Optimization of a quadrupole ion storage trap as a source for time‐of‐flight mass spectrometry

Designs of a quadrupole ion trap (QIT) as a source for time‐of‐flight (TOF) mass spectrometry are evaluated for mass resolution, ion trapping, and laser activation of trapped ions. Comparisons are made with the standard hyperbolic electrode ion trap geometry for TOF mass analysis in both linear and reflectron modes. A parallel‐plate design for the QIT is found to give significantly improved TOF mass spectrometer performance. Effects of ion temperature, trapped ion cloud size, mass, and extraction field on mass resolution are investigated in detail by simulation of the TOF peak profiles. Mass resolution (m/Δm) values of several thousand are predicted even at room temperature with moderate extraction fields for the optimized design. The optimized design also allows larger radial ion collection size compared with the hyperbolic ion trap, without compromising the mass resolution. The proposed design of the QIT also improves the ion–laser interaction volume and photon collection efficiency for fluorescence measurements on trapped ions. Copyright © 2011 John Wiley & Sons, Ltd.     

Ion detection limitations to mass resolution in matrix-assisted laser desorption time-of-flight mass spectrometry.

The ion detection process in a discrete-dynode electron multiplier can result in significant mass resolution losses in time-of-flight mass spectrometry (TOF-MS) for higher mass-to-charge (m/z) ion species. This resolution loss is attributed to propagation time delays and signal broadening in the ion detector. This is presumed to be due to the generation of a distribution of secondary ion species produced initially upon impact of a primary ion with the first dynode surface of the ion detector. Comparisons are made between the signals produced by a standard discrete dynode ion detector (which amplifies the negatively charged species produced by impact of a primary ion) and a detector modified to respond to only the positively charged secondary ion species produced by a primary ion impact. Ion signals for higher m/z ions with the standard detector geometry are seen to be due to a narrow signal component, most likely due to the generation of secondary electrons and/or very low mass secondary ions (H-), and a broad signal component, apparently due to secondary ions which take significant amounts of time to traverse the low potential fields between the first and second detector dynode. This results in ion signal tailing for higher m/z ion species. Numerical subtraction of the ion signal obtained with the standard and modified detector geometries (singly protonated molecular ion species of equine myoglobin) results in an improvement in mass resolution, such that a new adduct ion species (from trifluoroacetic acid) can be resolved.     

High mass accuracy and high mass resolving power FT-ICR secondary ion mass spectrometry for biological tissue imaging

Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the sub-micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for elemental formula assignment based on exact mass measurement. We have recently reported a secondary ion mass spectrometer with the combination of a C₆₀ primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy, and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 μm spatial resolution (75 μm primary ion spot size) with mass resolving power (m/Δm _50%) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/Δm _50%?>?3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 μm. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging.

Mapping Dicorynia guianensis Amsh. wood constituents by submicron resolution cluster‐TOF‐SIMS imaging

The preparation of tropical wood surface sections for time‐of‐flight secondary ion mass spectrometry imaging is described, and the use of delayed extraction of secondary ions and its interest for the analysis of vegetal surface are shown. The method has been applied to the study by time‐of‐flight secondary ion mass spectrometry imaging with a resolution of less than one micron of a tropical wood species, Dicorynia guianensis, which is one of the most exploited wood in French Guiana for its durable heartwood. The heartwood of this species exhibits an economical importance, but its production is not controlled in forestry. Results show an increase of tryptamine from the transition zone and a concomitant decrease of inorganic ions and starch fragment ions. These experiments lead to a better understanding of the heartwood formation and the origin of the natural durability of D. guianensis. Copyright © 2016 John Wiley & Sons, Ltd.     

