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

Charge detection mass spectrometry: Instrumentation & applications to viruses

NASA Astrophysics Data System (ADS)

Pierson, Elizabeth E.

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

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.

An adaptable multiple power source for mass spectrometry and other scientific instruments.

PubMed

Lin, T-Y; Anderson, G A; Norheim, R V; Prost, S A; LaMarche, B L; Leach, F E; Auberry, K J; Smith, R D; Koppenaal, D W; Robinson, E W; Paša-Tolić, L

2015-09-01

An Adaptable Multiple Power Source (AMPS) system has been designed and constructed. The AMPS system can provide up to 16 direct current (DC) (±400 V; 5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz) channels, 2 high voltage sources (±6 kV), and one ∼40 W, 250 °C temperature-regulated heater. The system is controlled by a microcontroller, capable of communicating with its front panel or a computer. It can assign not only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS system is capable of driving many mass spectrometry components and ancillary devices and can be adapted to other instrumentation/engineering projects.

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.

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation.

PubMed

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi 3 + beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm 2 . The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation

NASA Astrophysics Data System (ADS)

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi3+ beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm2. The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

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)

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…

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

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

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

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 spectrometry in the U.S. space program: past, present, and future.

PubMed

Palmer, P T; Limero, T F

2001-06-01

Recent years have witnessed significant progress on the miniaturization of mass spectrometers for a variety of field applications. This article describes the development and application of mass spectrometry (MS) instrumentation to support of goals of the U.S. space program. Its main focus is on the two most common space-related applications of MS: studying the composition of planetary atmospheres and monitoring air quality on manned space missions. Both sets of applications present special requirements in terms of analytical performance (sensitivity, selectivity, speed, etc.), logistical considerations (space, weight, and power requirements), and deployment in perhaps the harshest of all possible environments (space). The MS instruments deployed on the Pioneer Venus and Mars Viking Lander missions are reviewed for the purposes of illustrating the unique features of the sample introduction systems, mass analyzers, and vacuum systems, and for presenting their specifications which are impressive even by today's standards. The various approaches for monitoring volatile organic compounds (VOCs) in cabin atmospheres are also reviewed. In the past, ground-based GC/MS instruments have been used to identify and quantify VOCs in archival samples collected during the Mercury, Apollo, Skylab, Space Shuttle, and Mir missions. Some of the data from the more recent missions are provided to illustrate the composition data obtained and to underscore the need for instrumentation to perform such monitoring in situ. Lastly, the development of two emerging technologies, Direct Sampling Ion Trap Mass Spectrometry (DSITMS) and GC/Ion Mobility Spectrometry (GC/IMS), will be discussed to illustrate their potential utility for future missions. c 2001 American Society for Mass Spectrometry.

Mass spectrometry in the U.S. space program: past, present, and future

NASA Technical Reports Server (NTRS)

Palmer, P. T.; Limero, T. F.

2001-01-01

Recent years have witnessed significant progress on the miniaturization of mass spectrometers for a variety of field applications. This article describes the development and application of mass spectrometry (MS) instrumentation to support of goals of the U.S. space program. Its main focus is on the two most common space-related applications of MS: studying the composition of planetary atmospheres and monitoring air quality on manned space missions. Both sets of applications present special requirements in terms of analytical performance (sensitivity, selectivity, speed, etc.), logistical considerations (space, weight, and power requirements), and deployment in perhaps the harshest of all possible environments (space). The MS instruments deployed on the Pioneer Venus and Mars Viking Lander missions are reviewed for the purposes of illustrating the unique features of the sample introduction systems, mass analyzers, and vacuum systems, and for presenting their specifications which are impressive even by today's standards. The various approaches for monitoring volatile organic compounds (VOCs) in cabin atmospheres are also reviewed. In the past, ground-based GC/MS instruments have been used to identify and quantify VOCs in archival samples collected during the Mercury, Apollo, Skylab, Space Shuttle, and Mir missions. Some of the data from the more recent missions are provided to illustrate the composition data obtained and to underscore the need for instrumentation to perform such monitoring in situ. Lastly, the development of two emerging technologies, Direct Sampling Ion Trap Mass Spectrometry (DSITMS) and GC/Ion Mobility Spectrometry (GC/IMS), will be discussed to illustrate their potential utility for future missions. c 2001 American Society for Mass Spectrometry.

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.

The Use of Gas Chromatography and Mass Spectrometry to Introduce General Chemistry Students to Percent Mass and Atomic Mass Calculations

ERIC Educational Resources Information Center

Pfennig, Brian W.; Schaefer, Amy K.

2011-01-01

A general chemistry laboratory experiment is described that introduces students to instrumental analysis using gas chromatography-mass spectrometry (GC-MS), while simultaneously reinforcing the concepts of mass percent and the calculation of atomic mass. Working in small groups, students use the GC to separate and quantify the percent composition…

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.

Extending the frontiers of mass spectrometric instrumentation and methods

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

Schieffer, Gregg Martin

2010-01-01

The focus of this dissertation is two-fold: developing novel analysis methods using mass spectrometry and the implementation and characterization of a novel ion mobility mass spectrometry instrumentation. The novel mass spectrometry combines ion trap for ion/ion reactions coupled to an ion mobility cell. The long term goal of this instrumentation is to use ion/ion reactions to probe the structure of gas phase biomolecule ions. The three ion source - ion trap - ion mobility - qTOF mass spectrometer (IT - IM - TOF MS) instrument is described. The analysis of the degradation products in coal (Chapter 2) and the imagingmore » plant metabolites (Appendix III) fall under the methods development category. These projects use existing commercial instrumentation (JEOL AccuTOF MS and Thermo Finnigan LCQ IT, respectively) for the mass analysis of the degraded coal products and the plant metabolites, respectively. The coal degradation paper discusses the use of the DART ion source for fast and easy sample analysis. The sample preparation consisted of a simple 50 fold dilution of the soluble coal products in water and placing the liquid in front of the heated gas stream. This is the first time the DART ion source has been used for analysis of coal. Steven Raders under the guidance of John Verkade came up with the coal degradation projects. Raders performed the coal degradation reactions, worked up the products, and sent them to me. Gregg Schieffer developed the method and wrote the paper demonstrating the use of the DART ion source for the fast and easy sample analysis. The plant metabolite imaging project extends the use of colloidal graphite as a sample coating for atmospheric pressure LDI. DC Perdian and I closely worked together to make this project work. Perdian focused on building the LDI setup whereas Schieffer focused on the MSn analysis of the metabolites. Both Perdian and I took the data featured in the paper. Perdian was the primary writer of the paper and used it

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.

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.

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

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.

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.

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.

Mass Spectrometry Theatre: A Model for Big-Screen Instrumental Analysis

ERIC Educational Resources Information Center

Allison, John

2008-01-01

Teaching lecture or lab courses in instrumental analysis can be a source of frustration since one can only crowd a small number of students around a single instrument, typically leading to round-robin approaches. Round-robin labs can spread students into multiple labs and limit instructor-student interactions. We discuss "Mass Spectrometry…

Mass Spectrometry for Planetary Probes: Past, Present and Future

NASA Technical Reports Server (NTRS)

Niemann, Hasso B.; Harpold, Dan N.; Jamieson, Brian G.; Mahaffy, Paul R.

2005-01-01

Atmospheric entry probes present a unique opportunity for performing quantitative analysis of extra-terrestrial atmospheres in cases where remote sensing alone may not be sufficient and measurements with balloons or aircraft is not practical. An entry probe can provide a complete vertical profile of atmospheric parameters including chemical composition, which cannot be obtained with most other techniques. There are, however, unique challenges associated with building instruments for an entry probe, as compared to orbiters, landers, or rovers. Conditions during atmospheric entry are extreme, there are inherent time constraints due to the short duration of the experiment, and the instrument experiences rapid environmental changes in temperature and pressure as it descends. In addition, there are resource limitations, i.e. mass, power, size and bandwidth. Finally, the demands on the instrument design are determined in large part by conditions (pressure, temperature, composition) unique to the particular body under study, and as a result there is no one-size-fits-all instrument for an atmospheric probe. Many of these requirements can be more easily met by miniaturizing the probe instrument. Our experience building mass spectrometers for atmospheric entry probes leads us to believe that the time is right for a fundamental change in the way spaceflight mass spectrometers are built. The emergence over the past twenty years of Micro-electro- mechanical Systems (MEMS), utilizing lithographic semiconductor fabrication techniques to produce instrument systems in miniature, holds great promise for application to spaceflight mass spectrometry. A highly miniaturized, high performance and low-power mass spectrometer would be an enormous benefit to future entry probe missions, allowing, for example, parallel measurements (e.g., multiple simultaneous gas chromatographic analyses and direct atmospheric leaks.) Such an instrument would also enable mass spectrometry on board small

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling

NASA Astrophysics Data System (ADS)

Comi, Troy J.; Neumann, Elizabeth K.; Do, Thanh D.; Sweedler, Jonathan V.

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. [Figure not available: see fulltext.

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling.

PubMed

Comi, Troy J; Neumann, Elizabeth K; Do, Thanh D; Sweedler, Jonathan V

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. Graphical Abstract ᅟ.

An automated gas chromatography time-of-flight mass spectrometry instrument for the quantitative analysis of halocarbons in air

NASA Astrophysics Data System (ADS)

Obersteiner, F.; Bönisch, H.; Engel, A.

2016-01-01

We present the characterization and application of a new gas chromatography time-of-flight mass spectrometry instrument (GC-TOFMS) for the quantitative analysis of halocarbons in air samples. The setup comprises three fundamental enhancements compared to our earlier work (Hoker et al., 2015): (1) full automation, (2) a mass resolving power R = m/Δm of the TOFMS (Tofwerk AG, Switzerland) increased up to 4000 and (3) a fully accessible data format of the mass spectrometric data. Automation in combination with the accessible data allowed an in-depth characterization of the instrument. Mass accuracy was found to be approximately 5 ppm in mean after automatic recalibration of the mass axis in each measurement. A TOFMS configuration giving R = 3500 was chosen to provide an R-to-sensitivity ratio suitable for our purpose. Calculated detection limits are as low as a few femtograms by means of the accurate mass information. The precision for substance quantification was 0.15 % at the best for an individual measurement and in general mainly determined by the signal-to-noise ratio of the chromatographic peak. Detector non-linearity was found to be insignificant up to a mixing ratio of roughly 150 ppt at 0.5 L sampled volume. At higher concentrations, non-linearities of a few percent were observed (precision level: 0.2 %) but could be attributed to a potential source within the detection system. A straightforward correction for those non-linearities was applied in data processing, again by exploiting the accurate mass information. Based on the overall characterization results, the GC-TOFMS instrument was found to be very well suited for the task of quantitative halocarbon trace gas observation and a big step forward compared to scanning, quadrupole MS with low mass resolving power and a TOFMS technique reported to be non-linear and restricted by a small dynamical range.

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

Operational Experience of an Open-Access, Subscription-Based Mass Spectrometry and Proteomics Facility.

PubMed

Williamson, Nicholas A

2018-03-01

This paper discusses the successful adoption of a subscription-based, open-access model of service delivery for a mass spectrometry and proteomics facility. In 2009, the Mass Spectrometry and Proteomics Facility at the University of Melbourne (Australia) moved away from the standard fee for service model of service provision. Instead, the facility adopted a subscription- or membership-based, open-access model of service delivery. For a low fixed yearly cost, users could directly operate the instrumentation but, more importantly, there were no limits on usage other than the necessity to share available instrument time with all other users. All necessary training from platform staff and many of the base reagents were also provided as part of the membership cost. These changes proved to be very successful in terms of financial outcomes for the facility, instrument access and usage, and overall research output. This article describes the systems put in place as well as the overall successes and challenges associated with the operation of a mass spectrometry/proteomics core in this manner. Graphical abstract ᅟ.

Operational Experience of an Open-Access, Subscription-Based Mass Spectrometry and Proteomics Facility

NASA Astrophysics Data System (ADS)

Williamson, Nicholas A.

2018-03-01

This paper discusses the successful adoption of a subscription-based, open-access model of service delivery for a mass spectrometry and proteomics facility. In 2009, the Mass Spectrometry and Proteomics Facility at the University of Melbourne (Australia) moved away from the standard fee for service model of service provision. Instead, the facility adopted a subscription- or membership-based, open-access model of service delivery. For a low fixed yearly cost, users could directly operate the instrumentation but, more importantly, there were no limits on usage other than the necessity to share available instrument time with all other users. All necessary training from platform staff and many of the base reagents were also provided as part of the membership cost. These changes proved to be very successful in terms of financial outcomes for the facility, instrument access and usage, and overall research output. This article describes the systems put in place as well as the overall successes and challenges associated with the operation of a mass spectrometry/proteomics core in this manner. [Figure not available: see fulltext.

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...

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

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.

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

Biomark/Organic Analysis with Time-of-Flight Mass Spectrometry

NASA Technical Reports Server (NTRS)

Waite, J. Hunter, Jr.

2004-01-01

The concept of a Comprehensive 2-Dimensional Gas Chromatography coupled with Time-of-Flight Mass Spectrometry (GCxGC-TOWS) for the analysis of organic compounds has been proven with commercially available instrumentation (LECO Corp). The performance of a GCxGC instrument has been characterized in various stages using two independent breadboard systems. The GCxGC separation systems, including the thermal modulator, have been miniaturized to the size of a benchtop configuration. One breadboard system employs a Flame Ionization Detector (FID), whereas the second breadboard system employs a Time-of-Fight mass spectrometer (TOFWS) as a detection system.

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.

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.

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

Imaging Mass Spectrometry on the Nanoscale with Cluster Ion Beams

PubMed Central

2015-01-01

Imaging with cluster secondary ion mass spectrometry (SIMS) is reaching a mature level of development. Using a variety of molecular ion projectiles to stimulate desorption, 3-dimensional imaging with the selectivity of mass spectrometry can now be achieved with submicrometer spatial resolution and <10 nm depth resolution. In this Perspective, stock is taken regarding what it will require to routinely achieve these remarkable properties. Issues include the chemical nature of the projectile, topography formation, differential erosion rates, and perhaps most importantly, ionization efficiency. Shortcomings of existing instrumentation are also noted. Speculation about how to successfully resolve these issues is a key part of the discussion. PMID:25458665

Liulin-type spectrometry-dosimetry instruments.

PubMed

Dachev, Ts; Dimitrov, Pl; Tomov, B; Matviichuk, Yu; Spurny, F; Ploc, O; Brabcova, K; Jadrnickova, I

2011-03-01

The main purpose of Liulin-type spectrometry-dosimetry instruments (LSDIs) is cosmic radiation monitoring at the workplaces. An LSDI functionally is a low mass, low power consumption or battery-operated dosemeter. LSDIs were calibrated in a wide range of radiation fields, including radiation sources, proton and heavy-ion accelerators and CERN-EC high-energy reference field. Since 2000, LSDIs have been used in the scientific programmes of four manned space flights on the American Laboratory and ESA Columbus modules and on the Russian segment of the International Space Station, one Moon spacecraft and three spacecraft around the Earth, one rocket, two balloons and many aircraft flights. In addition to relative low price, LSDIs have proved their ability to qualify the radiation field on the ground and on the above-mentioned carriers.

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

Bio-Aerosol Detection Using Mass Spectrometry: Public Health Applications

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

Ludvigson, Laura D.

2004-01-01

I recently spent a summer as an intern at the Lawrence Livermore National Laboratory. I worked on a project involving the real-time, reagentless, single cell detection of aerosolized pathogens using a novel mass spectrometry approach called Bio-Aerosol Mass Spectrometry (BAMS). Based upon preliminary results showing the differentiation capabilities of BAMS, I would like to explore the development and use of this novel detection system in the context of both environmental and clinical sample pathogen detection. I would also like to explore the broader public health applications that a system such as BAMS might have in terms of infectious disease preventionmore » and control. In order to appreciate the potential of this instrument, I will demonstrate the need for better pathogen detection methods, and outline the instrumentation, data analysis and preliminary results that lead me toward a desire to explore this technology further. I will also discuss potential experiments for the future along with possible problems that may be encountered along the way.« less

Clinical protein mass spectrometry.

PubMed

Scherl, Alexander

2015-06-15

Quantitative protein analysis is routinely performed in clinical chemistry laboratories for diagnosis, therapeutic monitoring, and prognosis. Today, protein assays are mostly performed either with non-specific detection methods or immunoassays. Mass spectrometry (MS) is a very specific analytical method potentially very well suited for clinical laboratories. Its unique advantage relies in the high specificity of the detection. Any protein sequence variant, the presence of a post-translational modification or degradation will differ in mass and structure, and these differences will appear in the mass spectrum of the protein. On the other hand, protein MS is a relatively young technique, demanding specialized personnel and expensive instrumentation. Many scientists and opinion leaders predict MS to replace immunoassays for routine protein analysis, but there are only few protein MS applications routinely used in clinical chemistry laboratories today. The present review consists of a didactical introduction summarizing the pros and cons of MS assays compared to immunoassays, the different instrumentations, and various MS protein assays that have been proposed and/or are used in clinical laboratories. An important distinction is made between full length protein analysis (top-down method) and peptide analysis after enzymatic digestion of the proteins (bottom-up method) and its implication for the protein assay. The document ends with an outlook on what type of analyses could be used in the future, and for what type of applications MS has a clear advantage compared to immunoassays. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Co-registered Topographical, Band Excitation Nanomechanical, and Mass Spectral Imaging Using a Combined Atomic Force Microscopy/Mass Spectrometry Platform

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

Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera

The advancement of a hybrid atomic force microscopy/mass spectrometry imaging platform demonstrating for the first time co-registered topographical, band excitation nanomechanical, and mass spectral imaging of a surface using a single instrument is reported. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for pyrolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. We discuss the basic instrumental setup and operation and the multimodal imaging capability and utility are demonstrated using a phase separated polystyrene/poly(2-vinylpyridine) polymer blend thin film. The topography and band excitation images showedmore » that the valley and plateau regions of the thin film surface were comprised primarily of one of the two polymers in the blend with the mass spectral chemical image used to definitively identify the polymers at the different locations. Data point pixel size for the topography (390 nm x 390 nm), band excitation (781 nm x 781 nm), mass spectrometry (690 nm x 500 nm) images was comparable and submicrometer in all three cases, but the data voxel size for each of the three images was dramatically different. The topography image was uniquely a surface measurement, whereas the band excitation image included information from an estimated 10 nm deep into the sample and the mass spectral image from 110-140 nm in depth. Moreover, because of this dramatic sampling depth variance, some differences in the band excitation and mass spectrometry chemical images were observed and were interpreted to indicate the presence of a buried interface in the sample. The spatial resolution of the mass spectral image was estimated to be between 1.5 m 2.6 m, based on the ability to distinguish surface features in that image that were also observed in the other images.« less

Co-registered Topographical, Band Excitation Nanomechanical, and Mass Spectral Imaging Using a Combined Atomic Force Microscopy/Mass Spectrometry Platform

DOE PAGES

Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera; ...

2015-03-18

The advancement of a hybrid atomic force microscopy/mass spectrometry imaging platform demonstrating for the first time co-registered topographical, band excitation nanomechanical, and mass spectral imaging of a surface using a single instrument is reported. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for pyrolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. We discuss the basic instrumental setup and operation and the multimodal imaging capability and utility are demonstrated using a phase separated polystyrene/poly(2-vinylpyridine) polymer blend thin film. The topography and band excitation images showedmore » that the valley and plateau regions of the thin film surface were comprised primarily of one of the two polymers in the blend with the mass spectral chemical image used to definitively identify the polymers at the different locations. Data point pixel size for the topography (390 nm x 390 nm), band excitation (781 nm x 781 nm), mass spectrometry (690 nm x 500 nm) images was comparable and submicrometer in all three cases, but the data voxel size for each of the three images was dramatically different. The topography image was uniquely a surface measurement, whereas the band excitation image included information from an estimated 10 nm deep into the sample and the mass spectral image from 110-140 nm in depth. Moreover, because of this dramatic sampling depth variance, some differences in the band excitation and mass spectrometry chemical images were observed and were interpreted to indicate the presence of a buried interface in the sample. The spatial resolution of the mass spectral image was estimated to be between 1.5 m 2.6 m, based on the ability to distinguish surface features in that image that were also observed in the other images.« less

Selective-Reagent-Ionization Mass Spectrometry: New Prospects for Atmospheric Research

NASA Astrophysics Data System (ADS)

Sulzer, Philipp; Jordan, Alfons; Hartungen, Eugen; Hanel, Gernot; Jürschik, Simone; Herbig, Jens; Märk, Lukas; Märk, Tilmann D.

2014-05-01

Proton-Transfer-Reaction Mass Spectrometry (PTR-MS), which was introduced to the scientific community in the 1990's, has quickly evolved into a well-established technology for atmospheric research and environmental chemistry [1]. Advantages of PTR-MS are i) high sensitivities of several hundred cps/ppbv, ii) detection limits at or below the pptv level, iii) direct injection sampling (i.e. no sample preparation), iv) response times in the 100 ms regime and v) online quantification. However, one drawback is a somehow limited selectivity, as in case of quadrupole mass filter based instruments only information about nominal m/z are available. In Time-Of-Flight (TOF) mass analyzer based instruments selectivity is drastically increased by a high mass resolution of up to 8000 m/Δm, but e.g. isomers still cannot be separated. In 2009 we introduced an advanced version of PTR-MS, which permits switching the reagent ions from H3O+ to NO+ and O2+, respectively [2]. This novel type of instrumentation was called Selective-Reagent-Ionization Mass Spectrometry (SRI-MS) and has been successfully used to separate isomers, e.g. the biogenic compounds isoprene and 2-methyl-3-buten-2-ol as shown by Karl et al. [3]. Switching the reagent ions dramatically increases selectivity and thus applicability of SRI-MS in atmospheric research. Here we report on the latest results utilizing an even more advanced embodiment of SRI-MS enabling the use of the additional reagent ions Kr+ and Xe+ [4]. With this technology important atmospheric compounds, such as CO2, CO, CH4, O2, etc. can be quantified and selectivity is increased even further. We present comparison data between diesel and gasoline car exhaust gases and quantitative data on indoor air for these compounds, which are not detectable with classical PTR-MS. Additionally, we show very recent examples of isomers which cannot be separated with PTR-MS but can clearly be distinguished with SRI-MS. Finally, we give an overview of ongoing SRI

Imaging Mass Spectrometry on the Nanoscale with Cluster Ion Beams

DOE PAGES

Winograd, Nicholas

2014-12-02

Imaging with cluster secondary ion mass spectrometry (SIMS) is reaching a mature level of development. When, using a variety of molecular ion projectiles to stimulate desorption, 3-dimensional imaging with the selectivity of mass spectrometry can now be achieved with submicrometer spatial resolution and <10 nm depth resolution. In this Perspective, stock is taken regarding what it will require to routinely achieve these remarkable properties. Some issues include the chemical nature of the projectile, topography formation, differential erosion rates, and perhaps most importantly, ionization efficiency. Shortcomings of existing instrumentation are also noted. One key part of this discussion involves speculation onmore » how best to resolve these issues.« less

Imaging Mass Spectrometry on the Nanoscale with Cluster Ion Beams

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

Winograd, Nicholas

Imaging with cluster secondary ion mass spectrometry (SIMS) is reaching a mature level of development. When, using a variety of molecular ion projectiles to stimulate desorption, 3-dimensional imaging with the selectivity of mass spectrometry can now be achieved with submicrometer spatial resolution and <10 nm depth resolution. In this Perspective, stock is taken regarding what it will require to routinely achieve these remarkable properties. Some issues include the chemical nature of the projectile, topography formation, differential erosion rates, and perhaps most importantly, ionization efficiency. Shortcomings of existing instrumentation are also noted. One key part of this discussion involves speculation onmore » how best to resolve these issues.« less

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.

