas (64%), followed by sulfur-containing compounds (23%) and nitrogen-containing compounds (8%). Pooling of corresponding fractions from two consecutive offline UHPLC runs prior to MS analysis resulted in ~50% more assignments than a single injection, resulting in 3-fold increase of identifications compared to EO-DI-FTICR-MS using the same volume of starting material. Liquid-liquid extraction followed by offline UHPLC fractionation thus holds enormous potential for a more comprehensive profiling of OSPW, which may provide a deeper understanding of its chemical nature and environmental impact.

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging.

PubMed

Burnum-Johnson, Kristin E; Baker, Erin S; Metz, Thomas O

2017-12-01

Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes. Copyright © 2017 IFPA, Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.

[Latest development in mass spectrometry for clinical application].

PubMed

Takino, Masahiko

2013-09-01

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen enormous growth in special clinical chemistry laboratories. It significantly increases the analytic potential in clinical chemistry, especially in the field of low molecular weight biomarker analysis. This review summarizes the state of the art in mass spectrometry and related techniques for clinical application with a main focus on recent developments in LC-MS. Current trends in ionization techniques, automated online sample preparation techniques coupled with LC-MS, and ion mobility spectrometry are discussed. Emerging mass spectrometric approaches complementary to LC-MS are discussed as well.

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

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.

Synthesis of model humic substances: a mechanistic study using controllable H/D exchange and Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Zherebker, Alexander Ya; Airapetyan, David; Konstantinov, Andrey I; Kostyukevich, Yury I; Kononikhin, Alexey S; Popov, Igor A; Zaitsev, Kirill V; Nikolaev, Eugene N; Perminova, Irina V

2015-07-07

The products of the oxidative coupling of phenols are frequently used as synthetic analogues to natural humic substances (HS) for biomedical research. However, their molecular compositions and exact structures remain largely unknown. The objective of this study was to develop a novel approach for the molecular-level analysis of phenolic polymerisates that is capable of inventorying molecular constituents and resolving their distinct structural formulas. For this purpose, we have synthesized the model HS using the oxidative coupling of a specifically designed phenylpropanoic monomer, 3-(4-hydroxy-3-methoxyphenyl)-3-oxopropionic acid, to hydroquinone. We have characterized the synthesized model HS using high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), (1)H NMR spectroscopy, and controllable hydrogen/deuterium (H/D) exchange. We succeeded in the molecular inventory of the model HS. The assigned molecular formulas occupied the substantial space of CHO compositions in the Van Krevelen diagram with a maximum density found in the regions of tannins and lignins, resembling those of natural HS. To identify the exact structural formulas of the individual constituents in the model HS, we have applied selective H/D exchange of non-labile backbone protons by a choice of basic or acidic catalytic conditions followed by FTICR MS. The determined formulas allowed us to verify the proposed pathways of hydroxylation and carboxylation in the course of the phenolic coupling and to identify the acetylation of aromatic rings as an important side reaction. We conclude that the proposed analytical approach may be used to identify the molecular carriers of biological activity within the phenolic polymerisates and eventually within natural HS.

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.

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

In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Switzar, Linda; Nicolardi, Simone; Rutten, Julie W.; Oberstein, Saskia A. J. Lesnik; Aartsma-Rus, Annemieke; van der Burgt, Yuri E. M.

2016-01-01

Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow. A key advantage of a LC-based strategy is the use of the retention time in identifying both intra- and interpeptide disulfide bonds. This is demonstrated by performing two sequential analyses of a certain protein digest, once without and once with electrochemical reduction. In this way, the "parent" disulfide-linked peptide detected in the first run has a retention time-based correlation with the EC-reduced peptides detected in the second run, thus simplifying disulfide bond mapping. Using this platform, both inter- and intra-disulfide-linked peptides were characterized in two different proteins, ß-lactoglobulin and ribonuclease B. In order to prevent disulfide reshuffling during the digestion process, proteins were digested at a relatively low pH, using (a combination of) the high specificity proteases trypsin and Glu-C. With this approach, disulfide bonds in ß-lactoglobulin and ribonuclease B were comprehensively identified and localized, showing that online LC-EC-MS is a useful tool for the characterization of protein disulfide bonds.

Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Si; Brown, Joseph N.; Tolic, Nikola

There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intactmore » N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.« less

Identification and Affinity-Quantification of ß-Amyloid and α-Synuclein Polypeptides Using On-Line SAW-Biosensor-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Slamnoiu, Stefan; Vlad, Camelia; Stumbaum, Mihaela; Moise, Adrian; Lindner, Kathrin; Engel, Nicole; Vilanova, Mar; Diaz, Mireia; Karreman, Christiaan; Leist, Marcel; Ciossek, Thomas; Hengerer, Bastian; Vilaseca, Marta; Przybylski, Michael

2014-08-01

Bioaffinity analysis using a variety of biosensors has become an established tool for detection and quantification of biomolecular interactions. Biosensors, however, are generally limited by the lack of chemical structure information of affinity-bound ligands. On-line bioaffinity-mass spectrometry using a surface-acoustic wave biosensor (SAW-MS) is a new combination providing the simultaneous affinity detection, quantification, and mass spectrometric structural characterization of ligands. We describe here an on-line SAW-MS combination for direct identification and affinity determination, using a new interface for MS of the affinity-isolated ligand eluate. Key element of the SAW-MS combination is a microfluidic interface that integrates affinity-isolation on a gold chip, in-situ sample concentration, and desalting with a microcolumn for MS of the ligand eluate from the biosensor. Suitable MS- acquisition software has been developed that provides coupling of the SAW-MS interface to a Bruker Daltonics ion trap-MS, FTICR-MS, and Waters Synapt-QTOF- MS systems. Applications are presented for mass spectrometric identifications and affinity (KD) determinations of the neurodegenerative polypeptides, ß-amyloid (Aß), and pathophysiological and physiological synucleins (α- and ß-synucleins), two key polypeptide systems for Alzheimer's disease and Parkinson's disease, respectively. Moreover, first in vivo applications of αSyn polypeptides from brain homogenate show the feasibility of on-line affinity-MS to the direct analysis of biological material. These results demonstrate on-line SAW-bioaffinity-MS as a powerful tool for structural and quantitative analysis of biopolymer interactions.

Sampling and analyte enrichment strategies for ambient mass spectrometry.

PubMed

Li, Xianjiang; Ma, Wen; Li, Hongmei; Ai, Wanpeng; Bai, Yu; Liu, Huwei

2018-01-01

Ambient mass spectrometry provides great convenience for fast screening, and has showed promising potential in analytical chemistry. However, its relatively low sensitivity seriously restricts its practical utility in trace compound analysis. In this review, we summarize the sampling and analyte enrichment strategies coupled with nine modes of representative ambient mass spectrometry (desorption electrospray ionization, paper vhspray ionization, wooden-tip spray ionization, probe electrospray ionization, coated blade spray ionization, direct analysis in real time, desorption corona beam ionization, dielectric barrier discharge ionization, and atmospheric-pressure solids analysis probe) that have dramatically increased the detection sensitivity. We believe that these advances will promote routine use of ambient mass spectrometry. Graphical abstract Scheme of sampling stretagies for ambient mass spectrometry.

Characterization of low molecular weight dissolved natural organic matter along the treatment trait of a waterworks using Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Zhang, Haifeng; Zhang, Yahe; Shi, Quan; Ren, Shuoyi; Yu, Jianwei; Ji, Feng; Luo, Wenbin; Yang, Min

2012-10-15

Dissolved natural organic matter (DOM), particularly the low molecular weight DOM, can affect the performance of water treatment processes and serve as a main precursor of disinfection by-products (DBPs) during chlorination. In this study, electrospray ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) was used to characterize the low molecular weight DOM along the treatment trait of a conventional drinking water treatment plant. The ESI FT-ICR MS data showed that various C, H, O-only class species were the major components in the source water. According to the van Krevelen diagram analysis, lignin- and tannin-like compounds were the most abundant components. Within an isobaric group, the DOM molecules with a high degree of oxidation (high O/C value) were preferentially removed during coagulation, while those with low degree of oxidation were found to be more reactive toward chlorine. In addition, 357 one-chlorine containing products and 199 two-chlorine containing products formed during chlorination were detected in the chlorination effluent sample at a high confidence level. The chlorinated products can be arranged into series, suggesting that they were originated from C, H, O-only precursor compounds, which were in series related by the replacement of CH(4) against oxygen. For the first time, this study explored the behavior of low molecular weight DOM along a drinking water treatment trait on the molecular level, and revealed the presence of abundant unknown chlorinated products, which are probably rich in carboxylic and phenolic groups, in drinking water. Copyright © 2012 Elsevier Ltd. All rights reserved.

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. Copyright © 2014. Published by Elsevier Ireland Ltd.

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

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.

Structural Characterization of a Thrombin-Aptamer Complex by High Resolution Native Top-Down Mass Spectrometry

NASA Astrophysics Data System (ADS)

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

2017-09-01

Native mass spectrometry (MS) with electrospray ionization (ESI) has evolved as an invaluable tool for the characterization of intact native proteins and non-covalently bound protein complexes. Here we report the structural characterization by high resolution native top-down MS of human thrombin and its complex with the Bock thrombin binding aptamer (TBA), a 15-nucleotide DNA with high specificity and affinity for thrombin. Accurate mass measurements revealed that the predominant form of native human α-thrombin contains a glycosylation mass of 2205 Da, corresponding to a sialylated symmetric biantennary oligosaccharide structure without fucosylation. Native MS showed that thrombin and TBA predominantly form a 1:1 complex under near physiological conditions (pH 6.8, 200 mM NH4OAc), but the binding stoichiometry is influenced by the solution ionic strength. In 20 mM ammonium acetate solution, up to two TBAs were bound to thrombin, whereas increasing the solution ionic strength destabilized the thrombin-TBA complex and 1 M NH4OAc nearly completely dissociated the complex. This observation is consistent with the mediation of thrombin-aptamer binding through electrostatic interactions and it is further consistent with the human thrombin structure that contains two anion binding sites on the surface. Electron capture dissociation (ECD) top-down MS of the thrombin-TBA complex performed with a high resolution 15 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer showed the primary binding site to be at exosite I located near the N-terminal sequence of the heavy chain, consistent with crystallographic data. High resolution native top-down MS is complementary to traditional structural biology methods for structurally characterizing native proteins and protein-DNA complexes. [Figure not available: see fulltext.

Unambiguous identification and discovery of bacterial siderophores by direct injection 21 Tesla Fourier transform ion cyclotron resonance mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, Lawrence R.; Tfaily, Malak M.; Shaw, Jared B.

Under iron-limiting conditions, bacteria produce low molecular mass Fe(III) binding molecules known as siderophores to sequester the Fe(III), along with other elements, increasing their bioavailibility. Siderophores are thought to influence iron cycling and biogeochemistry in both marine and terrestrial ecosystems and hence the need for rapid, confident characterization of these compounds has increased. In this study, the type of siderophores produced by two marine bacterial species, Synechococcus sp. PCC 7002 and Vibrio cyclitrophicus 1F53, were characterized using a newly developed 21T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR MS) with direct injection electrospray ionization. This technique allowed for themore » rapid detection of synechobactins from Synechococcus sp. PCC 7002 as well as amphibactins from Vibrio cyclitrophicus 1F53 based on high mass accuracy and resolution allowing for observation of specific Fe isotopic peaks and fine isotopic structure enables highly confident identification of these sideropohores. When combined with molecular network analysis two new amphibactins were discovered and verified by tandem MS. These results show that high-field FTICR MS is a powerful technique that will greatly improve the ability to rapidly identify and discover metal binding species in the environment.« less

Defining Putative Glycan Cancer Biomarkers by Mass Spectrometry

PubMed Central

Mechref, Yehia; Hu, Yunli; Garcia, Aldo; Hussein, Ahmed

2013-01-01

Summary For decades, the association between aberrant glycosylation and many types of cancers has been shown. However, defining the changes of glycan structures has not been demonstrated until recently. This has been facilitated by the major advances in mass spectrometry and separation science which allowed the detailed characterization of glycan changes associated with cancer. Mass spectrometry glycomics methods have been successfully employed to compare the glycomic profiles of different human specimen collected from disease-free individuals and patients with cancer. Additionally, comparing the glycomic profiles of glycoproteins purified from specimen collected from disease-free individuals and patients with cancer has also been performed. These types of glycan analyses employing mass spectrometry or liquid-chromatography mass spectrometry allowed the characterization of native, labeled, and permethylated glycans. This review discusses the different glycomic and glycoproteomic methods employed for defining glycans as cancer biomarkers of different organs, including breast, colon, esophagus, liver, lung, ovarian, pancreas and prostate. PMID:23157355

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.

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

21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Greatly Expands Mass Spectrometry Toolbox

NASA Astrophysics Data System (ADS)

Shaw, Jared B.; Lin, Tzu-Yung; Leach, Franklin E.; Tolmachev, Aleksey V.; Tolić, Nikola; Robinson, Errol W.; Koppenaal, David W.; Paša-Tolić, Ljiljana

2016-12-01

We provide the initial performance evaluation of a 21 Tesla Fourier transform ion cyclotron resonance mass spectrometer operating at the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory. The spectrometer constructed for the 21T system employs a commercial dual linear ion trap mass spectrometer coupled to a FTICR spectrometer designed and built in-house. Performance gains from moving to higher magnetic field strength are exemplified by the measurement of peptide isotopic fine structure, complex natural organic matter mixtures, and large proteins. Accurate determination of isotopic fine structure was demonstrated for doubly charged Substance P with minimal spectral averaging, and 8158 molecular formulas assigned to Suwannee River Fulvic Acid standard with root-mean-square (RMS) error of 10 ppb. We also demonstrated superior performance for intact proteins; namely, broadband isotopic resolution of the entire charge state distribution of apo-transferrin (78 kDa) and facile isotopic resolution of monoclonal antibody under a variety of acquisition parameters (e.g., 6 s time-domains with absorption mode processing yielded resolution of approximately 1 M at m/z = 2700).

21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer Greatly Expands Mass Spectrometry Toolbox

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaw, Jared B.; Lin, Tzu-Yung; Leach, Franklin E.

We provide the initial performance evaluation of a 21 Tesla Fourier transform ion cyclotron resonance mass spectrometer operating at the Environmental Molecular Sciences Laboratory at Pacific Northwest National Laboratory. The spectrometer constructed for the 21T system employs a commercial dual linear ion trap mass spectrometer coupled to a FTICR spectrometer designed and built in-house. Performance gains from moving to higher magnetic field strength are exemplified by the measurement of peptide isotopic fine structure, complex natural organic matter mixtures, and large proteins. Accurate determination of isotopic fine structure was demonstrated for doubly charged substance P with minimal spectral averaging, and 8,158more » molecular formulas assigned to Suwannee River Fulvic Acid standard with RMS error of 10 ppb. We also demonstrated superior performance for intact proteins; namely, broadband isotopic resolution of the entire charge state distribution of apotransferrin (78 kDa) and facile isotopic resolution of monoclonal antibody under a variety of acquisition parameters (e.g. 6 s time-domains with absorption mode processing yielded resolution of approximately 1M at m/z =2,700).« less

Insights into the Binding Sites of Organometallic Ruthenium Anticancer Compounds on Peptides Using Ultra-High Resolution Mass Spectrometry

NASA Astrophysics Data System (ADS)

Wills, Rebecca H.; Habtemariam, Abraha; Lopez-Clavijo, Andrea F.; Barrow, Mark P.; Sadler, Peter J.; O'Connor, Peter B.

2014-04-01

The binding sites of two ruthenium(II) organometallic complexes of the form [(η6-arene)Ru( N, N)Cl]+, where arene/ N, N = biphenyl (bip)/bipyridine (bipy) for complex AH076, and biphenyl (bip)/ o-phenylenediamine ( o-pda) for complex AH078, on the peptides angiotensin and bombesin have been investigated using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Fragmentation was performed using collisionally activated dissociation (CAD), with, in some cases, additional data being provided by electron capture dissociation (ECD). The primary binding sites were identified as methionine and histidine, with further coordination to phenylalanine, potentially through a π-stacking interaction, which has been observed here for the first time. This initial peptide study was expanded to investigate protein binding through reaction with insulin, on which the binding sites proposed are histidine, glutamic acid, and tyrosine. Further reaction of the ruthenium complexes with the oxidized B chain of insulin, in which two cysteine residues are oxidized to cysteine sulfonic acid (Cys-SO3H), and glutathione, which had been oxidized with hydrogen peroxide to convert the cysteine to cysteine sulfonic acid, provided further support for histidine and glutamic acid binding, respectively.

