Ion Flight Time Research Articles

Metastable BrO2+ and NBr2+ molecules in the gas phase

The doubly positively charged gas-phase molecules BrO(2+) and NBr(2+) have been produced by prolonged high-current energetic oxygen (17 keV (16)O(-)) ion surface bombardment (ion beam sputtering) of rubidium bromide (RbBr) and of ammonium bromide (NH(4)Br) powdered ionic salt samples, respectively, pressed into indium foil. These novel species were observed at half-integer m∕z values in positive ion mass spectra for ion flight times of roughly ∼12 μs through a magnetic-sector secondary ion mass spectrometer. Here we present these experimental results and combine them with a detailed theoretical investigation using high level ab initio calculations of the ground states of BrO(2+) and NBr(2+), and a manifold of excited electronic states. NBr(2+) and BrO(2+), in their ground states, are long-lived metastable gas-phase molecules with well depths of 2.73 × 10(4) cm(-1) (3.38 eV) and 1.62 × 10(4) cm(-1) (2.01 eV); their fragmentation channels into two monocations lie 2.31 × 10(3) cm(-1) (0.29 eV) and 2.14 × 10(4) cm(-1) (2.65 eV) below the ground state minimum. The calculated lifetimes for NBr(2+) (v(") < 35) and BrO(2+) (v(") < 18) are large enough to be considered stable against tunneling. For NBr(2+), we predicted R(e) = 3.051 a(0) and ω(e) = 984 cm(-1); for BrO(2+), we obtained 3.033 a(0) and 916 cm(-1), respectively. The adiabatic double ionization energies of BrO and NBr to form metastable BrO(2+) and NBr(2+) are calculated to be 30.73 and 29.08 eV, respectively. The effect of spin-orbit interactions on the low-lying (Λ + S) states is also discussed.

Gaussian mixture decomposition in the analysis of MALDI-TOF spectra

The article presents a method of protein matrix-assisted laser desorption and ionization-time of flight (TOF) spectra analysis. The method performs peaks detection. Spectra are analysed with Gaussian mixture decomposition. The results obtained are used for peaks identification purposes. The concept of the method is that a single peak is represented by one Gaussian distribution. The expectation-maximization algorithm and maximum likelihood rule are used for spectra processing. The analysis can be done for a set of spectra with use of the mean spectrum, or it may be performed for a single spectrum at a time. The number of mixture-model components is estimated by the Bayesian information criterion. Before the main analysis, a few pre-processing steps need to be done. Spectra should be subjected to calibration, normalization, denoising, baseline correction, etc. The aim of the work is to identify peptides in the analysed sample on the basis of the parameters of the mixture model and to find differences between spectra in the analysed set.

Calcium-containing diatomic dications in the gas phase

Sputtering (ion surface bombardment) of various calcium-containing powder samples with an energetic (17 keV), high-current (16)O(-) beam has produced the diatomic dications of CaSi(2+), CaP(2+), CaF(2+), CaH(2+), CaCl(2+), CaBr(2+) and CaI(2+). These molecular gas-phase species have been identified in positive ion mass spectra at half-integer m/z values; their ion flight times through a magnetic-sector mass spectrometer were roughly 10(-5) s. Most of them appear to be novel molecular ions; the stability of the latter four (CaH(2+), CaCl(2+), CaBr(2+) and CaI(2+)) had been demonstrated in previous theoretical studies, whereas only CaF(2+) and CaBr(2+) had been observed before. Here we combine the results of our experimental search with a detailed theoretical study of the remaining three systems CaSi(2+), CaP(2+) and CaF(2+). All electronic states correlating with the first dissociation channel are characterized using high level ab initio electronic structure calculations. In their ground states, we find CaSi(2+) to be a long-lived metastable molecule, whereas CaF(2+) and CaP(2+) are thermodynamically stable, with respective equilibrium internuclear distances of 6.253, 4.740, and 5.731 a(0). CaSi(2+) has a well depth of 7116 (0.88) cm(-1) (eV) and a dissociation asymptote 7956 (0.99) cm(-1) (eV) below the ground state minimum. The dissociation energy of CaF(2+) is estimated to be 3404 (0.42) cm(-1) (eV), whereas for CaP(2+) we found 2547 (0.32) cm(-1) (eV), and a barrier height of 8118 (1.01) cm(-1) (eV). Their adiabatic double ionisation energies are 22.87, 16.91, and 17.32 eV, respectively, for the F, Si, and P containing dications.