Toward high pressure miniature protein mass spectrometer: Theory and initial results

Current miniature mass spectrometers mainly focus on the analyses of organic and small biological molecules. In this study, we explored the possibility of developing high resolution miniature ion trap mass spectrometers for whole protein analysis. Theoretical derivation, GPU assisted ion trajectory simulation, and initial experiments on home‐developed “brick” mass spectrometer were carried out. Results show that ion‐neutral collisions have smaller damping effect on large protein ions, and a higher buffer gas pressure should be applied during ion trap operations for protein ions. As a result, higher pressure ion trap operation not only benefits instrument miniaturization, but also improves mass resolution of protein ions. Dynamic mass scan rate and generation of low charge state protein ions are also found to be helpful in terms of improving mass resolutions. Theory and conclusions found in this work are also applicable in the development of benchtop mass spectrometers.     

Correlative mass spectrometry imaging,applying time‐of‐flight secondary ion mass spectrometry and atmospheric pressure matrix‐assisted laser desorption/ionization to a single tissue section

Rationale

Mass spectrometry imaging (MSI) is a powerful tool for mapping the surface of a sample. Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) and atmospheric pressure matrix‐assisted laser desorption/ionization (AP‐MALDI) offer complementary capabilities. Here, we present a workflow to apply both techniques to a single tissue section and combine the resulting data for the example of human colon cancer tissue.

Methods

Following cryo‐sectioning, images were acquired using the high spatial resolution (1 μm pixel size) provided by TOF‐SIMS. The same section was then coated with a para‐nitroaniline matrix and images were acquired using AP‐MALDI coupled to an Orbitrap mass spectrometer, offering high mass resolution, high mass accuracy and tandem mass spectrometry (MS/MS) capabilities. Datasets provided by both mass spectrometers were converted into the open and vendor‐independent imzML file format and processed with the open‐source software MSiReader.

Results

The TOF‐SIMS and AP‐MALDI mass spectra show strong signals of fatty acids, cholesterol, phosphatidylcholine and sphingomyelin. We showed a high correlation between the fatty acid ions detected with TOF‐SIMS in negative ion mode and the phosphatidylcholine ions detected with AP‐MALDI in positive ion mode using a similar setting for visualization. Histological staining on the same section allowed the identification of the anatomical structures and their correlation with the ion images.

Conclusions

This multimodal approach using two MSI platforms shows an excellent complementarity for the localization and identification of lipids. The spatial resolution of both systems is at or close to cellular dimensions, and thus spatial correlation can only be obtained if the same tissue section is analyzed sequentially. Data processing based on imzML allows a real correlation of the imaging datasets provided by these two technologies and opens the way for a more complete molecular view of the anatomical structures of biological tissues.

     

Accuracy of relative isotopic abundance and mass measurements in a single‐stage orbitrap mass spectrometer

Orbitrap technology offers a combination of different technical specifications which have not yet been achieved by other high‐resolution mass spectrometry instrumentation. This refers to the combination of sensitivity, dynamic range, mass accuracy, resolution and speed. The high stability of the mass axis and the general ease of use made the orbitrap instrumentation attractive for routine laboratories. However, there are circumstances where significantly deviating relative isotopic abundance (RIA) and shifting accurate masses can be observed. RIA becomes biased at low ion counts. Furthermore, two adjacent, only partially resolved near‐isobaric ions are detected with a deviating RIA. The presence of a very intensive mass peak does not only induce Fourier transformation related artefacts (side‐lobes) but can cause mass shifts of small adjacent near‐isobaric mass peaks. These effects are not as drastic as known for Fourier transform ion cyclotron resonance instruments. Still, users trying to identify or quantify trace level compounds should be aware about such limitations in order to avoid possible pitfalls. Copyright © 2012 John Wiley & Sons, Ltd.     