Polar Aprotic Modifiers for Chromatographic Separation and Back-Exchange Reduction for Protein Hydrogen/Deuterium Exchange Monitored by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

NASA Astrophysics Data System (ADS)

Valeja, Santosh G.; Emmett, Mark R.; Marshall, Alan G.

2012-04-01

Hydrogen/deuterium exchange monitored by mass spectrometry is an important non-perturbing tool to study protein structure and protein-protein interactions. However, water in the reversed-phase liquid chromatography mobile phase leads to back-exchange of D for H during chromatographic separation of proteolytic peptides following H/D exchange, resulting in incorrect identification of fast-exchanging hydrogens as unexchanged hydrogens. Previously, fast high-performance liquid chromatography (HPLC) and supercritical fluid chromatography have been shown to decrease back-exchange. Here, we show that replacement of up to 40% of the water in the LC mobile phase by the modifiers, dimethylformamide (DMF) and N-methylpyrrolidone (NMP) (i.e., polar organic modifiers that lack rapid exchanging hydrogens), significantly reduces back-exchange. On-line LC micro-ESI FT-ICR MS resolves overlapped proteolytic peptide isotopic distributions, allowing for quantitative determination of the extent of back-exchange. The DMF modified solvent composition also improves chromatographic separation while reducing back-exchange relative to conventional solvent.

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

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

MEASURING OF PROTEIN SYNTHESIS USING METABOLIC 2H-LABELING, HIGH-RESOLUTION MASS SPECTROMETRY AND AN ALGORITHM

PubMed Central

Kasumov, Takhar; Ilchenko, Sergey; Li, Ling; Rachdaoui, Nadia; Sadigov, Rovshan; Willard, Belinda; McCullough, Arthur J.; Previs, Stephen

2013-01-01

We recently developed a method for estimating protin dynamics in vivo with 2H2O using MALDI-TOF MS (Rachdaoui N. et al., MCP, 8, 2653-2662, 2009) and we confirmed that 2H-labeling of many hepatic free amino acids rapidly equilibrated with body water. Although this is a reliable method, it required modest sample purification and necessitated the determination of tissue-specific amino acid labeling. Another approach for quantifying protein kinetics is to measure the 2H-enrichments of body water (precursor) and protein-bound amino acid or proteolytic peptide (product) and to estimate how many copies of deuterium are incorporated into a product. In this study we have used nanospray LTQ-FTICR mass spectrometry to simultaneously measure the isotopic enrichment of peptides and protein-bound amino acids. A mathematical algorithm was developed to aid the data processing. The most notable improvement centers on the fact that the precursor:product labeling ratio can be obtained by measuring the labeling of water and a protein(s) (or peptides) of interest, therein minimizing the need to measure the amino acid labeling. As a proof of principle, we demonstrate that this approach can detect the effect of nutritional status on albumin synthesis in rats given 2H2O. PMID:21256107

Proteomic Mass Spectrometry Imaging for Skin Cancer Diagnosis.

PubMed

Lazova, Rossitza; Seeley, Erin H

2017-10-01

Mass spectrometry imaging can be successfully used for skin cancer diagnosis, particularly for the diagnosis of challenging melanocytic lesions. This method analyzes proteins within benign and malignant melanocytic tumor cells and, based on their differences, which constitute a unique molecular signature of 5 to 20 proteins, can render a diagnosis of benign nevus versus malignant melanoma. Mass spectrometry imaging may assist in the differentiation between metastases and nevi as well as between proliferative nodules in nevi and melanoma arising in a nevus. In the difficult area of atypical Spitzoid neoplasms, mass spectrometry diagnosis can predict clinical outcome better than histopathology. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Quantitative thin-layer chromatography/mass spectrometry analysis of caffeine using a surface sampling probe electrospray ionization tandem mass spectrometry system.

PubMed

Ford, Michael J; Deibel, Michael A; Tomkins, Bruce A; Van Berkel, Gary J

2005-07-15

Quantitative determination of caffeine on reversed-phase C8 thin-layer chromatography plates using a surface sampling electrospray ionization system with tandem mass spectrometry detection is reported. The thin-layer chromatography/electrospray tandem mass spectrometry method employed a deuterium-labeled caffeine internal standard and selected reaction monitoring detection. Up to nine parallel caffeine bands on a single plate were sampled in a single surface scanning experiment requiring 35 min at a surface scan rate of 44 mum/s. A reversed-phase HPLC/UV caffeine assay was developed in parallel to assess the mass spectrometry method performance. Limits of detection for the HPLC/UV and thin-layer chromatography/electrospray tandem mass spectrometry methods determined from the calibration curve statistics were 0.20 ng injected (0.50 muL) and 1.0 ng spotted on the plate, respectively. Spike recoveries with standards and real samples ranged between 97 and 106% for both methods. The caffeine content of three diet soft drinks (Diet Coke, Diet Cherry Coke, Diet Pepsi) and three diet sport drinks (Diet Turbo Tea, Speed Stack Grape, Speed Stack Fruit Punch) was measured. The HPLC/UV and mass spectrometry determinations were in general agreement, and these values were consistent with the quoted values for two of the three diet colas. In the case of Diet Cherry Coke and the diet sports drinks, the determined caffeine amounts using both methods were consistently higher (by approximately 8% or more) than the literature values.

Quantitative Thin-Layer Chromatography/Mass Spectrometry Analysis of Caffeine Using a Surface Sampling Probe Electrospray Ionization Tandem Mass Spectrometry System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, Michael J; Deibel, Michael A.; Tomkins, Bruce A

Quantitative determination of caffeine on reversed-phase C8 thin-layer chromatography plates using a surface sampling electrospray ionization system with tandem mass spectrometry detection is reported. The thin-layer chromatography/electrospray tandem mass spectrometry method employed a deuterium-labeled caffeine internal standard and selected reaction monitoring detection. Up to nine parallel caffeine bands on a single plate were sampled in a single surface scanning experiment requiring 35 min at a surface scan rate of 44 {mu}m/s. A reversed-phase HPLC/UV caffeine assay was developed in parallel to assess the mass spectrometry method performance. Limits of detection for the HPLC/UV and thin-layer chromatography/electrospray tandem mass spectrometry methodsmore » determined from the calibration curve statistics were 0.20 ng injected (0.50 {mu}L) and 1.0 ng spotted on the plate, respectively. Spike recoveries with standards and real samples ranged between 97 and 106% for both methods. The caffeine content of three diet soft drinks (Diet Coke, Diet Cherry Coke, Diet Pepsi) and three diet sport drinks (Diet Turbo Tea, Speed Stack Grape, Speed Stack Fruit Punch) was measured. The HPLC/UV and mass spectrometry determinations were in general agreement, and these values were consistent with the quoted values for two of the three diet colas. In the case of Diet Cherry Coke and the diet sports drinks, the determined caffeine amounts using both methods were consistently higher (by 8% or more) than the literature values.« less

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.

Guideline on Isotope Dilution Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaffney, Amy

Isotope dilution mass spectrometry is used to determine the concentration of an element of interest in a bulk sample. It is a destructive analysis technique that is applicable to a wide range of analytes and bulk sample types. With this method, a known amount of a rare isotope, or ‘spike’, of the element of interest is added to a known amount of sample. The element of interest is chemically purified from the bulk sample, the isotope ratio of the spiked sample is measured by mass spectrometry, and the concentration of the element of interest is calculated from this result. Thismore » method is widely used, although a mass spectrometer required for this analysis may be fairly expensive.« less

Environmental applications for the analysis of chlorinated dibenzo-p-dioxins and dibenzofurans using mass spectrometry/mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiner, E.J.; Schellenberg, D.H.; Taguchi, V.Y.

1991-01-01

A mass spectrometry/mass spectrometry-multiple reaction monitoring (MS/MS-MRM) technique for the analysis of all tetra- through octachlorinated dibenzo-p-dioxins (Cl{sub x}DD, x = 4-8) and dibenzofurans (Cl{sub x}DF, x = 4-8) has been developed at the Ministry of the Environment (MOE) utilizing a triple quadrupole mass spectrometer. Optimization of instrumental parameters using the analyte of interest in a direct insertion probe (DIP) resulted in sensitivities approaching those obtainable by high-resolution mass spectrometric (HRMS) methods. All congeners of dioxins and furans were detected in the femtogram range. Results on selected samples indicated that for some matrices, fewer chemical interferences were observed by MS/MSmore » than by HRMS. The technique used to optimize the instrument for chlorinated dibenzo-p-dioxins (CDDs) and chlorinated dibenzofurans (CDFs) analysis is adaptable to other analytes.« less

Recent applications of gas chromatography with high-resolution mass spectrometry.

PubMed

Špánik, Ivan; Machyňáková, Andrea

2018-01-01

Gas chromatography coupled to high-resolution mass spectrometry is a powerful analytical method that combines excellent separation power of gas chromatography with improved identification based on an accurate mass measurement. These features designate gas chromatography with high-resolution mass spectrometry as the first choice for identification and structure elucidation of unknown volatile and semi-volatile organic compounds. Gas chromatography with high-resolution mass spectrometry quantitative analyses was previously focused on the determination of dioxins and related compounds using magnetic sector type analyzers, a standing requirement of many international standards. The introduction of a quadrupole high-resolution time-of-flight mass analyzer broadened interest in this method and novel applications were developed, especially for multi-target screening purposes. This review is focused on the development and the most interesting applications of gas chromatography coupled to high-resolution mass spectrometry towards analysis of environmental matrices, biological fluids, and food safety since 2010. The main attention is paid to various approaches and applications of gas chromatography coupled to high-resolution mass spectrometry for non-target screening to identify contaminants and to characterize the chemical composition of environmental, food, and biological samples. The most interesting quantitative applications, where a significant contribution of gas chromatography with high-resolution mass spectrometry over the currently used methods is expected, will be discussed as well. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mass spectrometry imaging under ambient conditions.

PubMed

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

2013-01-01

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 for example 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 on 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

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

MPAI (mass probes aided ionization) method for total analysis of biomolecules by mass spectrometry.

PubMed

Honda, Aki; Hayashi, Shinichiro; Hifumi, Hiroki; Honma, Yuya; Tanji, Noriyuki; Iwasawa, Naoko; Suzuki, Yoshio; Suzuki, Koji

2007-01-01

We have designed and synthesized various mass probes, which enable us to effectively ionize various molecules to be detected with mass spectrometry. We call the ionization method using mass probes the "MPAI (mass probes aided ionization)" method. We aim at the sensitive detection of various biological molecules, and also the detection of bio-molecules by a single mass spectrometry serially without changing the mechanical settings. Here, we review mass probes for small molecules with various functional groups and mass probes for proteins. Further, we introduce newly developed mass probes for proteins for highly sensitive detection.

Chemometrics comparison of gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry Daphnia magna metabolic profiles exposed to salinity.

PubMed

Parastar, Hadi; Garreta-Lara, Elba; Campos, Bruno; Barata, Carlos; Lacorte, Silvia; Tauler, Roma

2018-06-01

The performances of gas chromatography with mass spectrometry and of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry are examined through the comparison of Daphnia magna metabolic profiles. Gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with mass spectrometry were used to compare the concentration changes of metabolites under saline conditions. In this regard, a chemometric strategy based on wavelet compression and multivariate curve resolution-alternating least squares is used to compare the performances of gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry for the untargeted metabolic profiling of Daphnia magna in control and salinity-exposed samples. Examination of the results confirmed the outperformance of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry over gas chromatography with mass spectrometry for the detection of metabolites in D. magna samples. The peak areas of multivariate curve resolution-alternating least squares resolved elution profiles in every sample analyzed by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry were arranged in a new data matrix that was then modeled by partial least squares discriminant analysis. The control and salt-exposed daphnids samples were discriminated and the most relevant metabolites were estimated using variable importance in projection and selectivity ratio values. Salinity de-regulated 18 metabolites from metabolic pathways involved in protein translation, transmembrane cell transport, carbon metabolism, secondary metabolism, glycolysis, and osmoregulation. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Advances in mass spectrometry-based approaches for neuropeptide analysis].

PubMed

Ji, Qianyue; Ma, Min; Peng, Xin; Jia, Chenxi; Ji, Qianyue

2017-07-25

Neuropeptides are an important class of endogenous bioactive substances involved in the function of the nervous system, and connect the brain and other neural and peripheral organs. Mass spectrometry-based neuropeptidomics are designed to study neuropeptides in a large-scale manner and obtain important molecular information to further understand the mechanism of nervous system regulation and the pathogenesis of neurological diseases. This review summarizes the basic strategies for the study of neuropeptides using mass spectrometry, including sample preparation and processing, qualitative and quantitative methods, and mass spectrometry imagining.

Improved ion optics for introduction of ions into a 9.4-T Fourier transform ion cyclotron resonance mass spectrometer

DOE PAGES

Chen, Yu; Leach, Franklin E.; Kaiser, Nathan K.; ...

2015-01-19

Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry provides unparalleled mass accuracy and resolving power.[1],[2] With electrospray ionization (ESI), ions are typically transferred into the mass spectrometer through a skimmer, which serves as a conductance-limiting orifice. However, the skimmer allows only a small fraction of incoming ions to enter the mass spectrometer. An ion funnel, originally developed by Smith and coworkers at Pacific Northwest National Laboratory (PNNL)[3-5] provides much more efficient ion focusing and transfer. The large entrance aperture of the ion funnel allows almost all ions emanating from a heated capillary to be efficiently captured and transferred, resulting inmore » nearly lossless transmission.« less

Identification of Fatty Acids, Phospholipids, and Their Oxidation Products Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry and Electrospray Ionization Mass Spectrometry

ERIC Educational Resources Information Center

Harmon, Christopher W.; Mang, Stephen A.; Greaves, John; Finlayson-Pitts, Barbara J.

2010-01-01

Electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) have found increasing application in the analysis of biological samples. Using these techniques to solve problems in analytical chemistry should be an essential component of the training of undergraduate chemists. We…

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. © 2015 American Association for Clinical Chemistry.

Recent developments in atmospheric pressure photoionization-mass spectrometry.

PubMed

Kauppila, Tiina J; Syage, Jack A; Benter, Thorsten

2017-05-01

Recent developments in atmospheric pressure photoionization (APPI), which is one of the three most important ionization techniques in liquid chromatography-mass spectrometry, are reviewed. The emphasis is on the practical aspects of APPI analysis, its combination with different separation techniques, novel instrumental developments - especially in gas chromatography and ambient mass spectrometry - and the applications that have appeared in 2009-2014. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:423-449, 2017. © 2015 Wiley Periodicals, Inc.

Molecular Characterization of Thiols in Fossil Fuels by Michael Addition Reaction Derivatization and Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

PubMed

Wang, Meng; Zhao, Suoqi; Liu, Xuxia; Shi, Quan

2016-10-04

Thiols widely occur in sediments and fossil fuels. However, the molecular composition of these compounds is unclear due to the lack of appropriate analytical methods. In this work, a characterization method for thiols in fossil fuels was developed on the basis of Michael addition reaction derivatization followed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). Model thiol compound studies showed that thiols were selectively reacted with phenylvinylsulfone and transformed to sulfones with greater than 98% conversions. This method was applied to a coker naphtha, light and heavy gas oils, and crude oils from various geological sources. The results showed that long alkyl chain thiols are readily present in petroleum, which have up to 30 carbon atoms. Large DBE dispersity of thiols indicates that naphthenic and aromatic thiols are also present in the petroleum. This method is capable of detecting thiol compounds in the part per million range by weight. This method allows characterization of thiols in a complex hydrocarbon matrix, which is complementary to the comprehensive analysis of sulfur compounds in fossil fuels.

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

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'.

Sequencing Cyclic Peptides by Multistage Mass Spectrometry

PubMed Central

Mohimani, Hosein; Yang, Yu-Liang; Liu, Wei-Ting; Hsieh, Pei-Wen; Dorrestein, Pieter C.; Pevzner, Pavel A.

2012-01-01

Some of the most effective antibiotics (e.g., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of mass spectrometry based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage mass spectrometry, and show its advantages over single stage mass spectrometry. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. PMID:21751357

"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.

Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top-Down Mass Spectrometry

NASA Astrophysics Data System (ADS)

Lin, Ziqing; Guo, Fang; Gregorich, Zachery R.; Sun, Ruixiang; Zhang, Han; Hu, Yang; Shanmuganayagam, Dhanansayan; Ge, Ying

2018-04-01

Cardiac troponin T (cTnT) regulates the Ca2+-mediated interaction between myosin thick filaments and actin thin filaments during cardiac contraction and relaxation. cTnT is released into the blood following injury, and increased serum levels of the protein are used clinically as a biomarker for myocardial infarction. Moreover, mutations in cTnT are causative in a number of familial cardiomyopathies. With the increasing use of large animal (swine) model to recapitulate human diseases, it is essential to characterize species-dependent protein sequence variants, alternative RNA splicing, and post-translational modifications (PTMs), but challenges remain due to the incomplete database and lack of validation of the predicted splicing isoforms. Herein, we integrated top-down mass spectrometry (MS) with online liquid chromatography (LC) and immunoaffinity purification to comprehensively characterize miniature swine cTnT proteoforms, including those arising from alternative RNA splicing and PTMs. A total of seven alternative splicing isoforms of cTnT were identified by LC/MS from swine left ventricular tissue, with each isoform containing un-phosphorylated and mono-phosphorylated proteoforms. The phosphorylation site was localized to Ser1 for the mono-phosphorylated proteoforms of cTnT1, 3, 4, and 6 by online MS/MS combining collisionally activated dissociation (CAD) and electron transfer dissociation (ETD). Offline MS/MS on Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer with CAD and electron capture dissociation (ECD) was then utilized to achieve deep sequencing of mono-phosphorylated cTnT1 (35.2 kDa) with a high sequence coverage of 87%. Taken together, this study demonstrated the unique advantage of top-down MS in the comprehensive characterization of protein alternative splicing isoforms together with PTMs. [Figure not available: see fulltext.

Mass spectrometry in systems biology an introduction.

PubMed

Dunn, Warwick B

2011-01-01

The qualitative detection, quantification, and structural characterization of analytes in biological systems are important requirements for objectives to be fulfilled in systems biology research. One analytical tool applied to a multitude of systems biology studies is mass spectrometry, particularly for the study of proteins and metabolites. Here, the role of mass spectrometry in systems biology will be assessed, the advantages and disadvantages discussed, and the instrument configurations available described. Finally, general applications will be briefly reviewed. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of stereotactic mass spectrometry for brain tumor surgery.

PubMed

Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

2011-02-01

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of

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

Ambient Mass Spectrometry in Cancer Research.

PubMed

Takats, Z; Strittmatter, N; McKenzie, J S

2017-01-01

Ambient ionization mass spectrometry was developed as a sample preparation-free alternative to traditional MS-based workflows. Desorption electrospray ionization (DESI)-MS methods were demonstrated to allow the direct analysis of a broad range of samples including unaltered biological tissue specimens. In contrast to this advantageous feature, nowadays DESI-MS is almost exclusively used for sample preparation intensive mass spectrometric imaging (MSI) in the area of cancer research. As an alternative to MALDI, DESI-MSI offers matrix deposition-free experiment with improved signal in the lower (<500m/z) range. DESI-MSI enables the spatial mapping of tumor metabolism and has been broadly demonstrated to offer an alternative to frozen section histology for intraoperative tissue identification and surgical margin assessment. Rapid evaporative ionization mass spectrometry (REIMS) was developed exclusively for the latter purpose by the direct combination of electrosurgical devices and mass spectrometry. In case of the REIMS technology, aerosol particles produced by electrosurgical dissection are subjected to MS analysis, providing spectral information on the structural lipid composition of tissues. REIMS technology was demonstrated to give real-time information on the histological nature of tissues being dissected, deeming it an ideal tool for intraoperative tissue identification including surgical margin control. More recently, the method has also been used for the rapid lipidomic phenotyping of cancer cell lines as it was demonstrated in case of the NCI-60 cell line collection. © 2017 Elsevier Inc. All rights reserved.

Molecular characterization of lake sediment WEON by Fourier transform ion cyclotron resonance mass spectrometry and its environmental implications.

PubMed

Zhang, Li; Wang, Shengrui; Xu, Yisheng; Shi, Quan; Zhao, Haichao; Jiang, Bin; Yang, Jiachun

2016-12-01

The compositional properties of water-extractable organic nitrogen (WEON) affect its behavior in lake ecosystems. This work is the first comprehensive study using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for the characterization of the molecular composition of WEON in lake sediment. In sediments of Erhai Lake in China, this study found complex WEON species, with N-containing compounds in the northern, central, and southern regions contributing 34.47%, 42.44%, and 40.6%, respectively, of total compounds. Additionally, a van Krevelen diagram revealed that lignin components were dominant in sediment WEON structures (68% of the total), suggesting terrestrial sources. Furthermore, this study applied ESI-FT-ICR-MS to the examination of the environmental processes of lake sediment WEON on a molecular level. The results indicated that sediment depth impacted WEON composition and geochemical processes. Compared with other ecosystems, the double bond equivalent (DBE) value was apparently lower in Erhai sediment, indicating the presence of relatively fewer and smaller aromatic compounds. In addition, the presence of a large number of N-containing species and abundant oxidized nitrogen functional compounds that were likely to biodegrade may have further increased the potential releasing risk of WEON from Erhai sediment under certain environmental conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Observation of CO2 and solvent adduct ions during negative mode electrospray ionization Fourier transform ion cyclotron resonance mass spectrometric analysis of monohydric alcohols.

PubMed

Zhou, Xibin; Zhang, Yahe; Zhao, Suoqi; Hsu, Chang Samuel; Shi, Quan

2013-12-15

Monohydric alcohols are common in natural products, bio-oils, and medicine. We have found that monohydric alcohols can form O3 (ions containing three oxygen atoms) and O4 adduct ions in negative electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), which would significantly affect the composition analysis of alcohols, especially in a complex mixture. It is necessary to study the reaction pathways and the method to eliminate or reduce the 'artifact' adducts. Octadecanol, cholesterol, squalanol and two complex monohydric alcohol mixtures were selected as model compounds. These samples were subjected to negative ion ESI FT-ICR MS analysis. The composition and formation mechanism of adducts were studied by the ultrahigh-resolution accurate mass measurement for elemental composition, along with the MS(2) isolation and collision-induced dissociation (CID) experiments for structural determination. The reaction pathway of O3 adduct formation is the coupling of a monohydric alcohol ion with a CO2 to form a stable O3 ionic species by likely a covalent bond (source of CO2 is not clear). The O4 species are formed by O3 ionic species adducted with an alcohol molecule of the solvent, such as methanol or ethanol, by likely a hydrogen bond. These adduct ions could be eliminated or reduced by increasing collision energy. However, excessive collision energy would fragment monohydric alcohol ions. The formation mechanisms of O3 and O4 adducts from monohydric alcohols in negative ion ESI FT-ICR MS were proposed. The solvent adduction effects can be eliminated or reduced by optimizing the collision energy of CID in FT-ICR MS. Copyright © 2013 John Wiley & Sons, Ltd.

Determination of soyasaponins in Fagioli di Sarconi beans (Phaseolus vulgaris L.) by LC-ESI-FTICR-MS and evaluation of their hypoglycemic activity.

PubMed

Bianco, Giuliana; Pascale, Raffaella; Carbone, Cecilia F; Acquavia, Maria A; Cataldi, Tommaso R I; Schmitt-Kopplin, Philippe; Buchicchio, Alessandro; Russo, Daniela; Milella, Luigi

2018-02-01

Soyasaponins are oleanene-type triterpenoid saponins, naturally occurring in many edible plants that have attracted a great deal of attention for their role in preventing chronic diseases. The aim of this study was to establish the distribution and the content of soyasaponins in 21 ecotypes of Fagioli di Sarconi beans (Phaseolus vulgaris, Leguminosae). High-performance reversed-phase liquid chromatography (RPLC) with positive electrospray ionization (ESI(+)) and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) in conjunction with infrared multiphoton dissociation (IRMPD) was applied for the unambiguous identification of soyasaponins Ba (m/z 959.5213, [C 48 H 79 O 19 ] + ), Bb (m/z 943.5273, [C 48 H 79 O 18 ] + ), Bd (m/z 957.5122, [C 48 H 77 O 19 ] + ), and Be (m/z 941.5166, [C 48 H 77 O 18 ] + ), which are the only commercially available reference standards. In addition, the several diagnostic product ions generated by IRMPD in the ICR-MS cell allowed us the putative identification of soyasaponins Bb' (m/z 797.4680, [C 42 H 69 O 14 ] + ), αg (m/z 1085.5544, [C 54 H 85 O 22 ] + ), βg (m/z 1069.5600, [C 54 H 85 O 21 ] + ), and γg (m/z 923.5009, [C 48 H 75 O 17 ] + ), establishing thus their membership in the soyasaponin group. Quantitative and semiquantitative analysis of identified soyasaponins were also performed by RPLC-ESI(+) FTICR-MS; the total concentration levels were found ranging from 83.6 ± 9.3 to 767 ± 37 mg/kg. In vitro hypoglycemic outcomes of four soyasaponin standards were evaluated; significant inhibitory activities were obtained with IC 50 values ranging from 1.5 ± 0.1 to 2.3 ± 0.2 μg/mL and 12.0 ± 1.1 to 29.4 ± 1.4 μg/mL for α-glucosidase and α-amylase, respectively. This study represents the first detailed investigation on the antidiabetic activity of bioactive constituents found in Fagioli di Sarconi beans. Graphical abstract The first detailed RPLC-ESI(+) FTICR-MS investigation of

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

The expanding role of mass spectrometry in the field of vaccine development.

PubMed

Sharma, Vaneet Kumar; Sharma, Ity; Glick, James

2018-05-31

Biological mass spectrometry has evolved as a core analytical technology in the last decade mainly because of its unparalleled ability to perform qualitative as well as quantitative profiling of enormously complex biological samples with high mass accuracy, sensitivity, selectivity and specificity. Mass spectrometry-based techniques are also routinely used to assess glycosylation and other post-translational modifications, disulfide bond linkage, and scrambling as well as for the detection of host cell protein contaminants in the field of biopharmaceuticals. The role of mass spectrometry in vaccine development has been very limited but is now expanding as the landscape of global vaccine development is shifting towards the development of recombinant vaccines. In this review, the role of mass spectrometry in vaccine development is presented, some of the ongoing efforts to develop vaccines for diseases with global unmet medical need are discussed and the regulatory challenges of implementing mass spectrometry techniques in a quality control laboratory setting are highlighted. © 2018 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc.

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

May the Best Molecule Win: Competition ESI Mass Spectrometry

PubMed Central

Laughlin, Sarah; Wilson, W. David

2015-01-01

Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor groove binding molecules. Such an approach acts as a high-throughput screening method to determine important information including the stoichiometry, binding mode, cooperativity, and relative binding affinity. In addition to small molecule-DNA complexes, we highlight other applications in which competition mass spectrometry has been used. A competitive approach to simultaneously investigate complex interactions promises to be a powerful tool in the discovery of small molecule inhibitors with high specificity and for specific, important DNA sequences. PMID:26501262

Diagnosis of gastroenterological diseases by metabolome analysis using gas chromatography-mass spectrometry.

PubMed

Yoshida, Masaru; Hatano, Naoya; Nishiumi, Shin; Irino, Yasuhiro; Izumi, Yoshihiro; Takenawa, Tadaomi; Azuma, Takeshi

2012-01-01

Recently, metabolome analysis has been increasingly applied to biomarker detection and disease diagnosis in medical studies. Metabolome analysis is a strategy for studying the characteristics and interactions of low molecular weight metabolites under a specific set of conditions and is performed using mass spectrometry and nuclear magnetic resonance spectroscopy. There is a strong possibility that changes in metabolite levels reflect the functional status of a cell because alterations in their levels occur downstream of DNA, RNA, and protein. Therefore, the metabolite profile of a cell is more likely to represent the current status of a cell than DNA, RNA, or protein. Thus, owing to the rapid development of mass spectrometry analytical techniques metabolome analysis is becoming an important experimental method in life sciences including the medical field. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis-mass spectrometry, and matrix assisted laser desorption ionization-mass spectrometry. Then, the findings of studies about GC-MS-based metabolome analysis of gastroenterological diseases are summarized, and our research results are also introduced. Finally, we discuss the realization of disease diagnosis by metabolome analysis. The development of metabolome analysis using mass spectrometry will aid the discovery of novel biomarkers, hopefully leading to the early detection of various diseases.

Hands-on Electrospray Ionization-Mass Spectrometry for Upper-Level Undergraduate and Graduate Students

ERIC Educational Resources Information Center

Stock, Naomi L.; March, Raymond E.

2014-01-01

Electrospray ionization-mass spectrometry (ESI-MS) is a powerful technique for the detection, identification, and quantification of organic compounds. As mass spectrometers have become more user-friendly and affordable, many students--often with little experience in mass spectrometry--find themselves needing to incorporate mass spectrometry into…

High Resolution Laser Mass Spectrometry Bioimaging

PubMed Central

Murray, Kermit K.; Seneviratne, Chinthaka A.; Ghorai, Suman

2016-01-01

MSI (MSI) was introduced more than five decades ago with secondary ion mass spectrometry (SIMS) and a decade later with laser desorption/ionization (LDI) mass spectrometry (MS). Large biomolecule imaging by matrix-assisted laser desorption/ionization (MALDI) was developed in the 1990s and ambient laser MS a decade ago. Although SIMS has been capable of imaging with a moderate mass range at sub-micrometer lateral resolution from its inception, laser MS requires additional effort to achieve a lateral resolution of 10 μm or below which is required to image at the size scale of single mammalian cells. This review covers untargeted large biomolecule MSI using lasers for desorption/ionization or laser desorption and post-ionization. These methods include laser microprobe (LDI) MSI, MALDI MSI, laser ambient and atmospheric pressure MSI, and near-field laser ablation MS. Novel approaches to improving lateral resolution are discussed, including oversampling, beam shaping, transmission geometry, reflective and through-hole objectives, microscope mode, and near-field optics. PMID:26972785

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.

Identification of chemical components in Baidianling Capsule based on gas chromatography-mass spectrometry and high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Wu, Wenying; Chen, Yu; Wang, Binjie; Sun, Xiaoyang; Guo, Ping; Chen, Xiaohui

2017-08-01

Baidianling Capsule, which is made from 16 Chinese herbs, has been widely used for treating vitiligo clinically. In this study, the sensitive and rapid method has been developed for the analysis of chemical components in Baidianling Capsule by gas chromatography-mass spectrometry in combination with retention indices and high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry. Firstly, a total of 110 potential volatile compounds obtained from different extraction procedures including alkanes, alkenes, alkynes, ketones, ethers, aldehydes, alcohols, phenols, organic acids, esters, furans, pyrrole, acid amides, heterocycles, and oxides were detected from Baidianling Capsule by gas chromatography-mass spectrometry, of which 75 were identified by mass spectrometry in combination with the retention index. Then, a total of 124 components were tentatively identified by high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry. Fifteen constituents from Baidianling Capsule were accurately identified by comparing the retention times with those of reference compounds, others were identified by comparing the retention times and mass spectrometry data, as well as retrieving the reference literature. This study provides a practical strategy for rapidly screening and identifying the multiple constituents of a complex traditional Chinese medicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

MASS SPECTROMETRY OF FATTY ALDEHYDES

PubMed Central

Berdyshev, Evgeny V.

2011-01-01

Fatty aldehydes are important components of the cellular lipidome. Significant interest has been developed towards the analysis of the short chain α,β-unsaturated and hydroxylated aldehydes formed as a result of oxidation of polyunsaturated fatty acids. Multiple gas chromatography-mass spectrometry (GC/MS) and subsequently liquid chromatography-mass spectrometry (LC/MS) approaches have been developed to identify and quantify short-chain as well as long-chain fatty aldehydes. Due to the ability to non-enzymaticaly form Schiff bases with amino groups of proteins, lipids, and with DNA guanidine, free aldehydes are viewed as a marker or metric of fatty acid oxidation and not the part of intracellular signaling pathways which has significantly limited the overall attention this group of molecules have received. This review provides an overview of current GC/MS and LC/MS approaches of fatty aldehyde analysis as well as discusses technical challenges standing in the way of free fatty aldehyde quantitation. PMID:21930240

Application of Laser Mass Spectrometry to Art and Archaeology

NASA Technical Reports Server (NTRS)

Gulian, Lase Lisa E.; Callahan, Michael P.; Muliadi, Sarah; Owens, Shawn; McGovern, Patrick E.; Schmidt, Catherine M.; Trentelman, Karen A.; deVries, Mattanjah S.