Spectroscopic studies on lipoprotein structure modification under oxidative stress

Matrix assisted laser desorption–ionization time of flight (MALDI-ToF) and infrared techniques were used to study oxidative modification of low density lipoproteins (LDL), considered to have the key role in biological process that initiates and accelerates the development of cardiovascular disease. The early identification of lipoperoxidation products creates the opportunity of the efficient prevention of eventual oxidative damages. MALDI analysis of LDL subjected toin vitrooxidation process initiated by 2,2-azobis(2-amidinopropane) dihydrochloride revealed that some fragments of lipoprotein changed the molecular weight by 16 and 32 Da due to the oxygen or hydroxyl groups attachment, and peroxide or hydroperoxide formation, while Fourier Transformed Infrared studies proved that lipoprotein changes its protein secondary conformation from predominantlyα-helix in predominantlyβ-turn. The increase in free radicals concentration correlated to structural changes, and the presence of transitional metal ion, copper (II), in the oxidation process lead to an enhancing of the damaging effects of free radicals on lipoprotein substrate. It was shown that the toxic effects of oxidants are delayed by the presence of glutathione (10 mM), an endogenous antioxidant.

Proteomic Analysis of the Serum from Chicken Infected by Avian Influenza Virus

Avian influenza (AI) is an infectious, low pathogenic virus that is endemic all over the world and poses a potential threat to the poultry industry. Vaccination is a widely used effective method to prevent avian influenza virus. Here we employed a comparative proteomics approach [two-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF)] to characterize proteome in the sera from the specific pathogen free (SPF) chickens, the vaccinated chickens, and the naturally infected chickens. We identified total 58 proteins that were differentially expressed in the sera of three groups. Among them ovotransferrin and vitamin D-binding protein were more expressed in the sera of naturally infected chickens compare with other groups. Our results suggested that the level of these two proteins in the serum may help to discriminate the naturally infected chicken from the vaccinated chicken.

On the stability and lifetime of GaO2+ in the gas phase

The electronic structure, stability, and lifetime of GaO2+ have been investigated using high-level ab initio calculations. The potential energy curves have been calculated at the CCSD(T)/aug-cc-pV5Z and at the MS-CASPT2/ANO-RCC levels of theory. Lifetimes were evaluated using the Exterior Complex Scaling (ECS) method and B-spline basis functions. Our calculations show that GaO2+ is a metastable species in the gas phase, since the diatomic dication, in its ground state, lies 97.1 kcal/mol above the Ga+ (1S) + O+ (4S) dissociation limit. However, the energy barrier that has to be overcome to reach this limit is 3 kcal/mol high so that five vibrational resonances can be accommodated between the bottom of the well and the top of the barrier. The evaluated lifetimes vary from hundreds of femtoseconds to approximately 1 s, so at least two of them have long enough lifetimes (1 s and 91 μs) to be detected using mass spectrometry techniques, in agreement with the experimental evidence. In the experiment (Fiser et al. in Eur J Mass Spectrom 15:315–324, 2009), GaO2+ was observed for an ion flight time of about ~12 μs through a magnetic-sector mass spectrometer and unambiguously identified by its isotopic abundance. Our results also show that isotopic effects on the resonances’ energies and on their lifetimes, when 70Ga is replaced by 69Ga or 71Ga, are very small (~0.1 and ~1%, respectively), reflecting the large mass of the system.

HPLC Retention time prediction for metabolome analysis

Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF-MS) is widely used for profiling metabolite compounds. LC-TOF-MS is a chemical analysis technique that combines the physical separation capabilities of high-pressure liquid chromatography (HPLC) with the mass analysis capabilities of Time-of-Flight Mass Spectrometry (TOF-MS) which utilizes the difference in the flight time of ions due to difference in the mass-to-charge ratio. Since metabolite compounds have various chemical characteristics, their precise identification is a crucial problem of metabolomics research. Contemporaneously analyzed reference standards are commonly required for mass spectral matching and retention time matching, but there are far fewer reference standards than there are compounds in the organism. We therefore developed a retention time prediction method for HPLC to improve the accuracy of identification of metabolite compounds. This method uses a combination of Support Vector Regression and Multiple Linear Regression adaptively to the measured retention time. We achieved a strong correlation (correlation coefficient = 0.974) between measured and predicted retention times for our experimental data. We also demonstrated a successful identification of an E. coli metabolite compound that cannot be identified by precise mass alone.