Isotope ratio analysis by Orbitrap mass spectrometry

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

Carbohydrate profiling of bacteria by gas chromatography-mass spectrometry and their trace detection in complex matrices by gas chromatography-tandem mass spectrometry.

PubMed

Fox, A

1999-05-28

Bacterial cellular polysaccharides are composed of a variety of sugar monomers. These sugars serve as chemical markers to identify specific species or genera or to determine their physiological status. Some of these markers can also be used for trace detection of bacteria or their constituents in complex clinical or environmental matrices. Analyses are performed, in our hands, employing hydrolysis followed by the alditol acetate derivatization procedure. Substantial improvements have been made to sample preparation including simplification and computer-controlled automation. For characterization of whole cell bacterial hydrolysates, sugars are analyzed by gas chromatography-mass spectrometry (GC-MS). Simple chromatograms are generated using selected ion monitoring (SIM). Using total ion GC-MS, sugars can be readily identified. In more complex clinical and environmental samples, markers for bacteria are present at sufficiently low concentrations that more advanced instrumentation, gas chromatography-tandem mass spectrometry (GC-MS-MS), is preferred for optimal analysis. Using multiple reaction monitoring, MS-MS is used (replacing more conventional SIM) to ignore extraneous chromatographic peaks. Triple quadrupole and ion trap GC-MS-MS instruments have both been used successfully. Absolute chemical identification of sugar markers at trace levels is achieved, using MS-MS, by the product spectrum.

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

Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control.

PubMed

Ojanperä, Ilkka; Kolmonen, Marjo; Pelander, Anna

2012-05-01

Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography-mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology.

A survey of mass analyzers. [characteristics and features of various instruments and techniques

NASA Technical Reports Server (NTRS)

Moore, W. W., Jr.; Tashbar, P. W.

1973-01-01

With the increasing applications of mass spectrometry technology to diverse services areas, a need has developed for a consolidated survey of the essential characteristics and features of the various instruments and techniques. This report is one approach to satisfying this need. Information has been collected and consolidated into a format which includes for each approach: (1) a general technique description, (2) instrument features information, and (3) a summary of pertinent advantages and disadvantages. With this information, the potential mass spectrometer user should be able to more efficiently select the most appropriate instrument.

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

Isotope ratio mass spectrometry in nutrition research

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

Luke, A.H.

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

File formats commonly used in mass spectrometry proteomics.

PubMed

Deutsch, Eric W

2012-12-01

The application of mass spectrometry (MS) to the analysis of proteomes has enabled the high-throughput identification and abundance measurement of hundreds to thousands of proteins per experiment. However, the formidable informatics challenge associated with analyzing MS data has required a wide variety of data file formats to encode the complex data types associated with MS workflows. These formats encompass the encoding of input instruction for instruments, output products of the instruments, and several levels of information and results used by and produced by the informatics analysis tools. A brief overview of the most common file formats in use today is presented here, along with a discussion of related topics.

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

TEMPO-Assisted Free Radical-Initiated Peptide Sequencing Mass Spectrometry (FRIPS MS) in Q-TOF and Orbitrap Mass Spectrometers: Single-Step Peptide Backbone Dissociations in Positive Ion Mode

NASA Astrophysics Data System (ADS)

Jang, Inae; Lee, Sun Young; Hwangbo, Song; Kang, Dukjin; Lee, Hookeun; Kim, Hugh I.; Moon, Bongjin; Oh, Han Bin

2017-01-01

The present study demonstrates that one-step peptide backbone fragmentations can be achieved using the TEMPO [2-(2,2,6,6-tetramethyl piperidine-1-oxyl)]-assisted free radical-initiated peptide sequencing (FRIPS) mass spectrometry in a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometer and a Q-Exactive Orbitrap instrument in positive ion mode, in contrast to two-step peptide fragmentation in an ion-trap mass spectrometer (reference Anal. Chem. 85, 7044-7051 (30)). In the hybrid Q-TOF and Q-Exactive instruments, higher collisional energies can be applied to the target peptides, compared with the low collisional energies applied by the ion-trap instrument. The higher energy deposition and the additional multiple collisions in the collision cell in both instruments appear to result in one-step peptide backbone dissociations in positive ion mode. This new finding clearly demonstrates that the TEMPO-assisted FRIPS approach is a very useful tool in peptide mass spectrometry research.

Advanced capabilities for in situ planetary mass spectrometry

NASA Astrophysics Data System (ADS)

Arevalo, R. D., Jr.; Mahaffy, P. R.; Brinckerhoff, W. B.; Getty, S.; Benna, M.; van Amerom, F. H. W.; Danell, R.; Pinnick, V. T.; Li, X.; Grubisic, A.; Cornish, T.; Hovmand, L.

2015-12-01

NASA GSFC has delivered highly capable quadrupole mass spectrometers (QMS) for missions to Venus (Pioneer Venus), Jupiter (Galileo), Saturn/Titan (Cassini-Huygens), Mars (MSL and MAVEN), and the Moon (LADEE). Our understanding of the Solar System has been expanded significantly by these exceedingly versatile yet low risk and cost efficient instruments. GSFC has developed more recently a suite of advanced instrument technologies promising enhanced science return while selectively leveraging heritage designs. Relying on a traditional precision QMS, the Analysis of Gas Evolved from Samples (AGES) instrument measures organic inventory, determines exposure age and establishes the absolute timing of deposition/petrogenesis of interrogated samples. The Mars Organic Molecule Analyzer (MOMA) aboard the ExoMars 2018 rover employs a two-dimensional ion trap, built analogously to heritage QMS rod assemblies, which can support dual ionization sources, selective ion enrichment and tandem mass spectrometry (MS/MS). The same miniaturized analyzer serves as the core of the Linear Ion Trap Mass Spectrometer (LITMS) instrument, which offers negative ion detection (switchable polarity) and an extended mass range (>2000 Da). Time-of-flight mass spectrometers (TOF-MS) have been interfaced to a range of laser sources to progress high-sensitivity laser ablation and desorption methods for analysis of inorganic and non-volatile organic compounds, respectively. The L2MS (two-step laser mass spectrometer) enables the desorption of neutrals and/or prompt ionization at IR (1.0 up to 3.1 µm, with an option for tunability) or UV wavelengths (commonly 266 or 355 nm). For the selective ionization of specific classes of organics, such as aromatic hydrocarbons, a second UV laser may be employed to decouple the desorption and ionization steps and limit molecular fragmentation. Mass analyzers with substantially higher resolving powers (up to m/Δm > 100,000), such as the Advanced Resolution Organic

Advances in 193 nm excimer lasers for mass spectrometry applications

NASA Astrophysics Data System (ADS)

Delmdahl, Ralph; Esser, Hans-Gerd; Bonati, Guido

2016-03-01

Ongoing progress in mass analysis applications such as laser ablation inductively coupled mass spectrometry of solid samples and ultraviolet photoionization mediated sequencing of peptides and proteins is to a large extent driven by ultrashort wavelength excimer lasers at 193 nm. This paper will introduce the latest improvements achieved in the development of compact high repetition rate excimer lasers and elaborate on the impact on mass spectrometry instrumentation. Various performance and lifetime measurements obtained in a long-term endurance test over the course of 18 months will be shown and discussed in view of the laser source requirements of different mass spectrometry tasks. These sampling type applications are served by excimer lasers delivering pulsed 193 nm output of several mJ as well as fast repetition rates which are already approaching one Kilohertz. In order to open up the pathway from the laboratory to broader market industrial use, sufficient component lifetimes and long-term stable performance behavior have to be ensured. The obtained long-term results which will be presented are based on diverse 193 nm excimer laser tube improvements aiming at e.g. optimizing the gas flow dynamics and have extended the operational life the laser tube for the first time over several billion pulses even under high duty-cycle conditions.

Ion mobility-mass spectrometry of complex carbohydrates: collision cross sections of sodiated N-linked glycans.

PubMed

Pagel, Kevin; Harvey, David J

2013-05-21

Currently, the vast majority of complex carbohydrates are characterized using mass spectrometry (MS)-based techniques. Measuring the molecular mass of a sugar, however, immediately poses a fundamental problem: entire classes of the constituting monosaccharide building blocks exhibit an identical atomic composition and, consequently, also an identical mass. Therefore, carbohydrate MS data can be highly ambiguous and often it is simply not possible to clearly assign a particular molecular structure. A promising approach to overcome the above-mentioned limitation is to implement an additional gas-phase separation dimension using ion mobility spectrometry (IMS), which is a method in which molecules of identical mass and structure but different structure can be separated according to their shape and collision cross section (CCS). With the emergence of commercially available hybrid ion mobility-mass spectrometry (IM-MS) instruments in 2006, IMS technology became readily available. Because of the nonhomogeneous, traveling wave (TW) field utilized in these instruments, however, CCS values currently cannot be determined directly from the drift times measured. Instead, an external calibration using compounds of known CCS and similar molecular identity is required. Here, we report a calibration protocol for TW IMS instruments using a series of sodiated N-glycans that were released from commercially available glycoproteins using an easy-to-follow protocol. The underlying CCS values were determined using a modified Synapt HDMS instrument with a linear drift tube, which was described in detail previously. Our data indicate that, under in-source fragmentation conditions, only a few glycans are required to obtain a TW IMS calibration of sufficient quality. In this context, however, the type of glycan was shown to be of tremendous importance. Furthermore, our data clearly demonstrate that carbohydrate isomers with identical mass but different conformation can be distinguished based

Challenges ahead for mass spectrometry and proteomics applications in epigenetics.

PubMed

Kessler, Benedikt M

2010-02-01

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

Tandem Mass Spectrometry on a Miniaturized Laser Desorption Time-of-Flight Mass Spectrometer

NASA Technical Reports Server (NTRS)

Li, Xiang; Cornish, Timothy; Getty, Stephanie A.; Brinckerhoff, William B.

2016-01-01

Tandem mass spectrometry (MSMS) is a powerful and widely-used technique for identifying the molecular structure of organic constituents of a complex sample. Application of MSMS to the study of unknown planetary samples on a remote space mission would contribute to our understanding of the origin, evolution, and distribution of extraterrestrial organics in our solar system. Here we report on the realization of MSMS on a miniaturized laser desorption time-of-flight mass spectrometer (LD-TOF-MS), which is one of the most promising instrument types for future planetary missions. This achievement relies on two critical components: a curved-field reflectron and a pulsed-pin ion gate. These enable use of the complementary post-source decay (PSD) and laser-assisted collision induced dissociation (L-CID) MSMS methods on diverse measurement targets with only modest investment in instrument resources such as volume and weight. MSMS spectra of selected molecular targets in various organic standards exhibit excellent agreement when compared with results from a commercial, laboratory-scale TOF instrument, demonstrating the potential of this powerful technique in space and planetary environments.

File Formats Commonly Used in Mass Spectrometry Proteomics*

PubMed Central

Deutsch, Eric W.

2012-01-01

The application of mass spectrometry (MS) to the analysis of proteomes has enabled the high-throughput identification and abundance measurement of hundreds to thousands of proteins per experiment. However, the formidable informatics challenge associated with analyzing MS data has required a wide variety of data file formats to encode the complex data types associated with MS workflows. These formats encompass the encoding of input instruction for instruments, output products of the instruments, and several levels of information and results used by and produced by the informatics analysis tools. A brief overview of the most common file formats in use today is presented here, along with a discussion of related topics. PMID:22956731

Measuring Thermodynamic Properties of Metals and Alloys With Knudsen Effusion Mass Spectrometry

NASA Technical Reports Server (NTRS)

Copland, Evan H.; Jacobson, Nathan S.

2010-01-01

This report reviews Knudsen effusion mass spectrometry (KEMS) as it relates to thermodynamic measurements of metals and alloys. First, general aspects are reviewed, with emphasis on the Knudsen-cell vapor source and molecular beam formation, and mass spectrometry issues germane to this type of instrument are discussed briefly. The relationship between the vapor pressure inside the effusion cell and the measured ion intensity is the key to KEMS and is derived in detail. Then common methods used to determine thermodynamic quantities with KEMS are discussed. Enthalpies of vaporization, the fundamental measurement, are determined from the variation of relative partial pressure with temperature using the second-law method or by calculating a free energy of formation and subtracting the entropy contribution using the third-law method. For single-cell KEMS instruments, measurements can be used to determine the partial Gibbs free energy if the sensitivity factor remains constant over multiple experiments. The ion-current ratio method and dimer-monomer method are also viable in some systems. For a multiple-cell KEMS instrument, activities are obtained by direct comparison with a suitable component reference state or a secondary standard. Internal checks for correct instrument operation and general procedural guidelines also are discussed. Finally, general comments are made about future directions in measuring alloy thermodynamics with KEMS.

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.

Oil-in-water monitoring using membrane inlet mass spectrometry.

PubMed

Brkić, Boris; France, Neil; Taylor, Stephen

2011-08-15

A membrane inlet mass spectrometry (MIMS) system has been used for detection and analysis of two types of North Sea crude oil. The system was installed on-field on the Flotta Oil Terminal (Orkney, UK). It consisted of a quadrupole mass spectrometer (QMS) connected to the capillary probe with a silicone-based membrane. The produced mass spectra and calibration plots from the MIMS instrument showed the capability to measure levels of individual hydrocarbons within crude oil in seawater. The generated mass spectra from the field tests also showed the ability to distinguish between different types of oil and to determine concentrations of toxic hydrocarbons in oil (e.g., benzene, toluene, and xylene (BTX)). The performance of the instrument at different temperatures of seawater and oil droplet sizes was also investigated. The results showed that the QMS-based MIMS system has a potential to complement existing oil-in-water (OiW) monitors by being able to detect different oil types and specific hydrocarbon concentrations with high accuracy, which are currently not supported in commercially available OiW monitors.

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)

Analysis of sulfates on low molecular weight heparin using mass spectrometry: structural characterization of enoxaparin.

PubMed

Gupta, Rohitesh; Ponnusamy, Moorthy P

2018-05-31

Structural characterization of low molecular weight heparin (LMWH) is critical to meet biosimilarity standards. In this context, the review focuses on structural analysis of labile sulfates attached to the side-groups of LMWH using mass spectrometry. A comprehensive review of this topic will help readers to identify key strategies for tackling the problem related to sulfate loss. At the same time, various mass spectrometry techniques are presented to facilitate compositional analysis of LMWH, mainly enoxaparin. Areas covered: This review summarizes findings on mass spectrometry application for LMWH, including modulation of sulfates, using enzymology and sample preparation approaches. Furthermore, popular open-source software packages for automated spectral data interpretation are also discussed. Successful use of LC/MS can decipher structural composition for LMWH and help evaluate their sameness or biosimilarity with the innovator molecule. Overall, the literature has been searched using PubMed by typing various search queries such as 'enoxaparin', 'mass spectrometry', 'low molecular weight heparin', 'structural characterization', etc. Expert commentary: This section highlights clinically relevant areas that need improvement to achieve satisfactory commercialization of LMWHs. It also primarily emphasizes the advancements in instrumentation related to mass spectrometry, and discusses building automated software for data interpretation and analysis.

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.

Newborn screening for sickling and other haemoglobin disorders using tandem mass spectrometry: A pilot study of methodology in laboratories in England.

PubMed

Daniel, Yvonne A; Henthorn, Joan

2016-12-01

To determine (i) if electrospray mass spectrometry-mass spectrometry with the SpOtOn Diagnostics Ltd reagent kit for sickle cell screening could be integrated into the English newborn screening programme, under routine screening conditions, and provide mass spectrometry-mass spectrometry results which match existing methods, and (ii) if common action values could be set for all manufacturers in the study, for all assessed haemoglobins, to indicate which samples require further investigation. Anonymised residual blood spots were analysed using the SpOtOn reagent kit as per manufacturer's instructions, in parallel with existing techniques at four laboratories. Mass spectrometry-mass spectrometry instrumentation at Laboratories A and B was AB Sciex (Warrington, UK) AP4000, and at Laboratories C and D, Waters Micromass (Manchester, UK), Xevo TQMS and Premier, respectively. There were 23,898 results accepted from the four laboratories. Excellent specificity at 100% sensitivity was observed for haemoglobin S, haemoglobin C, haemoglobin E and haemoglobin O Arab . A common action value was not possible for Hb C, but action values were set by manufacturer. The two haemoglobin D Punjab cases at Laboratory D were not detected using the common action value. Conversely, false-positive results with haemoglobin D Punjab were a problem at the remaining three laboratories. This multicentre study demonstrates that it is possible to implement mass spectrometry-mass spectrometry into an established screening programme while maintaining consistency with existing methods for haemoglobinopathy screening. However, one of the instruments investigated cannot be recommended for use with this application. © The Author(s) 2016.

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

Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology.

PubMed

Peters, Frank T

2011-01-01

Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) has become increasingly important in clinical and forensic toxicology as well as doping control and is now a robust and reliable technique for routine analysis in these fields. In recent years, methods for LC-MS(/MS)-based systematic toxicological analysis using triple quadrupole or ion trap instruments have been considerably improved and a new screening approach based on high-resolution MS analysis using benchtop time-of-flight MS instruments has been developed. Moreover, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in various biomatrices have been published. The present paper will provide an overview and discuss these recent developments focusing on the literature published after 2006. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

Mass Spectrometry as a Powerful Analytical Technique for the Structural Characterization of Synthesized and Natural Products

NASA Astrophysics Data System (ADS)

Es-Safi, Nour-Eddine; Essassi, El Mokhtar; Massoui, Mohamed; Banoub, Joseph

Mass spectrometry is an important tool for the identification and structural elucidation of natural and synthesized compounds. Its high sensitivity and the possibility of coupling liquid chromatography with mass spectrometry detection make it a technique of choice for the investigation of complex mixtures like raw natural extracts. The mass spectrometer is a universal detector that can achieve very high sensitivity and provide information on the molecular mass. More detailed information can be subsequently obtained by resorting to collision-induced dissociation tandem mass spectrometry (CID-MS/MS). In this review, the application of mass spectrometric techniques for the identification of natural and synthetic compounds is presented. The gas-phase fragmentation patterns of a series of four natural flavonoid glycosides, three synthesized benzodiazepines and two synthesized quinoxalinone derivatives were investigated using electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry techniques. Exact accurate masses were measured using a modorate resolution quadrupole orthogonal time-of-flight QqTOF-MS/MS hybrid mass spectrometer instrument. Confirmation of the molecular masses and the chemical structures of the studied compounds were achieved by exploring the gas-phase breakdown routes of the ionized molecules. This was rationalized by conducting low-energy collision CID-MS/MS analyses (product ion- and precursor ion scans) using a conventional quadrupole hexapole-quadrupole (QhQ) tandem mass spectrometer.

Investigating quantitation of phosphorylation using MALDI-TOF mass spectrometry.

PubMed

Parker, Laurie; Engel-Hall, Aaron; Drew, Kevin; Steinhardt, George; Helseth, Donald L; Jabon, David; McMurry, Timothy; Angulo, David S; Kron, Stephen J

2008-04-01

Despite advances in methods and instrumentation for analysis of phosphopeptides using mass spectrometry, it is still difficult to quantify the extent of phosphorylation of a substrate because of physiochemical differences between unphosphorylated and phosphorylated peptides. Here we report experiments to investigate those differences using MALDI-TOF mass spectrometry for a set of synthetic peptides by creating calibration curves of known input ratios of peptides/phosphopeptides and analyzing their resulting signal intensity ratios. These calibration curves reveal subtleties in sequence-dependent differences for relative desorption/ionization efficiencies that cannot be seen from single-point calibrations. We found that the behaviors were reproducible with a variability of 5-10% for observed phosphopeptide signal. Although these data allow us to begin addressing the issues related to modeling these properties and predicting relative signal strengths for other peptide sequences, it is clear that this behavior is highly complex and needs to be further explored. John Wiley & Sons, Ltd

Investigating quantitation of phosphorylation using MALDI-TOF mass spectrometry

PubMed Central

Parker, Laurie; Engel-Hall, Aaron; Drew, Kevin; Steinhardt, George; Helseth, Donald L.; Jabon, David; McMurry, Timothy; Angulo, David S.; Kron, Stephen J.

2010-01-01

Despite advances in methods and instrumentation for analysis of phosphopeptides using mass spectrometry, it is still difficult to quantify the extent of phosphorylation of a substrate due to physiochemical differences between unphosphorylated and phosphorylated peptides. Here we report experiments to investigate those differences using MALDI-TOF mass spectrometry for a set of synthetic peptides by creating calibration curves of known input ratios of peptides/phosphopeptides and analyzing their resulting signal intensity ratios. These calibration curves reveal subtleties in sequence-dependent differences for relative desorption/ionization efficiencies that cannot be seen from single-point calibrations. We found that the behaviors were reproducible with a variability of 5–10% for observed phosphopeptide signal. Although these data allow us to begin addressing the issues related to modeling these properties and predicting relative signal strengths for other peptide sequences, it is clear this behavior is highly complex and needs to be further explored. PMID:18064576

Mass spectrometry of peptides and proteins from human blood.

PubMed

Zhu, Peihong; Bowden, Peter; Zhang, Du; Marshall, John G

2011-01-01

It is difficult to convey the accelerating rate and growing importance of mass spectrometry applications to human blood proteins and peptides. Mass spectrometry can rapidly detect and identify the ionizable peptides from the proteins in a simple mixture and reveal many of their post-translational modifications. However, blood is a complex mixture that may contain many proteins first expressed in cells and tissues. The complete analysis of blood proteins is a daunting task that will rely on a wide range of disciplines from physics, chemistry, biochemistry, genetics, electromagnetic instrumentation, mathematics and computation. Therefore the comprehensive discovery and analysis of blood proteins will rank among the great technical challenges and require the cumulative sum of many of mankind's scientific achievements together. A variety of methods have been used to fractionate, analyze and identify proteins from blood, each yielding a small piece of the whole and throwing the great size of the task into sharp relief. The approaches attempted to date clearly indicate that enumerating the proteins and peptides of blood can be accomplished. There is no doubt that the mass spectrometry of blood will be crucial to the discovery and analysis of proteins, enzyme activities, and post-translational processes that underlay the mechanisms of disease. At present both discovery and quantification of proteins from blood are commonly reaching sensitivities of ∼1 ng/mL. Copyright © 2010 Wiley Periodicals, Inc.

Protein Sequencing with Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Ziady, Assem G.; Kinter, Michael

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

Estimating the Efficiency of Phosphopeptide Identification by Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

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.

U/Th dating by SHRIMP RG ion-microprobe mass spectrometry using single ion-exchange beads

NASA Astrophysics Data System (ADS)

Bischoff, James L.; Wooden, Joe; Murphy, Fred; Williams, Ross W.