2011-01-01

REMPI laser mass spectrometry is a combination of resonance enhanced multiphoton ionization spectroscopy and time of flight mass spectrometry, This technique enables the collection of mass specific optical spectra as well as of optically selected mass spectra. Analytes are jet-cooled by entrainment in a molecular beam, and this low temperature gas phase analysis has the benefit of excellent vibronic resolution. Utilizing this method, mass spectrometric analysis of historically relevant samples can be simplified and improved; Optical selection of targets eliminates the need for chromatography while knowledge of a target's gas phase spectroscopy allows for facile differentiation of molecules that are in the aqueous phase considered spectroscopically indistinguishable. These two factors allow smaller sample sizes than commercial MS instruments, which in turn will require less damage to objects of antiquity. We have explored methods to optimize REMPI laser mass spectrometry as an analytical tool to archaeology using theobromine and caffeine as molecular markers in Mesoamerican pottery, and are expanding this approach to the field of art to examine laccaic acid in shellacs.

Hydrogen/deuterium exchange in mass spectrometry.

PubMed

Kostyukevich, Yury; Acter, Thamina; Zherebker, Alexander; Ahmed, Arif; Kim, Sunghwan; Nikolaev, Eugene

2018-03-30

The isotopic exchange approach is in use since the first observation of such reactions in 1933 by Lewis. This approach allows the investigation of the pathways of chemical and biochemical reactions, determination of structure, composition, and conformation of molecules. Mass spectrometry has now become one of the most important analytical tools for the monitoring of the isotopic exchange reactions. Investigation of conformational dynamics of proteins, quantitative measurements, obtaining chemical, and structural information about individual compounds of the complex natural mixtures are mainly based on the use of isotope exchange in combination with high resolution mass spectrometry. The most important reaction is the Hydrogen/Deuterium exchange, which is mainly performed in the solution. Recently we have developed the approach allowing performing of the Hydrogen/Deuterium reaction on-line directly in the ionization source under atmospheric pressure. Such approach simplifies the sample preparation and can accelerate the exchange reaction so that certain hydrogens that are considered as non-labile will also participate in the exchange. The use of in-ionization source H/D exchange in modern mass spectrometry for structural elucidation of molecules serves as the basic theme in this review. We will focus on the mechanisms of the isotopic exchange reactions and on the application of in-ESI, in-APCI, and in-APPI source Hydrogen/Deuterium exchange for the investigation of petroleum, natural organic matter, oligosaccharides, and proteins including protein-protein complexes. The simple scenario for adaptation of H/D exchange reactions into mass spectrometric method is also highlighted along with a couple of examples collected from previous studies. © 2018 Wiley Periodicals, Inc.

Evaluating lipid mediator structural complexity using ion mobility spectrometry combined with mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kyle, Jennifer E.; Aly, Noor; Zheng, Xueyun

Lipid mediators (LMs) are broadly defined as a class of bioactive lipophilic molecules that regulate cell-to-cell communication events with many having a strong correlation with various human diseases and conditions. LMs are usually analyzed with liquid chromatography and mass spectrometry (LC-MS), but their numerous isomers greatly complicate the measurements with essentially identical fragmentation spectra and LC separations not always sufficient for distinguishing the features. In this work, we characterized LMs having specific categories using ion mobility spectrometry coupled with mass spectrometry (IMS-MS). The IMS collision cross sections and MS m/z values displayed distinct trends for each LM category studied. LC-IMS-MSmore » analyses on flu infected mouse tissue samples also illustrated the presence of additional LM species not in our databases.« less

Mass spectrometry in grape and wine chemistry. Part II: The consumer protection.

PubMed

Flamini, Riccardo; Panighel, Annarita

2006-01-01

Controls in food industry are fundamental to protect the consumer health. For products of high quality, warranty of origin and identity is required and analytical control is very important to prevent frauds. In this article, the "state of art" of mass spectrometry in enological chemistry as a consumer safety contribute is reported. Gas chromatography-mass spectrometry (GC/MS) and liquid-chromatography-mass spectrometry (LC/MS) methods have been developed to determine pesticides, ethyl carbamate, and compounds from the yeast and bacterial metabolism in wine. The presence of pesticides in wine is mainly linked to the use of dicarboxyimide fungicides on vineyard shortly before the harvest to prevent the Botrytis cinerea attack of grape. Pesticide residues are regulated at maximum residue limits in grape of low ppm levels, but significantly lower levels in wine have to be detected, and mass spectrometry offers effective and sensitive methods. Moreover, mass spectrometry represent an advantageous alternative to the radioactive-source-containing electron capture detector commonly used in GC analysis of pesticides. Analysis of ochratoxin A (OTA) in wine by LC/MS and multiple mass spectrometry (MS/MS) permits to confirm the toxin presence without the use of expensive immunoaffinity columns, or time and solvent consuming sample derivatization procedures. Inductively coupled plasma-mass spectrometry (ICP/MS) is used to control heavy metals contamination in wine, and to verify the wine origin and authenticity. Isotopic ratio-mass spectrometry (IRMS) is applied to reveal wine watering and sugar additions, and to determine the product origin and traceability.

Structural analysis of commercial ceramides by gas chromatography-mass spectrometry.

PubMed

Bleton, J; Gaudin, K; Chaminade, P; Goursaud, S; Baillet, A; Tchapla, A

2001-05-11

A simple method using gas chromatography-mass spectrometry was applied to analyse structures of ceramides. Identification of trimethylsilylated ceramides were obtained in short analysis times (derivatization of ceramides in 30 min at room temperature and 20 min gas chromatography mass spectrometry run) even for complex mixtures. For example in ceramide Type III, 18 peaks were observed which represent 27 various structures. The coeluted compounds were ceramides containing the same functional groups and the same carbon number but with a different distribution on the two alkyl chains of the molecule. They were accurately differentiated by mass spectrometry. Therefore, 83 structures of trimethylsilylated ceramides were identified in 11 different commercial mixtures. For 52 structures of these, mass spectral data were not described in the literature, neither full mass spectra nor characteristic fragments.

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...

Inductively coupled plasma mass spectrometry and electrospray mass spectrometry for speciation analysis: applications and instrumentation

NASA Astrophysics Data System (ADS)

Rosen, Amy L.; Hieftje, Gary M.

2004-02-01

To gain an understanding of the function, toxicity and distribution of trace elements, it is necessary to determine not only the presence and concentration of the elements of interest, but also their speciation, by identifying and characterizing the compounds within which each is present. For sensitive detection of compounds containing elements of interest, inductively coupled plasma mass spectrometry (ICP-MS) is a popular method, and for identification of compounds via determination of molecular weight, electrospray ionization mass spectrometry (ESI-MS) is gaining increasing use. ICP-MS and ESI-MS, usually coupled to a separation technique such as chromatography or capillary electrophoresis, have already been applied to a large number of research problems in such diverse fields as environmental chemistry, nutritional science, and bioinorganic chemistry, but a great deal of work remains to be completed. Current areas of research to which ICP-MS and ESI-MS have been applied are discussed, and the existing instrumentation used to solve speciation problems is described.

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.

A mass spectrometry proteomics data management platform.

PubMed

Sharma, Vagisha; Eng, Jimmy K; Maccoss, Michael J; Riffle, Michael

2012-09-01

Mass spectrometry-based proteomics is increasingly being used in biomedical research. These experiments typically generate a large volume of highly complex data, and the volume and complexity are only increasing with time. There exist many software pipelines for analyzing these data (each typically with its own file formats), and as technology improves, these file formats change and new formats are developed. Files produced from these myriad software programs may accumulate on hard disks or tape drives over time, with older files being rendered progressively more obsolete and unusable with each successive technical advancement and data format change. Although initiatives exist to standardize the file formats used in proteomics, they do not address the core failings of a file-based data management system: (1) files are typically poorly annotated experimentally, (2) files are "organically" distributed across laboratory file systems in an ad hoc manner, (3) files formats become obsolete, and (4) searching the data and comparing and contrasting results across separate experiments is very inefficient (if possible at all). Here we present a relational database architecture and accompanying web application dubbed Mass Spectrometry Data Platform that is designed to address the failings of the file-based mass spectrometry data management approach. The database is designed such that the output of disparate software pipelines may be imported into a core set of unified tables, with these core tables being extended to support data generated by specific pipelines. Because the data are unified, they may be queried, viewed, and compared across multiple experiments using a common web interface. Mass Spectrometry Data Platform is open source and freely available at http://code.google.com/p/msdapl/.

A Mass Spectrometry Proteomics Data Management Platform*

PubMed Central

Sharma, Vagisha; Eng, Jimmy K.; MacCoss, Michael J.; Riffle, Michael

2012-01-01

Mass spectrometry-based proteomics is increasingly being used in biomedical research. These experiments typically generate a large volume of highly complex data, and the volume and complexity are only increasing with time. There exist many software pipelines for analyzing these data (each typically with its own file formats), and as technology improves, these file formats change and new formats are developed. Files produced from these myriad software programs may accumulate on hard disks or tape drives over time, with older files being rendered progressively more obsolete and unusable with each successive technical advancement and data format change. Although initiatives exist to standardize the file formats used in proteomics, they do not address the core failings of a file-based data management system: (1) files are typically poorly annotated experimentally, (2) files are “organically” distributed across laboratory file systems in an ad hoc manner, (3) files formats become obsolete, and (4) searching the data and comparing and contrasting results across separate experiments is very inefficient (if possible at all). Here we present a relational database architecture and accompanying web application dubbed Mass Spectrometry Data Platform that is designed to address the failings of the file-based mass spectrometry data management approach. The database is designed such that the output of disparate software pipelines may be imported into a core set of unified tables, with these core tables being extended to support data generated by specific pipelines. Because the data are unified, they may be queried, viewed, and compared across multiple experiments using a common web interface. Mass Spectrometry Data Platform is open source and freely available at http://code.google.com/p/msdapl/. PMID:22611296

FT-ICR MS analysis of blended pine-microalgae feedstock HTL biocrudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Jacqueline M.; Billing, Justin M.; Corilo, Yuri E.

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is utilized for direct comparison of the chemical composition of biocrudes generated from the hydrothermal liquefaction of 100% pine, 100% algae, 75:25 pine:algae, and 50:50 pine:algae feedstocks. This analysis reveals that the of the 72:25 and 50:50 pine:algal HTL biocrudes is essentially a composite of the two parent feeds (i.e., pine and algae) with a lower relative abundance of Ox species and a higher relative abundance of nitrogen-containing species than the pine HTL biocrude. Alternatively, the biocrude blends have a lower relative abundance of nitrogen-containing species where N>2 than the algalmore » HTL biocrude. The 75:25 pine:algal HTL biocrude has more elemental formulae in common with the pine HTL biocrude than the 50:50 blend; however, both blends have more elemental formulae in common with the algal HTL biocrude. Interestingly, >20% of the elemental formulae assigned to monoisotopic peaks within the 75:25 and 50:50 biocrude blends are species not present in either the pine or algal HTL biocrudes. The highest relative abundance of these new species belong to the N2O4-6 classes, which correspond to heteroatom classes with a moderate number of nitrogen atoms and higher number of oxygen atoms per molecules than the species within the pure algal HTL biocrude. Compositionally, the novel species have the same structural motif but are of higher DBE and carbon numbers than the species within the algal HTL biocrude. These original species are most likely generated from reactions between molecules from both feeds, which results in compounds wotj higher oxygen content than typically seen in the algal HTL biocrude but also higher nitrogen contents than observed in the pine HTL biocrude.« less

Deciphering Dorin M glycosylation by mass spectrometry.

PubMed

Man, Petr; Kovár, Vojtech; Sterba, Ján; Strohalm, Martin; Kavan, Daniel; Kopácek, Petr; Grubhoffer, Libor; Havlícek, Vladimír

2008-01-01

The soft tick, Ornithodoros moubata, is a vector of several bacterial and viral pathogens including Borrelia duttoni, a causative agent of relapsing fever and African swine fever virus. Previously, a sialic acid-specific lectin Dorin M was isolated from its hemolymph. Here, we report on the complete characterization of the primary sequence of Dorin M. Using liquid chromatography coupled to mass spectrometry, we identified three different glycopeptides in the tryptic digest of Dorin M. The peptide, as well as the glycan part of all glycopeptides, were further fully sequenced by means of tandem mass spectrometry (MS2) and multiple-stage mass spectrometry (MS3). Two classical N-glycosylation sites were modified by high-mannose-type glycans containing up to nine mannose residues. The third site bore a glycan with four to five mannose residues and a deoxyhexose (fucose) attached to the proximal N-acetylglycosamine. The microheterogeneity at each site was estimated based on chromatographic behavior of different glycoforms. The fourth, a non-classical N-glycosylation site (Asn-Asn-Cys), was not glycosylated, probably due to the involvement of the cysteine residue in a disulfide bridge.

[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.

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.

POTAMOS mass spectrometry calculator: computer aided mass spectrometry to the post-translational modifications of proteins. A focus on histones.

PubMed

Vlachopanos, A; Soupsana, E; Politou, A S; Papamokos, G V

2014-12-01

Mass spectrometry is a widely used technique for protein identification and it has also become the method of choice in order to detect and characterize the post-translational modifications (PTMs) of proteins. Many software tools have been developed to deal with this complication. In this paper we introduce a new, free and user friendly online software tool, named POTAMOS Mass Spectrometry Calculator, which was developed in the open source application framework Ruby on Rails. It can provide calculated mass spectrometry data in a time saving manner, independently of instrumentation. In this web application we have focused on a well known protein family of histones whose PTMs are believed to play a crucial role in gene regulation, as suggested by the so called "histone code" hypothesis. The PTMs implemented in this software are: methylations of arginines and lysines, acetylations of lysines and phosphorylations of serines and threonines. The application is able to calculate the kind, the number and the combinations of the possible PTMs corresponding to a given peptide sequence and a given mass along with the full set of the unique primary structures produced by the possible distributions along the amino acid sequence. It can also calculate the masses and charges of a fragmented histone variant, which carries predefined modifications already implemented. Additional functionality is provided by the calculation of the masses of fragments produced upon protein cleavage by the proteolytic enzymes that are most widely used in proteomics studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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...

Fourier transform ion cyclotron resonance mass resolution and dynamic range limits calculated by computer modeling of ion cloud motion.

PubMed

Vladimirov, Gleb; Hendrickson, Christopher L; Blakney, Greg T; Marshall, Alan G; Heeren, Ron M A; Nikolaev, Eugene N

2012-02-01

was determined for two ion ensembles of different m/z, equal abundance, and equal cyclotron radius. We find that N and dynamic range depend quadratically on magnetic field strength in the range 1-21 Tesla. Dependences on cyclotron radius and Δm/z are linear. N depends on m/z as (m/z)(-2). Empirical expressions for mass resolution as a function of each of the experimental parameters are presented. Here, we provide the first exposition of the origin and extent of trade-off between FT-ICR MS dynamic range and mass resolution (defined not as line width, but as the separation between the most closely resolved masses). © American Society for Mass Spectrometry, 2011

Quantitative correlations between collision induced dissociation mass spectrometry coupled with electrospray ionization or atmospheric pressure chemical ionization mass spectrometry - Experiment and theory

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka; Spiteller, Michael

2018-04-01

The problematic that we consider in this paper treats the quantitative correlation model equations between experimental kinetic and thermodynamic parameters of coupled electrospray ionization (ESI) mass spectrometry (MS) or atmospheric pressure chemical ionization (APCI) mass spectrometry with collision induced dissociation mass spectrometry, accounting for the fact that the physical phenomena and mechanisms of ESI- and APCI-ion formation are completely different. There are described forty two fragment reactions of three analytes under independent ESI- and APCI-measurements. The developed new quantitative models allow us to study correlatively the reaction kinetics and thermodynamics using the methods of mass spectrometry, which complementary application with the methods of the quantum chemistry provide 3D structural information of the analytes. Both static and dynamic quantum chemical computations are carried out. The object of analyses are [2,3-dimethyl-4-(4-methyl-benzoyl)-2,3-di-p-tolyl-cyclobutyl]-p-tolyl-methanone (1) and the polycyclic aromatic hydrocarbons derivatives of dibenzoperylen (2) and tetrabenzo [a,c,fg,op]naphthacene (3), respectively. As far as (1) is known to be a product of [2π+2π] cycloaddition reactions of chalcone (1,3-di-p-tolyl-propenone), however producing cyclic derivatives with different stereo selectivity, so that the study provide crucial data about the capability of mass spectrometry to provide determine the stereo selectivity of the analytes. This work also first provides quantitative treatment of the relations '3D molecular/electronic structures'-'quantum chemical diffusion coefficient'-'mass spectrometric diffusion coefficient', thus extending the capability of the mass spectrometry for determination of the exact 3D structure of the analytes using independent measurements and computations of the diffusion coefficients. The determination of the experimental diffusion parameters is carried out within the 'current monitoring method

Hydrogen Exchange Mass Spectrometry

PubMed Central

Mayne, Leland

2018-01-01

Hydrogen exchange (HX) methods can reveal much about the structure, energetics, and dynamics of proteins. The addition of mass spectrometry (MS) to an earlier fragmentation-separation HX analysis now extends HX studies to larger proteins at high structural resolution and can provide information not available before. This chapter discusses experimental aspects of HX labeling, especially with respect to the use of MS and the analysis of MS data. PMID:26791986

Through a Glass Darkly: Glimpses into the Future of Mass Spectrometry

PubMed Central

Cooks, R. Graham; Mueller, Thomas

2013-01-01

The paper has three parts, (i) a brief overview of the main achievements made using mass spectrometry across all the fields of science, (ii) a survey of some of the topics currently being pursued most activity, including both applications and fundamental studies, and (iii) some hints as to what the future of mass spectrometry might hold with particular emphasis on revolutionary changes in the subject. Emphasis is given to ambient methods of ionization and their use in disease diagnosis and to their use in combination with miniature mass spectrometers for in-situ measurements. Special attention goes to the chemical aspects of mass spectrometry, including its emerging role as a preparative method based on accelerated bimolecular reaction rates in solution and on ion soft landing as a means of surface tailoring. In summary, the paper covers the proud history, vibrant present and expansive future of mass spectrometry. PMID:24349920

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

Targeted quantitation of proteins by mass spectrometry.