Animal urine as painting materials in African rock art revealed by cluster ToF‐SIMS mass spectrometry imaging

The rock art site at the village of Songo in Mali is a very important Dogon ritual place where, since the end of the nineteenth century until today, takes place the ceremony of circumcision. During these ceremonies, paintings are performed on the walls of the shelter with mainly three colors: red, black and white. Ethnological literature mentions the use of animal urine of different species such as birds, lizards or snakes as a white pigment. Urine of these animals is mainly composed of uric acid or urate salts. In this article, time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) is used to compare uric acid, snake urine and a sample of a white pigment of a Dogon painting coming from the rock art site of Songo. ToF‐SIMS measurements in both positive and negative ion modes on reference compounds and snake urine proved useful for the study of uric acid and urate salts. This method enables to identify unambiguously these compounds owing to the detection in negative ion mode of the ion corresponding to the deprotonated molecule ([M ? H]^? at m/z 167.01) and its fragment ions. Moreover, the mass spectra obtained in positive ion mode permit to differentiate uric acid and urate salts on the basis of specific ions. Applying this method to the Dogon white pigments sample, we show that the sample is entirely composed of uric acid. This proves for the first time, that animal urine was used as a pigment by the Dogon. The presence of uric acid instead of urate salts as normally expected in animal urine could be explained by the preparation of the pigment for its application on the stone. Copyright © 2010 John Wiley & Sons, Ltd.     

Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling

Isobaric product ions cannot be differentiated by exact mass determinations, although in some cases deuterium labeling can provide useful structural information for identifying isobaric ions. Proposed fragmentation pathways of fentanyl were investigated by electrospray ionization ion trap mass spectrometry coupled with deuterium labeling experiments and spectra of regiospecific deuterium labeled analogs. The major product ion of fentanyl under tandem mass spectrometry (MS/MS) conditions (m/z 188) was accounted for by a neutral loss of N‐phenylpropanamide. 1‐(2‐Phenylethyl)‐1,2,3,6‐tetrahydropyridine (1) was proposed as the structure of the product ion. However, further fragmentation (MS³) of the fentanyl m/z 188 ion gave product ions that were different from the product ion in the MS/MS fragmentation of synthesized 1, suggesting that the m/z 188 product ion from fentanyl includes an isobaric structure different from the structure of 1. MS/MS fragmentation of fentanyl in deuterium oxide moved one of the isobars to 1 Da higher mass, and left the other isobar unchanged in mass. Multistage mass spectral data from deuterium‐labeled proposed isobaric structures provided support for two fragmentation pathways. The results illustrate the utility of multistage mass spectrometry and deuterium labeling in structural assignment of isobaric product ions. Copyright © 2010 John Wiley & Sons, Ltd.     

Differentiation of isomeric dinitrotoluenes and aminodinitrotoluenes using electrospray high resolution mass spectrometry

Explosive detection and identification play an important role in the environmental and forensic sciences. However, accurate identification of isomeric compounds remains a challenging task for current analytical methods. The combination of electrospray multistage mass spectrometry (ESI‐MSⁿ) and high resolution mass spectrometry (HRMS) is a powerful tool for the structure characterization of isomeric compounds. We show herein that resonant ion activation performed in a linear quadrupole ion trap allows the differentiation of dinitrotoluene isomers as well as aminodinitrotoluene isomers. The explosive‐related compounds: 2,4‐dinitrotoluene (2,4‐DNT), 2,6‐dinitrotoluene (2,6‐DNT), 2‐amino‐4,6‐dinitrotoluene (2A‐4,6‐DNT) and 4‐amino‐2,6‐dinitrotoluene (4A‐2,6‐DNT) were analyzed by ESI‐MS in the negative ion mode; they produced mainly deprotonated molecules [M ? H]^?. Subsequent low resolution MSⁿ experiments provided support for fragment ion assignments and determination of consecutive dissociation pathways. Resonant activation of deprotonated dinitrotoluene isomers gave different fragment ions according to the position of the nitro and amino groups on the toluene backbone. Fragment ion identification was bolstered by accurate mass measurements performed using Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR/MS). Notably, unexpected results were found from accurate mass measurements performed at high resolution for 2,6‐DNT where a 30‐Da loss was observed that corresponds to CH₂O departure instead of the expected isobaric NO^? loss. Moreover, 2,4‐DNT showed a diagnostic fragment ion at m/z 116, allowing the unambiguous distinction between 2,4‐ and 2,6‐DNT isomers. Here, CH₂O loss is hindered by the presence of an amino group in both 2A‐4,6‐DNT and 4A‐2,6‐DNT isomers, but nevertheless, these isomers showed significant differences in their fragmentation sequences, thus allowing their differentiation. DFT calculations were also performed to support experimental observations. Copyright © 2014 John Wiley & Sons, Ltd.     

