Parallel Operation of Electron Ionization and Chemical Ionization for GC-MS Using a Single TOF Mass Analyzer.

This work describes a novel mass spectrometer coupled to gas chromatography (GC-MS) that simultaneously displays the mass spectral information of electron (EI)- and chemical ionization (CI)-generated ion populations for a single chromatographic peak. After GC separation, the eluent is equally split and supplied in parallel to an EI and a novel CI source, both operating continuously. Precise switching of the ion optics provides the exact timing to consecutively extract the respective ion population from both sources and transfer them into a time-of-flight (TOF) mass analyzer. This technique enables the acquisition of complementary information from both ion populations (EI and CI) within a single chromatographic run and with sufficient data points to retain the chromatographic fidelity. The carefully designed GC transfer setup, fast ion optical switching, and synchronized TOF data acquisition system provide an automatic and straightforward spectral alignment of two ion populations. With an eluent split ratio of about 50% between the two ion sources, instrument detection limits of <40 fg on the column (octafluoronaphthalene) for the EI and <2 pg (benzophenone) for the CI source were obtained. The system performance and the additional analytical value for compound identification are demonstrated by means of different common GC standard mixtures and a commercial perfume sample of unknown composition.

Time-Of-Flight Mass Spectrometers Made in Switzerland: Examples of Mobile Applications.

Over the past decade, the technical requirements of analytical instrumentation have continuously risen driven by the demand for increasingly complex and demanding applications. TOFWERK, a Swiss company with the headquarters in Thun, has been at the forefront of this development by producing modular and ruggedized Time-Of-Flight Mass Spectrometers (TOFMS). They are often used to replace quadrupole mass analysers with more powerful TOF mass analysers. Starting with first customers in atmospheric sciences, TOFWERK TOFMS are now used across a wide range of research areas and lately also in industry. Here we present an overview of mobile applications in which Tofwerk TOFMS are in operation while moved around in space.

Thermal Desorption-Vocus Enables Online Nondestructive Quantification of 2,4,6-Trichloroanisole in Cork Stoppers below the Perception Threshold.

2,4,6-Trichloroanisole (TCA) contamination of wine determines huge economic losses for the wine industry estimated to amount to several billion dollars yearly. Over 50 years of studies have determined that this problem is often caused by TCA contamination of the cork stopper, which releases TCA into the wine. The human threshold for TCA is extremely low. A wine contaminated by 1-2 ng/L TCA can be perceived as tainted. Contaminations with <0.5 ng/L TCA are commonly considered negligible and are not perceivable. The possibility of prescreening cork stoppers for TCA contamination would be an enormous advantage. Therefore, the demand for a fast, nondestructive method capable of quantifying the TCA contamination in cork stoppers is impelling. Vastly used analytical methods have so far struggled to provide a fast and reliable solution, whereas sensory analysis by trained panelists is expensive and time-consuming. Here we propose a novel approach based on chemical ionization-time-of-flight (CI-TOF) mass spectrometry employing the "Vocus" ion source and ion-molecule reactor. The technique proved capable of nondestructively quantifying TCA contamination in a single cork stopper in 3 s, with a limit of quantification below the perception threshold. A real test on the industrial scale, quantifying TCA contamination in more than 10000 cork stoppers in a few hours is presented, representing the largest data set of TCA analysis on cork stoppers within the literature and proving the possibility to apply the technique in an industrial environment. The correlation with standard methods for releasable TCA quantification is also discussed.

Evaluation of a New Reagent-Ion Source and Focusing Ion-Molecule Reactor for Use in Proton-Transfer-Reaction Mass Spectrometry.

We evaluate the performance of a new chemical ionization source called Vocus, consisting of a discharge reagent-ion source and focusing ion-molecule reactor (FIMR) for use in proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF) measurements of volatile organic compounds (VOCs) in air. The reagent ion source uses a low-pressure discharge. The FIMR consists of a glass tube with a resistive coating, mounted inside a radio frequency (RF) quadrupole. The axial electric field is used to enhance ion collision energies and limit cluster ion formation. The RF field focuses ions to the central axis of the reactor and improves the detection efficiency of product ions. Ion trajectory calculations demonstrate the mass-dependent focusing of ions and enhancement of the ion collision energy by the RF field, in particular for the lighter ions. Product ion signals are increased by a factor of 10 when the RF field is applied (5000-18 000 cps ppbv-1), improving measurement precision and detection limits while operating at very similar reaction conditions as traditional PTR instruments. Because of the high water mixing ratio in the FIMR, we observe no dependence of the sensitivity on ambient sample humidity. In this work, the Vocus is interfaced to a TOF mass analyzer with a mass resolving power up to 12 000, which allows clear separation of isobaric ions, observed at nearly every nominal mass when measuring ambient air. Measurement response times are determined for a range of ketones with saturation vapor concentrations down to 5 × 104 µg m-3 and compare favorably with previously published results for a PTR-MS instrument.