PubMed

Liebler, Daniel C; Zimmerman, Lisa J

2013-06-04

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.

Mass spectrometry-based biomarker discovery: toward a global proteome index of individuality.

PubMed

Hawkridge, Adam M; Muddiman, David C

2009-01-01

Biomarker discovery and proteomics have become synonymous with mass spectrometry in recent years. Although this conflation is an injustice to the many essential biomolecular techniques widely used in biomarker-discovery platforms, it underscores the power and potential of contemporary mass spectrometry. Numerous novel and powerful technologies have been developed around mass spectrometry, proteomics, and biomarker discovery over the past 20 years to globally study complex proteomes (e.g., plasma). However, very few large-scale longitudinal studies have been carried out using these platforms to establish the analytical variability relative to true biological variability. The purpose of this review is not to cover exhaustively the applications of mass spectrometry to biomarker discovery, but rather to discuss the analytical methods and strategies that have been developed for mass spectrometry-based biomarker-discovery platforms and to place them in the context of the many challenges and opportunities yet to be addressed.

Methods for recalibration of mass spectrometry data

DOEpatents

Tolmachev, Aleksey V [Richland, WA; Smith, Richard D [Richland, WA

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.

Native Mass Spectrometry: What is in the Name?

NASA Astrophysics Data System (ADS)

Leney, Aneika C.; Heck, Albert J. R.

2017-01-01

Electrospray ionization mass spectrometry (ESI-MS) is nowadays one of the cornerstones of biomolecular mass spectrometry and proteomics. Advances in sample preparation and mass analyzers have enabled researchers to extract much more information from biological samples than just the molecular weight. In particular, relevant for structural biology, noncovalent protein-protein and protein-ligand complexes can now also be analyzed by MS. For these types of analyses, assemblies need to be retained in their native quaternary state in the gas phase. This initial small niche of biomolecular mass spectrometry, nowadays often referred to as "native MS," has come to maturation over the last two decades, with dozens of laboratories using it to study mostly protein assemblies, but also DNA and RNA-protein assemblies, with the goal to define structure-function relationships. In this perspective, we describe the origins of and (re)define the term native MS, portraying in detail what we meant by "native MS," when the term was coined and also describing what it does (according to us) not entail. Additionally, we describe a few examples highlighting what native MS is, showing its successes to date while illustrating the wide scope this technology has in solving complex biological questions.

Trends in biochemical and biomedical applications of mass spectrometry

NASA Astrophysics Data System (ADS)

Gelpi, Emilio

1992-09-01

This review attempts an in-depth evaluation of progress and achievements made since the last 11th International Mass Spectrometry Conference in the application of mass spectrometric techniques to biochemistry and biomedicine. For this purpose, scientific contributions in this field at major international meetings have been monitored, together with an extensive appraisal of literature data covering the period from 1988 to 1991. A bibliometric evaluation of the MEDLINE database for this period provides a total of almost 4000 entries for mass spectrometry. This allows a detailed study of literature and geographical sources of the most frequent applications, of disciplines where mass spectrometry is most active and of types of sample and instrumentation most commonly used. In this regard major efforts according to number of publications (over 100 literature reports) are concentrated in countries like Canada, France, Germany, Italy, Japan, Sweden, UK and the USA. Also, most of the work using mass spectrometry in biochemistry and biomedicine is centred on studies on biotransformation, metabolism, pharmacology, pharmacokinetics and toxicology, which have been carried out on samples of blood, urine, plasma and tissue, by order of frequency of use. Human and animal studies appear to be evenly distributed in terms of the number of reports published in the literature in which the authors make use of experimental animals or describe work on human samples. Along these lines, special attention is given to the real usefulness of mass spectrometry (MS) technology in routine medical practice. Thus the review concentrates on evaluating the progress made in disease diagnosis and overall patient care. As regards prevailing techniques, GCMS continues to be the mainstay of the state of the art methods for multicomponent analysis, stable isotope tracer studies and metabolic profiling, while HPLC--MS and tandem MS are becoming increasingly important in biomedical research. However

"EMERGING" POLLUTANTS, MASS SPECTROMETRY, AND COMMUNICATING SCIENCE: PHARMACEUTICALS IN THE ENVIRONMENT

EPA Science Inventory

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...

Analysis of Silicones Released from Household Items and Baby Articles by Direct Analysis in Real Time-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Gross, Jürgen H.

2015-03-01

Direct analysis in real time-mass spectrometry (DART-MS) enables screening of articles of daily use made of polydimethylsiloxanes (PDMS), commonly known as silicone rubber, to assess their tendency to release low molecular weight silicone oligomers. DART-MS analyses were performed on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Flexible silicone baking molds, a watch band, and a dough scraper, as baby articles different brands of pacifiers, nipples, and a teething ring have been examined. While somewhat arbitrarily chosen, the set can be regarded as representative of household items, baby articles, and other objects made of silicone rubber. For comparison, two brands of silicone septa and as blanks a glass slide and a latex pacifier were included. Differences between the objects were mainly observed in terms of molecular weight distribution and occasional release of other compounds in addition to PDMS. Other than that, all objects made of silicone rubber released significant amounts of PDMS during DART analysis. To provide a coarse quantification, a calibration based on silicone oil was established, which delivered PDMS losses from 20 μg to >100 μg during the 16-s period per measurement. Also, the extraction of baking molds in rapeseed oil demonstrated a PDMS release at the level of 1 μg mg-1. These findings indicate a potential health hazard from frequent or long-term use of such items. This work does not intend to blame certain brands of such articles. Nonetheless, a higher level of awareness of this source of daily silicone intake is suggested.

Analysis of silicones released from household items and baby articles by direct analysis in real time-mass spectrometry.

PubMed

Gross, Jürgen H

2015-03-01

Direct analysis in real time-mass spectrometry (DART-MS) enables screening of articles of daily use made of polydimethylsiloxanes (PDMS), commonly known as silicone rubber, to assess their tendency to release low molecular weight silicone oligomers. DART-MS analyses were performed on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Flexible silicone baking molds, a watch band, and a dough scraper, as baby articles different brands of pacifiers, nipples, and a teething ring have been examined. While somewhat arbitrarily chosen, the set can be regarded as representative of household items, baby articles, and other objects made of silicone rubber. For comparison, two brands of silicone septa and as blanks a glass slide and a latex pacifier were included. Differences between the objects were mainly observed in terms of molecular weight distribution and occasional release of other compounds in addition to PDMS. Other than that, all objects made of silicone rubber released significant amounts of PDMS during DART analysis. To provide a coarse quantification, a calibration based on silicone oil was established, which delivered PDMS losses from 20 μg to >100 μg during the 16-s period per measurement. Also, the extraction of baking molds in rapeseed oil demonstrated a PDMS release at the level of 1 μg mg(-1). These findings indicate a potential health hazard from frequent or long-term use of such items. This work does not intend to blame certain brands of such articles. Nonetheless, a higher level of awareness of this source of daily silicone intake is suggested.

Parsimonious Charge Deconvolution for Native Mass Spectrometry

PubMed Central

2018-01-01

Charge deconvolution infers the mass from mass over charge (m/z) measurements in electrospray ionization mass spectra. When applied over a wide input m/z or broad target mass range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half or one-third of the correct mass. Indeed, a maximum entropy term in the objective function of MaxEnt, the most commonly used charge deconvolution algorithm, favors a deconvolved spectrum with many peaks over one with fewer peaks. Here we describe a new “parsimonious” charge deconvolution algorithm that produces fewer artifacts. The algorithm is especially well-suited to high-resolution native mass spectrometry of intact glycoproteins and protein complexes. Deconvolution of native mass spectra poses special challenges due to salt and small molecule adducts, multimers, wide mass ranges, and fewer and lower charge states. We demonstrate the performance of the new deconvolution algorithm on a range of samples. On the heavily glycosylated plasma properdin glycoprotein, the new algorithm could deconvolve monomer and dimer simultaneously and, when focused on the m/z range of the monomer, gave accurate and interpretable masses for glycoforms that had previously been analyzed manually using m/z peaks rather than deconvolved masses. On therapeutic antibodies, the new algorithm facilitated the analysis of extensions, truncations, and Fab glycosylation. The algorithm facilitates the use of native mass spectrometry for the qualitative and quantitative analysis of protein and protein assemblies. PMID:29376659

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.

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.

The current role of high-resolution mass spectrometry in food analysis.

PubMed

Kaufmann, Anton

2012-05-01

High-resolution mass spectrometry (HRMS), which is used for residue analysis in food, has gained wider acceptance in the last few years. This development is due to the availability of more rugged, sensitive, and selective instrumentation. The benefits provided by HRMS over classical unit-mass-resolution tandem mass spectrometry are considerable. These benefits include the collection of full-scan spectra, which provides greater insight into the composition of a sample. Consequently, the analyst has the freedom to measure compounds without previous compound-specific tuning, the possibility of retrospective data analysis, and the capability of performing structural elucidations of unknown or suspected compounds. HRMS strongly competes with classical tandem mass spectrometry in the field of quantitative multiresidue methods (e.g., pesticides and veterinary drugs). It is one of the most promising tools when moving towards nontargeted approaches. Certain hardware and software issues still have to be addressed by the instrument manufacturers for it to dislodge tandem mass spectrometry from its position as the standard trace analysis tool.

Revealing Individual Lifestyles through Mass Spectrometry Imaging of Chemical Compounds in Fingerprints.

PubMed

Hinners, Paige; O'Neill, Kelly C; Lee, Young Jin

2018-03-26

Fingerprints, specifically the ridge details within the print, have long been used in forensic investigations for individual identification. Beyond the ridge detail, fingerprints contain useful chemical information. The study of fingerprint chemical information has become of interest, especially with mass spectrometry imaging technologies. Mass spectrometry imaging visualizes the spatial relationship of each compound detected, allowing ridge detail and chemical information in a single analysis. In this work, a range of exogenous fingerprint compounds that may reveal a personal lifestyle were studied using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Studied chemical compounds include various brands of bug sprays and sunscreens, as well as food oils, alcohols, and citrus fruits. Brand differentiation and source determination were possible based on the active ingredients or exclusive compounds left in fingerprints. Tandem mass spectrometry was performed for the key compounds, so that these compounds could be confidently identified in a single multiplex mass spectrometry imaging data acquisition.

FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry.

PubMed

Palmer, Andrew; Phapale, Prasad; Chernyavsky, Ilya; Lavigne, Regis; Fay, Dominik; Tarasov, Artem; Kovalev, Vitaly; Fuchser, Jens; Nikolenko, Sergey; Pineau, Charles; Becker, Michael; Alexandrov, Theodore

2017-01-01

High-mass-resolution imaging mass spectrometry promises to localize hundreds of metabolites in tissues, cell cultures, and agar plates with cellular resolution, but it is hampered by the lack of bioinformatics tools for automated metabolite identification. We report pySM, a framework for false discovery rate (FDR)-controlled metabolite annotation at the level of the molecular sum formula, for high-mass-resolution imaging mass spectrometry (https://github.com/alexandrovteam/pySM). We introduce a metabolite-signal match score and a target-decoy FDR estimate for spatial metabolomics.

Structure Determination of Natural Products by Mass Spectrometry.

PubMed

Biemann, Klaus

2015-01-01

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.

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).

Optimization of Whole-Body Zebrafish Sectioning Methods for Mass Spectrometry Imaging

EPA Science Inventory

Mass spectrometry imaging methods and protocols have become widely adapted to a variety of tissues and species. However, the mass spectrometry imaging literature contains minimal information on whole-body cryosection preparation for the zebrafish (Danio rerio), a model organism ...

Total mass difference statistics algorithm: a new approach to identification of high-mass building blocks in electrospray ionization Fourier transform ion cyclotron mass spectrometry data of natural organic matter.

PubMed

Kunenkov, Erast V; Kononikhin, Alexey S; Perminova, Irina V; Hertkorn, Norbert; Gaspar, Andras; Schmitt-Kopplin, Philippe; Popov, Igor A; Garmash, Andrew V; Nikolaev, Evgeniy N

2009-12-15

The ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrum of natural organic matter (NOM) contains several thousand peaks with dozens of molecules matching the same nominal mass. Such a complexity poses a significant challenge for automatic data interpretation, in which the most difficult task is molecular formula assignment, especially in the case of heavy and/or multielement ions. In this study, a new universal algorithm for automatic treatment of FTICR mass spectra of NOM and humic substances based on total mass difference statistics (TMDS) has been developed and implemented. The algorithm enables a blind search for unknown building blocks (instead of a priori known ones) by revealing repetitive patterns present in spectra. In this respect, it differs from all previously developed approaches. This algorithm was implemented in designing FIRAN-software for fully automated analysis of mass data with high peak density. The specific feature of FIRAN is its ability to assign formulas to heavy and/or multielement molecules using "virtual elements" approach. To verify the approach, it was used for processing mass spectra of sodium polystyrene sulfonate (PSS, M(w) = 2200 Da) and polymethacrylate (PMA, M(w) = 3290 Da) which produce heavy multielement and multiply-charged ions. Application of TMDS identified unambiguously monomers present in the polymers consistent with their structure: C(8)H(7)SO(3)Na for PSS and C(4)H(6)O(2) for PMA. It also allowed unambiguous formula assignment to all multiply-charged peaks including the heaviest peak in PMA spectrum at mass 4025.6625 with charge state 6- (mass bias -0.33 ppm). Application of the TMDS-algorithm to processing data on the Suwannee River FA has proven its unique capacities in analysis of spectra with high peak density: it has not only identified the known small building blocks in the structure of FA such as CH(2), H(2), C(2)H(2)O, O but the heavier unit at 154.027 amu. The latter was

Steroid Profiling by Gas Chromatography–Mass Spectrometry and High Performance Liquid Chromatography–Mass Spectrometry for Adrenal Diseases

PubMed Central

McDonald, Jeffrey G.; Matthew, Susan

2012-01-01

The ability to measure steroid hormone concentrations in blood and urine specimens is central to the diagnosis and proper treatment of adrenal diseases. The traditional approach has been to assay each steroid hormone, precursor, or metabolite using individual aliquots of serum, each with a separate immunoassay. For complex diseases, such as congenital adrenal hyperplasia and adrenocortical cancer, in which the assay of several steroids is essential for management, this approach is time consuming and costly, in addition to using large amounts of serum. Gas chromatography/mass spectrometry profiling of steroid metabolites in urine has been employed for many years but only in a small number of specialized laboratories and suffers from slow throughput. The advent of commercial high-performance liquid chromatography instruments coupled to tandem mass spectrometers offers the potential for medium- to high-throughput profiling of serum steroids using small quantities of sample. Here, we review the physical principles of mass spectrometry, the instrumentation used for these techniques, the terminology used in this field and applications to steroid analysis. PMID:22170384

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…

Novel software for data analysis of Fourier transform ion cyclotron resonance mass spectra applied to natural organic matter.