On the high‐resolution mass analysis of the product ions in tandem time‐of‐flight (TOF/TOF) mass spectrometers using a time‐dependent re‐acceleration technique

The time‐dependent reacceleration of product ions produced as a result of dissociation of a single precursor ion in a tandem time‐of‐flight mass spectrometer is considered for the first time. Analytical expressions for the shapes of electric pulses bringing all the kinetic energies of the product ions to the same value are derived for two cases: forward acceleration mode and deceleration, followed by re‐acceleration in the reversed direction (reversed mode). Secondary time‐of‐flight focusing resulting from the re‐acceleration in the reversed mode is shown to be mass‐dependent and, when averaged over a wide mass range, the focusing is tight enough to provide mass resolution exceeding 10 000. After time‐dependent re‐acceleration, additional compression of the ion packet width leading to better mass resolution can be obtained by decelerating the ions in a constant field. Copyright © 2009 John Wiley & Sons, Ltd.     

Multidimensional mass spectrometry to characterize degradation products generated during MALDI of polystyrenes prepared by controlled radical polymerization techniques

An analytical workflow involving high resolution mass analysis, collision‐induced dissociation and ion mobility was implemented to structurally characterize polymeric by‐products detected in lieu of intact species when performing matrix‐assisted laser desorption/ionization (MALDI) of polystyrenes with fragile end groups. Studied samples were prepared by atom transfer radical polymerization, reversible addition–fragmentation transfer polymerization and nitroxide‐mediated polymerization. Spectral resolution enabled by orthogonal injection of MALDI ions into a reflectron time‐of‐flight mass analyzer allowed a thorough inventory of species, including some with the same nominal m/z value but different elemental composition. Individual end‐group mass determination was achieved in MS/MS experiments, implementing an additional separative dimension based on ion mobility prior to CID to assist precursor ion selection in case of interferences. Besides validating commonly reported polystyrene chains terminated with either endo‐ or exo‐double bond, this multidimensional approach permitted to show that initiating moiety could also be affected by the MALDI process. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3388–3397     

Food contaminant analysis at ultra‐high mass resolution: application of hybrid linear ion trap – orbitrap mass spectrometry for the determination of the polyether toxins,azaspiracids, in shellfish

The biotoxins, azaspiracids (AZAs), from marine phytoplankton accumulate in shellfish and affect human health by causing severe gastrointestinal disturbance, diarrhea, nausea and vomiting. Specific and sensitive methods have been developed and validated for the determination of the most commonly occurring azaspiracid analogs. An LTQ Orbitrap mass spectrometer is a hybrid instrument that combines linear ion trap (LIT) mass spectrometry (MS) with high‐resolution Fourier transform (FT) MS and this was exploited to perform simultaneous ultra‐high‐resolution full‐scan MS analysis and collision‐induced dissociation (CID) tandem mass spectrometry (MS/MS). Using the highest mass resolution setting (100 000 FWHM) in full‐scan mode, the methodology was validated for the determination of six AZAs in mussel (Mytilus galloprovincialis) tissue extracts. Ultra‐high mass resolution, together with a narrow mass tolerance window of ±2 mDa, dramatically improved detection sensitivity. In addition to employing chromatographic resolution to distinguish between the isomeric azaspiracid analogs, AZA1/AZA6 and AZA4/AZA5, higher energy collisionally induced dissociation (HCD) fragmentation on selected precursor ions were performed in parallel with full‐scan FTMS. Using HCD MS/MS, most precursor and product ion masses were determined within 1 ppm of the theoretical m/z values throughout the mass spectral range and this enhanced the reliability of analyte identity. For the analysis of mussels (M. galloprovincialis), the method limit of quantitation (LOQ) was 0.010 µg/g using full‐scan FTMS and this was comparable with the LOQ (0.007 µg/g) using CID MS/MS. The repeatability data were; intra‐day RSD% (1.8–4.4%; n = 6) and inter‐day RSD% (4.7–8.6%; n = 3). Application of these methods to the analysis of mussels (M. edulis) that were naturally contaminated with azaspiracids, using high‐resolution full‐scan Orbitrap MS and low‐resolution CID MS/MS, produced equivalent quantitative data. Copyright © 2010 John Wiley & Sons, Ltd.     