2005-04-01

We present a new analytical method for U-series isotopes using the SHRIMP RG (Sensitive High mass Resolution Ion MicroProbe) mass spectrometer that utilizes the preconcentration of the U-series isotopes from a sample onto a single ion-exchange bead. Ion-microprobe mass spectrometry is capable of producing Th ionization efficiencies in excess of 2%. Analytical precision is typically better than alpha spectroscopy, but not as good as thermal ionization mass spectroscopy (TIMS) and inductively coupled plasma multicollector mass spectrometry (ICP-MS). Like TIMS and ICP-MS the method allows analysis of small samples sizes, but also adds the advantage of rapidity of analysis. A major advantage of ion-microprobe analysis is that U and Th isotopes are analyzed in the same bead, simplifying the process of chemical separation. Analytical time on the instrument is ˜60 min per sample, and a single instrument-loading can accommodate 15-20 samples to be analyzed in a 24-h day. An additional advantage is that the method allows multiple reanalyses of the same bead and that samples can be archived for reanalysis at a later time. Because the ion beam excavates a pit only a few μm deep, the mount can later be repolished and reanalyzed numerous times. The method described of preconcentrating a low concentration sample onto a small conductive substrate to allow ion-microprobe mass spectrometry is potentially applicable to many other systems.

U/Th dating by SHRIMP RG ion-microprobe mass spectrometry using single ion-exchange beads

USGS Publications Warehouse

Bischoff, J.L.; Wooden, J.; Murphy, F.; Williams, Ross W.

2005-01-01

We present a new analytical method for U-series isotopes using the SHRIMP RG (Sensitive High mass Resolution Ion MicroProbe) mass spectrometer that utilizes the preconcentration of the U-series isotopes from a sample onto a single ion-exchange bead. Ion-microprobe mass spectrometry is capable of producing Th ionization efficiencies in excess of 2%. Analytical precision is typically better than alpha spectroscopy, but not as good as thermal ionization mass spectroscopy (TIMS) and inductively coupled plasma multicollector mass spectrometry (ICP-MS). Like TIMS and ICP-MS the method allows analysis of small samples sizes, but also adds the advantage of rapidity of analysis. A major advantage of ion-microprobe analysis is that U and Th isotopes are analyzed in the same bead, simplifying the process of chemical separation. Analytical time on the instrument is ???60 min per sample, and a single instrument-loading can accommodate 15-20 samples to be analyzed in a 24-h day. An additional advantage is that the method allows multiple reanalyses of the same bead and that samples can be archived for reanalysis at a later time. Because the ion beam excavates a pit only a few ??m deep, the mount can later be repolished and reanalyzed numerous times. The method described of preconcentrating a low concentration sample onto a small conductive substrate to allow ion-microprobe mass spectrometry is potentially applicable to many other systems. Copyright ?? 2005 Elsevier Ltd.

Laser Time-of-Flight Mass Spectrometry for Future In Situ Planetary Missions

NASA Technical Reports Server (NTRS)

Getty, S. A.; Brinckerhoff, W. B.; Cornish, T.; Ecelberger, S. A.; Li, X.; Floyd, M. A. Merrill; Chanover, N.; Uckert, K.; Voelz, D.; Xiao, X.;

MALDI mass spectrometry imaging, from its origins up to today: the state of the art.

PubMed

Francese, Simona; Dani, Francesca R; Traldi, Pietro; Mastrobuoni, Guido; Pieraccini, Giuseppe; Moneti, Gloriano

2009-02-01

Mass Spectrometry (MS) has a number of features namely sensitivity, high dynamic range, high resolution, and versatility which make it a very powerful analytical tool for a wide spectrum of applications spanning all the life science fields. Among all the MS techniques, MALDI Imaging mass spectrometry (MALDI MSI) is currently one of the most exciting both for its rapid technological improvements, and for its great potential in high impact bioscience fields. Here, MALDI MSI general principles are described along with technical and instrumental details as well as application examples. Imaging MS instruments and imaging mass spectrometric techniques other than MALDI, are presented along with examples of their use. As well as reporting MSI successes in several bioscience fields, an attempt is made to take stock of what has been achieved so far with this technology and to discuss the analytical and technological advances required for MSI to be applied as a routine technique in clinical diagnostics, clinical monitoring and in drug discovery.

Determination of selected non-authorized insecticides in peppers by liquid chromatography time-of-flight mass spectrometry and tandem mass spectrometry.

PubMed

Mezcua, Milagros; Ferrer, Carmen; García-Reyes, Juan F; Martínez-Bueno, María Jesús; Albarracín, Micaela; Claret, María; Fernández-Alba, Amadeo R

2008-05-01

In this work, two analytical methods based on liquid chromatography coupled to electrospray time-of-flight mass spectrometry (LC/ESI-TOFMS) and tandem mass spectrometry (LC/ESI-MS/MS) are described for the identification, confirmation and quantitation of three insecticides non-authorized in the European Union (nitenpyram, isocarbophos and isofenphos-methyl) but detected in recent monitoring programmes in pepper samples. The proposed methodologies involved a sample extraction procedure using liquid-liquid partition with acetonitrile followed by a cleanup step based on dispersive solid-phase extraction. Recovery studies performed on peppers spiked at different fortification levels (10 and 50 microg kg(-1)) yielded average recoveries in the range 76-100% with relative standard deviation (RSD) (%) values below 10%. Identification, confirmation and quantitation were carried out by LC/TOFMS and LC/MS/MS using a hybrid triple quadrupole linear ion trap (QqLIT) instrument in multiple-reaction monitoring (MRM) mode. The obtained limits of quantitation (LOQs) were in the range 0.1-5 microg kg(-1), depending on each individual technique. Finally, the proposed methods were successfully applied to the analysis of suspected pepper samples. Copyright (c) 2008 John Wiley & Sons, Ltd.

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

Mass spectrometry for the determination of fission products 135Cs, 137Cs and 90Sr: A review of methodology and applications

NASA Astrophysics Data System (ADS)

Bu, Wenting; Zheng, Jian; Liu, Xuemei; Long, Kaiming; Hu, Sheng; Uchida, Shigeo

2016-05-01

The radioactive fission products 135Cs, 137Cs and 90Sr have been released into the environment by human activities such as nuclear weapon tests, nuclear fuel reprocessing and nuclear power plant accidents. Monitoring of these radionuclides is important for dose assessment. Moreover, the 135Cs/137Cs isotopic ratio can be used as an important long-term fingerprint for radioactive source identification as it varies with weapon, reactor and fuel types. In recent years, mass spectrometry has become a powerful method for the determination of 135Cs, 137Cs and 90Sr in environmental samples. Mass spectrometry is characterized by the high sensitivity and low detection limit and the relatively shorter sample preparation and analysis times compared with radiometric methods. However, the mass spectrometric determination of radiocesium and 90Sr is affected by the peak tailings of the stable nuclides 133Cs and 88Sr, respectively, and the related isobaric and polyatomic interferences. Chemical separation and optimization of the mass spectrometry instrumental setup are strongly needed prior to the mass spectrometry detection. In this paper, we have reviewed the published works about the determination of 135Cs, 137Cs and 90Sr by mass spectrometry. The mass spectrometric techniques we cover are resonance ionization mass spectrometry (RIMS), thermal ionization mass spectrometry (TIMS), accelerator mass spectrometry (AMS) and inductively coupled plasma mass spectrometry (ICP-MS). For each technique, the principles or strategies used for the analysis of these radionuclides are discussed; these included the abundance sensitivity, ways to suppress the interference signals, and the instrumental setup. In particular, the chemical procedures for eliminating the interferences are also summarized. To date, triple quadrupole ICP-MS (ICP-QQQ) showed great ability for the analysis of these radionuclides and the detection limits were as low as 0.01 pg/mL levels. Finally, some investigations on the

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.

Critical comparison of mass analyzers for forensic hair analysis by ambient ionization mass spectrometry.

PubMed

Duvivier, Wilco F; van Beek, Teris A; Nielen, Michel W F

2016-11-15

Recently, several direct and/or ambient mass spectrometry (MS) approaches have been suggested for drugs of abuse imaging in hair. The use of mass spectrometers with insufficient selectivity could result in false-positive measurements due to isobaric interferences. Different mass analyzers have been evaluated regarding their selectivity and sensitivity for the detection of Δ9-tetrahydrocannabinol (THC) from intact hair samples using direct analysis in real time (DART) ionization. Four different mass analyzers, namely (1) an orbitrap, (2) a quadrupole orbitrap, (3) a triple quadrupole, and (4) a quadrupole time-of-flight (QTOF), were evaluated. Selectivity and sensitivity were assessed by analyzing secondary THC standard dilutions on stainless steel mesh screens and blank hair samples, and by the analysis of authentic cannabis user hair samples. Additionally, separation of isobaric ions by use of travelling wave ion mobility (TWIM) was investigated. The use of a triple quadrupole instrument resulted in the highest sensitivity; however, transitions used for multiple reaction monitoring were only found to be specific when using high mass resolution product ion measurements. A mass resolution of at least 30,000 FWHM at m/z 315 was necessary to avoid overlap of THC with isobaric ions originating from the hair matrix. Even though selectivity was enhanced by use of TWIM, the QTOF instrument in resolution mode could not indisputably differentiate THC from endogenous isobaric ions in drug user hair samples. Only the high resolution of the (quadrupole) orbitrap instruments and the QTOF instrument in high-resolution mode distinguished THC in hair samples from endogenous isobaric interferences. As expected, enhanced selectivity compromises sensitivity and THC was only detectable in hair from heavy users. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Electrospray ionization tandem mass spectrometry of ammonium cationized polyethers.

PubMed

Nasioudis, Andreas; Heeren, Ron M A; van Doormalen, Irene; de Wijs-Rot, Nicolette; van den Brink, Oscar F

2011-05-01

Quaternary ammonium salts (Quats) and amines are known to facilitate the MS analysis of high molar mass polyethers by forming low charge state adduct ions. The formation, stability, and behavior upon collision-induced dissociation (CID) of adduct ions of polyethers with a variety of Quats and amines were studied by electrospray ionization quadrupole time-of-flight, quadrupole ion trap, and linear ion trap tandem mass spectrometry (MS/MS). The linear ion trap instrument was part of an Orbitrap hybrid mass spectrometer that allowed accurate mass MS/MS measurements. The Quats and amines studied were of different degree of substitution, structure, and size. The stability of the adduct ions was related to the structure of the cation, especially the amine's degree of substitution. CID of singly/doubly charged primary and tertiary ammonium cationized polymers resulted in the neutral loss of the amine followed by fragmentation of the protonated product ions. The latter reveals information about the monomer unit, polymer sequence, and endgroup structure. In addition, the detection of product ions retaining the ammonium ion was observed. The predominant process in the CID of singly charged quaternary ammonium cationized polymers was cation detachment, whereas their doubly charged adduct ions provided the same information as the primary and tertiary ammonium cationized adduct ions. This study shows the potential of specific amines as tools for the structural elucidation of high molar mass polyethers. © American Society for Mass Spectrometry, 2011

Challenging developments in three decades of accelerator mass spectrometry at ETH: from large particle accelerators to table size instruments.

PubMed

Suter, Martin

2010-01-01

Accelerator mass spectrometry (AMS) was invented for the detection of radiocarbon at natural isotopic concentrations (10(-12) to 10(-15)) more than 30 years ago. Meanwhile this method has also been applied for the analysis of many other long-lived radioisotopes, which are found at very low concentrations. The first investigations were made at large tandem accelerators originally built for nuclear physics research and operating at voltages of 6-12 MV. Today dedicated instruments are mostly used for AMS, which are optimized for associated applications. In the past 15 years, a new generation of much smaller instruments has been developed. For many years it was believed that accelerators with voltages of 2 MV or higher are needed to eliminate the molecular interferences. At these energies the ions are predominantly stripped to charge state 3+, thereby removing the binding electrons of the molecules. In contrast, the new compact facilities use 1+ or 2+ ions. In this case the molecular destruction process is based on molecule-atom collisions in the gas cell. The cross sections for this destruction are sufficiently large that the intensity of molecular components such as (12)CH(2) and (13)CH can be reduced by 10 orders of magnitude. These new facilities can be built much smaller due to the lower energies. Universal instruments providing analysis for many isotopes over the whole range of periodic table have a space requirement of about 4 x 6 m(2); dedicated radiocarbon facilities based on a 200 kV accelerator have a footprint of about 2.5 x 3 m(2). This smallest category of instruments use special technologies: The high voltage terminal with the gas stripper canal is vacuum insulated and the gas is pumped to ground potential through a ceramic pipe. A conventional 200 kV power supply provides the terminal voltage from outside. A review of this new generation of compact AMS facilities is given. Design considerations and performance of these new instruments will be presented

Characterization of polyesters by matrix-assisted laser desorption/ionization and Fourier transform mass spectrometry.

PubMed

Mize, Todd H; Simonsick, William J; Amster, I Jonathan

2003-01-01

Two homopolyesters, poly(neopentyl glycol-alt-isophthalic acid) and poly(hexanediol-alt-azelaic acid), and two copolyesters, poly(dipropoxylated bisphenol-A-alt-(isophthalic acid-co-adipic acid)) and poly(neopentyl glycol-alt-(adipic acid-co-isophthalic acid)) were analyzed by internal source matrix assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS). The high resolution and high mass accuracy provided by FTMS greatly facilitate the characterization of the polyester and copolyester samples. Isobaric resolution allows the ion abundances of overlapping isotopic envelopes to be assessed. Repeat units were confirmed and end functionality assigned. Single shot mass spectra of the entire polymeric distribution demonstrate that the dynamic range of this internal MALDI source instrument and the analyzer cell exceeds performance of those previously reported for higher field instruments. Corrections of space charge mass shift effects are demonstrated for the analytes using an external calibrant and (subsequent to confirmation of structure) via internal calibration which removes ambiguity due to space charge differences in calibrant and analyte spectra. Capillary gel permeation chromatography was used to prepare low polydispersity samples from a high polydispersity polyester, improving the measurement of molecular weight distribution two-fold while retaining the benefits of high resolution mass spectrometry for elucidation of oligomer identity.

"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

Analytical considerations for mass spectrometry profiling in serum biomarker discovery.

PubMed

Whiteley, Gordon R; Colantonio, Simona; Sacconi, Andrea; Saul, Richard G

2009-03-01

The potential of using mass spectrometry profiling as a diagnostic tool has been demonstrated for a wide variety of diseases. Various cancers and cancer-related diseases have been the focus of much of this work because of both the paucity of good diagnostic markers and the knowledge that early diagnosis is the most powerful weapon in treating cancer. The implementation of mass spectrometry as a routine diagnostic tool has proved to be difficult, however, primarily because of the stringent controls that are required for the method to be reproducible. The method is evolving as a powerful guide to the discovery of biomarkers that could, in turn, be used either individually or in an array or panel of tests for early disease detection. Using proteomic patterns to guide biomarker discovery and the possibility of deployment in the clinical laboratory environment on current instrumentation or in a hybrid technology has the possibility of being the early diagnosis tool that is needed.

Accelerator mass spectrometry of strontium-90 for homeland security, environmental monitoring and human health

NASA Astrophysics Data System (ADS)

Tumey, Scott J.; Brown, Thomas A.; Hamilton, Terry E.; Hillegonds, Darren J.

2008-05-01

Strontium-90 is one of the most hazardous materials managed by agencies charged with protecting the public from radiation. Traditional radiometric methods have been limited by low sample throughput and slow turnaround times. Mass spectrometry offers the advantage of shorter analysis times and the ability to measure samples immediately after processing, however conventional mass spectrometric techniques are susceptible to molecular isobaric interferences that limit their overall sensitivity. In contrast, accelerator mass spectrometry is insensitive to molecular interferences and we have therefore begun developing a method for determination of 90Sr by accelerator mass spectrometry. Despite a pervasive interference from 90Zr, our initial development has yielded an instrumental background of ∼108 atoms (75 mBq) per sample. Further refinement of our system (e.g. redesign of our detector, use of alternative target materials) is expected to push the background below 106 atoms, close to the theoretical limit for AMS. Once we have refined our system and developed suitable sample preparation protocols, we will utilize our capability in applications to homeland security, environmental monitoring and human health.

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…

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.

Mapping Cellular Polarity Networks Using Mass Spectrometry-based Strategies.

PubMed

Daulat, Avais M; Puvirajesinghe, Tania M; Camoin, Luc; Borg, Jean-Paul

2018-05-18

Cell polarity is a vital biological process involved in the building, maintenance and normal functioning of tissues in invertebrates and vertebrates. Unsurprisingly, molecular defects affecting polarity organization and functions have a strong impact on tissue homeostasis, embryonic development and adult life, and may directly or indirectly lead to diseases. Genetic studies have demonstrated the causative effect of several polarity genes in diseases; however, much remains to be clarified before a comprehensive view of the molecular organization and regulation of the protein networks associated with polarity proteins is obtained. This challenge can be approached head-on using proteomics to identify protein complexes involved in cell polarity and their modifications in a spatio-temporal manner. We review the fundamental basics of mass spectrometry techniques and provide an in-depth analysis of how mass spectrometry has been instrumental in understanding the complex and dynamic nature of some cell polarity networks at the tissue (apico-basal and planar cell polarities) and cellular (cell migration, ciliogenesis) levels, with the fine dissection of the interconnections between prototypic cell polarity proteins and signal transduction cascades in normal and pathological situations. This review primarily focuses on epithelial structures which are the fundamental building blocks for most metazoan tissues, used as the archetypal model to study cellular polarity. This field offers broad perspectives thanks to the ever-increasing sensitivity of mass spectrometry and its use in combination with recently developed molecular strategies able to probe in situ proteomic networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

The Effect of Collimating Lens Focusing on Laser Beam Shape in Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS)

NASA Astrophysics Data System (ADS)

O'Rourke, Matthew B.; Raymond, Benjamin B. A.; Djordjevic, Steven P.; Padula, Matthew P.

2018-03-01

Tissue imaging using matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a well-established technique that, in recent years, has seen wider adoption and novel application. Applications such imaging mass spectrometry (IMS) and biotyping are beginning to gain greater exposure and use; however, with limitations in optimization methods, producing the best result often relies on the ability to customize the physical characteristics of the instrumentation, a task that is challenging for most mass spectrometry laboratories. With this in mind, we have described the effect of making simple adjustments to the laser optics at the final collimating lens area, to adjust the laser beam size and shape in order to allow greater customization of the instrument for improving techniques such as IMS. We have therefore been able to demonstrate that improvements can be made without requiring the help of an electrical engineer or external funding in a way that only costs a small amount of time. [Figure not available: see fulltext.

The Effect of Collimating Lens Focusing on Laser Beam Shape in Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS).

PubMed

O'Rourke, Matthew B; Raymond, Benjamin B A; Djordjevic, Steven P; Padula, Matthew P

2018-03-01

Tissue imaging using matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a well-established technique that, in recent years, has seen wider adoption and novel application. Applications such imaging mass spectrometry (IMS) and biotyping are beginning to gain greater exposure and use; however, with limitations in optimization methods, producing the best result often relies on the ability to customize the physical characteristics of the instrumentation, a task that is challenging for most mass spectrometry laboratories. With this in mind, we have described the effect of making simple adjustments to the laser optics at the final collimating lens area, to adjust the laser beam size and shape in order to allow greater customization of the instrument for improving techniques such as IMS. We have therefore been able to demonstrate that improvements can be made without requiring the help of an electrical engineer or external funding in a way that only costs a small amount of time. Graphical Abstract ᅟ.

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

PubMed Central

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

2013-01-01

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

Quantitative mass spectrometry methods for pharmaceutical analysis

PubMed Central

Loos, Glenn; Van Schepdael, Ann

2016-01-01

Quantitative pharmaceutical analysis is nowadays frequently executed using mass spectrometry. Electrospray ionization coupled to a (hybrid) triple quadrupole mass spectrometer is generally used in combination with solid-phase extraction and liquid chromatography. Furthermore, isotopically labelled standards are often used to correct for ion suppression. The challenges in producing sensitive but reliable quantitative data depend on the instrumentation, sample preparation and hyphenated techniques. In this contribution, different approaches to enhance the ionization efficiencies using modified source geometries and improved ion guidance are provided. Furthermore, possibilities to minimize, assess and correct for matrix interferences caused by co-eluting substances are described. With the focus on pharmaceuticals in the environment and bioanalysis, different separation techniques, trends in liquid chromatography and sample preparation methods to minimize matrix effects and increase sensitivity are discussed. Although highly sensitive methods are generally aimed for to provide automated multi-residue analysis, (less sensitive) miniaturized set-ups have a great potential due to their ability for in-field usage. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644982

Stable isotope labelling methods in mass spectrometry-based quantitative proteomics.

PubMed

Chahrour, Osama; Cobice, Diego; Malone, John

2015-09-10

Mass-spectrometry based proteomics has evolved as a promising technology over the last decade and is undergoing a dramatic development in a number of different areas, such as; mass spectrometric instrumentation, peptide identification algorithms and bioinformatic computational data analysis. The improved methodology allows quantitative measurement of relative or absolute protein amounts, which is essential for gaining insights into their functions and dynamics in biological systems. Several different strategies involving stable isotopes label (ICAT, ICPL, IDBEST, iTRAQ, TMT, IPTL, SILAC), label-free statistical assessment approaches (MRM, SWATH) and absolute quantification methods (AQUA) are possible, each having specific strengths and weaknesses. Inductively coupled plasma mass spectrometry (ICP-MS), which is still widely recognised as elemental detector, has recently emerged as a complementary technique to the previous methods. The new application area for ICP-MS is targeting the fast growing field of proteomics related research, allowing absolute protein quantification using suitable elemental based tags. This document describes the different stable isotope labelling methods which incorporate metabolic labelling in live cells, ICP-MS based detection and post-harvest chemical label tagging for protein quantification, in addition to summarising their pros and cons. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

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

Accelerator mass spectrometry of Strontium-90 for homeland security, environmental monitoring, and human health

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

Tumey, S J; Brown, T A; Hamilton, T F

2008-03-03

Strontium-90 is one of the most hazardous materials managed by agencies charged with protecting the public from radiation. Traditional radiometric methods have been limited by low sample throughput and slow turnaround times. Mass spectrometry offers the advantage of shorter analysis times and the ability to measure samples immediately after processing, however conventional mass spectrometric techniques are susceptible to molecular isobaric interferences that limit their overall sensitivity. In contrast, accelerator mass spectrometry is insensitive to molecular interferences and we have therefore begun developing a method for determination of {sup 90}Sr by accelerator mass spectrometry. Despite a pervasive interference from {sup 90}Zr,more » our initial development has yielded an instrumental background of {approx} 10{sup 8} atoms (75 mBq) per sample. Further refinement of our system (e.g., redesign of our detector, use of alternative target materials) is expected to push the background below 10{sup 6} atoms, close to the theoretical limit for AMS. Once we have refined our system and developed suitable sample preparation protocols, we will utilize our capability in applications to homeland security, environmental monitoring, and human health.« less

Characterization of extreme ultraviolet laser ablation mass spectrometry for actinide trace analysis and nanoscale isotopic imaging

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

Green, Tyler; Kuznetsov, Ilya; Willingham, David

The purpose of this research was to characterize Extreme Ultraviolet Time-of-Flight (EUV TOF) Laser Ablation Mass Spectrometry for high spatial resolution elemental and isotopic analysis. We compare EUV TOF results with Secondary Ionization Mass Spectrometry (SIMS) to orient the EUV TOF method within the overall field of analytical mass spectrometry. Using the well-characterized NIST 61x glasses, we show that the EUV ionization approach produces relatively few molecular ion interferences in comparison to TOF SIMS. We demonstrate that the ratio of element ion to element oxide ion is adjustable with EUV laser pulse energy and that the EUV TOF instrument hasmore » a sample utilization efficiency of 0.014%. The EUV TOF system also achieves a lateral resolution of 80 nm and we demonstrate this lateral resolution with isotopic imaging of closely spaced particles or uranium isotopic standard materials.« less

Sequencing of Oligourea Foldamers by Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

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 of the photolysis of sulfonylurea herbicides in Prairie waters.