Improved resolution of hydrocarbon structures and constitutional isomers in complex mixtures using gas chromatography-vacuum ultraviolet-mass spectrometry.

Understanding the composition of complex hydrocarbon mixtures is important for environmental studies in a variety of fields, but many prevalent compounds cannot be confidently identified using traditional gas chromatography/mass spectrometry (GC/MS) techniques. This work uses vacuum-ultraviolet (VUV) ionization to elucidate the structures of a traditionally "unresolved complex mixture" by separating components by GC retention time, t(R), and mass-to-charge ratio, m/z, which are used to determine carbon number, N(C), and the number of rings and double bonds, N(DBE). Constitutional isomers are resolved on the basis of t(R), enabling the most complete quantitative analysis to date of structural isomers in an environmentally relevant hydrocarbon mixture. Unknown compounds are classified in this work by carbon number, degree of saturation, presence of rings, and degree of branching, providing structural constraints. The capabilities of this analysis are explored using diesel fuel, in which constitutional isomer distribution patterns are shown to be reproducible between carbon numbers and follow predictable rules. Nearly half of the aliphatic hydrocarbon mass is shown to be branched, suggesting branching is more important in diesel fuel than previously shown. The classification of unknown hydrocarbons and the resolution of constitutional isomers significantly improves resolution capabilities for any complex hydrocarbon mixture.

Quasi-simultaneous acquisition of hard electron ionization and soft single-photon ionization mass spectra during GC/MS analysis by rapid switching between both ionization methods: analytical concept, setup, and application on diesel fuel.

This work describes the realization of rapid switching between hard electron ionization (EI) and soft single-photon ionization (SPI) integrated in a compact orthogonal acceleration time-of-flight mass spectrometer. Vacuum-ultraviolet (VUV) photons of 9.8 eV (126 nm) emitted from the innovative electron-beam-pumped rare-gas excimer light source (EBEL) filled with argon are focused into the ion chamber by an ellipsoidal mirror optic for accomplishing of SPI. This novel orthogonal acceleration time-of-flight mass spectrometer with switching capability was hyphenated to one-dimensional gas chromatography (GC) and comprehensive two-dimensional (2D) gas chromatography (GC × GC) for the first time. Within this demonstration study, a maximum switching frequency of 80 Hz was applied for investigation of a mineral-oil-type diesel sample. This approach allows the quasi-simultaneous acquisition of complementary information about the fragmentation pattern (EI) as well as the molecular mass (SPI) of compounds within a single analysis. Furthermore, by application of a polar GC column for separation, the SPI data can be displayed in a 2D contour plot, leading to a comprehensive 2D characterization (GC × MS), whereas the typical group-type assignment for diesel is also met.

Resistive glass IM-TOFMS.

The design of a new ion mobility mass spectrometer (IM-MS) is presented. This new design features an ambient-pressure resistive glass ion mobility drift tube (RGIMS) coupled to a high-resolution time-of-flight mass spectrometer (TOFMS) by an enhanced interface that includes two segmented quadrupoles. The interface design demonstrates an increase in sensitivity while maintaining high resolving power typically achieved for ambient-pressure IMS drift tubes. Performance of the prototype instrument was evaluated and the analytical figures of merit for standard solutions as well as complex samples such as human blood were determined. For a 3 µM solution of caffeine, the peak was collected in 36 s and gave a response of 10 counts/s. The detection limit (defined as 1 count/s) was calculated to be 300 nM concentration of caffeine from the response rate from the 36 s run. Controlled fragmentation of caffeine was achieved through adjustment of voltages applied on the interface lenses. Over 300 tentative metabolites were detected in human blood along with 80 isomers/isobars with ion counts >5. Isotope ratios from extracted mass spectra of selected mobility peaks were used to identify selected metabolite compounds. High separation power for both IMS (resolving power, t(d)/Δt(w1/2), was 85) and MS (mass resolving power, m/Δm, maximum was 7000 with a mass accuracy between 2 and 10 ppm) was measured. Developed software for data acquisition, control and display allowed flexibility in instrument control, data evaluation and visualization.