PubMed

Grinhut, Tzafrir; Lansky, Dedy; Gaspar, Andras; Hertkorn, Norbert; Schmitt-Kopplin, Philippe; Hadar, Yitzhak; Chen, Yona

2010-10-15

Natural organic matter (NOM) occurs as an extremely complex mixture of large, charged molecules that are formed by secondary synthesis reactions. Due to their nature, their full characterization is an important challenge to scientists specializing in NOM as well as analytical chemistry. Ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis enables the identification of thousands of masses in a single measurement. A major challenge in the data analysis process of NOM using the FT-ICR MS technique is the need to sort the entire data set and to present it in an accessible mode. Here we present a simple targeted algorithm called the David Mass Sort (DMS) algorithm which facilitates the detection and counting of consecutive series of masses correlated to any selected mass spacing. This program searches for specific mass differences among all of the masses in a single spectrum against all of the masses in the same spectrum. As a representative case, the current study focuses on the analysis of the well-characterized Suwannee River humic and fulvic acid (SRHA and SRFA, respectively). By applying this algorithm, we were able to find and assess the amount of singly and doubly charged molecules. In addition we present the capabilities of the program to detect any series of consecutive masses correlated to specific mass spacing, e.g. COO, H(2), OCH(2) and O(2). Under several limitations, these mass spacings may be correlated to both chemical and biochemical changes which occur simultaneously during the formation and/or degradation of large mixtures of compounds. Copyright © 2010 John Wiley & Sons, Ltd.

Boundaries of mass resolution in native mass spectrometry.

PubMed

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.

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.

Ambient Ionization Mass Spectrometry for Cancer Diagnosis and Surgical Margin Evaluation

PubMed Central

Ifa, Demian R.; Eberlin, Livia S.

2017-01-01

Background There is a clinical need for new technologies that would enable rapid disease diagnosis based on diagnostic molecular signatures. Ambient ionization mass spectrometry has revolutionized the means by which molecular information can be obtained from tissue samples in real time and with minimal sample pretreatment. New developments in ambient ionization techniques applied to clinical research suggest that ambient ionization mass spectrometry will soon become a routine medical tool for tissue diagnosis. Content This review summarizes the main developments in ambient ionization techniques applied to tissue analysis, with focus on desorption electrospray ionization mass spectrometry, probe electrospray ionization, touch spray, and rapid evaporative ionization mass spectrometry. We describe their applications to human cancer research and surgical margin evaluation, highlighting integrated approaches tested for ex vivo and in vivo human cancer tissue analysis. We also discuss the challenges for clinical implementation of these tools and offer perspectives on the future of the field. Summary A variety of studies have showcased the value of ambient ionization mass spectrometry for rapid and accurate cancer diagnosis. Small molecules have been identified as potential diagnostic biomarkers, including metabolites, fatty acids, and glycerophospholipids. Statistical analysis allows tissue discrimination with high accuracy rates (>95%) being common. This young field has challenges to overcome before it is ready to be broadly accepted as a medical tool for cancer diagnosis. Growing research in new, integrated ambient ionization mass spectrometry technologies and the ongoing improvements in the existing tools make this field very promising for future translation into the clinic. PMID:26555455

High-Performance Liquid Chromatography-Mass Spectrometry.

ERIC Educational Resources Information Center

Vestal, Marvin L.

1984-01-01

Reviews techniques for online coupling of high-performance liquid chromatography with mass spectrometry, emphasizing those suitable for application to nonvolatile samples. Also summarizes the present status, strengths, and weaknesses of various techniques and discusses potential applications of recently developed techniques for combined liquid…

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.

Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

PubMed Central

Lavenant, Gwendoline Thiery; Zavalin, Andrey I.; Caprioli, Richard M.

2013-01-01

Targeted multiplex Imaging Mass Spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This manuscript describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet. PMID:23397138

Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

NASA Astrophysics Data System (ADS)

Thiery-Lavenant, Gwendoline; Zavalin, Andre I.; Caprioli, Richard M.

2013-04-01

Targeted multiplex imaging mass spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This article describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet.

A Compressive Sensing Approach for Glioma Margin Delineation Using Mass Spectrometry

PubMed Central

Gholami, Behnood; Agar, Nathalie Y. R.; Jolesz, Ferenc A.; Haddad, Wassim M.; Tannenbaum, Allen R.

2013-01-01

Surgery, and specifically, tumor resection, is the primary treatment for most patients suffering from brain tumors. Medical imaging techniques, and in particular, magnetic resonance imaging are currently used in diagnosis as well as image-guided surgery procedures. However, studies show that computed tomography and magnetic resonance imaging fail to accurately identify the full extent of malignant brain tumors and their microscopic infiltration. Mass spectrometry is a well-known analytical technique used to identify molecules in a given sample based on their mass. In a recent study, it is proposed to use mass spectrometry as an intraoperative tool for discriminating tumor and non-tumor tissue. Integration of mass spectrometry with the resection module allows for tumor resection and immediate molecular analysis. In this paper, we propose a framework for tumor margin delineation using compressive sensing. Specifically, we show that the spatial distribution of tumor cell concentration can be efficiently reconstructed and updated using mass spectrometry information from the resected tissue. In addition, our proposed framework is model-free, and hence, requires no prior information of spatial distribution of the tumor cell concentration. PMID:22255629

A new hybrid electrospray Fourier transform mass spectrometer: design and performance characteristics.

PubMed

O'connor, Peter B; Pittman, Jason L; Thomson, Bruce A; Budnik, Bogdan A; Cournoyer, Jason C; Jebanathirajah, Judith; Lin, Cheng; Moyer, Susanne; Zhao, Cheng

2006-01-01

A new hybrid electrospray quadrupole Fourier transform mass spectrometry (FTMS) instrument design is shown and characterized. This instrument involves coupling an electrospray source and mass-resolving quadrupole, ion accumulation, and collision cell linear ion trap system developed by MDS Sciex with a home-built ion guide and ion cyclotron resonance (ICR) cell. The iterative progression of this design is shown. The final design involves a set of hexapole ion guides to transfer the ions from the accumulation/collision trap through the magnetic field gradient and into the cell. These hexapole ion guides are separated by a thin gate valve and two conduction limits to maintain the required <10(-9) mbar vacuum for FTICR. Low-attomole detection limits for a pure peptide are shown, 220 000 resolving power in broadband mode and 820 000 resolving power in narrow-band mode are demonstrated, and mass accuracy in the <2 ppm range is routinely available provided the signal is abundant, cleanly resolved, and internally calibrated. This instrument design provides high experimental flexibility, allowing Q2 CAD, SORI-CAD, IRMPD, and ECD experiments with selected ion accumulation as well as experiments such as nozzle skimmer dissociation. Initial top-down mass spectrometry experiments on a protein is shown using ECD.

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. Copyright © 2012 Wiley Periodicals, Inc., A Wiley Company.

Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

PubMed Central

Law, Kai P.; Han, Ting-Li; Tong, Chao; Baker, Philip N.

2015-01-01

Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. PMID:26006232

[Mass spectrometry in medicine and biotechnology].

PubMed

Polunina, T A; Kireev, M N; Khramchenkova, T A; Spitsyn, A N; Grigor'eva, G V

2013-01-01

History of development and improvement of tandem mass spectrometry, possibilities of its application at the contemporary stage in various fields of medicine and biotechnology including production of novel medicinal preparations, identification of biologically active substances, pathogenic microorganisms and causative agents of especially dangerous infections is given.

Significant advancement of mass spectrometry imaging for food chemistry.

PubMed

Yoshimura, Yukihiro; Goto-Inoue, Naoko; Moriyama, Tatsuya; Zaima, Nobuhiro

2016-11-01

Food contains various compounds that have an impact on our daily lives. Many technologies have been established to analyze these molecules of interest in foods. However, the analysis of the spatial distribution of these compounds in foods using conventional technology, such as high-performance liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry is difficult. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is considered an ideal complementary approach. MALDI-MSI is a two-dimensional MALDI-MS technology that can detect compounds in a tissue section without extraction, purification, separation, or labeling. MALDI-MSI can be used to visualize the spatial distribution of chemical compounds or biomolecules in foods. Although the methodology of MALDI-MSI in food science is not yet fully established, the versatility of MALDI-MSI is expected to open a new frontier in food science. Herein, we describe the principles and applications of MALDI-MSI in food science and related fields. Copyright © 2016 Elsevier Ltd. All rights reserved.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Comprehensive Urine Drug Screen by Gas Chromatography/Mass Spectrometry (GC/MS).

PubMed

Ramoo, Bheemraj; Funke, Melissa; Frazee, Clint; Garg, Uttam

2016-01-01

Drug screening is an essential component of clinical toxicology laboratory service. Some laboratories use only automated chemistry analyzers for limited screening of drugs of abuse and few other drugs. Other laboratories use a combination of various techniques such as immunoassays, colorimetric tests, and mass spectrometry to provide more detailed comprehensive drug screening. Mass spectrometry, gas or liquid, can screen for hundreds of drugs and is often considered the gold standard for comprehensive drug screening. We describe an efficient and rapid gas chromatography/mass spectrometry (GC/MS) method for comprehensive drug screening in urine which utilizes a liquid-liquid extraction, sample concentration, and analysis by GC/MS.

Focus on Advancing High Performance Mass Spectrometry, Honoring Dr. Richard D. Smith, Recipient of the 2013 Award for a Distinguished Contribution in Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Erin Shammel; Muddiman, David C.; Loo, Joseph

This special focus issue of the Journal of the American Society for Mass Spectrometry celebrates the accomplishments of Dr. Richard D. Smith, the recipient of the 2013ASMS Award for a Distinguished Contribution in Mass Spectrometry, and who serves as a Battelle Fellow, Chief Scientist in the Biological Sciences Division, and Director of Proteomics Research at Pacific Northwest National Laboratory (PNNL) in Richland, WA. The award is for his development of the electrodynamic ion funnel.

Impact of comprehensive two-dimensional gas chromatography with mass spectrometry on food analysis.

PubMed

Tranchida, Peter Q; Purcaro, Giorgia; Maimone, Mariarosa; Mondello, Luigi

2016-01-01

Comprehensive two-dimensional gas chromatography with mass spectrometry has been on the separation-science scene for about 15 years. This three-dimensional method has made a great positive impact on various fields of research, and among these that related to food analysis is certainly at the forefront. The present critical review is based on the use of comprehensive two-dimensional gas chromatography with mass spectrometry in the untargeted (general qualitative profiling and fingerprinting) and targeted analysis of food volatiles; attention is focused not only on its potential in such applications, but also on how recent advances in comprehensive two-dimensional gas chromatography with mass spectrometry will potentially be important for food analysis. Additionally, emphasis is devoted to the many instances in which straightforward gas chromatography with mass spectrometry is a sufficiently-powerful analytical tool. Finally, possible future scenarios in the comprehensive two-dimensional gas chromatography with mass spectrometry food analysis field are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Native Mass Spectrometry in Fragment-Based Drug Discovery.

PubMed

Pedro, Liliana; Quinn, Ronald J

2016-07-28

The advent of native mass spectrometry (MS) in 1990 led to the development of new mass spectrometry instrumentation and methodologies for the analysis of noncovalent protein-ligand complexes. Native MS has matured to become a fast, simple, highly sensitive and automatable technique with well-established utility for fragment-based drug discovery (FBDD). Native MS has the capability to directly detect weak ligand binding to proteins, to determine stoichiometry, relative or absolute binding affinities and specificities. Native MS can be used to delineate ligand-binding sites, to elucidate mechanisms of cooperativity and to study the thermodynamics of binding. This review highlights key attributes of native MS for FBDD campaigns.

A MASSive Laboratory Tour. An Interactive Mass Spectrometry Outreach Activity for Children

NASA Astrophysics Data System (ADS)

Jungmann, Julia H.; Mascini, Nadine E.; Kiss, Andras; Smith, Donald F.; Klinkert, Ivo; Eijkel, Gert B.; Duursma, Marc C.; Cillero Pastor, Berta; Chughtai, Kamila; Chughtai, Sanaullah; Heeren, Ron M. A.

2013-07-01

It is imperative to fascinate young children at an early stage in their education for the analytical sciences. The exposure of the public to mass spectrometry presently increases rapidly through the common media. Outreach activities can take advantage of this exposure and employ mass spectrometry as an exquisite example of an analytical science in which children can be fascinated. The presented teaching modules introduce children to mass spectrometry and give them the opportunity to experience a modern research laboratory. The modules are highly adaptable and can be applied to young children from the age of 6 to 14 y. In an interactive tour, the students explore three major scientific concepts related to mass spectrometry; the building blocks of matter, charged particle manipulation by electrostatic fields, and analyte identification by mass analysis. Also, the students carry out a mass spectrometry experiment and learn to interpret the resulting mass spectra. The multistage, inquiry-based tour contains flexible methods, which teach the students current-day research techniques and possible applications to real research topics. Besides the scientific concepts, laboratory safety and hygiene are stressed and the students are enthused for the analytical sciences by participating in "hands-on" work. The presented modules have repeatedly been successfully employed during laboratory open days. They are also found to be extremely suitable for (early) high school science classes during laboratory visit-focused field trips.

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

Antibodies as means for selective mass spectrometry.

PubMed

Boström, Tove; Takanen, Jenny Ottosson; Hober, Sophia

2016-05-15

For protein analysis of biological samples, two major strategies are used today; mass spectrometry (MS) and antibody-based methods. Each strategy offers advantages and drawbacks. However, combining the two using an immunoenrichment step with MS analysis brings together the benefits of each method resulting in increased sensitivity, faster analysis and possibility of higher degrees of multiplexing. The immunoenrichment can be performed either on protein or peptide level and quantification standards can be added in order to enable determination of the absolute protein concentration in the sample. The combination of immunoenrichment and MS holds great promise for the future in both proteomics and clinical diagnostics. This review describes different setups of immunoenrichment coupled to mass spectrometry and how these can be utilized in various applications. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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)

Rapid characterization of microorganisms by mass spectrometry--what can be learned and how?

PubMed

Fenselau, Catherine C

2013-08-01

Strategies for the rapid and reliable analysis of microorganisms have been sought to meet national needs in defense, homeland security, space exploration, food and water safety, and clinical diagnosis. Mass spectrometry has long been a candidate technique because it is extremely rapid and can provide highly specific information. It has excellent sensitivity. Molecular and fragment ion masses provide detailed fingerprints, which can also be interpreted. Mass spectrometry is also a broad band method--everything has a mass--and it is automatable. Mass spectrometry is a physiochemical method that is orthogonal and complementary to biochemical and morphological methods used to characterize microorganisms.

DMS-prefiltered mass spectrometry for the detection of biomarkers

NASA Astrophysics Data System (ADS)

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

2008-04-01

Technologies based on Differential Mobility Spectrometry (DMS) are ideally matched to rapid, sensitive, and selective detection of chemicals like biomarkers. Biomarkers linked to exposure to radiation, exposure to CWA's, exposure to toxic materials (TICs and TIMs) and to specific diseases are being examined in a number of laboratories. Screening for these types of exposure can be improved in accuracy and greatly speeded up by using DMS-MS instead of slower techniques like LC-MS and GC-MS. We have performed an extensive series of tests with nanospray-DMS-mass spectroscopy and standalone nanospray-DMS obtaining extensive information on chemistry and detectivity. DMS-MS systems implemented with low-resolution, low-cost, portable mass-spectrometry systems are very promising. Lowresolution mass spectrometry alone would be inadequate for the task, but with DMS pre-filtration to suppress interferences, can be quite effective, even for quantitative measurement. Bio-fluids and digests are well suited to ionization by electrospray and detection by mass-spectrometry, but signals from critical markers are overwhelmed by chemical noise from unrelated species, making essential quantitative analysis impossible. Sionex and collaborators have presented data using DMS to suppress chemical noise, allowing detection of cancer biomarkers in 10,000-fold excess of normal products 1,2. In addition, a linear dynamic range of approximately 2,000 has been demonstrated with accurate quantitation 3. We will review the range of possible applications and present new data on DMS-MS biomarker detection.

Application of Atmospheric Solids Analysis Probe Mass Spectrometry (ASAP-MS) in Petroleomics: Analysis of Condensed Aromatics Standards, Crude Oil, and Paraffinic Fraction.

PubMed

Tose, Lilian V; Murgu, Michael; Vaz, Boniek G; Romão, Wanderson

2017-11-01

Atmospheric solids analysis probe mass spectrometry (ASAP-MS) is a powerful tool for analysis of solid and liquid samples. It is an excellent alternative for crude oil analysis without any sample preparation step. Here, ASAP-MS in positive ion mode, ASAP(+)-MS, has been optimized for analysis of condensed aromatics (CA) standards, crude oil, and paraffinic fraction samples using a Synapt G2-S HDMS. Initially, two methodologies were used to access the chemical composition of samples: (1) using a temperature gradient varying from 150 to 600 °C at a heating rate of 150 °C min -1 , and (2) with constant temperature of 300 and 400 °C. ASAP(+)-MS ionized many compounds with a typical petroleum profile, showing a greater signals range of m/z 250-1300 and 200-1400 for crude oil and paraffin samples, respectively. Such performance, mainly related to the detection of high molecular weight compounds (>1000 Da), is superior to that of other traditional ionization sources, such as ESI, APCI, DART, and DESI. Additionally, the CA standards were identified in both forms: radicals, [M] +• , and protonated cations, [M + H] + , with minimum fragmentation. Therefore, ASAP was more efficient in accessing the chemical composition of nonpolar and polar compounds. It is promising in its application with ultrahigh resolution MS instruments, such as FT-ICR MS and Orbitrap, since molecular formulas with greater resolution and mass accuracy (<1 ppm) would be assigned. Graphical Abstract ᅟ.