PubMed

Headley, John V; Du, Jing-Long; Peru, Kerry M; McMartin, Dena W

2010-01-01

This review of mass spectrometry of sulfonylurea herbicides includes a focus on studies relevant to Canadian Prairie waters. Emphasis is given to data gaps in the literature for the rates of photolysis of selected sulfonylurea herbicides in different water matrices. Specifically, results are evaluated for positive ion electrospray tandem mass spectrometry with liquid chromatography separation for the study of the photolysis of chlorsulfuron, tribenuron-methyl, thifensulfuron-methyl, metsulfuron-methyl, and ethametsulfuron-methyl. LC-MS/MS is shown to be the method of choice for the quantification of sulfonylurea herbicides with instrumental detection limits ranging from 1.3 to 7.2 pg (on-column). Tandem mass spectrometry coupled with the use of authentic standards likewise has proven to be well suited for the identification of transformation products. To date, however, the power of time-of-flight MS and ultrahigh resolution MS has not been exploited fully for the identification of unknown photolysis products. Dissipation of the herbicides under natural sunlight fit pseudo-first-order kinetics with half-life values ranging from 4.4 to 99 days. For simulated sunlight, radiation wavelengths shorter than 400 nm are required to induce significant photolytic reactions. The correlation between field dissipation studies and laboratory photolysis experiments suggests that photolysis is a major pathway for the dissipation of some sulfonylurea herbicides in natural Prairie waters. 2009 Wiley Periodicals, Inc.

An Adaptable Multiple Power Source for Mass Spectrometry and other Scientific Instruments

DOE PAGES

Lin, Tzu-Yung; Anderson, Gordon A.; Norheim, Randolph V.; ...

2015-09-18

Power supplies are commonly used in the operation of many types of scientific equipment, including mass spectrometers and ancillary instrumentation. A generic modern mass spectrometer comprises an ionization source, such as electrospray ionization (ESI), ion transfer devices such as ion funnels and multipole ion guides, and ion signal detection apparatus. Very often such platforms include, or are interfaced with ancillary elements in order to manipulate samples before or after ionization. In order to operate such scientific instruments, numerous direct current (DC) channels and radio frequency (RF) signals are required, along with other controls such as temperature regulation. In particular, DCmore » voltages in the range of ±400 V, along with MHz range RF signals with peak-to-peak amplitudes in the hundreds of volts range are commonly used to transfer ionized samples under vacuum. Additionally, an ESI source requires a high voltage (HV) DC source capable of producing several thousand volts and heaters capable of generating temperatures up to 300°C. All of these signals must be properly synchronized and managed in order to carry out ion trapping, accumulation and detection.« less

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

Surface Desorption Dielectric-Barrier Discharge Ionization Mass Spectrometry.

PubMed

Zhang, Hong; Jiang, Jie; Li, Na; Li, Ming; Wang, Yingying; He, Jing; You, Hong

2017-07-18

A variant of dielectric-barrier discharge named surface desorption dielectric-barrier discharge ionization (SDDBDI) mass spectrometry was developed for high-efficiency ion transmission and high spatial resolution imaging. In SDDBDI, a tungsten nanotip and the inlet of the mass spectrometer are used as electrodes, and a piece of coverslip is used as a sample plate as well as an insulating dielectric barrier, which simplifies the configuration of instrument and thus the operation. Different from volume dielectric-barrier discharge (VDBD), the microdischarges are generated on the surface at SDDBDI, and therefore the plasma density is extremely high. Analyte ions are guided directly into the MS inlet without any deflection. This configuration significantly improves the ion transmission efficiency and thus the sensitivity. The dependence of sensitivity and spatial resolution of the SDDBDI on the operation parameters were systematically investigated. The application of SDDBDI was successfully demonstrated by analysis of multiple species including amino acids, pharmaceuticals, putative cancer biomarkers, and mixtures of both fatty acids and hormones. Limits of detection (S/N = 3) were determined to be 0.84 and 0.18 pmol, respectively, for the analysis of l-alanine and metronidazole. A spatial resolution of 22 μm was obtained for the analysis of an imprinted cyclophosphamide pattern, and imaging of a "T" character was successfully demonstrated under ambient conditions. These results indicate that SDDBDI has high-efficiency ion transmission, high sensitivity, and high spatial resolution, which render it a potential tool for mass spectrometry imaging.

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

Measurement and Visualization of Mass Transport for the Flowing Atmospheric Pressure Afterglow (FAPA) Ambient Mass-Spectrometry Source

PubMed Central

Pfeuffer, Kevin P.; Ray, Steven J.; Hieftje, Gary M.

2014-01-01

Ambient desorption/ionization mass spectrometry (ADI-MS) has developed into an important analytical field over the last nine years. The ability to analyze samples under ambient conditions while retaining the sensitivity and specificity of mass spectrometry has led to numerous applications and a corresponding jump in the popularity of this field. Despite the great potential of ADI-MS, problems remain in the areas of ion identification and quantification. Difficulties with ion identification can be solved through modified instrumentation, including accurate-mass or MS/MS capabilities for analyte identification. More difficult problems include quantification due to the ambient nature of the sampling process. To characterize and improve sample volatilization, ionization, and introduction into the mass-spectrometer interface, a method of visualizing mass transport into the mass spectrometer is needed. Schlieren imaging is a well-established technique that renders small changes in refractive index visible. Here, schlieren imaging was used to visualize helium flow from a plasma-based ADI-MS source into a mass spectrometer while ion signals were recorded. Optimal sample positions for melting-point capillary and transmission-mode (stainless steel mesh) introduction were found to be near (within 1 mm of) the mass spectrometer inlet. Additionally, the orientation of the sampled surface plays a significant role. More efficient mass transport resulted for analyte deposits directly facing the MS inlet. Different surfaces (glass slide and rough surface) were also examined; for both it was found that the optimal position is immediately beneath the MS inlet. PMID:24658804

Measurement and visualization of mass transport for the flowing atmospheric pressure afterglow (FAPA) ambient mass-spectrometry source.

PubMed

Pfeuffer, Kevin P; Ray, Steven J; Hieftje, Gary M

2014-05-01

Ambient desorption/ionization mass spectrometry (ADI-MS) has developed into an important analytical field over the last 9 years. The ability to analyze samples under ambient conditions while retaining the sensitivity and specificity of mass spectrometry has led to numerous applications and a corresponding jump in the popularity of this field. Despite the great potential of ADI-MS, problems remain in the areas of ion identification and quantification. Difficulties with ion identification can be solved through modified instrumentation, including accurate-mass or MS/MS capabilities for analyte identification. More difficult problems include quantification because of the ambient nature of the sampling process. To characterize and improve sample volatilization, ionization, and introduction into the mass spectrometer interface, a method of visualizing mass transport into the mass spectrometer is needed. Schlieren imaging is a well-established technique that renders small changes in refractive index visible. Here, schlieren imaging was used to visualize helium flow from a plasma-based ADI-MS source into a mass spectrometer while ion signals were recorded. Optimal sample positions for melting-point capillary and transmission-mode (stainless steel mesh) introduction were found to be near (within 1 mm of) the mass spectrometer inlet. Additionally, the orientation of the sampled surface plays a significant role. More efficient mass transport resulted for analyte deposits directly facing the MS inlet. Different surfaces (glass slide and rough surface) were also examined; for both it was found that the optimal position is immediately beneath the MS inlet.

Measurement and Visualization of Mass Transport for the Flowing Atmospheric Pressure Afterglow (FAPA) Ambient Mass-Spectrometry Source

NASA Astrophysics Data System (ADS)

Pfeuffer, Kevin P.; Ray, Steven J.; Hieftje, Gary M.

2014-05-01

Ambient desorption/ionization mass spectrometry (ADI-MS) has developed into an important analytical field over the last 9 years. The ability to analyze samples under ambient conditions while retaining the sensitivity and specificity of mass spectrometry has led to numerous applications and a corresponding jump in the popularity of this field. Despite the great potential of ADI-MS, problems remain in the areas of ion identification and quantification. Difficulties with ion identification can be solved through modified instrumentation, including accurate-mass or MS/MS capabilities for analyte identification. More difficult problems include quantification because of the ambient nature of the sampling process. To characterize and improve sample volatilization, ionization, and introduction into the mass spectrometer interface, a method of visualizing mass transport into the mass spectrometer is needed. Schlieren imaging is a well-established technique that renders small changes in refractive index visible. Here, schlieren imaging was used to visualize helium flow from a plasma-based ADI-MS source into a mass spectrometer while ion signals were recorded. Optimal sample positions for melting-point capillary and transmission-mode (stainless steel mesh) introduction were found to be near (within 1 mm of) the mass spectrometer inlet. Additionally, the orientation of the sampled surface plays a significant role. More efficient mass transport resulted for analyte deposits directly facing the MS inlet. Different surfaces (glass slide and rough surface) were also examined; for both it was found that the optimal position is immediately beneath the MS inlet.

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.

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

[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.

Time-of-flight mass spectrometry: Introduction to the basics.

PubMed

Boesl, Ulrich

2017-01-01

The intention of this tutorial is to introduce into the basic concepts of time-of-flight mass spectrometry, beginning with the most simple single-stage ion source with linear field-free drift region and continuing with two-stage ion sources combined with field-free drift regions and ion reflectors-the so-called reflectrons. Basic formulas are presented and discussed with the focus on understanding the physical relations of geometric and electric parameters, initial distribution of ionic parameters, ion flight times, and ion flight time incertitude. This tutorial is aimed to help the applicant to identify sources of flight time broadening which limit good mass resolution and sources of ion losses which limit sensitivity; it is aimed to stimulate creativity for new experimental approaches by discussing a choice of instrumental options and to encourage those who toy with the idea to build an own time-of-flight mass spectrometer. Large parts of mathematics are shifted into a separate chapter in order not to overburden the text with too many mathematical deviations. Rather, thumb-rule formulas are supplied for first estimations of geometry and potentials when designing a home-built instrument, planning experiments, or searching for sources of flight time broadening. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:86-109, 2017. © 2016 Wiley Periodicals, Inc.

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...

BioAerosol Mass Spectrometry: Reagentless Detection of Individual Airborne Spores and Other Bioagent Particles Based on Laser Desorption/Ionization Mass Spectrometry

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

Steele, Paul Thomas

2004-09-01

Better devices are needed for the detection of aerosolized biological warfare agents. Advances in the ongoing development of one such device, the BioAerosol Mass Spectrometry (BAMS) system, are described here in detail. The system samples individual, micrometer-sized particles directly from the air and analyzes them in real-time without sample preparation or use of reagents. At the core of the BAMS system is a dual-polarity, single-particle mass spectrometer with a laser based desorption and ionization (DI) system. The mass spectra produced by early proof-of-concept instruments were highly variable and contained limited information to differentiate certain types of similar biological particles. Themore » investigation of this variability and subsequent changes to the DI laser system are described. The modifications have reduced the observed variability and thereby increased the usable information content in the spectra. These improvements would have little value without software to analyze and identify the mass spectra. Important improvements have been made to the algorithms that initially processed and analyzed the data. Single particles can be identified with an impressive level of accuracy, but to obtain significant reductions in the overall false alarm rate of the BAMS instrument, alarm decisions must be made dynamically on the basis of multiple analyzed particles. A statistical model has been developed to make these decisions and the resulting performance of a hypothetical BAMS system is quantitatively predicted. The predictions indicate that a BAMS system, with reasonably attainable characteristics, can operate with a very low false alarm rate (orders of magnitude lower than some currently fielded biodetectors) while still being sensitive to small concentrations of biological particles in a large range of environments. Proof-of-concept instruments, incorporating some of the modifications described here, have already performed well in independent testing.« less

A new processing scheme for ultra-high resolution direct infusion mass spectrometry data

NASA Astrophysics Data System (ADS)

Zielinski, Arthur T.; Kourtchev, Ivan; Bortolini, Claudio; Fuller, Stephen J.; Giorio, Chiara; Popoola, Olalekan A. M.; Bogialli, Sara; Tapparo, Andrea; Jones, Roderic L.; Kalberer, Markus

2018-04-01

High resolution, high accuracy mass spectrometry is widely used to characterise environmental or biological samples with highly complex composition enabling the identification of chemical composition of often unknown compounds. Despite instrumental advancements, the accurate molecular assignment of compounds acquired in high resolution mass spectra remains time consuming and requires automated algorithms, especially for samples covering a wide mass range and large numbers of compounds. A new processing scheme is introduced implementing filtering methods based on element assignment, instrumental error, and blank subtraction. Optional post-processing incorporates common ion selection across replicate measurements and shoulder ion removal. The scheme allows both positive and negative direct infusion electrospray ionisation (ESI) and atmospheric pressure photoionisation (APPI) acquisition with the same programs. An example application to atmospheric organic aerosol samples using an Orbitrap mass spectrometer is reported for both ionisation techniques resulting in final spectra with 0.8% and 8.4% of the peaks retained from the raw spectra for APPI positive and ESI negative acquisition, respectively.

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.

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.

Examining the Heterogeneous Genome Content of Multipartite Viruses BMV and CCMV by Native Mass Spectrometry

NASA Astrophysics Data System (ADS)

van de Waterbeemd, Michiel; Snijder, Joost; Tsvetkova, Irina B.; Dragnea, Bogdan G.; Cornelissen, Jeroen J.; Heck, Albert J. R.

2016-06-01

Since the concept was first introduced by Brian Chait and co-workers in 1991, mass spectrometry of proteins and protein complexes under non-denaturing conditions (native MS) has strongly developed, through parallel advances in instrumentation, sample preparation, and data analysis tools. However, the success rate of native MS analysis, particularly in heterogeneous mega-Dalton (MDa) protein complexes, still strongly depends on careful instrument modification. Here, we further explore these boundaries in native mass spectrometry, analyzing two related endogenous multipartite viruses: the Brome Mosaic Virus (BMV) and the Cowpea Chlorotic Mottle Virus (CCMV). Both CCMV and BMV are approximately 4.6 megadalton (MDa) in mass, of which approximately 1 MDA originates from the genomic content of the virion. Both viruses are produced as mixtures of three particles carrying different segments of the genome, varying by approximately 0.1 MDA in mass (~2%). This mixture of particles poses a challenging analytical problem for high-resolution native MS analysis, given the large mass scales involved. We attempt to unravel the particle heterogeneity using both Q-TOF and Orbitrap mass spectrometers extensively modified for analysis of very large assemblies. We show that manipulation of the charging behavior can provide assistance in assigning the correct charge states. Despite their challenging size and heterogeneity, we obtained native mass spectra with resolved series of charge states for both BMV and CCMV, demonstrating that native MS of endogenous multipartite virions is feasible.

A new technique for high performance tandem time-of- flight mass spectrometry

NASA Astrophysics Data System (ADS)

Katz, Daniel Louis

2001-08-01

The main result of this written dissertation is a mathematical solution to the problem of multiplex recording for high performance tandem time-of-flight mass spectrometry. The prescription is to use a time-lag accelerator in the second stage to match the ion optical properties of the decay fragments to the requirements of the electrostatic ion mirror. With this technique the ion mirror is able to focus the full mass range of fragment ions at a single voltage setting, permitting acquisition of the entire mass spectrum from a single ionization event. This work was performed in support of a joint project carried out by researchers at Oregon State University and The University of Uppsala, Sweden, to design, build and test a tandem instrument featuring precision selection of the precursor species in the first stage of the spectrometer, a means of fragmenting the precursor species, and multiplex recording of the resulting fragment spectrum in the second stage. A patent application has been filed on the complete instrument with the United States Patent Office, a copy of which has been included as an appendix, and a prototype of that instrument has been constructed and awaits testing at Oregon State University.

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.

Fourier transform ion cyclotron resonance mass spectrometry

NASA Astrophysics Data System (ADS)

Marshall, Alan G.

1998-06-01

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

Comprehensive combinatory standard correction: a calibration method for handling instrumental drifts of gas chromatography-mass spectrometry systems.

PubMed

Deport, Coralie; Ratel, Jérémy; Berdagué, Jean-Louis; Engel, Erwan

2006-05-26

The current work describes a new method, the comprehensive combinatory standard correction (CCSC), for the correction of instrumental signal drifts in GC-MS systems. The method consists in analyzing together with the products of interest a mixture of n selected internal standards, and in normalizing the peak area of each analyte by the sum of standard areas and then, select among the summation operator sigma(p = 1)(n)C(n)p possible sums, the sum that enables the best product discrimination. The CCSC method was compared with classical techniques of data pre-processing like internal normalization (IN) or single standard correction (SSC) on their ability to correct raw data from the main drifts occurring in a dynamic headspace-gas chromatography-mass spectrometry system. Three edible oils with closely similar compositions in volatile compounds were analysed using a device which performance was modulated by using new or used dynamic headspace traps and GC-columns, and by modifying the tuning of the mass spectrometer. According to one-way ANOVA, the CCSC method increased the number of analytes discriminating the products (31 after CCSC versus 25 with raw data or after IN and 26 after SSC). Moreover, CCSC enabled a satisfactory discrimination of the products irrespective of the drifts. In a factorial discriminant analysis, 100% of the samples (n = 121) were well-classified after CCSC versus 45% for raw data, 90 and 93%, respectively after IN and SSC.

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.

Mass spectrometry. [in organic ion and biorganic chemistry and medicine

NASA Technical Reports Server (NTRS)

Burlingame, A. L.; Cox, R. E.; Derrick, P. J.

1974-01-01

Review of the present status of mass spectrometry in the light of pertinent recent publications spanning the period from December 1971 to January 1974. Following an initial survey of techniques, instruments, and computer applications, a sharp distinction is made between the chemistry of organic (radical-)ions and analytical applications in biorganic chemistry and medicine. The emphasis is on the chemistry of organic (radical-)ions at the expense of inorganic, organometallic, and surface ion chemistry. Biochemistry and medicine are chosen because of their contemporary importance and because of the stupendous contributions of mass spectroscopy to these fields in the past two years. In the review of gas-phase organic ion chemistry, special attention is given to studies making significant contributions to the understanding of ion chemistry.

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.

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.

Recent trends in atomic fluorescence spectrometry towards miniaturized instrumentation-A review.

PubMed

Zou, Zhirong; Deng, Yujia; Hu, Jing; Jiang, Xiaoming; Hou, Xiandeng

2018-08-17

Atomic fluorescence spectrometry (AFS), as one of the common atomic spectrometric techniques with high sensitivity, simple instrumentation, and low acquisition and running cost, has been widely used in various fields for trace elemental analysis, notably the determination of hydride-forming elements by hydride generation atomic fluorescence spectrometry (HG-AFS). In recent years, the soaring demand of field analysis has significantly promoted the miniaturization of analytical atomic spectrometers or at least instrumental components. Various techniques have also been developed to approach the goal of portable/miniaturized AFS instrumentation for field analysis. In this review, potentially portable/miniaturized AFS techniques, primarily involving advanced instrumental components and whole instrumentation with references since 2000, are summarized and discussed. The discussion mainly includes five aspects: radiation source, atomizer, detector, sample introduction, and miniaturized atomic fluorescence spectrometer/system. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Quantification of steroid hormones in human serum by liquid chromatography-high resolution tandem mass spectrometry.

PubMed

Matysik, Silke; Liebisch, Gerhard

2017-12-01

A limited specificity is inherent to immunoassays for steroid hormone analysis. To improve selectivity mass spectrometric analysis of steroid hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced in the clinical laboratory over the past years usually with low mass resolution triple-quadrupole instruments or more recently by high resolution mass spectrometry (HR-MS). Here we introduce liquid chromatography-high resolution tandem mass spectrometry (LC-MS/HR-MS) to further increase selectivity of steroid hormone quantification. Application of HR-MS demonstrates an enhanced selectivity compared to low mass resolution. Separation of isobaric interferences reduces background noise and avoids overestimation. Samples were prepared by automated liquid-liquid extraction with MTBE. The LC-MS/HR-MS method using a quadrupole-Orbitrap analyzer includes eight steroid hormones i.e. androstenedione, corticosterone, cortisol, cortisone, 11-deoxycortisol, 17-hydroxyprogesterone, progesterone, and testosterone. It has a run-time of 5.3min and was validated according to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines. For most of the analytes coefficient of variation were 10% or lower and LOQs were determined significantly below 1ng/ml. Full product ion spectra including accurate masses substantiate compound identification by matching their masses and ratios with authentic standards. In summary, quantification of steroid hormones by LC-MS/HR-MS is applicable for clinical diagnostics and holds also promise for highly selective quantification of other small molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

A review on recent developments in mass spectrometry instrumentation and quantitative tools advancing bacterial proteomics.

PubMed

Van Oudenhove, Laurence; Devreese, Bart

2013-06-01

Proteomics has evolved substantially since its early days, some 20 years ago. In this mini-review, we aim to provide an overview of general methodologies and more recent developments in mass spectrometric approaches used for relative and absolute quantitation of proteins. Enhancement of sensitivity of the mass spectrometers as well as improved sample preparation and protein fractionation methods are resulting in a more comprehensive analysis of proteomes. We also document some upcoming trends for quantitative proteomics such as the use of label-free quantification methods. Hopefully, microbiologists will continue to explore proteomics as a tool in their research to understand the adaptation of microorganisms to their ever changing environment. We encourage them to incorporate some of the described new developments in mass spectrometry to facilitate their analyses and improve the general knowledge of the fascinating world of microorganisms.

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

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.

Secondary Ion Mass Spectrometry SIMS XI

NASA Astrophysics Data System (ADS)

Gillen, G.; Lareau, R.; Bennett, J.; Stevie, F.

2003-05-01

This volume contains 252 contributions presented as plenary, invited and contributed poster and oral presentations at the 11th International Conference on Secondary Ion Mass Spectrometry (SIMS XI) held at the Hilton Hotel, Walt Disney World Village, Orlando, Florida, 7 12 September, 1997. The book covers a diverse range of research, reflecting the rapid growth in advanced semiconductor characterization, ultra shallow depth profiling, TOF-SIMS and the new areas in which SIMS techniques are being used, for example in biological sciences and organic surface characterization. Papers are presented under the following categories: Isotopic SIMS Biological SIMS Semiconductor Characterization Techniques and Applications Ultra Shallow Depth Profiling Depth Profiling Fundamental/Modelling and Diffusion Sputter-Induced Topography Fundamentals of Molecular Desorption Organic Materials Practical TOF-SIMS Polyatomic Primary Ions Materials/Surface Analysis Postionization Instrumentation Geological SIMS Imaging Fundamentals of Sputtering Ion Formation and Cluster Formation Quantitative Analysis Environmental/Particle Characterization Related Techniques These proceedings provide an invaluable source of reference for both newcomers to the field and experienced SIMS users.

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.