Comprehensive multidimensional separation methods by hyphenation of single-photon ionization time-of-flight mass spectrometry (SPI-TOF-MS) with GC and GCxGC.

One- and comprehensive two-dimensional gas chromatography were hyphenated with soft photoionization mass spectrometry. The characteristics of these two- and three-dimensional comprehensive separation techniques are discussed in detail. Using the innovative electron beam pumped excimer light source (EBEL) for single-photon ionization (SPI), organic molecules with ionization energies (E ( i )) of below 9.8 eV can be detected by a time-of-flight mass spectrometer (TOF-MS). SPI with 126 nm vacuum ultraviolet (VUV) photons enables the universal and soft ionization of organic molecules. SPI-TOF-MS hyphenated to one-dimensional gas chromatography results in a comprehensive two-dimensional separation method (GCxMS). To demonstrate this, diesel fuel was analyzed, and the resulting GCxMS chromatograms are discussed in depth. A three-dimensional separation method was also realized by combining comprehensive two-dimensional gas chromatography (GCxGC) with SPI-MS. In the resulting separation space, constituents originating from mineral oil diesel blended with biodiesel were dispersed along the two GC separation axes, while the molecular mass axis served as a third separation dimension.

An ion trap-ion mobility-time of flight mass spectrometer with three ion sources for ion/ion reactions.

This instrument combines the capabilities of ion/ion reactions with ion mobility (IM) and time-of-flight (TOF) measurements for conformation studies and top-down analysis of large biomolecules. Ubiquitin ions from either of two electrospray ionization (ESI) sources are stored in a three dimensional (3D) ion trap (IT) and reacted with negative ions from atmospheric sampling glow discharge ionization (ASGDI). The proton transfer reaction products are then separated by IM and analyzed via a TOF mass analyzer. In this way, ubiquitin +7 ions are converted to lower charge states down to +1; the ions in lower charge states tend to be in compact conformations with cross sections down to approximately 880 A(2). The duration and magnitude of the ion ejection pulse on the IT exit and the entrance voltage on the IM drift tube can affect the measured distribution of conformers for ubiquitin +7 and +6. Alternatively, protein ions are fragmented by collision-induced dissociation (CID) in the IT, followed by ion/ion reactions to reduce the charge states of the CID product ions, thus simplifying assignment of charge states and fragments using the mobility-resolved tandem mass spectrum. Instrument characteristics and the use of a new ion trap controller and software modifications to control the entire instrument are described.

Development and characterization of an aircraft aerosol time-of-flight mass spectrometer.

Vertical and horizontal profiles of atmospheric aerosols are necessary for understanding the impact of air pollution on regional and global climate. To gain further insight into the size-resolved chemistry of individual atmospheric particles, a smaller aerosol time-of-flight mass spectrometer (ATOFMS) with increased data acquisition capabilities was developed for aircraft-based studies. Compared to previous ATOFMS systems, the new instrument has a faster data acquisition rate with improved ion transmission and mass resolution, as well as reduced physical size and power consumption, all required advances for use in aircraft studies. In addition, real-time source apportionment software allows the immediate identification and classification of individual particles to guide sampling decisions while in the field. The aircraft (A)-ATOFMS was field-tested on the ground during the Study of Organic Aerosols in Riverside, CA (SOAR) and aboard an aircraft during the Ice in Clouds Experiment-Layer Clouds (ICE-L). Initial results from ICE-L represent the first reported aircraft-based single-particle dual-polarity mass spectrometry measurements and provide an increased understanding of particle mixing state as a function of altitude. Improved ion transmission allows for the first single-particle detection of species out to approximately m/z 2000, an important mass range for the detection of biological aerosols and oligomeric species. In addition, high time resolution measurements of single-particle mixing state are demonstrated and shown to be important for airborne studies where particle concentrations and chemistry vary rapidly.

Performance, resolving power, and radial ion distributions of a prototype nanoelectrospray ionization resistive glass atmospheric pressure ion mobility spectrometer.