Application of Atmospheric Solids Analysis Probe Mass Spectrometry (ASAP-MS) in Petroleomics: Analysis of Condensed Aromatics Standards, Crude Oil, and Paraffinic Fraction

NASA Astrophysics Data System (ADS)

Tose, Lilian V.; Murgu, Michael; Vaz, Boniek G.; Romão, Wanderson

2017-08-01

Atmospheric solids analysis probe mass spectrometry (ASAP-MS) is a powerful tool for analysis of solid and liquid samples. It is an excellent alternative for crude oil analysis without any sample preparation step. Here, ASAP-MS in positive ion mode, ASAP(+)-MS, has been optimized for analysis of condensed aromatics (CA) standards, crude oil, and paraffinic fraction samples using a Synapt G2-S HDMS. Initially, two methodologies were used to access the chemical composition of samples: (1) using a temperature gradient varying from 150 to 600 °C at a heating rate of 150 °C min-1, and (2) with constant temperature of 300 and 400 °C. ASAP(+)-MS ionized many compounds with a typical petroleum profile, showing a greater signals range of m/z 250-1300 and 200-1400 for crude oil and paraffin samples, respectively. Such performance, mainly related to the detection of high molecular weight compounds (>1000 Da), is superior to that of other traditional ionization sources, such as ESI, APCI, DART, and DESI. Additionally, the CA standards were identified in both forms: radicals, [M]+•, and protonated cations, [M + H]+, with minimum fragmentation. Therefore, ASAP was more efficient in accessing the chemical composition of nonpolar and polar compounds. It is promising in its application with ultrahigh resolution MS instruments, such as FT-ICR MS and Orbitrap, since molecular formulas with greater resolution and mass accuracy (<1 ppm) would be assigned. [Figure not available: see fulltext.

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.

Clinical, biopsy, and mass spectrometry findings of renal gelsolin amyloidosis.

PubMed

Sethi, Sanjeev; Dasari, Surendra; Amin, Md Shahrier; Vrana, Julie A; Theis, Jason D; Alexander, Mariam P; Kurtin, Paul J

2017-04-01

Gelsolin amyloidosis is a rare type of amyloidosis typically involving the cranial and peripheral nerves, but rarely the kidney. Here we report the clinical, kidney biopsy, and mass spectrometry findings in 12 cases of renal gelsolin amyloidosis. Of the 12 patients, five were men and seven were women with mean age at diagnosis of 63.8 years. Gelsolin amyloidosis was most common in Caucasians (six patients) and Asians (four patients), and included one each African-American and Hispanic patients. Nephrotic syndrome was the most common cause of biopsy, although most patients also had progressive loss of kidney function. Hematological and serological evaluation was negative in 11 patients, while one patient had a monoclonal gammopathy. The renal biopsy showed large amounts of pale eosinophilic Congo red-positive amyloid deposits typically restricted to the glomeruli. Immunofluorescence studies were negative for immunoglobulins in nine cases with three cases of smudgy glomerular staining for IgG. Electron microscopy showed mostly random arrangement of amyloid fibrils with focally parallel bundles/sheets of amyloid fibrils present. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra numbers for gelsolin, serum amyloid P component, and apolipoproteins E and AIV. Furthermore, the p. Asn211Lys gelsolin mutation on mass spectrometry studies was detected in three patients by mass spectrometry, which appears to represent a renal-limited form of gelsolin amyloidosis. Thus, renal gelsolin amyloidosis is seen in older patients, presents with nephrotic syndrome and progressive chronic kidney disease, and histologically exhibits glomerular involvement. The diagnosis can be confirmed by mass spectrometry studies. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

LILBID-mass spectrometry of the mitochondrial preprotein translocase TOM.

PubMed

Mager, Frauke; Sokolova, Lucie; Lintzel, Julia; Brutschy, Bernhard; Nussberger, Stephan

2010-11-17

In the present work we applied a novel mass spectrometry method termed laser-induced liquid bead ion desorption mass spectrometry (LILBID-MS) to the outer mitochondrial membrane protein translocon TOM to analyze its subunit composition and stoichiometry. With TOM core complex, purified at high pH, we demonstrate that a TOM core complex of Neurospora crassa is composed of at least two Tom40 and Tom22 molecules, respectively, and more than five small Tom subunits between 5.5 and 6.4 kDa. We show that the multiprotein complex has a total molecular mass higher than 170 depending on the number of Tom5, Tom6 and Tom7 molecules bound.

LILBID-mass spectrometry of the mitochondrial preprotein translocase TOM

NASA Astrophysics Data System (ADS)

Mager, Frauke; Sokolova, Lucie; Lintzel, Julia; Brutschy, Bernhard; Nussberger, Stephan

2010-11-01

In the present work we applied a novel mass spectrometry method termed laser-induced liquid bead ion desorption mass spectrometry (LILBID-MS) to the outer mitochondrial membrane protein translocon TOM to analyze its subunit composition and stoichiometry. With TOM core complex, purified at high pH, we demonstrate that a TOM core complex of Neurospora crassa is composed of at least two Tom40 and Tom22 molecules, respectively, and more than five small Tom subunits between 5.5 and 6.4 kDa. We show that the multiprotein complex has a total molecular mass higher than 170 depending on the number of Tom5, Tom6 and Tom7 molecules bound.

Integrating Mass Spectrometry of Intact Protein Complexes into Structural Proteomics

PubMed Central

Hyung, Suk-Joon; Ruotolo, Brandon T.

2013-01-01

Summary Mass spectrometry analysis of intact protein complexes has emerged as an established technology for assessing the composition and connectivity within dynamic, heterogeneous multiprotein complexes at low concentrations and in the context of mixtures. As this technology continues to move forward, one of the main challenges is to integrate the information content of such intact protein complex measurements with other mass spectrometry approaches in structural biology. Methods such as H/D exchange, oxidative foot-printing, chemical cross-linking, affinity purification, and ion mobility separation add complementary information that allows access to every level of protein structure and organization. Here, we survey the structural information that can be retrieved by such experiments, demonstrate the applicability of integrative mass spectrometry approaches in structural proteomics, and look to the future to explore upcoming innovations in this rapidly-advancing area. PMID:22611037

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.

Clinical review: improving the measurement of serum thyroglobulin with mass spectrometry.

PubMed

Hoofnagle, Andrew N; Roth, Mara Y

2013-04-01

Serum thyroglobulin (Tg) measurements are central to the management of patients treated for differentiated thyroid carcinoma. For decades, Tg measurements have relied on methods that are subject to interference by commonly found substances in human serum and plasma, such as Tg autoantibodies. As a result, many patients need additional imaging studies to rule out cancer persistence or recurrence that could be avoided with more sensitive and specific testing methods. The aims of this review are to: 1) briefly review the interferences common to Tg immunoassays; 2) introduce readers to liquid chromatography-tandem mass spectrometry as a method for quantifying proteins in human serum/plasma; and 3) discuss the potential benefits and limitations of the method in the quantification of serum Tg. Mass spectrometric methods have traditionally lacked the sensitivity, robustness, and throughput to be useful clinical assays. These methods failed to meet the necessary clinical benchmarks due to the nature of the mass spectrometry workflow and instrumentation. Over the past few years, there have been major advances in reagents, automation, and instrumentation for the quantification of proteins using mass spectrometry. More recently, methods using mass spectrometry to detect and quantify Tg have been developed and are of sufficient quality to be used in the management of patients. Novel serum Tg assays that use mass spectrometry may avoid the issue of autoantibody interference and other problems with currently available immunoassays for Tg. Prospective studies are needed to fully understand the potential benefits of novel Tg assays to patients and care providers.

Atmospheric pressure ionization-tandem mass spectrometry of the phenicol drug family.

PubMed

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

2013-11-01

In this work, the mass spectrometry behaviour of the veterinary drug family of phenicols, including chloramphenicol (CAP) and its related compounds thiamphenicol (TAP), florfenicol (FF) and FF amine (FFA), was studied. Several atmospheric pressure ionization sources, electrospray (ESI), atmospheric pressure chemical ionization and atmospheric pressure photoionization were compared. In all atmospheric pressure ionization sources, CAP, TAP and FF were ionized in both positive and negative modes; while for the metabolite FFA, only positive ionization was possible. In general, in positive mode, [M + H](+) dominated the mass spectrum for FFA, while the other compounds, CAP, TAP and FF, with lower proton affinity showed intense adducts with species present in the mobile phase. In negative mode, ESI and atmospheric pressure photoionization showed the deprotonated molecule [M-H](-), while atmospheric pressure chemical ionization provided the radical molecular ion by electron capture. All these ions were characterized by tandem mass spectrometry using the combined information obtained by multistage mass spectrometry and high-resolution mass spectrometry in a quadrupole-Orbitrap instrument. In general, the fragmentation occurred via cyclization and losses or fragmentation of the N-(alkyl)acetamide group, and common fragmentation pathways were established for this family of compounds. A new chemical structure for the product ion at m/z 257 for CAP, on the basis of the MS(3) and MS(4) spectra is proposed. Thermally assisted ESI and selected reaction monitoring are proposed for the determination of these compounds by ultra high-performance liquid chromatography coupled to tandem mass spectrometry, achieving instrumental detection limits down to 0.1 pg. Copyright © 2013 John Wiley & Sons, Ltd.

Elucidating rhizosphere processes by mass spectrometry - A review.

PubMed

Rugova, Ariana; Puschenreiter, Markus; Koellensperger, Gunda; Hann, Stephan

2017-03-01

The presented review discusses state-of-the-art mass spectrometric methods, which have been developed and applied for investigation of chemical processes in the soil-root interface, the so-called rhizosphere. Rhizosphere soil's physical and chemical characteristics are to a great extent influenced by a complex mixture of compounds released from plant roots, i.e. root exudates, which have a high impact on nutrient and trace element dynamics in the soil-root interface as well as on microbial activities or soil physico-chemical characteristics. Chemical characterization as well as accurate quantification of the compounds present in the rhizosphere is a major prerequisite for a better understanding of rhizosphere processes and requires the development and application of advanced sampling procedures in combination with highly selective and sensitive analytical techniques. During the last years, targeted and non-targeted mass spectrometry-based methods have emerged and their combination with specific separation methods for various elements and compounds of a wide polarity range have been successfully applied in several studies. With this review we critically discuss the work that has been conducted within the last decade in the context of rhizosphere research and elemental or molecular mass spectrometry emphasizing different separation techniques as GC, LC and CE. Moreover, selected applications such as metal detoxification or nutrient acquisition will be discussed regarding the mass spectrometric techniques applied in studies of root exudates in plant-bacteria interactions. Additionally, a more recent isotope probing technique as novel mass spectrometry based application is highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative aspects of inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Bulska, Ewa; Wagner, Barbara

2016-10-01

Accurate determination of elements in various kinds of samples is essential for many areas, including environmental science, medicine, as well as industry. Inductively coupled plasma mass spectrometry (ICP-MS) is a powerful tool enabling multi-elemental analysis of numerous matrices with high sensitivity and good precision. Various calibration approaches can be used to perform accurate quantitative measurements by ICP-MS. They include the use of pure standards, matrix-matched standards, or relevant certified reference materials, assuring traceability of the reported results. This review critically evaluates the advantages and limitations of different calibration approaches, which are used in quantitative analyses by ICP-MS. Examples of such analyses are provided. This article is part of the themed issue 'Quantitative mass spectrometry'.

[Clinical application of mass spectrometry in the pediatric field: current topics].

PubMed

Yamaguchi, Seiji

2013-09-01

Mass spectrometry, including tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), is becoming prominent in the diagnosis of metabolic disorders in the pediatric field. It enables biochemical diagnosis of metabolic disorders from the metabolic profiles obtained by MS/MS and/or GC/MS. In neonatal mass screening for inherited metabolic disease (IMD) using MS/MS, amino acids and acylcarnitines on dried blood spots are analyzed. The target diseases include amino acidemia, urea cycle disorder, organic acidemia, and fatty acid oxidation disorder. In the MS/MS screening, organic acid analysis using GC/MS is required for differential and/or definite diagnosis of the IMDs. GC/MS data processing, however, is difficult, and metabolic diagnosis often requires the necessary skills and expertize. We developed an automated system of GC/MS data processing and autodiagnosis, and the biochemical diagnosis using GC/MS became markedly easier and user-friendly. Mass spectrometric techniques will expand from research laboratories to clinical laboratories in the near future.

History of mass spectrometry at the Olympic Games.

PubMed

Hemmersbach, Peter

2008-07-01

Mass spectrometry has played a decisive role in doping analysis and doping control in human sport for almost 40 years. The standard of qualitative and quantitative determinations in body fluids has always attracted maximum attention from scientists. With its unique sensitivity and selectivity properties, mass spectrometry provides state-of-the-art technology in analytical chemistry. Both anti-doping organizations and the athletes concerned expect the utmost endeavours to prevent false-positive and false-negative results of the analytical evidence. The Olympic Games play an important role in international sport today and are milestones for technical development in doping analysis. This review of the part played by mass spectrometry in doping control from Munich 1972 to Beijing 2008 Olympics gives an overview of how doping analysis has developed and where we are today. In recognizing the achievements made towards effective doping control, it is of the utmost importance to applaud the joint endeavours of the World Anti-Doping Agency, the International Olympic Committee, the international federations and national anti-doping agencies to combat doping. Advances against the misuse of prohibited substances and methods, which are performance-enhancing, dangerous to health and violate the spirit of sport, can be achieved only if all the stakeholders work together. Copyright 2008 John Wiley & Sons, Ltd.

Nanomanipulation-coupled nanospray mass spectrometry as an approach for single cell analysis

NASA Astrophysics Data System (ADS)

Phelps, Mandy; Hamilton, Jason; Verbeck, Guido F.

2014-12-01

Electrospray mass spectrometry is now a widely used technique for observing cell content of various biological tissues. However, electrospray techniques (liquid chromatography and direct infusion) often involve lysing a group of cells and extracting the biomolecules of interest, rather than a sensitive, individual cell method to observe local chemistry. Presented here is an approach of combining a nanomanipulator workstation with nanospray mass spectrometry, which allows for extraction of a single cell, followed by rapid mass analysis that can provide a detailed metabolic profile. Triacylglycerol content was profiled with this tool coupled to mass spectrometry to investigate heterogeneity between healthy and tumorous tissues as well as lipid droplet containing adipocytes in vitro as proof of concept. This selective approach provides cellular resolution and complements existing bioanalytical techniques with minimal invasion to samples. In addition, the coupling of nanomanipulation and mass spectrometry holds the potential to be used in a great number of applications for individual organelles, diseased tissues, and in vitro cell cultures for observing heterogeneity even amongst cells and organelles of the same tissue.

Surface analysis of lipids by mass spectrometry: more than just imaging.

PubMed

Ellis, Shane R; Brown, Simon H; In Het Panhuis, Marc; Blanksby, Stephen J; Mitchell, Todd W

2013-10-01

Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the "omics" age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of mass spectrometric imaging of lipids in recent years. While imaging mass spectrometry provides new and exciting possibilities, it is but one of the many opportunities direct surface analysis offers the lipid researcher. In this review we describe the current state-of-the-art in the direct surface analysis of lipids with a focus on tissue sections, intact cells and thin-layer chromatography substrates. The suitability of these different approaches towards analysis of the major lipid classes along with their current and potential applications in the field of lipid analysis are evaluated. Copyright © 2013 Elsevier Ltd. All rights reserved.

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...

Quantitation of acrylamide in foods by high-resolution mass spectrometry.