Ion optics of the LAMAS-10 laser time-of-flight mass spectrometer

In laser time-of-flight mass spectrometers, satisfactory resolution by weight is achieved for a fixed initial kinetic energy acquired by the ions in the plasma. The integration of mass spectra in a wide energy range intended for obtaining satisfactory results of analysis leads to a 3–5-fold reduction of the resolving capacity. In the case of the LAMAS-10 device, the resolution for W = 50–300 eV energy dispersion of the ions varies from R ∼ 1000 (for W = 300 eV) to R ∼ 150 (for W = 50 eV), such values being insufficient for quantitative elemental analysis. It has been demonstrated that the main reason for the differences in the resolution values for LAMAS-10 are time aberrations by energies in the laser plasma drift space. The modification of the ion optics theory for LAMAS-10 allows the determination of the principles of the influence of the initial ion energies generated in the laser plasma on the resolution. The dependence of the conditions of the time focusing of ions by energies has been determined in a wide range of the initial values. This dependence provides software-controlled readjustment of the time focusing before the registration of the mass spectra for each initial ion energy. When time focusing of the ions was performed in a wide range of the initial energies, the resolution increased to R = 1300 at W = 50 eV, such parameters providing the quantitative analysis of solid bodies and powders.     

Improvement of biological time-of-flight-secondary ion mass spectrometry imaging with a bismuth cluster ion source

A new liquid metal ion gun (LMIG) filled with bismuth has been fitted to a time-of-flight-secondary ion mass spectrometer (TOF-SIMS). This source provides beams of Bi(n)q+ clusters with n = 1-7 and q = 1 and 2. The appropriate clusters have much better intensities and efficiencies than the Au3+ gold clusters recently used in TOF-SIMS imaging, and allow better lateral and mass resolution. The different beams delivered by this ion source have been tested for biological imaging of rat brain sections. The results show a great improvement of the imaging capabilities in terms of accessible mass range and useful lateral resolution. Secondary ion yields Y, disappearance cross sections sigma, efficiencies E = Y/sigma , and useful lateral resolutions deltaL have been compared using the different bismuth clusters, directly onto the surface of rat brain sections and for several positive and negative secondary ions with m/z ranging from 23 up to more than 750. The efficiency and the imaging capabilities of the different primary ions are compared by taking into account the primary ion current for reasonable acquisition times. The two best primary ions are Bi3+ and Bi5(2+). The Bi3+ ion beam has a current at least five times larger than Au3+ and therefore is an excellent beam for large-area imaging. Bi5(2+) ions exhibit large secondary ions yields and a reasonable intensity making them suitable for small-area images with an excellent sensitivity and a possible useful lateral resolution <400 nm.     