In this article, we describe and characterize a novel ion mobility spectrometer constructed with monolithic resistive glass desolvation and drift regions. This instrument is equipped with switchable corona discharge and nanoelectrospray ionization sources and a Faraday plate detector. Following description of the instrument, pulsing electronics, and data acquisition system, we examine the effects of drift gas flow rate and temperature, and of the aperture grid to anode distance on the observed resolving power and sensitivity. Once optimum experimental parameters are identified, different ion gate pulse lengths, and their effect on the temporal spread of the ion packet were investigated. Resolving power ranged from an average value of 50 ms/ms for a 400-micros ion gate pulse, up to an average value of 68 ms/ms for a 100-micros ion gate pulse, and a 26-cm drift tube operated at 383 V cm(-1). Following these experiments, the radial distribution of ions in the drift region of the spectrometer was studied by using anodes of varying sizes, showing that the highest ionic density was located at the center of the drift tube. Finally, we demonstrate the applicability of this instrument to the study of small molecules of environmental relevance by analyzing a commercially available siderophore, deferoxamine mesylate, in both the free ligand and Fe-bound forms. Ion mobility experiments showed a dramatic shift to shorter drift times caused by conformational changes upon metal binding, in agreement with previous reversed-phase liquid chromatography observations.

Field-deployable, high-resolution, time-of-flight aerosol mass spectrometer.

The development of a new high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is reported. The high-resolution capabilities of this instrument allow the direct separation of most ions from inorganic and organic species at the same nominal m/z, the quantification of several types of organic fragments (CxHy, CxHyOz, CxHyNp, CxHyOzNp), and the direct identification of organic nitrogen and organosulfur content. This real-time instrument is field-deployable, and its high time resolution (0.5 Hz has been demonstrated) makes it well-suited for studies in which time resolution is critical, such as aircraft studies. The instrument has two ion optical modes: a single-reflection configuration offers higher sensitivity and lower resolving power (up to approximately 2100 at m/z 200), and a two-reflectron configuration yields higher resolving power (up to approximately 4300 at m/z 200) with lower sensitivity. The instrument also allows the determination of the size distributions of all ions. One-minute detection limits for submicrometer aerosol are <0.04 microg m(-3) for all species in the high-sensitivity mode and <0.4 microg m(-3) in the high-resolution mode. Examples of ambient aerosol data are presented from the SOAR-1 study in Riverside, CA, in which the spectra of ambient organic species are dominated by CxHy and CxHyOz fragments, and different organic and inorganic fragments at the same nominal m/z show different size distributions. Data are also presented from the MIRAGE C-130 aircraft study near Mexico City, showing high correlation with independent measurements of surrogate aerosol mass concentration.

Evaluation of a pulsed glow discharge time-of-flight mass spectrometer as a detector for gas chromatography and the influence of the glow discharge source parameters on the information volume in chemical speciation analysis.

The figures of merit of a pulsed glow discharge time-of-flight mass spectrometer (GD-TOFMS) as a detector for gas chromatography (GC) analysis were evaluated. The mass resolution for the GD-TOFMS was determined on FWHM in the high mass range (208Pb+) as high as 5,500. Precision of 400 subsequent analyses was calculated on 63Cu+ to be better than 1% RSD with no significant drift over the time of the analysis. Isotope precision based on the 63Cu+/65Cu+ ratio over 400 analyses was 1.5% RSD. The limits of detection for gaseous analytes (toluene in methanol as solvent) were determined to be as low as several hundred ppb or several hundred pg absolute without using any pre-concentration technique. Furthermore, the different GD source parameters like capillary distance, cathode-anode spacing, and GD source pressure with regards to the accessible elemental, structural, and molecular information were evaluated. It was demonstrated that each of these parameters has severe influence on the ratio of elemental, structural, and parent molecular information in chemical speciation analysis.

Lipid/peptide/nucleotide separation with MALDI-ion mobility-TOF MS.

Matrix-assisted laser desorption/ionization when combined with ion mobility-orthogonal time-of-flight mass spectrometry is a viable technique for fast separation and analysis of biomolecules in complex mixtures. Isobaric lipid, peptide, and oligonucleotide ions are preseparated before mass analysis by differences of up to 30% in mobility drift time. Ions of similar chemical type fall along well-defined "trend lines" (with deviations of approximately 3%) when plotted in two-dimensional representations of ion mobility as a function of m/z. Discussion of fundamental and technical limitations of the technique point to its potential for being most useful when applied to systems such as bodily fluids and intact tissue, where an alternative chemical or chromatographic preseparation step prior to mass analysis is either impractical or undesirable.