A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications

NASA Astrophysics Data System (ADS)

Rogstad, Sarah; Faustino, Anneliese; Ruth, Ashley; Keire, David; Boyne, Michael; Park, Jun

2017-05-01

The characterization sections of biologics license applications (BLAs) approved by the United States Food and Drug Administration (FDA) between 2000 and 2015 were investigated to examine the extent of the use of mass spectrometry. Mass spectrometry was found to be integral to the characterization of these biotherapeutics. Of the 80 electronically submitted monoclonal antibody and protein biotherapeutic BLAs included in this study, 79 were found to use mass spectrometric workflows for protein or impurity characterization. To further examine how MS is being used in successful BLAs, the applications were filtered based on the type and number of quality attributes characterized, the mass spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved glycan analysis), the methods used to introduce the proteins into the gas phase (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses were conducted over a time course based on the FDA BLA approval to determine if any trends in utilization could be observed over time. Additionally, the different classes of protein-based biotherapeutics among the approved BLAs were clustered to determine if any trends could be attributed to the specific type of biotherapeutic.

Parallel Exploration of Interaction Space by BioID and Affinity Purification Coupled to Mass Spectrometry.

PubMed

Hesketh, Geoffrey G; Youn, Ji-Young; Samavarchi-Tehrani, Payman; Raught, Brian; Gingras, Anne-Claude

2017-01-01

Complete understanding of cellular function requires knowledge of the composition and dynamics of protein interaction networks, the importance of which spans all molecular cell biology fields. Mass spectrometry-based proteomics approaches are instrumental in this process, with affinity purification coupled to mass spectrometry (AP-MS) now widely used for defining interaction landscapes. Traditional AP-MS methods are well suited to providing information regarding the temporal aspects of soluble protein-protein interactions, but the requirement to maintain protein-protein interactions during cell lysis and AP means that both weak-affinity interactions and spatial information is lost. A more recently developed method called BioID employs the expression of bait proteins fused to a nonspecific biotin ligase, BirA*, that induces in vivo biotinylation of proximal proteins. Coupling this method to biotin affinity enrichment and mass spectrometry negates many of the solubility and interaction strength issues inherent in traditional AP-MS methods, and provides unparalleled spatial context for protein interactions. Here we describe the parallel implementation of both BioID and FLAG AP-MS allowing simultaneous exploration of both spatial and temporal aspects of protein interaction networks.

Investigation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput liquid chromatography/tandem mass spectrometry assays.

PubMed

Yang, Liyu; Amad, Ma'an; Winnik, Witold M; Schoen, Alan E; Schweingruber, Hans; Mylchreest, Iain; Rudewicz, Patrick J

2002-01-01

Triple quadrupole mass spectrometers, when operated in multiple reaction monitoring (MRM) mode, offer a unique combination of sensitivity, specificity, and dynamic range. Consequently, the triple quadrupole is the workhorse for high-throughput quantitation within the pharmaceutical industry. However, in the past, the unit mass resolution of quadrupole instruments has been a limitation when interference from matrix or metabolites cannot be eliminated. With recent advances in instrument design, triple quadrupole instruments now afford mass resolution of less than 0.1 Dalton (Da) full width at half maximum (FWHM). This paper describes the evaluation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput bioanalysis with emphasis on comparison of selectivity, sensitivity, dynamic range, precision, accuracy, and stability under both unit mass (1 Da FWHM) and enhanced (mass resolution, the transmitted precursor ion from the first quadrupole contained not only protonated molecules from mometasone, but also PPG interference. At enhanced resolution only selected mometasone peaks were transmitted, and no interference from PPG was detected. Sensitivity of the instrument was demonstrated with 10 femtograms of descarboethoxyloratadine injected on-column, for which a signal-to-noise (S/N) ratio of 24 was obtained for MRM chromatograms at both unit and enhanced resolution. Absolute signals obtained at enhanced resolution were about one-third those obtained at unit mass resolution. However, S/N was maintained at enhanced resolution due to the proportional decrease in noise level. Finally, the stability of the instrument operating at enhanced resolution was demonstrated during an overnight 17 h period that was used to validate a liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for

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

Pivotal role of computers and software in mass spectrometry - SEQUEST and 20 years of tandem MS database searching.

PubMed

Yates, John R

2015-11-01

Advances in computer technology and software have driven developments in mass spectrometry over the last 50 years. Computers and software have been impactful in three areas: the automation of difficult calculations to aid interpretation, the collection of data and control of instruments, and data interpretation. As the power of computers has grown, so too has the utility and impact on mass spectrometers and their capabilities. This has been particularly evident in the use of tandem mass spectrometry data to search protein and nucleotide sequence databases to identify peptide and protein sequences. This capability has driven the development of many new approaches to study biological systems, including the use of "bottom-up shotgun proteomics" to directly analyze protein mixtures. Graphical Abstract ᅟ.

Rapid Quantitative Analysis of Multiple Explosive Compound Classes on a Single Instrument via Flow-Injection Analysis Tandem Mass Spectrometry.

PubMed

Ostrinskaya, Alla; Kunz, Roderick R; Clark, Michelle; Kingsborough, Richard P; Ong, Ta-Hsuan; Deneault, Sandra

2018-05-24

A flow-injection analysis tandem mass spectrometry (FIA MSMS) method was developed for rapid quantitative analysis of 10 different inorganic and organic explosives. Performance is optimized by tailoring the ionization method (APCI/ESI), de-clustering potentials, and collision energies for each specific analyte. In doing so, a single instrument can be used to detect urea nitrate, potassium chlorate, 2,4,6-trinitrotoluene, 2,4,6-trinitrophenylmethylnitramine, triacetone triperoxide, hexamethylene triperoxide diamine, pentaerythritol tetranitrate, 1,3,5-trinitroperhydro-1,3,5-triazine, nitroglycerin, and octohy-dro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine with sensitivities all in the picogram per milliliter range. In conclusion, FIA APCI/ESI MSMS is a fast (<1 min/sample), sensitive (~pg/mL LOQ), and precise (intraday RSD < 10%) method for trace explosive detection that can play an important role in criminal and attributional forensics, counterterrorism, and environmental protection areas, and has the potential to augment or replace several of the existing explosive detection methods. © 2018 American Academy of Forensic Sciences.

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'.

Absorption Mode FT-ICR Mass Spectrometry Imaging

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

Smith, Donald F.; Kilgour, David P.; Konijnenburg, Marco

2013-12-03

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

A Researcher's Guide to Mass Spectrometry-Based Proteomics

PubMed Central

Savaryn, John P.; Toby, Timothy K.; Kelleher, Neil L.

2016-01-01

Mass spectrometry (MS) is widely recognized as a powerful analytical tool for molecular research. MS is used by researchers around the globe to identify, quantify, and characterize biomolecules like proteins from any number of biological conditions or sample types. As instrumentation has advanced, and with the coupling of liquid chromatography (LC) for high-throughput LC-MS/MS, a proteomics experiment measuring hundreds to thousands of proteins/protein groups is now commonplace. While expert practitioners who best understand the operation of LC-MS systems tend to have strong backgrounds in physics and engineering, consumers of proteomics data and technology are not exposed to the physio-chemical principles underlying the information they seek. Since articles and reviews tend not to focus on bridging this divide, our goal here is to span this gap and translate MS ion physics into language intuitive to the general reader active in basic or applied biomedical research. Here, we visually describe what happens to ions as they enter and move around inside a mass spectrometer. We describe basic MS principles, including electric current, ion optics, ion traps, quadrupole mass filters, and Orbitrap FT-analyzers. PMID:27553853

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

PubMed Central

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

2010-01-01

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

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

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.

"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.

An Integrated Hot-Stage Microscope-Direct Analysis in Real Time-Mass Spectrometry System for Studying the Thermal Behavior of Materials.

PubMed

Ashton, Gage P; Harding, Lindsay P; Parkes, Gareth M B

2017-12-19

This paper describes a new analytical instrument that combines a precisely temperature-controlled hot-stage with digital microscopy and Direct Analysis in Real Time-mass spectrometry (DART-MS) detection. The novelty of the instrument lies in its ability to monitor processes as a function of temperature through the simultaneous recording of images, quantitative color changes, and mass spectra. The capability of the instrument was demonstrated through successful application to four very varied systems including profiling an organic reaction, decomposition of silicone polymers, and the desorption of rhodamine B from an alumina surface. The multidimensional, real-time analytical data provided by this instrument allow for a much greater insight into thermal processes than could be achieved previously.

Determination of T-2 and HT-2 toxins from maize by direct analysis in real time mass spectrometry

USDA-ARS?s Scientific Manuscript database

Direct analysis in real time (DART) ionization coupled to mass spectrometry (MS) was used for the rapid quantitative analysis of T-2 toxin, and the related HT-2 toxin, extracted from corn. Sample preparation procedures and instrument parameters were optimized to obtain sensitive and accurate determi...

Measuring masses of large biomolecules and bioparticles using mass spectrometric techniques.

PubMed

Peng, Wen-Ping; Chou, Szu-Wei; Patil, Avinash A

2014-07-21

Large biomolecules and bioparticles play a vital role in biology, chemistry, biomedical science and physics. Mass is a critical parameter for the characterization of large biomolecules and bioparticles. To achieve mass analysis, choosing a suitable ion source is the first step and the instruments for detecting ions, mass analyzers and detectors should also be considered. Abundant mass spectrometric techniques have been proposed to determine the masses of large biomolecules and bioparticles and these techniques can be divided into two categories. The first category measures the mass (or size) of intact particles, including single particle quadrupole ion trap mass spectrometry, cell mass spectrometry, charge detection mass spectrometry and differential mobility mass analysis; the second category aims to measure the mass and tandem mass of biomolecular ions, including quadrupole ion trap mass spectrometry, time-of-flight mass spectrometry, quadrupole orthogonal time-of-flight mass spectrometry and orbitrap mass spectrometry. Moreover, algorithms for the mass and stoichiometry assignment of electrospray mass spectra are developed to obtain accurate structure information and subunit combinations.

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

Recent progress in microchip electrophoresis-mass spectrometry.

PubMed

Kitagawa, Fumihiko; Otsuka, Koji

2011-06-25

This review highlights the methodological and instrumental developments in microchip electrophoresis (MCE)-mass spectrometry (MS) from 1997. In MCE-MS, the development of ionization interface is one of the most important issues to realize highly sensitive detection and high separation efficiency. Among several interfaces, electrospray ionization (ESI) has been mainly employed to MCE-MS since a simple structure of the ESI interface is suitable for coupling with the microchips. Although the number of publications is still limited, laser desorption ionization (LDI) interface has also been developed for MCE-MS. The characteristics of the ESI and LDI interfaces applied to the electrophoresis microchips are presented in this review. The scope of applications in MCE-MS covers mainly biogenic compounds such as bioactive amines, peptides, tryptic digests and proteins. This review provides a comprehensive table listing the applications in MCE-MS. Copyright © 2010 Elsevier B.V. All rights reserved.

Multi-elemental analysis of aqueous geochemical samples by quadrupole inductively coupled plasma-mass spectrometry (ICP-MS)

USGS Publications Warehouse

Wolf, Ruth E.; Adams, Monique

2015-01-01

Typically, quadrupole inductively coupled plasma-mass spectrometry (ICP-MS) is used to determine as many as 57 major, minor, and trace elements in aqueous geochemical samples, including natural surface water and groundwater, acid mine drainage water, and extracts or leachates from geological samples. The sample solution is aspirated into the inductively coupled plasma (ICP) which is an electrodeless discharge of ionized argon gas at a temperature of approximately 6,000 degrees Celsius. The elements in the sample solution are subsequently volatilized, atomized, and ionized by the ICP. The ions generated are then focused and introduced into a quadrupole mass filter which only allows one mass to reach the detector at a given moment in time. As the settings of the mass analyzer change, subsequent masses are allowed to impact the detector. Although the typical quadrupole ICP-MS system is a sequential scanning instrument (determining each mass separately), the scan speed of modern instruments is on the order of several thousand masses per second. Consequently, typical total sample analysis times of 2–3 minutes are readily achievable for up to 57 elements.

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.

Using laser micro mass spectrometry with the LAMMA-1000 instrument for monitoring relative elemental concentrations in vitrinite

USGS Publications Warehouse

Morelli, J.J.; Hercules, D.M.; Lyons, P.C.; Palmer, C.A.; Fletcher, J.D.

1988-01-01

The variation in relative elemental concentrations among a series of coal macerals belonging to the vitrinite maceral group was determined using laser micro mass spectrometry (LAMMS). Variations in Ba, Cr, Ga, Sr, Ti, and V concentrations among the coals were determined using the LAMM A-1000 instrument. LAMMS analysis is not limited to these elements; their selection illustrates the application of the technique. Ba, Cr, Ga, Sr, Ti, and V have minimal site-to-site variance in the vitrinite macerals of the studied coals as measured by LAMMS. The LAMMS data were compared with bulk elemental data obtained by instrumental neutron activation analysis (INAA) and D. C. arc optical emission spectroscopy (DCAS) in order to determine the reliability of the LAMMS data. The complex nature of the ionization phenomena in LAMMS and the lack of standards characterized on a microscale makes obtaining quantitative elemental data within the ionization microvolume difficult; however, we demonstrate that the relative variation of an element among vitrinites from different coal beds in the eastern United States can be observed using LAMMS in a "bulk" mode by accumulating signal intensities over several microareas of each vitrinite. Our studies indicate gross changes (greater than a factor of 2 to 5 depending on the element) can be monitored when the elemental concentration is significantly above the detection limit. "Bulk" mode analysis was conducted to evaluate the accuracy of future elemental LAMMS microanalyses. The primary advantage of LAMMS is the inherent spatial resolution, ~ 20 ??m for coal. Two different vitrite bands in the Lower Bakerstown coal bed (CLB-1) were analyzed. The analysis did not establish any certain concentration differences in Ba, Cr, Ga, Sr, Ti, and V between the two bands. ?? 1988 Springer-Verlag.

Background correction in separation techniques hyphenated to high-resolution mass spectrometry - Thorough correction with mass spectrometry scans recorded as profile spectra.

PubMed

Erny, Guillaume L; Acunha, Tanize; Simó, Carolina; Cifuentes, Alejandro; Alves, Arminda

2017-04-07

Separation techniques hyphenated with high-resolution mass spectrometry have been a true revolution in analytical separation techniques. Such instruments not only provide unmatched resolution, but they also allow measuring the peaks accurate masses that permit identifying monoisotopic formulae. However, data files can be large, with a major contribution from background noise and background ions. Such unnecessary contribution to the overall signal can hide important features as well as decrease the accuracy of the centroid determination, especially with minor features. Thus, noise and baseline correction can be a valuable pre-processing step. The methodology that is described here, unlike any other approach, is used to correct the original dataset with the MS scans recorded as profiles spectrum. Using urine metabolic studies as examples, we demonstrate that this thorough correction reduces the data complexity by more than 90%. Such correction not only permits an improved visualisation of secondary peaks in the chromatographic domain, but it also facilitates the complete assignment of each MS scan which is invaluable to detect possible comigration/coeluting species. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of Biomarkers of Pathogenic Naegleria fowleri Through Mass Spectrometry and Proteomics

PubMed Central

Moura, Hercules; Izquierdo, Fernando; Woolfitt, Adrian R.; Wagner, Glauber; Pinto, Tatiana; del Aguila, Carmen; Barr, John R.

2017-01-01

Emerging methods based on mass spectrometry (MS) can be used in the rapid identification of microorganisms. Thus far, these practical and rapidly evolving methods have mainly been applied to characterize prokaryotes. We applied matrix-assisted laser-desorption-ionization-time-of-flight mass spectrometry MALDI-TOF MS in the analysis of whole cells of 18 N. fowleri isolates belonging to three genotypes. Fourteen originated from the cerebrospinal fluid or brain tissue of primary amoebic meningoencephalitis patients and four originated from water samples of hot springs, rivers, lakes or municipal water supplies. Whole Naegleria trophozoites grown in axenic cultures were washed and mixed with MALDI matrix. Mass spectra were acquired with a 4700 TOF-TOF instrument. MALDI-TOF MS yielded consistent patterns for all isolates examined. Using a combination of novel data processing methods for visual peak comparison, statistical analysis and proteomics database searching we were able to detect several biomarkers that can differentiate all species and isolates studied, along with common biomarkers for all N. fowleri isolates. Naegleria fowleri could be easily separated from other species within the genus Naegleria. A number of peaks detected were tentatively identified. MALDI-TOF MS fingerprinting is a rapid, reproducible, high-throughput alternative method for identifying Naegleria isolates. This method has potential for studying eukaryotic agents. PMID:25231600

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

Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using electrospray ionization with multi-stage tandem mass spectrometry.

PubMed

Johnson, Byron S; Burinsky, David J; Burova, Svetlana A; Davis, Roman; Fitzgerald, Russ N; Matsuoka, Richard T

2012-05-15

The 2-aminoaniline scaffold is of significant value to the pharmaceutical industry and is embedded in a number of pharmacophores including 2-aminoanilides and benzimidazoles. A novel application of coordination ion spray mass spectrometry (CIS-MS) for interrogating the silver ion (Ag(+)) complexes of a homologous series of these compounds using multi-stage tandem mass spectrometry is described. Unlike the ubiquitous alkali metal ion complexes, Ag(+) complexes of 2-aminoanilides and benzimidazoles were found to yield [M - H](+) ions in significant abundance via gas-phase elimination of the metal hydride (AgH) resulting in unique product ion cascades. Sample introduction was by liquid chromatography with mass spectrometry analysis performed on a hybrid linear ion trap/orbitrap instrument capable of high-resolution measurements. Rigorous structural characterization by multi-stage tandem mass spectrometry using [M +  H](+), [M - H](-) and [M - H](+) precursor ions derived from ESI and CIS experiments was performed for the homologous series of 2-aminoanilide and benzimidazole compounds. A full tabular comparison of structural information resulting from these product ion cascades was produced. Multi-stage tandem mass spectrometry of [M - H](+) ions resulting from Ag(+) complexes of 2-aminoanilides and benzimidazoles in CIS-MS experiments produced unique product ion cascades that exhibited complementary structural information to that obtained from tandem mass spectrometry of [M  +  H](+) and [M - H](-) ions by electrospray ionization (ESI). These observations may be broadly applicable to other compounds that are observed to form Ag(+) complexes and eliminate AgH. Copyright © 2012 John Wiley & Sons, Ltd.

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.

New Cs sputter ion source with polyatomic ion beams for secondary ion mass spectrometry applications

NASA Astrophysics Data System (ADS)

Belykh, S. F.; Palitsin, V. V.; Veryovkin, I. V.; Kovarsky, A. P.; Chang, R. J. H.; Adriaens, A.; Dowsett, M. G.; Adams, F.

2007-08-01

A simple design for a cesium sputter ion source compatible with vacuum and ion-optical systems as well as with electronics of the commercially available Cameca IMS-4f instrument is reported. This ion source has been tested with the cluster primary ions of Sin- and Cun-. Our experiments with surface characterization and depth profiling conducted to date demonstrate improvements of the analytical capabilities of the secondary ion mass spectrometry instrument due to the nonadditive enhancement of secondary ion emission and shorter ion ranges of polyatomic projectiles compared to atomic ones with the same impact energy.

Proton-transfer reaction mass spectrometry (PTRMS) in combination with thermal desorption (TD) for sensitive off-line analysis of volatiles.

PubMed

Crespo, Elena; Devasena, Samudrala; Sikkens, Cor; Centeno, Raymund; Cristescu, Simona M; Harren, Frans J M

2012-04-30

When performing trace gas analysis, it is not always possible to bring the source of volatiles and the gas analyzer together. In these cases, volatile storage containers, such as thermal desorption (TD) tubes, can be used for off-line measurement. TD is routinely combined with gas chromatography/mass spectrometry (GC/MS), but so far not with proton-transfer reaction mass spectrometry (PTRMS), which has a faster response. A PTR-quadrupole-MS instrument and a PTR-ion-trap-MS instrument were separately coupled to a TD unit for off-line analysis of trace volatiles in air. Carbograph 1TD/Carbopack X sorbent tubes were filled with different concentrations of a trace gas mixture containing low molecular weight volatiles (32 g/mol up to 136 g/mol) and measured with the above-mentioned combinations. The carrier gas in the TD unit was changed from helium to nitrogen to be able to combine this instrument with the mass spectrometer. Good linearity and reproducibility with the amount of gas stored were obtained. The storage capacity over time (up to 14 days) showed larger variability (<11% for all compounds, except for acetone 27%). Several tubes were filled with breath of different persons, and the breath of a smoker showed increased levels of acetonitrile and benzene. The combination of the PTR ion-trap instrument with the TD unit was also investigated. Due to its higher sampling rate, the ion-trap system showed higher throughput capabilities than the quadrupole system. The combination of TD with PTRMS using both a quadrupole and an ion trap for off-line volatile analysis has been validated. TD tubes can be a robust and compact volatile storage method when the mass spectrometry and the sampling cannot be performed in the same place, for example in large screening studies. In addition, a higher measurement throughput than with GC/MS could be obtained. Copyright © 2012 John Wiley & Sons, Ltd.

The Assessment of Selectivity in Different Quadrupole-Orbitrap Mass Spectrometry Acquisition Modes

NASA Astrophysics Data System (ADS)

Berendsen, Bjorn J. A.; Wegh, Robin S.; Meijer, Thijs; Nielen, Michel W. F.

2015-02-01

Selectivity of the confirmation of identity in liquid chromatography (tandem) mass spectrometry using Q-Orbitrap instrumentation was assessed using different acquisition modes based on a representative experimental data set constructed from 108 samples, including six different matrix extracts and containing over 100 analytes each. Single stage full scan, all ion fragmentation, and product ion scanning were applied. By generating reconstructed ion chromatograms using unit mass window in targeted MS2, selected reaction monitoring (SRM), regularly applied using triple-quadrupole instruments, was mimicked. This facilitated the comparison of single stage full scan, all ion fragmentation, (mimicked) SRM, and product ion scanning applying a mass window down to 1 ppm. Single factor Analysis of Variance was carried out on the variance (s2) of the mass error to determine which factors and interactions are significant parameters with respect to selectivity. We conclude that selectivity is related to the target compound (mainly the mass defect), the matrix, sample clean-up, concentration, and mass resolution. Selectivity of the different instrumental configurations was quantified by counting the number of interfering peaks observed in the chromatograms. We conclude that precursor ion selection significantly contributes to selectivity: monitoring of a single product ion at high mass accuracy with a 1 Da precursor ion window proved to be equally selective or better to monitoring two transition products in mimicked SRM. In contrast, monitoring a single fragment in all ion fragmentation mode results in significantly lower selectivity versus mimicked SRM. After a thorough inter-laboratory evaluation study, the results of this study can be used for a critical reassessment of the current identification points system and contribute to the next generation of evidence-based and robust performance criteria in residue analysis and sports doping.

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

Two-step Laser Time-of-Flight Mass Spectrometry to Elucidate Organic Diversity in Planetary Surface Materials.

NASA Technical Reports Server (NTRS)

Getty, Stephanie A.; Brinckerhoff, William B.; Cornish, Timothy; Li, Xiang; Floyd, Melissa; Arevalo, Ricardo Jr.; Cook, Jamie Elsila; Callahan, Michael P.

2013-01-01

Laser desorption/ionization time-of-flight mass spectrometry (LD-TOF-MS) holds promise to be a low-mass, compact in situ analytical capability for future landed missions to planetary surfaces. The ability to analyze a solid sample for both mineralogical and preserved organic content with laser ionization could be compelling as part of a scientific mission pay-load that must be prepared for unanticipated discoveries. Targeted missions for this instrument capability include Mars, Europa, Enceladus, and small icy bodies, such as asteroids and comets.