Enhancement of the static SIMS secondary ion yields of lipid moieties by ultrathin gold coating of aged oil paint surfaces

Static secondary ion mass spectrometry (SIMS) is a powerful technique for identification and localization of pigments and binding media present in traditional paintings. Coating the surface of a cross‐section with a 20 Å thick gold layer improves the yields of secondary ions from the fatty acids and diacids. A chalk tablet containing 1% stearic acid, which was partially covered during gold deposition, is used as a test system to investigate the increase of the organic secondary ion yields upon gold deposition in SIMS imaging. A comparative study of a native and gold‐coated aged surface of a lead white‐containing linseed oil paint demonstrates the enhancement of the organic ion yields on a sample relevant for painting studies. The yields of oil paint‐derived negative ions increase by a factor of 3 whereas the yields of positive ions increase by a factor of 2–4. The different types of charged functional groups determine the degree of improvement in yield. Gold coating improves the ionization process of the fatty acids and does not influence their fragmentation. The dissociation of the lead white by the primary ion beam is reduced due to the gold coating. Copyright © 2004 John Wiley & Sons, Ltd.     

Isotope abundance analysis for improved sample identification with tandem mass spectrometry

Tandem mass spectrometry (MS/MS) is widely used for trace level sample analysis in complex mixtures. However, sample identification in MS/MS is challenging and not as trustworthy as with electron ionization (EI) mass spectral libraries. This paper presents a novel method for the combination of isotope abundance analysis (IAA) and EI‐MS/MS for improved sample identification even at trace level in complex matrices. Accordingly, the first quadrupole is scanned in a narrow range around the molecular ion group of isotopomers such as M⁺, [M+1]⁺ and [M+2]⁺, Q2 serves for collision‐induced dissociation to produce product ions while Q3 transfers the major sample product ions with low resolution, thus encompassing and uniformly transmitting all the product ion isotopomers. IAA can then be used to derive elemental formula information from the cleansed experimental data. IAA‐MS/MS was experimentally tested with perfluorotributylamine and a very good matching factor of 995 (out of 1000) was obtained for IAA on m/z 502, 503 and 504 (fragment ion isotopomers) while Q3 transmitted the m/z 264 product ion with a mass window of 6 m/z units. The IAA‐MS/MS method was further tested with the pesticide diazinon on its molecular ions m/z 304, 305 and 306 while Q3 was locked on its m/z 179 product ion with a mass window of 6 m/z units. Again, very good matching factors were obtained, even for 40 pg diazinon on‐column during its GC/MS analysis (match = 981). IAA‐MS/MS combines the traditional benefits of MS/MS in the removal of matrix interferences with the IAA power of elemental analysis. Copyright © 2009 John Wiley & Sons, Ltd.     

Use of high‐resolution mass spectrometry to investigate a metabolite interference during liquid chromatography/tandem mass spectrometric quantification of a small molecule in toxicokinetic study samples

During routine liquid chromatography/tandem mass spectrometric (LC/MS/MS) bioanalysis of a small molecule analyte in rat serum samples from a toxicokinetic study, an unexpected interfering peak was observed in the extracted ion chromatogram of the internal standard. No interfering peaks were observed in the extracted ion chromatogram of the analyte. The dose‐dependent peak area response and peak area response versus time profiles of the interfering peak suggested that it might have been related to a metabolite of the dosed compound. Further investigation using high‐resolution mass spectrometry led to unequivocal identification of the interfering peak as an N‐desmethyl metabolite of the parent analyte. High‐resolution mass spectrometry (HRMS) was also used to demonstrate that the interfering response of the metabolite in the multiple reaction monitoring (MRM) channel of the internal standard was due to an isobaric relationship between the ¹³C‐isotope of the metabolite and the internal standard (i.e., common precursor ion mass), coupled with a metabolite product ion with identical mass to the product ion used in the MRM transition of the internal standard. These results emphasize (1) the need to carefully evaluate internal standard candidates with regard to potential interferences from metabolites during LC/MS/MS method development, validation and bioanalysis of small molecule analytes in biological matrices; (2) the value of HRMS as a tool to investigate unexpected interferences encountered during LC/MS/MS analysis of small molecules in biological matrices; and (3) the potential for interference regardless of choice of IS and therefore the importance of conducting assay robustness on incurred in vitro or in vivo study samples. Copyright © 2010 John Wiley & Sons, Ltd.