PubMed

Troise, Antonio Dario; Fiore, Alberto; Fogliano, Vincenzo

2014-01-08

Acrylamide detection still represents one of the hottest topics in food chemistry. Solid phase cleanup coupled to liquid chromatography separation and tandem mass spectrometry detection along with GC-MS detection are nowadays the gold standard procedure for acrylamide quantitation thanks to high reproducibility, good recovery, and low relative standard deviation. High-resolution mass spectrometry (HRMS) is particularly suitable for the detection of low molecular weight amides, and it can provide some analytical advantages over other MS techniques. In this paper a liquid chromatography (LC) method for acrylamide determination using HRMS detection was developed and compared to LC coupled to tandem mass spectrometry. The procedure applied a simplified extraction, no cleanup steps, and a 4 min chromatography. It proved to be solid and robust with an acrylamide mass accuracy of 0.7 ppm, a limit of detection of 2.65 ppb, and a limit of quantitation of 5 ppb. The method was tested on four acrylamide-containing foods: cookies, French fries, ground coffee, and brewed coffee. Results were perfectly in line with those obtained by LC-MS/MS.

Quantification of Global DNA Methylation Levels by Mass Spectrometry.

PubMed

Fernandez, Agustin F; Valledor, Luis; Vallejo, Fernando; Cañal, Maria Jesús; Fraga, Mario F

2018-01-01

Global DNA methylation was classically considered the relative percentage of 5-methylcysine (5mC) with respect to total cytosine (C). Early approaches were based on the use of high-performance separation technologies and UV detection. However, the recent development of protocols using mass spectrometry for the detection has increased sensibility and permitted the precise identification of peak compounds based on their molecular masses. This allows work to be conducted with much less genomic DNA starting material and also to quantify 5-hydroxymethyl-cytosine (5hmC), a recently identified form of methylated cytosine that could play an important role in active DNA demethylation. Here, we describe the protocol that we currently use in our laboratory to analyze 5mC and 5hmC by mass spectrometry. The protocol, which is based on the method originally developed by Le and colleagues using Ultra Performance Liquid Chromatography (UPLC) and mass spectrometry (triple Quadrupole (QqQ)) detection, allows for the rapid and accurate quantification of relative global 5mC and 5hmC levels starting from just 1 μg of genomic DNA, which allows for the rapid and accurate quantification of relative global 5mC and 5hmC levels.

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.

Static Time-of-Flight Secondary Ion Mass Spectrometry (SIMS) | Materials

Science.gov Websites

-Flight Secondary Ion Mass Spectrometry (SIMS) Image of high mass resolution and mass accuracy provided by TOF SIMS We used the high mass resolution and mass accuracy of TOF SIMS to study surface cleanliness acidic wash resulted in contamination by Fe and other metals. Without high mass accuracy, the CaO signal

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...

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 .

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.

Simulation of Two Dimensional Electrophoresis and Tandem Mass Spectrometry for Teaching Proteomics

ERIC Educational Resources Information Center

Fisher, Amanda; Sekera, Emily; Payne, Jill; Craig, Paul

2012-01-01

In proteomics, complex mixtures of proteins are separated (usually by chromatography or electrophoresis) and identified by mass spectrometry. We have created 2DE Tandem MS, a computer program designed for use in the biochemistry, proteomics, or bioinformatics classroom. It contains two simulations--2D electrophoresis and tandem mass spectrometry.…

Direct Analysis of Large Living Organism by Megavolt Electrostatic Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Ng, Kwan-Ming; Tang, Ho-Wai; Man, Sin-Heng; Mak, Pui-Yuk; Choi, Yi-Ching; Wong, Melody Yee-Man

2014-09-01

A new ambient ionization method allowing the direct chemical analysis of living human body by mass spectrometry (MS) was developed. This MS method, namely Megavolt Electrostatic Ionization Mass Spectrometry, is based on electrostatic charging of a living individual to megavolt (MV) potential, illicit drugs, and explosives on skin/glove, flammable solvent on cloth/tissue paper, and volatile food substances in breath were readily ionized and detected by a mass spectrometer.

Direct analysis of large living organism by megavolt electrostatic ionization mass spectrometry.

PubMed

Ng, Kwan-Ming; Tang, Ho-Wai; Man, Sin-Heng; Mak, Pui-Yuk; Choi, Yi-Ching; Wong, Melody Yee-Man

2014-09-01

A new ambient ionization method allowing the direct chemical analysis of living human body by mass spectrometry (MS) was developed. This MS method, namely Megavolt Electrostatic Ionization Mass Spectrometry, is based on electrostatic charging of a living individual to megavolt (MV) potential, illicit drugs, and explosives on skin/glove, flammable solvent on cloth/tissue paper, and volatile food substances in breath were readily ionized and detected by a mass spectrometer.

Evolution of Orbitrap Mass Spectrometry Instrumentation

NASA Astrophysics Data System (ADS)

Eliuk, Shannon; Makarov, Alexander

2015-07-01

We discuss the evolution of OrbitrapTM mass spectrometry (MS) from its birth in the late 1990s to its current role as one of the most prominent techniques for MS. The Orbitrap mass analyzer is the first high-performance mass analyzer that employs trapping of ions in electrostatic fields. Tight integration with the ion injection process enables the high-resolution, mass accuracy, and sensitivity that have become essential for addressing analytical needs in numerous areas of research, as well as in routine analysis. We examine three major families of instruments (related to the LTQ Orbitrap, Q Exactive, and Orbitrap Fusion mass spectrometers) in the context of their historical development over the past ten eventful years. We discuss as well future trends and perspectives of Orbitrap MS. We illustrate the compelling potential of Orbitrap-based mass spectrometers as (ultra) high-resolution platforms, not only for high-end proteomic applications, but also for routine targeted analysis.

Mass Spectrometry Parameters Optimization for the 46 Multiclass Pesticides Determination in Strawberries with Gas Chromatography Ion-Trap Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Fernandes, Virgínia C.; Vera, Jose L.; Domingues, Valentina F.; Silva, Luís M. S.; Mateus, Nuno; Delerue-Matos, Cristina

2012-12-01

Multiclass analysis method was optimized in order to analyze pesticides traces by gas chromatography with ion-trap and tandem mass spectrometry (GC-MS/MS). The influence of some analytical parameters on pesticide signal response was explored. Five ion trap mass spectrometry (IT-MS) operating parameters, including isolation time (IT), excitation voltage (EV), excitation time (ET), maximum excitation energy or " q" value (q), and isolation mass window (IMW) were numerically tested in order to maximize the instrument analytical signal response. For this, multiple linear regression was used in data analysis to evaluate the influence of the five parameters on the analytical response in the ion trap mass spectrometer and to predict its response. The assessment of the five parameters based on the regression equations substantially increased the sensitivity of IT-MS/MS in the MS/MS mode. The results obtained show that for most of the pesticides, these parameters have a strong influence on both signal response and detection limit. Using the optimized method, a multiclass pesticide analysis was performed for 46 pesticides in a strawberry matrix. Levels higher than the limit established for strawberries by the European Union were found in some samples.

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

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.

Analysis of the Proteome of Hair-Cell Stereocilia by Mass Spectrometry

PubMed Central

Krey, Jocelyn F.; Wilmarth, Philip A.; David, Larry L.; Barr-Gillespie, Peter G.

2017-01-01

Characterization of proteins that mediate mechanotransduction by hair cells, the sensory cells of the inner ear, is hampered by the scarcity of these cells and their sensory organelle, the hair bundle. Mass spectrometry, with its high sensitivity and identification precision, is the ideal method for determining which proteins are present in bundles and what proteins they interact with. We describe here the isolation of mouse hair bundles, as well as preparation of bundle-protein samples for mass spectrometry. We also describe protocols for data-dependent (shotgun) and parallel-reaction-monitoring (targeted) mass spectrometry that allow us to identify and quantify proteins of the hair bundle. These sensitive methods are particularly useful for comparing proteomes of wild-type and mice with deafness mutations affecting hair-bundle proteins. (120 words; maximum 250) PMID:28109437

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…

Diagnosing Prion Diseases: Mass Spectrometry-Based Approaches

USDA-ARS?s Scientific Manuscript database

Mass spectrometry is an established means of quantitating the prions present in infected hamsters. Calibration curves relating the area ratios of the selected analyte peptides and their oxidized analogs to stable isotope labeled internal standards were prepared. The limit of detection (LOD) and limi...

Staying Alive: Measuring Intact Viable Microbes with Electrospray Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Forsberg, Erica; Fang, Mingliang; Siuzdak, Gary

2017-01-01

Mass spectrometry has traditionally been the technology of choice for small molecule analysis, making significant inroads into metabolism, clinical diagnostics, and pharmacodynamics since the 1960s. In the mid-1980s, with the discovery of electrospray ionization (ESI) for biomolecule analysis, a new door opened for applications beyond small molecules. Initially, proteins were widely examined, followed by oligonucleotides and other nonvolatile molecules. Then in 1991, three intriguing studies reported using mass spectrometry to examine noncovalent protein complexes, results that have been expanded on for the last 25 years. Those experiments also raised the questions: How soft is ESI, and can it be used to examine even more complex interactions? Our lab addressed these questions with the analyses of viruses, which were initially tested for viability following electrospray ionization and their passage through a quadrupole mass analyzer by placing them on an active medium that would allow them to propagate. This observation has been replicated on multiple different systems, including experiments on an even bigger microbe, a spore. The question of analysis was also addressed in the early 2000s with charge detection mass spectrometry. This unique technology could simultaneously measure mass-to-charge and charge, allowing for the direct determination of the mass of a virus. More recent experiments on spores and enveloped viruses have given us insight into the range of mass spectrometry's capabilities (reaching 100 trillion Da), beginning to answer fundamental questions regarding the complexity of these organisms beyond proteins and genes, and how small molecules are integral to these supramolecular living structures.

Detection of new emerging type-A trichothecenes by untargeted mass spectrometry.

PubMed

González-Jartín, Jesús M; Alfonso, Amparo; Sainz, María J; Vieytes, Mercedes R; Botana, Luis M

2018-02-01

Mycotoxins occur naturally as agricultural contaminants all over the world. The toxic effects of some of their metabolites are known and their presence regulated in food and feed. This paper describes two methods for the detection of toxins of type-A trichothecenes group, and their modified forms, using mass spectrometry. Ultra-performance liquid chromatography coupled to mass spectrometry-ion trap-time of flight (UPLC-MS-IT-TOF) was employed to characterize the fragmentation pathways of 10 type-A trichothecenes, and characteristic ions were tentatively identified in scan mode through their accurate masses. Unknown signals were detected in a F. sporotrichioides extract, which afterwards were identified as seven modified forms of neosolaniol (NEO) and T-2 toxin. Then, UPLC coupled to tandem mass spectrometry (MS/MS) was employed to develop a precursor ion scanning method that can be used as a screening tool to detect any modified type-A trichothecenes. Copyright © 2017 Elsevier B.V. All rights reserved.

Ion mobility-mass spectrometry as a tool to investigate protein-ligand interactions.

PubMed

Göth, Melanie; Pagel, Kevin

2017-07-01

Ion mobility-mass spectrometry (IM-MS) is a powerful tool for the simultaneous analysis of mass, charge, size, and shape of ionic species. It allows the characterization of even low-abundant species in complex samples and is therefore particularly suitable for the analysis of proteins and their assemblies. In the last few years even complex and intractable species have been investigated successfully with IM-MS and the number of publications in this field is steadily growing. This trend article highlights recent advances in which IM-MS was used to study protein-ligand complexes and in particular focuses on the catch and release (CaR) strategy and collision-induced unfolding (CIU). Graphical Abstract Native mass spectrometry and ion mobility-mass spectrometry are versatile tools to follow the stoichiometry, energetics, and structural impact of protein-ligand binding.

Ion Mobility Spectrometry (IMS) and Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 newmore » 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.« less

Laser mass spectrometry of chemical warfare agents using ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Weickhardt, C.; Grun, C.; Grotemeyer, J.

1998-12-01

Fast relaxation processes in excited molecules such as IC, ISC, and fragmentation are observed in many environmentally and technically relevant substances. They cause severe problems to resonance ionization mass spectrometry because they reduce the ionization yield and lead to mass spectra which do not allow the identification of the compound. By the use of ultrashort laser pulses these problems can be overcome and the advantages of REMPI over conventional ionization techniques in mass spectrometry can be regained. This is demonstrated using soil samples contaminated with a chemical warfare agent.

Polymer and Additive Mass Spectrometry Literature Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shear, Trevor Allan

The use of mass spectrometry in fields related to polymers has increased significantly over the past three decades and will be explored in this literature review. The importance of this technique is highlighted when exploring how polymers degrade, verifying purchased materials, and as internal requirements change. The primary focus will be on four ionization techniques and the triple quadrupole and quadrupole / time-of-flight mass spectrometers. The advantages and limitations of each will also be explored.

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.

Broad Separation of Isomeric Lipids by High-Resolution Differential Ion Mobility Spectrometry with Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Bowman, Andrew P.; Abzalimov, Rinat R.; Shvartsburg, Alexandre A.

2017-08-01

Maturation of metabolomics has brought a deeper appreciation for the importance of isomeric identity of lipids to their biological role, mirroring that for proteoforms in proteomics. However, full characterization of the lipid isomerism has been thwarted by paucity of rapid and effective analytical tools. A novel approach is ion mobility spectrometry (IMS) and particularly differential or field asymmetric waveform IMS (FAIMS) at high electric fields, which is more orthogonal to mass spectrometry. Here we broadly explore the power of FAIMS to separate lipid isomers, and find a 75% success rate across the four major types of glycero- and phospho- lipids ( sn, chain length, double bond position, and cis/ trans). The resolved isomers were identified using standards, and (for the first two types) tandem mass spectrometry. These results demonstrate the general merit of incorporating high-resolution FAIMS into lipidomic analyses.

Analysis of hydroxamate siderophores in soil solution using liquid chromatography with mass spectrometry and tandem mass spectrometry with on-line sample preconcentration.

PubMed

Olofsson, Madelen A; Bylund, Dan

2015-10-01

A liquid chromatography with electrospray ionization mass spectrometry method was developed to quantitatively and qualitatively analyze 13 hydroxamate siderophores (ferrichrome, ferrirubin, ferrirhodin, ferrichrysin, ferricrocin, ferrioxamine B, D1 , E and G, neocoprogen I and II, coprogen and triacetylfusarinine C). Samples were preconcentrated on-line by a switch-valve setup prior to analyte separation on a Kinetex C18 column. Gradient elution was performed using a mixture of an ammonium formate buffer and acetonitrile. Total analysis time including column conditioning was 20.5 min. Analytes were fragmented by applying collision-induced dissociation, enabling structural identification by tandem mass spectrometry. Limit of detection values for the selected ion monitoring method ranged from 71 pM to 1.5 nM with corresponding values of two to nine times higher for the multiple reaction monitoring method. The liquid chromatography with mass spectrometry method resulted in a robust and sensitive quantification of hydroxamate siderophores as indicated by retention time stability, linearity, sensitivity, precision and recovery. The analytical error of the methods, assessed through random-order, duplicate analysis of soil samples extracted with a mixture of 10 mM phosphate buffer and methanol, appears negligible in relation to between-sample variations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neuropeptide Signaling in Crustaceans Probed by Mass Spectrometry

NASA Astrophysics Data System (ADS)

Liang, Zhidan

Neuropeptides are one of the most diverse classes of signaling molecules whose identities and functions are not yet fully understood. They have been implicated in the regulation of a wide range of physiological processes, including feeding-related and motivated behaviors, and also environmental adaptations. In this work, improved mass spectrometry-based analytical platforms were developed and applied to the crustacean systems to characterize signaling molecules. This dissertation begins with a review of mass spectrometry-based neuropeptide studies from both temporal- and spatial-domains. This review is then followed by several chapters detailing a few research projects related to the crustacean neuropeptidomic characterization and comparative analysis. The neuropeptidome of crayfish, Orconectes rusticus is characterized for the first time using mass spectrometry-based tools. In vivo microdialysis sampling technique offers the capability of direct sampling from extracellular space in a time-resolved manner. It is used to investigate the secreted neuropeptide and neurotransmitter content in Jonah crab, Cancer borealis, in this work. A new quantitation strategy using alternative mass spectrometry data acquisition approach is developed and applied for the first time to quantify neuropeptides. Coupling of this method with microdialysis enables the study of neuropeptide dynamics concurrent with different behaviors. Proof-of-principle experiments validating this approach have been carried out in Jonah crab, Cancer borealis to study feeding- and circadian rhythm-related neuropeptide changes using micoridialysis in a time-resolved manner. This permits a close correlation between behavioral and neurochemical changes, providing potential candidates for future validation of regulatory roles. In addition to providing spatial information, mass spectrometry imaging (MSI) technique enables the characterization of signaling molecules while preserving the temporal resolution. A

Characterization of low-molecular weight iodine-terminated polyethylenes by gas chromatography/mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with the use of derivatization.

PubMed