Improved Steroids Detection and Evidence for Their Regiospecific Decompositions Using Anion Attachment Mass Spectrometry.

PubMed

Dumont, Quentin; Bárcenas, Mariana; Dossmann, Héloïse; Bailloux, Isabelle; Buisson, Corinne; Mechin, Nathalie; Molina, Adeline; Lasne, Françoise; Rannulu, Nalaka S; Cole, Richard B

2016-04-05

Nonpolar anabolic steroids are doping agents that typically do not provide strong signals by electrospray ionization-mass spectrometry (ESI-MS) owing especially to the low polarity of the functional groups present. We have investigated the addition of anions, in ammonium salt form, to anabolic steroid samples as ionization enhancers and have confirmed that lower instrumental limits of detection (as low as 10 ng/mL for fluoxymesterone-M) are obtained by fluoride anion attachment mass spectrometry, as compared to ESI(+)/(-) or atmospheric pressure photoionization (APPI)(+). Moreover, collision-induced decomposition (CID) spectra of precursor fluoride adducts of the bifunctional steroid "reduced pregnenolone" (containing two hydroxyl groups) and its d4-analogue provide evidence of regiospecific decompositions after attachment of fluoride anion to a specific hydroxyl group of the steroid. This type of charting of specific CID reaction pathways can offer value to selected reaction monitoring experiments (SRM) as it may result in a gain in selectivity in detection as well as in improvements in quantification.

Mass Spectrometry in Studies of Protein Thiol Chemistry and Signaling: Opportunities and Caveats

PubMed Central

Devarie Baez, Nelmi O.; Reisz, Julie A.; Furdui, Cristina M.

2014-01-01

Mass spectrometry (MS) has become a powerful and widely utilized tool in the investigation of protein thiol chemistry, biochemistry, and biology. Very early biochemical studies of metabolic enzymes have brought to light the broad spectrum of reactivity profiles that distinguish cysteine thiols with functions in catalysis and protein stability from other cysteine residues in proteins. The development of MS methods for the analysis of proteins using electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) coupled with the emergence of high-resolution mass analyzers have been instrumental in advancing studies of thiol modifications, both in single proteins and within the cellular context. This article reviews MS instrumentation and methods of analysis employed in investigations of thiols and their reactivity toward a range of small biomolecules. A selected number of studies are detailed to highlight the advantages brought about by the MS technologies along with the caveats associated with these analyses. PMID:25261734

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

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry*

PubMed Central

Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.; Monroe, Matthew E.; Orton, Daniel J.; Ibrahim, Yehia M.; Gritsenko, Marina A.; Clauss, Therese R. W.; Shukla, Anil K.; Moore, Ronald J.; Purvine, Samuel O.; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S.; Smith, Richard D.

2016-01-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. PMID:27670688

Tandem Mass Spectrometry Imaging and in Situ Characterization of Bioactive Wood Metabolites in Amazonian Tree Species Sextonia rubra.

PubMed

Fu, Tingting; Touboul, David; Della-Negra, Serge; Houël, Emeline; Amusant, Nadine; Duplais, Christophe; Fisher, Gregory L; Brunelle, Alain

2018-06-19

Driven by a necessity for confident molecular identification at high spatial resolution, a new time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem mass spectrometry (tandem MS) imaging instrument has been recently developed. In this paper, the superior MS/MS spectrometry and imaging capability of this new tool is shown for natural product study. For the first time, via in situ analysis of the bioactive metabolites rubrynolide and rubrenolide in Amazonian tree species Sextonia rubra (Lauraceae), we were able both to analyze and to image by tandem MS the molecular products of natural biosynthesis. Despite the low abundance of the metabolites in the wood sample(s), efficient MS/MS analysis of these γ-lactone compounds was achieved, providing high confidence in the identification and localization. In addition, tandem MS imaging minimized the mass interferences and revealed specific localization of these metabolites primarily in the ray parenchyma cells but also in certain oil cells and, further, revealed the presence of previously unidentified γ-lactone, paving the way for future studies in biosynthesis.

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.

Detection of Gunshot Residues Using Mass Spectrometry

PubMed Central

Blanes, Lucas; Cole, Nerida; Doble, Philip; Roux, Claude

2014-01-01

In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR. Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further, modern MS instruments can detect and identify a number of explosives and additives which may require different ionization techniques. Finally, MS has been applied to the analysis of both OGSR and inorganic gunshot residue (IGSR), although the “gold standard” for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis. PMID:24977168

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

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

Chiral Analysis by Tandem Mass Spectrometry Using the Kinetic Method, by Polarimetry, and by [Superscript 1]H NMR Spectroscopy

ERIC Educational Resources Information Center

Fedick, Patrick W.; Bain, Ryan M.; Bain, Kinsey; Cooks, R. Graham

2017-01-01

The goal of this laboratory exercise was for students to understand the concept of chirality and how enantiomeric excess (ee) is experimentally determined using the analysis of ibuprofen as an example. Students determined the enantiomeric excess of the analyte by three different instrumental methods: mass spectrometry, nuclear magnetic resonance…

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

Detection systems for mass spectrometry imaging: a perspective on novel developments with a focus on active pixel detectors.

PubMed

Jungmann, Julia H; Heeren, Ron M A

2013-01-15

Instrumental developments for imaging and individual particle detection for biomolecular mass spectrometry (imaging) and fundamental atomic and molecular physics studies are reviewed. Ion-counting detectors, array detection systems and high mass detectors for mass spectrometry (imaging) are treated. State-of-the-art detection systems for multi-dimensional ion, electron and photon detection are highlighted. Their application and performance in three different imaging modes--integrated, selected and spectral image detection--are described. Electro-optical and microchannel-plate-based systems are contrasted. The analytical capabilities of solid-state pixel detectors--both charge coupled device (CCD) and complementary metal oxide semiconductor (CMOS) chips--are introduced. The Medipix/Timepix detector family is described as an example of a CMOS hybrid active pixel sensor. Alternative imaging methods for particle detection and their potential for future applications are investigated. Copyright © 2012 John Wiley & Sons, Ltd.

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.

Detection of bio-signature by microscopy and mass spectrometry

NASA Astrophysics Data System (ADS)

Tulej, M.; Wiesendanger, R.; Neuland, M., B.; Meyer, S.; Wurz, P.; Neubeck, A.; Ivarsson, M.; Riedo, V.; Moreno-Garcia, P.; Riedo, A.; Knopp, G.

2017-09-01

We demonstrate detection of micro-sized fossilized bacteria by means of microscopy and mass spectrometry. The characteristic structures of lifelike forms are visualized with a micrometre spatial resolution and mass spectrometric analyses deliver elemental and isotope composition of host and fossilized materials. Our studies show that high selectivity in isolation of fossilized material from host phase can be achieved while applying a microscope visualization (location), a laser ablation ion source with sufficiently small laser spot size and applying depth profiling method. Our investigations shows that fossilized features can be well isolated from host phase. The mass spectrometric measurements can be conducted with sufficiently high accuracy and precision yielding quantitative elemental and isotope composition of micro-sized objects. The current performance of the instrument allows the measurement of the isotope fractionation in per mill level and yield exclusively definition of the origin of the investigated species by combining optical visualization of investigated samples (morphology and texture), chemical characterization of host and embedded in the host micro-sized structure. Our isotope analyses involved bio-relevant B, C, S, and Ni isotopes which could be measured with sufficiently accuracy to conclude about the nature of the micro-sized objects.

The use of mass spectrometry to analyze dried blood spots.

PubMed

Wagner, Michel; Tonoli, David; Varesio, Emmanuel; Hopfgartner, Gérard

2016-01-01

Dried blood spots (DBS) typically consist in the deposition of small volumes of capillary blood onto dedicated paper cards. Comparatively to whole blood or plasma samples, their benefits rely in the fact that sample collection is easier and that logistic aspects related to sample storage and shipment can be relatively limited, respectively, without the need of a refrigerator or dry ice. Originally, this approach has been developed in the sixties to support the analysis of phenylalanine for the detection of phenylketonuria in newborns using bacterial inhibition test. In the nineties tandem mass spectrometry was established as the detection technique for phenylalanine and tyrosine. DBS became rapidly recognized for their clinical value: they were widely implemented in pediatric settings with mass spectrometric detection, and were closely associated to the debut of newborn screening (NBS) programs, as a part of public health policies. Since then, sample collection on paper cards has been explored with various analytical techniques in other areas more or less successfully regarding large-scale applications. Moreover, in the last 5 years a regain of interest for DBS was observed and originated from the bioanalytical community to support drug development (e.g., PK studies) or therapeutic drug monitoring mainly. Those recent applications were essentially driven by improved sensitivity of triple quadrupole mass spectrometers. This review presents an overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques. A general introduction to DBS will describe their advantages and historical aspects of their emergence. A second section will focus on blood collection, with a strong emphasis on specific parameters that can impact quantitative analysis, including chromatographic effects, hematocrit effects, blood effects, and analyte stability. A third part of the review is dedicated to

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...

An expert system/ion trap mass spectrometry approach for life support systems monitoring

NASA Technical Reports Server (NTRS)

Palmer, Peter T.; Wong, Carla M.; Yost, Richard A.; Johnson, Jodie V.; Yates, Nathan A.; Story, Michael

1992-01-01

Efforts to develop sensor and control system technology to monitor air quality for life support have resulted in the development and preliminary testing of a concept based on expert systems and ion trap mass spectrometry (ITMS). An ITMS instrument provides the capability to identify and quantitate a large number of suspected contaminants at trace levels through the use of a variety of multidimensional experiments. An expert system provides specialized knowledge for control, analysis, and decision making. The system is intended for real-time, on-line, autonomous monitoring of air quality. The key characteristics of the system, performance data and analytical capabilities of the ITMS instrument, the design and operation of the expert system, and results from preliminary testing of the system for trace contaminant monitoring are 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

Combining two-dimensional diffusion-ordered nuclear magnetic resonance spectroscopy, imaging desorption electrospray ionization mass spectrometry, and direct analysis in real-time mass spectrometry for the integral investigation of counterfeit pharmaceuticals.

PubMed

Nyadong, Leonard; Harris, Glenn A; Balayssac, Stéphane; Galhena, Asiri S; Malet-Martino, Myriam; Martino, Robert; Parry, R Mitchell; Wang, May Dongmei; Fernández, Facundo M; Gilard, Véronique

2009-06-15

During the past decade, there has been a marked increase in the number of reported cases involving counterfeit medicines in developing and developed countries. Particularly, artesunate-based antimalarial drugs have been targeted, because of their high demand and cost. Counterfeit antimalarials can cause death and can contribute to the growing problem of drug resistance, particularly in southeast Asia. In this study, the complementarity of two-dimensional diffusion-ordered (1)H nuclear magnetic resonance spectroscopy (2D DOSY (1)H NMR) with direct analysis in real-time mass spectrometry (DART MS) and desorption electrospray ionization mass spectrometry (DESI MS) was assessed for pharmaceutical forensic purposes. Fourteen different artesunate tablets, representative of what can be purchased from informal sources in southeast Asia, were investigated with these techniques. The expected active pharmaceutical ingredient was detected in only five formulations via both nuclear magnetic resonance (NMR) and mass spectrometry (MS) methods. Common organic excipients such as sucrose, lactose, stearate, dextrin, and starch were also detected. The graphical representation of DOSY (1)H NMR results proved very useful for establishing similarities among groups of samples, enabling counterfeit drug "chemotyping". In addition to bulk- and surface-average analyses, spatially resolved information on the surface composition of counterfeit and genuine antimalarial formulations was obtained using DESI MS that was performed in the imaging mode, which enabled one to visualize the homogeneity of both genuine and counterfeit drug samples. Overall, this study suggests that 2D DOSY (1)H NMR, combined with ambient MS, comprises a powerful suite of instrumental analysis methodologies for the integral characterization of counterfeit antimalarials.

Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms.

PubMed

Jaffe, Jacob D; Feeney, Caitlin M; Patel, Jinal; Lu, Xiaodong; Mani, D R

2016-11-01

Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently-trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques. Graphical Abstract ᅟ.

Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms

NASA Astrophysics Data System (ADS)

Jaffe, Jacob D.; Feeney, Caitlin M.; Patel, Jinal; Lu, Xiaodong; Mani, D. R.

2016-11-01

Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently-trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques.

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.

High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

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...

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.

Portable Dew Point Mass Spectrometry System for Real-Time Gas and Moisture Analysis

NASA Technical Reports Server (NTRS)

Arkin, C.; Gillespie, Stacey; Ratzel, Christopher

2010-01-01

A portable instrument incorporates both mass spectrometry and dew point measurement to provide real-time, quantitative gas measurements of helium, nitrogen, oxygen, argon, and carbon dioxide, along with real-time, quantitative moisture analysis. The Portable Dew Point Mass Spectrometry (PDP-MS) system comprises a single quadrupole mass spectrometer and a high vacuum system consisting of a turbopump and a diaphragm-backing pump. A capacitive membrane dew point sensor was placed upstream of the MS, but still within the pressure-flow control pneumatic region. Pressure-flow control was achieved with an upstream precision metering valve, a capacitance diaphragm gauge, and a downstream mass flow controller. User configurable LabVIEW software was developed to provide real-time concentration data for the MS, dew point monitor, and sample delivery system pressure control, pressure and flow monitoring, and recording. The system has been designed to include in situ, NIST-traceable calibration. Certain sample tubing retains sufficient water that even if the sample is dry, the sample tube will desorb water to an amount resulting in moisture concentration errors up to 500 ppm for as long as 10 minutes. It was determined that Bev-A-Line IV was the best sample line to use. As a result of this issue, it is prudent to add a high-level humidity sensor to PDP-MS so such events can be prevented in the future.

Time‐of‐flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions

PubMed Central

Vanbellingen, Quentin P.; Elie, Nicolas; Eller, Michael J.; Della‐Negra, Serge; Touboul, David

2015-01-01

Rationale In Time‐of‐Flight Secondary Ion Mass Spectrometry (TOF‐SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF‐SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub‐µm lateral resolution, but the combination of both is generally not possible. Methods With a TOF‐SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches. Results The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass‐to‐charge ratio. Conclusions Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF‐SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples. © 2015 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd. PMID:26395603

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.

Metabolomics by Gas Chromatography-Mass Spectrometry: the combination of targeted and untargeted profiling

PubMed Central

Fiehn, Oliver

2016-01-01

Gas chromatography-mass spectrometry (GC-MS)-based metabolomics is ideal for identifying and quantitating small molecular metabolites (<650 daltons), including small acids, alcohols, hydroxyl acids, amino acids, sugars, fatty acids, sterols, catecholamines, drugs, and toxins, often using chemical derivatization to make these compounds volatile enough for gas chromatography. This unit shows that on GC-MS- based metabolomics easily allows integrating targeted assays for absolute quantification of specific metabolites with untargeted metabolomics to discover novel compounds. Complemented by database annotations using large spectral libraries and validated, standardized standard operating procedures, GC-MS can identify and semi-quantify over 200 compounds per study in human body fluids (e.g., plasma, urine or stool) samples. Deconvolution software enables detection of more than 300 additional unidentified signals that can be annotated through accurate mass instruments with appropriate data processing workflows, similar to liquid chromatography-MS untargeted profiling (LC-MS). Hence, GC-MS is a mature technology that not only uses classic detectors (‘quadrupole’) but also target mass spectrometers (‘triple quadrupole’) and accurate mass instruments (‘quadrupole-time of flight’). This unit covers the following aspects of GC-MS-based metabolomics: (i) sample preparation from mammalian samples, (ii) acquisition of data, (iii) quality control, and (iv) data processing. PMID:27038389

Automated Lipid A Structure Assignment from Hierarchical Tandem Mass Spectrometry Data

NASA Astrophysics Data System (ADS)

Ting, Ying S.; Shaffer, Scott A.; Jones, Jace W.; Ng, Wailap V.; Ernst, Robert K.; Goodlett, David R.

2011-05-01

Infusion-based electrospray ionization (ESI) coupled to multiple-stage tandem mass spectrometry (MS n ) is a standard methodology for investigating lipid A structural diversity (Shaffer et al. J. Am. Soc. Mass. Spectrom. 18(6), 1080-1092, 2007). Annotation of these MS n spectra, however, has remained a manual, expert-driven process. In order to keep up with the data acquisition rates of modern instruments, we devised a computational method to annotate lipid A MS n spectra rapidly and automatically, which we refer to as hierarchical tandem mass spectrometry (HiTMS) algorithm. As a first-pass tool, HiTMS aids expert interpretation of lipid A MS n data by providing the analyst with a set of candidate structures that may then be confirmed or rejected. HiTMS deciphers the signature ions (e.g., A-, Y-, and Z-type ions) and neutral losses of MS n spectra using a species-specific library based on general prior structural knowledge of the given lipid A species under investigation. Candidates are selected by calculating the correlation between theoretical and acquired MS n spectra. At a false discovery rate of less than 0.01, HiTMS correctly assigned 85% of the structures in a library of 133 manually annotated Francisella tularensis subspecies novicida lipid A structures. Additionally, HiTMS correctly assigned 85% of the structures in a smaller library of lipid A species from Yersinia pestis demonstrating that it may be used across species.

Detection of biomarkers of pathogenic Naegleria fowleri through mass spectrometry and proteomics.

PubMed

Moura, Hercules; Izquierdo, Fernando; Woolfitt, Adrian R; Wagner, Glauber; Pinto, Tatiana; del Aguila, Carmen; Barr, John R

2015-01-01

Emerging methods based on mass spectrometry (MS) can be used in the rapid identification of microorganisms. Thus far, these practical and rapidly evolving methods have mainly been applied to characterize prokaryotes. We applied matrix-assisted laser-desorption-ionization-time-of-flight mass spectrometry MALDI-TOF MS in the analysis of whole cells of 18 N. fowleri isolates belonging to three genotypes. Fourteen originated from the cerebrospinal fluid or brain tissue of primary amoebic meningoencephalitis patients and four originated from water samples of hot springs, rivers, lakes or municipal water supplies. Whole Naegleria trophozoites grown in axenic cultures were washed and mixed with MALDI matrix. Mass spectra were acquired with a 4700 TOF-TOF instrument. MALDI-TOF MS yielded consistent patterns for all isolates examined. Using a combination of novel data processing methods for visual peak comparison, statistical analysis and proteomics database searching we were able to detect several biomarkers that can differentiate all species and isolates studied, along with common biomarkers for all N. fowleri isolates. Naegleria fowleri could be easily separated from other species within the genus Naegleria. A number of peaks detected were tentatively identified. MALDI-TOF MS fingerprinting is a rapid, reproducible, high-throughput alternative method for identifying Naegleria isolates. This method has potential for studying eukaryotic agents. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

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.

Using ProHits to store, annotate and analyze affinity purification - mass spectrometry (AP-MS) data

PubMed Central

Liu, Guomin; Zhang, Jianping; Choi, Hyungwon; Lambert, Jean-Philippe; Srikumar, Tharan; Larsen, Brett; Nesvizhskii, Alexey I.; Raught, Brian; Tyers, Mike; Gingras, Anne-Claude

2012-01-01

Affinity purification coupled with mass spectrometry (AP-MS) is a robust technique used to identify protein-protein interactions. With recent improvements in sample preparation, and dramatic advances in MS instrumentation speed and sensitivity, this technique is becoming more widely used throughout the scientific community. To meet the needs of research groups both large and small, we have developed software solutions for tracking, scoring and analyzing AP-MS data. Here, we provide details for the installation and utilization of ProHits, a Laboratory Information Management System designed specifically for AP-MS interaction proteomics. This protocol explains: (i) how to install the complete ProHits system, including modules for the management of mass spectrometry files and the analysis of interaction data, and (ii) alternative options for the use of pre-existing search results in simpler versions of ProHits, including a virtual machine implementation of our ProHits Lite software. We also describe how to use the main features of the software to analyze AP-MS data. PMID:22948730

"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...

Probabilistic consensus scoring improves tandem mass spectrometry peptide identification.

PubMed

Nahnsen, Sven; Bertsch, Andreas; Rahnenführer, Jörg; Nordheim, Alfred; Kohlbacher, Oliver

2011-08-05

Database search is a standard technique for identifying peptides from their tandem mass spectra. To increase the number of correctly identified peptides, we suggest a probabilistic framework that allows the combination of scores from different search engines into a joint consensus score. Central to the approach is a novel method to estimate scores for peptides not found by an individual search engine. This approach allows the estimation of p-values for each candidate peptide and their combination across all search engines. The consensus approach works better than any single search engine across all different instrument types considered in this study. Improvements vary strongly from platform to platform and from search engine to search engine. Compared to the industry standard MASCOT, our approach can identify up to 60% more peptides. The software for consensus predictions is implemented in C++ as part of OpenMS, a software framework for mass spectrometry. The source code is available in the current development version of OpenMS and can easily be used as a command line application or via a graphical pipeline designer TOPPAS.

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.

Strategies to avoid false negative findings in residue analysis using liquid chromatography coupled to time-of-flight mass spectrometry.

PubMed

Kaufmann, Anton; Butcher, Patrick

2006-01-01

Liquid chromatography coupled to orthogonal acceleration time-of-flight mass spectrometry (LC/TOF) provides an attractive alternative to liquid chromatography coupled to triple quadrupole mass spectrometry (LC/MS/MS) in the field of multiresidue analysis. The sensitivity and selectivity of LC/TOF approach those of LC/MS/MS. TOF provides accurate mass information and a significantly higher mass resolution than quadrupole analyzers. The available mass resolution of commercial TOF instruments ranging from 10 000 to 18 000 full width at half maximum (FWHM) is not, however, sufficient to completely exclude the problem of isobaric interferences (co-elution of analyte ions with matrix compounds of very similar mass). Due to the required data storage capacity, TOF raw data is commonly centroided before being electronically stored. However, centroiding can lead to a loss of data quality. The co-elution of a low intensity analyte peak with an isobaric, high intensity matrix compound can cause problems. Some centroiding algorithms might not be capable of deconvoluting such partially merged signals, leading to incorrect centroids.Co-elution of isobaric compounds has been deliberately simulated by injecting diluted binary mixtures of isobaric model substances at various relative intensities. Depending on the mass differences between the two isobaric compounds and the resolution provided by the TOF instrument, significant deviations in exact mass measurements and signal intensities were observed. The extraction of a reconstructed ion chromatogram based on very narrow mass windows can even result in the complete loss of the analyte signal. Guidelines have been proposed to avoid such problems. The use of sub-2 microm HPLC packing materials is recommended to improve chromatographic resolution and to reduce the risk of co-elution. The width of the extraction mass windows for reconstructed ion chromatograms should be defined according to the resolution of the TOF instrument

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.

Design and performance of an instrument for electron impact tandem mass spectrometry and action spectroscopy of mass/charge selected macromolecular ions stored in RF ion trap*

NASA Astrophysics Data System (ADS)

Ranković, Milos Lj.; Giuliani, Alexandre; Milosavljević, Aleksandar R.

2016-06-01

A new apparatus was designed, coupling an electron gun with a linear quadrupole ion trap mass spectrometer, to perform m/ z (mass over charge) selected ion activation by electron impact for tandem mass spectrometry and action spectroscopy. We present in detail electron tracing simulations of a 300 eV electron beam inside the ion trap, design of the mechanical parts, electron optics and electronic circuits used in the experiment. We also report examples of electron impact activation tandem mass spectra for Ubiquitin protein, Substance P and Melittin peptides, at incident electron energies in the range from 280 eV to 300 eV.