A resonant electron capture time-of-flight MS with trochoidal electron monochromator.

A prototype electron monochromator (EM) reflectron time-of-flight (TOF) mass spectrometer has been constructed and demonstrated to record resonant electron capture (REC) mass spectra of electron-capturing compounds. The electron energy is ramped from -1.7 to +25 eV at a preset frequency, and the energy spread of the electron beam at 15 nA is 100 meV or better. Ions are orthogonally extracted into the analyzer at a frequency of up to 80 kHz while maintaining an upper m/z-limit of at least 300 and a mass resolving power of approximately 1000. A complete REC mass spectrum, which includes an effective yield versus electron energy curve for each negative ion formed from the compound being analyzed, typically takes several days to produce with a quadrupole or magnetic sector mass spectrometer. With the EM TOF described in this work, three-dimensional negative ion electron capture spectra are recorded in an interval on the order of only 1 s and displayed in real time. This new analytical capability could make it possible to perform GC REC mass spectrometry as well as easier (a) to measure the temperature dependence of REC cross sections, (b) to determine enthalpies of negative ion formation (accurate determination of the enthalpy of ion formation requires knowledge of the translational energy released during a dissociative capture event), and (c) to provide complete thermochemical descriptions of dissociative electron attachment by measuring ion lifetimes.

Angiotensin II-acetylcholine noncovalent complexes analyzed with MALDI-ion mobility-TOF MS.

Matrix-assisted laser desorption ionization-ion mobility-orthogonal time-of-flight mass spectrometry (MALDI-IM oTOF MS) is a new technique that allows laser desorbed ion to be preseparated on the basis of their shape prior to mas analysis. Using this instrument, we tested the postulate that addition of a quaternary ammonium compound such as acetylcholine to the model phosphorylated peptide angio tensin II would enhance its detection by MALDI in two ways. First of all, the acetylcholine-peptide complex could ionize more efficiently than the bare phosphopeptide. Furthermore the ion mobility could separate the complex ion on the basis of its charge/volume from isobaric interferences, which would otherwise limit detection sensitivity.

Oligonucleotide analysis with MALDI-ion-mobility-TOFMS.

Matrix-assisted laser-desorption ionization followed by ion-mobility separation and time-of-flight mass analysis (MALDI-IM-TOFMS) has been used to characterize native and chemically modified DNA oligonucleotides up to eight bases in length. Mobility resolution between 20 and 30 can be used to separate oligonucleotides of different length, but not to differentiate between isomers or even different compositions of the same length. MALDI-IM-TOFMS does, however, have additional utility in the analysis of mixtures of DNA oligonucleotides and peptides, because these classes of molecules can be distinguished on the basis of differences in their mobility. Oligonucleotide sequencing is also possible by MALDI-IM-TOFMS. Ion signals corresponding to nucleobase losses, w-type, and y-type fragments were identified by use of differences in ion mobility. MALDI-IM-TOFMS was also used to resolve DNA-platinum adducts from the corresponding unmodified oligonucleotides.

A study of peptide-peptide interactions using MALDI ion mobility o-TOF and ESI mass spectrometry.

Matrix-assisted laser desorption ionization ion mobility coupled to orthogonal time-of-flight mass spectrometry (MALDI-IM-oTOF MS) is evaluated as a tool for studying non-covalent complex (NCX) formation between peptides. The NCX formed between dynorphin 1-7 and Mini Gastrin I is used as a model system for comparison to previous MALDI experiments (Woods, A. S.; Huestis, M. A. J. Am. Soc. Mass Spectrom. 2001, 12, 88-96). The dynorphin 1-7/Mini Gastrin I complex is stable after more than a ms drift time through the He filled mobility cell. Furthermore, the effects of solution pH on NCX ion signal intensity is measured both by MALDI-IM-MS analysis and by nanoelectrospray mass spectrometry. When compared to the previous MALDI study this work shows that all three techniques give similar results. In addition, fragmentation can be observed from of the non-covalent complex parent ion that occurs prior to TOF mass analysis but after mobility separation, thus providing NCX composition information.