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 ...

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.

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.

Introduction of organic/hydro-organic matrices in inductively coupled plasma optical emission spectrometry and mass spectrometry: a tutorial review. Part II. Practical considerations.

PubMed

Leclercq, Amélie; Nonell, Anthony; Todolí Torró, José Luis; Bresson, Carole; Vio, Laurent; Vercouter, Thomas; Chartier, Frédéric

2015-07-23

Inductively coupled plasma optical emission spectrometry (ICP-OES) and mass spectrometry (ICP-MS) are increasingly used to carry out analyses in organic/hydro-organic matrices. The introduction of such matrices into ICP sources is particularly challenging and can be the cause of numerous drawbacks. This tutorial review, divided in two parts, explores the rich literature related to the introduction of organic/hydro-organic matrices in ICP sources. Part I provided theoretical considerations associated with the physico-chemical properties of such matrices, in an attempt to understand the induced phenomena. Part II of this tutorial review is dedicated to more practical considerations on instrumentation, instrumental and operating parameters, as well as analytical strategies for elemental quantification in such matrices. Two important issues are addressed in this part: the first concerns the instrumentation and optimization of instrumental and operating parameters, pointing out (i) the description, benefits and drawbacks of different kinds of nebulization and desolvation devices and the impact of more specific instrumental parameters such as the injector characteristics and the material used for the cone; and, (ii) the optimization of operating parameters, for both ICP-OES and ICP-MS. Even if it is at the margin of this tutorial review, Electrothermal Vaporization and Laser Ablation will also be shortly described. The second issue is devoted to the analytical strategies for elemental quantification in such matrices, with particular insight into the isotope dilution technique, particularly used in speciation analysis by ICP-coupled separation techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

Fast and Efficient XML Data Access for Next-Generation Mass Spectrometry.

PubMed

Röst, Hannes L; Schmitt, Uwe; Aebersold, Ruedi; Malmström, Lars

2015-01-01

In mass spectrometry-based proteomics, XML formats such as mzML and mzXML provide an open and standardized way to store and exchange the raw data (spectra and chromatograms) of mass spectrometric experiments. These file formats are being used by a multitude of open-source and cross-platform tools which allow the proteomics community to access algorithms in a vendor-independent fashion and perform transparent and reproducible data analysis. Recent improvements in mass spectrometry instrumentation have increased the data size produced in a single LC-MS/MS measurement and put substantial strain on open-source tools, particularly those that are not equipped to deal with XML data files that reach dozens of gigabytes in size. Here we present a fast and versatile parsing library for mass spectrometric XML formats available in C++ and Python, based on the mature OpenMS software framework. Our library implements an API for obtaining spectra and chromatograms under memory constraints using random access or sequential access functions, allowing users to process datasets that are much larger than system memory. For fast access to the raw data structures, small XML files can also be completely loaded into memory. In addition, we have improved the parsing speed of the core mzML module by over 4-fold (compared to OpenMS 1.11), making our library suitable for a wide variety of algorithms that need fast access to dozens of gigabytes of raw mass spectrometric data. Our C++ and Python implementations are available for the Linux, Mac, and Windows operating systems. All proposed modifications to the OpenMS code have been merged into the OpenMS mainline codebase and are available to the community at https://github.com/OpenMS/OpenMS.

Fast and Efficient XML Data Access for Next-Generation Mass Spectrometry

PubMed Central

Röst, Hannes L.; Schmitt, Uwe; Aebersold, Ruedi; Malmström, Lars

2015-01-01

Motivation In mass spectrometry-based proteomics, XML formats such as mzML and mzXML provide an open and standardized way to store and exchange the raw data (spectra and chromatograms) of mass spectrometric experiments. These file formats are being used by a multitude of open-source and cross-platform tools which allow the proteomics community to access algorithms in a vendor-independent fashion and perform transparent and reproducible data analysis. Recent improvements in mass spectrometry instrumentation have increased the data size produced in a single LC-MS/MS measurement and put substantial strain on open-source tools, particularly those that are not equipped to deal with XML data files that reach dozens of gigabytes in size. Results Here we present a fast and versatile parsing library for mass spectrometric XML formats available in C++ and Python, based on the mature OpenMS software framework. Our library implements an API for obtaining spectra and chromatograms under memory constraints using random access or sequential access functions, allowing users to process datasets that are much larger than system memory. For fast access to the raw data structures, small XML files can also be completely loaded into memory. In addition, we have improved the parsing speed of the core mzML module by over 4-fold (compared to OpenMS 1.11), making our library suitable for a wide variety of algorithms that need fast access to dozens of gigabytes of raw mass spectrometric data. Availability Our C++ and Python implementations are available for the Linux, Mac, and Windows operating systems. All proposed modifications to the OpenMS code have been merged into the OpenMS mainline codebase and are available to the community at https://github.com/OpenMS/OpenMS. PMID:25927999

Detection of trace organics in Mars analog samples containing perchlorate by laser desorption/ionization mass spectrometry.

PubMed

Li, Xiang; Danell, Ryan M; Brinckerhoff, William B; Pinnick, Veronica T; van Amerom, Friso; Arevalo, Ricardo D; Getty, Stephanie A; Mahaffy, Paul R; Steininger, Harald; Goesmann, Fred

2015-02-01

Evidence from recent Mars missions indicates the presence of perchlorate salts up to 1 wt % level in the near-surface materials. Mixed perchlorates and other oxychlorine species may complicate the detection of organic molecules in bulk martian samples when using pyrolysis techniques. To address this analytical challenge, we report here results of laboratory measurements with laser desorption mass spectrometry, including analyses performed on both commercial and Mars Organic Molecule Analyzer (MOMA) breadboard instruments. We demonstrate that the detection of nonvolatile organics in selected spiked mineral-matrix materials by laser desorption/ionization (LDI) mass spectrometry is not inhibited by the presence of up to 1 wt % perchlorate salt. The organics in the sample are not significantly degraded or combusted in the LDI process, and the parent molecular ion is retained in the mass spectrum. The LDI technique provides distinct potential benefits for the detection of organics in situ on the martian surface and has the potential to aid in the search for signs of life on Mars.

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…

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry.

PubMed

Burnum-Johnson, Kristin E; Nie, Song; Casey, Cameron P; Monroe, Matthew E; Orton, Daniel J; Ibrahim, Yehia M; Gritsenko, Marina A; Clauss, Therese R W; Shukla, Anil K; Moore, Ronald J; Purvine, Samuel O; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S; Smith, Richard D

2016-12-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Time-Resolved Molecular Characterization of Limonene/Ozone Aerosol using High-Resolution Electrospray Ionization Mass Spectrometry

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

Bateman, Adam P.; Nizkorodov, Serguei; Laskin, Julia

2009-09-09

Molecular composition of limonene/O3 secondary organic aerosol (SOA) was investigated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) as a function of reaction time. SOA was generated by ozonation of D-limonene in a reaction chamber and sampled at different time intervals using a cascade impactor. The SOA samples were extracted into acetonitrile and analyzed using a HR-ESI-MS instrument with a resolving power of 100,000 (m/Δm). The resulting mass spectra provided detailed information about the extent of oxidation inferred from the O:C ratios, double bond equivalency (DBE) factors, and aromaticity indexes (AI) in hundreds of identified individual SOA species.

Combining Two-Dimensional Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy, Imaging Desorption Electrospray Ionization Mass Spectrometry, and Direct Analysis in Real-Time Mass Spectrometry for the Integral Investigation of Counterfeit Pharmaceuticals

PubMed Central

Nyadong, Leonard; Harris, Glenn A.; Balayssac, Stéphane; Galhena, Asiri S.; Malet-Martino, Myriam; Martino, Robert; Parry, R. Mitchell; Wang, May Dongmei; Fernández, Facundo M.; Gilard, Véronique

2016-01-01

During the past decade, there has been a marked increase in the number of reported cases involving counterfeit medicines in developing and developed countries. Particularly, artesunate-based antimalarial drugs have been targeted, because of their high demand and cost. Counterfeit antimalarials can cause death and can contribute to the growing problem of drug resistance, particularly in southeast Asia. In this study, the complementarity of two-dimensional diffusion-ordered 1H nuclear magnetic resonance spectroscopy (2D DOSY 1H NMR) with direct analysis in real-time mass spectrometry (DART MS) and desorption electrospray ionization mass spectrometry (DESI MS) was assessed for pharmaceutical forensic purposes. Fourteen different artesunate tablets, representative of what can be purchased from informal sources in southeast Asia, were investigated with these techniques. The expected active pharmaceutical ingredient was detected in only five formulations via both nuclear magnetic resonance (NMR) and mass spectrometry (MS) methods. Common organic excipients such as sucrose, lactose, stearate, dextrin, and starch were also detected. The graphical representation of DOSY 1H NMR results proved very useful for establishing similarities among groups of samples, enabling counterfeit drug “chemotyping”. In addition to bulk- and surface-average analyses, spatially resolved information on the surface composition of counterfeit and genuine antimalarial formulations was obtained using DESI MS that was performed in the imaging mode, which enabled one to visualize the homogeneity of both genuine and counterfeit drug samples. Overall, this study suggests that 2D DOSY 1H NMR, combined with ambient MS, comprises a powerful suite of instrumental analysis methodologies for the integral characterization of counterfeit antimalarials. PMID:19453162

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.

High Resolution Mass Spectrometry of Polyfluorinated Polyether-Based Formulation.

PubMed

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

2016-02-01

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

The emerging process of Top Down mass spectrometry for protein analysis: biomarkers, protein-therapeutics, and achieving high throughput†

PubMed Central

Kellie, John F.; Tran, John C.; Lee, Ji Eun; Ahlf, Dorothy R.; Thomas, Haylee M.; Ntai, Ioanna; Catherman, Adam D.; Durbin, Kenneth R.; Zamdborg, Leonid; Vellaichamy, Adaikkalam; Thomas, Paul M.

2011-01-01

Top Down mass spectrometry (MS) has emerged as an alternative to common Bottom Up strategies for protein analysis. In the Top Down approach, intact proteins are fragmented directly in the mass spectrometer to achieve both protein identification and characterization, even capturing information on combinatorial post-translational modifications. Just in the past two years, Top Down MS has seen incremental advances in instrumentation and dedicated software, and has also experienced a major boost from refined separations of whole proteins in complex mixtures that have both high recovery and reproducibility. Combined with steadily advancing commercial MS instrumentation and data processing, a high-throughput workflow covering intact proteins and polypeptides up to 70 kDa is directly visible in the near future. PMID:20711533

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

Estimating rates of denitrification enzyme activity in wetland soils and direct simultaneous quantification of nitrogen and nitrous oxide by membrane inlet mass spectrometry

EPA Science Inventory

Denitrification enzyme activity (DEA) was measured in short-term (4 h) anaerobic assays using Membrane Inlet Mass Spectrometry (MIMS) and electron capture gas chromatography (GC-ECD). Using MIMS, modifications of the instrument and sample handling allowed for the simultaneous me...

Characterization of high explosive particles using cluster secondary ion mass spectrometry.

PubMed

Gillen, Greg; Mahoney, Christine; Wight, Scott; Lareau, Richard

2006-01-01

The use of secondary ion mass spectrometry (SIMS) for the detection and spatially resolved analysis of individual high explosive particles is described. A C(8) (-) carbon cluster primary ion beam was used in a commercial SIMS instrument to analyze samples of high explosives dispersed as particles on silicon substrates. In comparison with monatomic primary ion bombardment, the carbon cluster primary ion beam was found to greatly enhance characteristic secondary ion signals from the explosive compounds while causing minimal beam-induced degradation. The resistance of these compounds to degradation under ion bombardment allows explosive particles to be analyzed under high primary ion dose bombardment (dynamic SIMS) conditions, facilitating the rapid acquisition of spatially resolved molecular information. The use of cluster SIMS combined with computer control of the sample stage position allows for the automated identification and counting of explosive particle distributions on silicon surfaces. This will be useful for characterizing the efficiency of transfer of particulates in trace explosive detection portal collectors and/or swipes utilized for ion mobility spectrometry applications.

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.

Profiling of patterned metal layers by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)

NASA Astrophysics Data System (ADS)

Bi, Melody; Ruiz, Antonio M.; Gornushkin, Igor; Smith, Ben W.; Winefordner, James D.

2000-02-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for profiling patterned thin metal layers on a polymer/silicon substrate. The parameters of the laser and ICP-MS operating conditions have been studied and optimized for this purpose. A new laser ablation chamber was designed and built to achieve the best spatial resolution. The results of the profiling by LA-ICP-MS were compared to those obtained from a laser ablation optical emission spectrometry (LA-OES) instrument, which measured the emission of the plasma at the sample surface, and thus, eliminated the time delay caused by the sample transport into the ICP-MS system. Emission spectra gave better spatial resolution than mass spectra. However, LA-ICP-MS provided much better sensitivity and was able to profile thin metal layers (on the order of a few nanometers) on the silicon surface. A lateral spatial resolution of 45 μm was achieved.

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

High-resolution quantitative imaging of mammalian and bacterial cells using stable isotope mass spectrometry.

PubMed

Lechene, Claude; Hillion, Francois; McMahon, Greg; Benson, Douglas; Kleinfeld, Alan M; Kampf, J Patrick; Distel, Daniel; Luyten, Yvette; Bonventre, Joseph; Hentschel, Dirk; Park, Kwon Moo; Ito, Susumu; Schwartz, Martin; Benichou, Gilles; Slodzian, Georges

2006-01-01

Secondary-ion mass spectrometry (SIMS) is an important tool for investigating isotopic composition in the chemical and materials sciences, but its use in biology has been limited by technical considerations. Multi-isotope imaging mass spectrometry (MIMS), which combines a new generation of SIMS instrument with sophisticated ion optics, labeling with stable isotopes, and quantitative image-analysis software, was developed to study biological materials. The new instrument allows the production of mass images of high lateral resolution (down to 33 nm), as well as the counting or imaging of several isotopes simultaneously. As MIMS can distinguish between ions of very similar mass, such as 12C15N- and 13C14N-, it enables the precise and reproducible measurement of isotope ratios, and thus of the levels of enrichment in specific isotopic labels, within volumes of less than a cubic micrometer. The sensitivity of MIMS is at least 1,000 times that of 14C autoradiography. The depth resolution can be smaller than 1 nm because only a few atomic layers are needed to create an atomic mass image. We illustrate the use of MIMS to image unlabeled mammalian cultured cells and tissue sections; to analyze fatty-acid transport in adipocyte lipid droplets using 13C-oleic acid; to examine nitrogen fixation in bacteria using 15N gaseous nitrogen; to measure levels of protein renewal in the cochlea and in post-ischemic kidney cells using 15N-leucine; to study DNA and RNA co-distribution and uridine incorporation in the nucleolus using 15N-uridine and 81Br of bromodeoxyuridine or 14C-thymidine; to reveal domains in cultured endothelial cells using the native isotopes 12C, 16O, 14N and 31P; and to track a few 15N-labeled donor spleen cells in the lymph nodes of the host mouse. MIMS makes it possible for the first time to both image and quantify molecules labeled with stable or radioactive isotopes within subcellular compartments.

[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

DOEpatents

Friedman, L.

1962-01-01

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

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.

Analysis of non-steroidal anti-inflammatory drugs in milk using QuEChERS and liquid chromatography coupled to mass spectrometry: triple quadrupole versus Q-Orbitrap mass analyzers.

PubMed

Rúbies, Antoni; Guo, Lili; Centrich, Francesc; Granados, Mercè

2016-08-01

We developed a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method for the high throughput determination of 10 non-steroidal anti-inflammatory drugs (NSAIDs) in milk samples using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with a triple quadrupole (QqQ) instrument and an electrospray ionization (ESI) source. The new extraction procedure is highly efficient, and we obtained absolute recoveries in the range 78.1-97.1 % for the extraction and clean-up steps. Chromatographic separation is performed in the gradient mode with a biphenyl column and acidic mobile phases consisting of water and acetonitrile containing formic acid. The chromatographic run time was about 12 min, and NSAID peaks showed a good symmetry factor. For MS/MS detection, we used multiple reaction monitoring (MRM) mode, using ESI in both positive and negative modes. Our method has been validated in compliance with the European Commission Decision 657/2002/EC, and we obtained very satisfactory results in inter-laboratory testing. Furthermore, we explored the use of a hybrid high resolution mass spectrometer, combining a quadrupole and an Orbitrap mass analyzer, for high resolution (HR) MS/MS detection of NSAIDs. We achieved lower NSAID quantification limits with Q-Orbitrap high resolution mass spectrometry (HRMS/MS) detection than those achieved with the QqQ instrument; however, its main feature is its very high selectivity, which makes HRMS/MS particularly suitable for confirmatory analysis.

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.

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.

An ultrahigh-resolution mass spectrometry index to estimate natural organic matter lability

PubMed Central

D'Andrilli, Juliana; Cooper, William T; Foreman, Christine M; Marshall, Alan G

2015-01-01

Rationale Determining the chemical constituents of natural organic matter (NOM) by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICRMS) remains the ultimate measure for probing its source material, evolution, and transport; however, lability and the fate of organic matter (OM) in the environment remain controversial. FTICRMS-derived elemental compositions are presented in this study to validate a new interpretative method to determine the extent of NOM lability from various environments. Methods FTICRMS data collected over the last decade from the same 9.4 tesla instrument using negative electrospray ionization at the National High Magnetic Field Laboratory in Tallahassee, Florida, was used to validate the application of a NOM lability index. Solid-phase extraction cartridges were used to isolate the NOM prior to FTICRMS; mass spectral peaks were calibrated internally by commonly identified NOM homologous series, and molecular formulae were determined for NOM composition and lability analysis. Results A molecular lability boundary (MLB) was developed from the FTICRMS molecular data, visualized from van Krevelen diagrams, dividing the data into more and less labile constituents. NOM constituents above the MLB at H/C ≥1.5 correspond to more labile material, whereas NOM constituents below the MLB, H/C <1.5, exhibit less labile, more recalcitrant character. Of all marine, freshwater, and glacial environments considered for this study, glacial ecosystems were calculated to contain the most labile OM. Conclusions The MLB extends our interpretation of FTICRMS NOM molecular data to include a metric of lability, and generally ranked the OM environments from most to least labile as glacial > marine > freshwater. Applying the MLB is useful not only for individual NOM FTICRMS studies, but also provides a lability threshold to compare and contrast molecular data with other FTICRMS instruments that survey NOM from around the world. Copyright © 2015

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.

Towards monitoring real-time cellular response using an integrated microfluidics-MALDI/nESI-ion mobility-mass spectrometry platform

PubMed Central

Enders, Jeffrey R.; Marasco, Christina C.; Kole, Ayeeshik; Nguyen, Bao; Sundarapandian, Sevugarajan; Seale, Kevin T.; Wikswo, John P.; McLean, John A.

2014-01-01

The combination of microfluidic cell trapping devices with ion mobility-mass spectrometry offers the potential for elucidating in real time the dynamic responses of small populations of cells to paracrine signals, changes in metabolite levels, and delivery of drugs and toxins. Preliminary experiments examining peptides in methanol and recording the interactions of yeast and Jurkat cells with their superfusate have identified instrumental setup and control parameters and on-line desalting procedures. Numerous initial experiments demonstrate and validate this new instrumental platform. Future outlooks and potential applications are addressed, specifically how this instrumentation may be used for fully automated systems biology studies of the significantly interdependent, dynamic internal workings of cellular metabolic and signaling pathways. PMID:21073240

Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

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

Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

Herein, a commercial optical microscope, laser microdissection instrument was coupled with an electrospray ionization mass spectrometer via a low profile liquid vortex capture probe to yield a hybrid optical microscopy/mass spectrometry imaging system. The instrument has bright-field and fluorescence microscopy capabilities in addition to a highly focused UV laser beam that is utilized for laser ablation of samples. With this system, material laser ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported in solution for analysis by electrospray ionization mass spectrometry. Both lane scanning and spot sampling mass spectral imaging modes weremore » used. The smallest area the system was able to ablate was ~0.544 μm × ~0.544 μm, achieved by oversampling of the smallest laser ablation spot size that could be obtained (~1.9 μm). With use of a model photoresist surface, known features as small as ~1.5 μm were resolved. The capabilities of the system with real world samples were demonstrated first with a blended polymer thin film containing poly(2-vinylpyridine) and poly(N-vinylcarbazole). Using spot sampling imaging, sub-micrometer sized features (0.62, 0.86, and 0.98 μm) visible by optical microscopy were clearly distinguished in the mass spectral images. A second real world example showed the imaging of trace amounts of cocaine in mouse brain thin tissue sections. Lastly, with use of a lane scanning mode with ~6 μm × ~6 μm data pixels, features in the tissue as small as 15 μm in size could be distinguished in both the mass spectral and optical images.« less

Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

DOE PAGES

Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

2015-10-22

Herein, a commercial optical microscope, laser microdissection instrument was coupled with an electrospray ionization mass spectrometer via a low profile liquid vortex capture probe to yield a hybrid optical microscopy/mass spectrometry imaging system. The instrument has bright-field and fluorescence microscopy capabilities in addition to a highly focused UV laser beam that is utilized for laser ablation of samples. With this system, material laser ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported in solution for analysis by electrospray ionization mass spectrometry. Both lane scanning and spot sampling mass spectral imaging modes weremore » used. The smallest area the system was able to ablate was ~0.544 μm × ~0.544 μm, achieved by oversampling of the smallest laser ablation spot size that could be obtained (~1.9 μm). With use of a model photoresist surface, known features as small as ~1.5 μm were resolved. The capabilities of the system with real world samples were demonstrated first with a blended polymer thin film containing poly(2-vinylpyridine) and poly(N-vinylcarbazole). Using spot sampling imaging, sub-micrometer sized features (0.62, 0.86, and 0.98 μm) visible by optical microscopy were clearly distinguished in the mass spectral images. A second real world example showed the imaging of trace amounts of cocaine in mouse brain thin tissue sections. Lastly, with use of a lane scanning mode with ~6 μm × ~6 μm data pixels, features in the tissue as small as 15 μm in size could be distinguished in both the mass spectral and optical images.« less

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.

Liquid Chromatography Mass Spectrometry-Based Proteomics: Biological and Technological Aspects

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

Karpievitch, Yuliya V.; Polpitiya, Ashoka D.; Anderson, Gordon A.

2010-12-01

Mass spectrometry-based proteomics has become the tool of choice for identifying and quantifying the proteome of an organism. Though recent years have seen a tremendous improvement in instrument performance and the computational tools used, significant challenges remain, and there are many opportunities for statisticians to make important contributions. In the most widely used "bottom-up" approach to proteomics, complex mixtures of proteins are first subjected to enzymatic cleavage, the resulting peptide products are separated based on chemical or physical properties and analyzed using a mass spectrometer. The two fundamental challenges in the analysis of bottom-up MS-based proteomics are: (1) Identifying themore » proteins that are present in a sample, and (2) Quantifying the abundance levels of the identified proteins. Both of these challenges require knowledge of the biological and technological context that gives rise to observed data, as well as the application of sound statistical principles for estimation and inference. We present an overview of bottom-up proteomics and outline the key statistical issues that arise in protein identification and quantification.« less

Applications of mass spectrometry to metabolomics and metabonomics: detection of biomarkers of aging and of age-related diseases.

PubMed

Mishur, Robert J; Rea, Shane L

2012-01-01

Every 5 years or so new technologies, or new combinations of old ones, seemingly burst onto the science scene and are then sought after until they reach the point of becoming commonplace. Advances in mass spectrometry instrumentation, coupled with the establishment of standardized chemical fragmentation libraries, increased computing power, novel data-analysis algorithms, new scientific applications, and commercial prospects have made mass spectrometry-based metabolomics the latest sought-after technology. This methodology affords the ability to dynamically catalogue and quantify, in parallel, femtomole quantities of cellular metabolites. The study of aging, and the diseases that accompany it, has accelerated significantly in the last decade. Mutant genes that alter the rate of aging have been found that increase lifespan by up to 10-fold in some model organisms, and substantial progress has been made in understanding fundamental alterations that occur at both the mRNA and protein level in tissues of aging organisms. The application of metabolomics to aging research is still relatively new, but has already added significant insight into the aging process. In this review we summarize these findings. We have targeted our manuscript to two audiences: mass spectrometrists interested in applying their technical knowledge to unanswered questions in the aging field, and gerontologists interested in expanding their knowledge of both mass spectrometry and the most recent advances in aging-related metabolomics. Copyright © 2011 Wiley Periodicals, Inc.

Categorizing Cells on the Basis of their Chemical Profiles: Progress in Single-Cell Mass Spectrometry.

PubMed

Comi, Troy J; Do, Thanh D; Rubakhin, Stanislav S; Sweedler, Jonathan V

2017-03-22

The chemical differences between individual cells within large cellular populations provide unique information on organisms' homeostasis and the development of diseased states. Even genetically identical cell lineages diverge due to local microenvironments and stochastic processes. The minute sample volumes and low abundance of some constituents in cells hinder our understanding of cellular heterogeneity. Although amplification methods facilitate single-cell genomics and transcriptomics, the characterization of metabolites and proteins remains challenging both because of the lack of effective amplification approaches and the wide diversity in cellular constituents. Mass spectrometry has become an enabling technology for the investigation of individual cellular metabolite profiles with its exquisite sensitivity, large dynamic range, and ability to characterize hundreds to thousands of compounds. While advances in instrumentation have improved figures of merit, acquiring measurements at high throughput and sampling from large populations of cells are still not routine. In this Perspective, we highlight the current trends and progress in mass-spectrometry-based analysis of single cells, with a focus on the technologies that will enable the next generation of single-cell measurements.

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.

Mass spectrometry based proteomics: existing capabilities and future directions

PubMed Central

Angel, Thomas E.; Aryal, Uma K.; Hengel, Shawna M.; Baker, Erin S.; Kelly, Ryan T.; Robinson, Errol W.; Smith, Richard D.

2012-01-01

Mass spectrometry (MS)-based proteomics is emerging as a broadly effective means for identification, characterization, and quantification of proteins that are integral components of the processes essential for life. Characterization of proteins at the proteome and sub-proteome (e.g., the phosphoproteome, proteoglycome, or degradome/peptidome) levels provides a foundation for understanding fundamental aspects of biology. Emerging technologies such as ion mobility separations coupled with MS and microchip-based-proteome measurements combined with MS instrumentation and chromatographic separation techniques, such as nanoscale reversed phase liquid chromatography and capillary electrophoresis, show great promise for both broad undirected and targeted highly sensitive measurements. MS-based proteomics is increasingly contribute to our understanding of the dynamics, interactions, and roles that proteins and peptides play, advancing our understanding of biology on a systems wide level for a wide range of applications including investigations of microbial communities, bioremediation, and human health. PMID:22498958

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.

Determination of phenylalanine isotope ratio enrichment by liquid chromatography/time- of-flight mass spectrometry.

PubMed

Wu, Zhanpin; Zhang, Xiao-Jun; Cody, Robert B; Wolfe, Robert R

2004-01-01

The application of time-of-flight mass spectrometry to isotope ratio measurements has been limited by the relatively low dynamic range of the time-to-digital converter detectors available on commercial LC/ToF-MS systems. Here we report the measurement of phenylalanine isotope ratio enrichment by using a new LC/ToF-MS system with wide dynamic range. Underivatized phenylalanine was injected onto a C18 column directly with 0.1% formic acid/acetonitrile as the mobile phase. The optimal instrument parameters for the time-of-flight mass spectrometer were determined by tuning the instrument with a phenylalanine standard. The accuracy of the isotope enrichment measurement was determined by the injection of standard solutions with known isotope ratios ranging from 0.02% to 9.2%. A plot of the results against the theoretical values gave a linear curve with R2 of 0.9999. The coefficient of variation for the isotope ratio measurement was below 2%. The method is simple, rapid, and accurate and presents an attractive alternative to traditional GC/MS applications.

Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry

PubMed Central

Pitt, James J

2009-01-01

Liquid chromatography-mass spectrometry (LC-MS) is now a routine technique with the development of electrospray ionisation (ESI) providing a simple and robust interface. It can be applied to a wide range of biological molecules and the use of tandem MS and stable isotope internal standards allows highly sensitive and accurate assays to be developed although some method optimisation is required to minimise ion suppression effects. Fast scanning speeds allow a high degree of multiplexing and many compounds can be measured in a single analytical run. With the development of more affordable and reliable instruments, LC-MS is starting to play an important role in several areas of clinical biochemistry and compete with conventional liquid chromatography and other techniques such as immunoassay. PMID:19224008

Miniaturized GC/MS instrumentation for in situ measurements: micro gas chromatography coupled with miniature quadrupole array and paul ion trap mass spectrometers

NASA Technical Reports Server (NTRS)

Holland, P.; Chutjian, A.; Darrach, M.; Orient, O.

2002-01-01

Miniaturized chemical instrumentation is needed for in situ measurements in planetary exploration and other spaceflight applications where factors such as reduction in payload requirements and enhanced robustness are important. In response to this need, we are 'continuing to develop miniaturized GC/MS instrumentation which combines chemical separations by gas chromatography (GC) with mass spectrometry (MS) to provide positive identification of chemical compounds in complex mixtures of gases, such as those found in the International Space Station's cabin atmosphere. Our design approach utilizes micro gas chromatography components coupled with either a miniature quadrupole mass spectrometer array (QMSA) or compact, high-resolution Paul ion trap.

Triple quadrupole tandem mass spectrometry: A real alternative to high resolution magnetic sector instrument for the analysis of polychlorinated dibenzo-p-dioxins, furans and dioxin-like polychlorinated biphenyls.

PubMed

García-Bermejo, Ángel; Ábalos, Manuela; Sauló, Jordi; Abad, Esteban; González, María José; Gómara, Belén

2015-08-19

This paper reports on the optimisation, characterisation, validation and applicability of gas chromatography coupled to triple quadrupole mass spectrometry in its tandem operation mode (GC-QqQ(MS/MS) for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs, dioxins) and dioxin-like polychlorinated biphenyls (DL-PCBs) in environmental and food matrices. MS/MS parameters were selected to achieve the high sensitivity and selectivity required for the analysis of this type of compounds and samples. Good repeatability for areas (RSD = 1-10%, for PCDD/Fs and DL-PCBs) and for ion transition ratios (RSD = 0.3-10%, for PCDD/Fs, and 0.2-15%, for DL-PCBs) and low instrumental limits of detection, 0.07-0.75 pg μL(-1) (for dioxins) and 0.05-0.63 pg μL(-1) (for DL-PCBs), were obtained. A comparative study of the congener specific determination using both GC-QqQ(MS/MS) and gas chromatography-high resolution mass spectrometry (GC-HRMS) was also performed by analysing several fortified samples and certified reference materials (CRMs) with low (feed and foodstuffs), median (sewage sludge) and high (fly ash) toxic equivalency (TEQ) concentration levels, i.e. 0.60, 1.83, 72.9 and 3609 pg WHO-TEQ(PCDD/Fs) g(-1). The agreement between the results obtained for the total TEQs (dioxins) on GC-QqQ(MS/MS) and GC-HRMS in all the investigated samples were within the range of ±4%, and that of DL-PCBs at concentration levels of 0.84 pg WHO-TEQs (DL-PCBs) g(-1), in the case of feedstuffs, was 0.11%. Both instrumental methods have similar and comparable linearity, precision and accuracy. The GC-QqQ(MS/MS) sensitivity, lower than that of GC-HRMS, is good enough (iLODs in the down to low pg levels) to detect the normal concentrations of these compounds in food and environmental samples. These results make GC-QqQ(MS/MS) suitable for the quantitative analysis of dioxins and DL-PCBs and a real alternative tool to the reference sector HRMS instruments. Copyright © 2015 Elsevier

Critical factors determining the quantification capability of matrix-assisted laser desorption/ionization– time-of-flight mass spectrometry

PubMed Central

Wang, Chia-Chen; Lai, Yin-Hung; Ou, Yu-Meng; Chang, Huan-Tsung; Wang, Yi-Sheng

2016-01-01

Quantitative analysis with mass spectrometry (MS) is important but challenging. Matrix-assisted laser desorption/ionization (MALDI) coupled with time-of-flight (TOF) MS offers superior sensitivity, resolution and speed, but such techniques have numerous disadvantages that hinder quantitative analyses. This review summarizes essential obstacles to analyte quantification with MALDI-TOF MS, including the complex ionization mechanism of MALDI, sensitive characteristics of the applied electric fields and the mass-dependent detection efficiency of ion detectors. General quantitative ionization and desorption interpretations of ion production are described. Important instrument parameters and available methods of MALDI-TOF MS used for quantitative analysis are also reviewed. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644968

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.

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.

Estimation of the quantification uncertainty from flow injection and liquid chromatography transient signals in inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Laborda, Francisco; Medrano, Jesús; Castillo, Juan R.

2004-06-01

The quality of the quantitative results obtained from transient signals in high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) and flow injection-inductively coupled plasma mass spectrometry (FI-ICPMS) was investigated under multielement conditions. Quantification methods were based on multiple-point calibration by simple and weighted linear regression, and double-point calibration (measurement of the baseline and one standard). An uncertainty model, which includes the main sources of uncertainty from FI-ICPMS and HPLC-ICPMS (signal measurement, sample flow rate and injection volume), was developed to estimate peak area uncertainties and statistical weights used in weighted linear regression. The behaviour of the ICPMS instrument was characterized in order to be considered in the model, concluding that the instrument works as a concentration detector when it is used to monitorize transient signals from flow injection or chromatographic separations. Proper quantification by the three calibration methods was achieved when compared to reference materials, although the double-point calibration allowed to obtain results of the same quality as the multiple-point calibration, shortening the calibration time. Relative expanded uncertainties ranged from 10-20% for concentrations around the LOQ to 5% for concentrations higher than 100 times the LOQ.

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.

Quantitative Clinical Chemistry Proteomics (qCCP) using mass spectrometry: general characteristics and application.

PubMed

Lehmann, Sylvain; Hoofnagle, Andrew; Hochstrasser, Denis; Brede, Cato; Glueckmann, Matthias; Cocho, José A; Ceglarek, Uta; Lenz, Christof; Vialaret, Jérôme; Scherl, Alexander; Hirtz, Christophe

2013-05-01

Proteomics studies typically aim to exhaustively detect peptides/proteins in a given biological sample. Over the past decade, the number of publications using proteomics methodologies has exploded. This was made possible due to the availability of high-quality genomic data and many technological advances in the fields of microfluidics and mass spectrometry. Proteomics in biomedical research was initially used in 'functional' studies for the identification of proteins involved in pathophysiological processes, complexes and networks. Improved sensitivity of instrumentation facilitated the analysis of even more complex sample types, including human biological fluids. It is at that point the field of clinical proteomics was born, and its fundamental aim was the discovery and (ideally) validation of biomarkers for the diagnosis, prognosis, or therapeutic monitoring of disease. Eventually, it was recognized that the technologies used in clinical proteomics studies [particularly liquid chromatography-tandem mass spectrometry (LC-MS/MS)] could represent an alternative to classical immunochemical assays. Prior to deploying MS in the measurement of peptides/proteins in the clinical laboratory, it seems likely that traditional proteomics workflows and data management systems will need to adapt to the clinical environment and meet in vitro diagnostic (IVD) regulatory constraints. This defines a new field, as reviewed in this article, that we have termed quantitative Clinical Chemistry Proteomics (qCCP).

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.

Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.

PubMed

Lazova, Rossitza; Yang, Zhe; El Habr, Constantin; Lim, Young; Choate, Keith Adam; Seeley, Erin H; Caprioli, Richard M; Yangqun, Li

2017-09-01

Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.L.) and mass spectrometry imaging analysis rendered a diagnosis of congenital melanocytic nevus with proliferative nodules. In this case, mass spectrometry imaging, a novel method capable of distinguishing benign from malignant melanocytic lesions on a proteomic level, was instrumental in making the diagnosis of a benign nevus. We emphasize the importance of this method as an ancillary tool in the diagnosis of difficult melanocytic lesions.

Simultaneous drug identification in urine of sexual assault victims by using liquid chromatography tandem mass spectrometry.

PubMed

Lee, Hei Hwa; Chen, Suen Chi; Lee, Jong Feng; Lin, Hsin Yu; Chen, Bai Hsiun

2018-01-01

According to domestic and international epidemiological investigation, the proportion of substance involved sexual assault has the trend of ascent. In the past, laboratory methods that investigated urine sample of the sexual assault victims was to screen with enzyme immunoassay and then confirmed with mass spectrometry. The objective of the study is to simultaneously identify abused drugs in 126 decoded urine samples of sexual assault victims by liquid chromatography tandem mass spectrometry. The instrument was operated in multiple-reaction monitoring with an electro-spray positive ionization mode. Chromatograms were separated with ACE5 C18 column on a gradient of acetonitrile. After liquid-liquid extraction, samples were passed through a 0.22μm PVDF filter before injection into the system. The limits of quantitation ranged from 0.2 to 10ng/mL. The precision (CV) results were below 12.9% (intraday) and 15.0% (interday). The intraday accuracy ranged from 84.8 to 121.0%, interday accuracy ranged from 72.0 to 117.3%. We found that 29 (23.0%) were positive for drugs. The most common drug identified is flunitrazepam (11.1%), followed by nimetazepam and ketamine (7.9%), some new psychoactive substances, such as 2C-B, mephedrone, methylone, PMA and PMMA were also identified. We identified abused drugs, benzodiazepines, and new psychoactive substances in urine of sexual assault victims by using liquid chromatography tandem mass spectrometry. Copyright © 2017 Elsevier B.V. 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...

Cloud parallel processing of tandem mass spectrometry based proteomics data.

PubMed

Mohammed, Yassene; Mostovenko, Ekaterina; Henneman, Alex A; Marissen, Rob J; Deelder, André M; Palmblad, Magnus

2012-10-05

Data analysis in mass spectrometry based proteomics struggles to keep pace with the advances in instrumentation and the increasing rate of data acquisition. Analyzing this data involves multiple steps requiring diverse software, using different algorithms and data formats. Speed and performance of the mass spectral search engines are continuously improving, although not necessarily as needed to face the challenges of acquired big data. Improving and parallelizing the search algorithms is one possibility; data decomposition presents another, simpler strategy for introducing parallelism. We describe a general method for parallelizing identification of tandem mass spectra using data decomposition that keeps the search engine intact and wraps the parallelization around it. We introduce two algorithms for decomposing mzXML files and recomposing resulting pepXML files. This makes the approach applicable to different search engines, including those relying on sequence databases and those searching spectral libraries. We use cloud computing to deliver the computational power and scientific workflow engines to interface and automate the different processing steps. We show how to leverage these technologies to achieve faster data analysis in proteomics and present three scientific workflows for parallel database as well as spectral library search using our data decomposition programs, X!Tandem and SpectraST.

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.

Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer.

PubMed

Hoffman, Melissa A; Fang, Bin; Haura, Eric B; Rix, Uwe; Koomen, John M

2018-01-05

Recent developments in instrumentation and bioinformatics have led to new quantitative mass spectrometry platforms including LC-MS/MS with data-independent acquisition (DIA) and targeted analysis using parallel reaction monitoring mass spectrometry (LC-PRM), which provide alternatives to well-established methods, such as LC-MS/MS with data-dependent acquisition (DDA) and targeted analysis using multiple reaction monitoring mass spectrometry (LC-MRM). These tools have been used to identify signaling perturbations in lung cancers and other malignancies, supporting the development of effective kinase inhibitors and, more recently, providing insights into therapeutic resistance mechanisms and drug repurposing opportunities. However, detection of kinases in biological matrices can be challenging; therefore, activity-based protein profiling enrichment of ATP-utilizing proteins was selected as a test case for exploring the limits of detection of low-abundance analytes in complex biological samples. To examine the impact of different MS acquisition platforms, quantification of kinase ATP uptake following kinase inhibitor treatment was analyzed by four different methods: LC-MS/MS with DDA and DIA, LC-MRM, and LC-PRM. For discovery data sets, DIA increased the number of identified kinases by 21% and reduced missingness when compared with DDA. In this context, MRM and PRM were most effective at identifying global kinome responses to inhibitor treatment, highlighting the value of a priori target identification and manual evaluation of quantitative proteomics data sets. We compare results for a selected set of desthiobiotinylated peptides from PRM, MRM, and DIA and identify considerations for selecting a quantification method and postprocessing steps that should be used for each data acquisition strategy.

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.

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

multiplierz v2.0: A Python-based ecosystem for shared access and analysis of native mass spectrometry data.

PubMed

Alexander, William M; Ficarro, Scott B; Adelmant, Guillaume; Marto, Jarrod A

2017-08-01

The continued evolution of modern mass spectrometry instrumentation and associated methods represents a critical component in efforts to decipher the molecular mechanisms which underlie normal physiology and understand how dysregulation of biological pathways contributes to human disease. The increasing scale of these experiments combined with the technological diversity of mass spectrometers presents several challenges for community-wide data access, analysis, and distribution. Here we detail a redesigned version of multiplierz, our Python software library which leverages our common application programming interface (mzAPI) for analysis and distribution of proteomic data. New features include support for a wider range of native mass spectrometry file types, interfaces to additional database search engines, compatibility with new reporting formats, and high-level tools to perform post-search proteomic analyses. A GUI desktop environment, mzDesktop, provides access to multiplierz functionality through a user friendly interface. multiplierz is available for download from: https://github.com/BlaisProteomics/multiplierz; and mzDesktop is available for download from: https://sourceforge.net/projects/multiplierz/. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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...

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.

Intact cell mass spectrometry (ICMS) used to type methicillin-resistant Staphylococcus aureus: media effects and inter-laboratory reproducibility.

PubMed

Walker, J; Fox, A J; Edwards-Jones, V; Gordon, D B

2002-02-01

Intact cell mass spectrometry (ICMS) rapidly analyses the surface composition of microorganisms providing rapid, discriminatory fingerprints for identification and subtyping of important nosocomial pathogens such as methicillin resistant Staphylocccus aureus (MRSA). In this study, ICMS using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI TOF/MS) was assessed for the identification and subtyping of MRSA. An intra- and inter-laboratory reproducibility study was carried out and the effects of culture media (an important source of variation for ICMS) were also studied. Several media used for the cultural identification of MRSA were examined using a panel of well-characterised staphylococcal isolates (n=26). Six MRSA isolates were analysed over a 1-month period for intra-laboratory reproducibility on the same instrument and three different culture media. Spectra were consistent for each isolate between the four experiments on the same culture medium. Individual isolates produced different spectral profiles on different culture media. Spectra from organisms grown on Columbia blood agar contained more peaks (approximately 120) compared to Columbia agar (approximately 50) and methicillin mannitol salt agar (approximately 25). All 26 staphylococcal isolates were subjected to an inter-laboratory study on two MALDI instruments. For each isolate, the overall spectral profile was the same for each of the two instruments but the baseline threshold values was adjusted due to instrument differences in detector sensitivities. Differences between certain regions of the spectra reproducibly identified isolates belonging to the two major MRSA strains (EMRSA phage group 15 and 16). These results demonstrate ICMS with appropriate media selection is a rapid and reproducible technique for identification and discrimination of MRSA.

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.

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.

The mass spectral density in quantitative time-of-flight mass spectrometry of polymers

NASA Astrophysics Data System (ADS)

Tate, Ranjeet S.; Ebeling, Dan; Smith, Lloyd M.

2001-03-01

Time-of-flight mass spectrometry (TOF-MS) is being increasingly used for the study of polymers, for example to obtain the distribution of molecular masses for polymer samples. Serious efforts have also been underway to use TOF-MS for DNA sequencing. In TOF-MS the data is obtained in the form of a time-series that represents the distribution in arrival times of ions of various m/z ratios. This time-series data is then converted to a "mass-spectrum" via a coordinate transformation from the arrival time (t) to the corresponding mass-to-charge ratio (m/z = const. t^2). In this transformation, it is important to keep in mind that spectra are distributions, or densities of weight +1, and thus do not transform as functions. To obtain the mass-spectral density, it is necessary to include a multiplicative factor of √m/z. Common commercial instruments do not take this factor into account. Dropping this factor has no effect on qualitative analysis (detection) or local quantitative measurements, since S/N or signal-to-baseline ratios are unaffected for peaks with small dispersions. However, there are serious consequences for general quantitative analyses. In DNA sequencing applications, loss of signal intensity is in part attributed to multiple charging; however, since the √m/z factor is not taken into account, this conclusion is based on an overestimate (by a factor of √z) of the relative amount of the multiply charged species. In the study of polymers, the normalized dispersion is underestimated by approximately (M_w/Mn -1)/2. In terms of M_w/Mn itself, for example, a M_w/M_n=1.5 calculated without the √m factor corresponds in fact to a M_w/M_n=1.88.

Analysis of Whiskey by Dispersive Liquid-Liquid Microextraction Coupled with Gas Chromatography/Mass Spectrometry: An Upper Division Analytical Chemistry Experiment Guided by Green Chemistry

ERIC Educational Resources Information Center

Owens, Janel E.; Zimmerman, Laura B.; Gardner, Michael A.; Lowe, Luis E.

2016-01-01

Analysis of whiskey samples prepared by a green microextraction technique, dispersive liquid-liquid microextraction (DLLME), before analysis by a qualitative gas chromatography-mass spectrometry (GC/MS) method, is described as a laboratory experiment for an upper division instrumental methods of analysis laboratory course. Here, aroma compounds in…

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.

Determination of the rare-earth elements in geological materials by inductively coupled plasma mass spectrometry

USGS Publications Warehouse

Lichte, F.E.; Meier, A.L.; Crock, J.G.

1987-01-01

A method of analysis of geological materials for the determination of the rare-earth elements using the Inductively coupled plasma mass spectrometric technique (ICP-MS) has been developed. Instrumental parameters and factors affecting analytical results have been first studied and then optimized. Samples are analyzed directly following an acid digestion, without the need for separation or preconcentration with limits of detection of 2-11 ng/g, precision of ?? 2.5% relative standard deviation, and accuracy comparable to inductively coupled plasma emission spectrometry and instrumental neutron activation analysis. A commercially available ICP-MS instrument is used with modifications to the sample introduction system, torch, and sampler orifice to reduce the effects of high salt content of sample solutions prepared from geologic materials. Corrections for isobaric interferences from oxide ions and other diatomic and triatomic ions are made mathematically. Special internal standard procedures are used to compensate for drift in metahmetal oxide ratios and sensitivity. Reference standard values are used to verify the accuracy and utility of the method.

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