Surface modified activated carbon with β-cyclodextrin – Part I. Synthesis and characterization

Surface functional groups produced from oxidation (carboxylic acid, lactone, quinine, phenol, and nitro groups), reduction (alcohol and amine groups), and grafting (imine and hemi-acetal) reactions were characterized (using surface analysis and chemical methods) and compared with unmodified activated carbon (AC) materials. The untreated, surface-modified, and grafted activated carbon materials were characterized by various surface sensitive methods: Diffuse Reflectance Infrared Fourier Transform Spectroscopy, Scanning Electron Microscopy, Raman spectroscopy, thermogravimetry analysis, and Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) mass spectrometry. A chemical method (Boehm titration) was used for estimating the amount of surface bound acidic and basic functional groups. Nitrogen porosimetry was used to analyze the surface area (95–1350 m2/g) and pore volume (0–0.31 cm3/g) characteristics of AC, surface modified AC, and AC materials grafted with β-cyclodextrin.

Human retinal proteomics study of adults and two-month old infants

Objective To identify proteins that have expressed in human eyes from adults and two-month old infants by proteomics approach, so as to build a two-dimensional gel electrophoresis (two-DE) reference map for human retina. The difference of proteomics between the retinas of adults and two-month old infants are also studied. Methods Human retina tissues were collected from donor eyes (nine adults and two infants). Proteins were separated by two-DE. The gels were analyzed by image software. Protein spots were excised from the gels and detected by matrix assisted laser desorption ionization time off light mass spectrometry (MALDI-TOF-MS). Results A total of 1179 spots and 1295 spots were detected respectively on two-DE gels of Coomassie-stained adults and two-month old infants retina, of which 1039 spots were matched in the position. Five spots up-regulated were successfully identified. Human serum albumin and 4 guanylate kinase 1 (GUK1) were identified in adult retina. β2-tubulin, transaldolasel and alpha A-crystallin were identified in infant retina. Conclusion The two-DE reference map for retina proteomics is successfully established. This study provides an evidence of changes in retinal protein levels between adults and infants and biochemical pathways for future studies of human retina development. Key words: Proteomics; Retina/physiology; Adult; Infant

Miniaturized High-Resolution Time-of-Flight Mass Spectrometer MULTUM-S II with an Infinite Flight Path

A new miniature multiturn time-of-flight (TOF) analyzer "MULTUM-S II" has been designed and constructed. This instrument consists of an electron ionization source, the multiturn TOF ion optics, a detector, vacuum system, and electronic circuits. The multiturn TOF analyzer consists of four electrostatic toroidal sectors and two additional electric toroidal sectors for the purpose of ion injection/ejection. The size and weight of the system is less than 50 cm × 57 cm × 30 cm and 35 kg (including vacuum pumps and electronic circuits). The multiturn TOF analyzer is capable of high mass resolution because of its infinite flight path utilizing perfect space and time focused closed flight orbit. To evaluate the resolution in MULTUM-S II, separation of pyridine (¹²C₅H₅N) and the isotopic component of benzene (¹³C¹²C₅H₆) was performed at a mass resolution of about 20,000. Another performance characteristic of the MULTUM-S II was demonstrated by the separation of the greenhouse gas doublet CO₂ and N₂O (Δm = 0.0113 Da). While the mass difference is a mere 0.01 Da, the instrument could easily separate the two peaks at a calculated mass resolution of 31,600. The MULTUM-S II offers high mass resolution mass spectrometry in a miniaturized/portable enclosure.

Synthesis and Characterization of Silica-zirconia Composite for the Enrichment of Phosphopeptides

Abstract Silica-zirconia composite (SiO2-ZrO2) was synthesized by sol-gel method, and its physical-chemical properties were investigated using several techniques. The enrichment capacity of silica-zirconia composite and zirconia was compared using tryptic digest of a-casein as probe. The results showed that the selectivity of SiO2-ZrO2 was better than that of ZrO2 when the pH of the loading solution was below 2. The enrichment capacity of SiO2-ZrO2 for multiple phosphorylated peptides was better than that of ZrO2. In combination with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based peptide mass finger printing technique, SiO2-ZrO2 was used to enrich the phosphopeptides from nonfat milk successfully.

A multiphoton ionization study of acetone using time-of-flight mass spectrometry

The 3p Rydberg states of acetone and photodissociation of the acetone cation were studied using time-of-flight (TOF) mass spectrometry. The 3p Rydberg state spectroscopy of acetone was investigated with linearly polarized two-photon resonance enhanced multiphoton ionization (REMPI) from 320 to 337 nm. Several new transition bands were observed in the spectra. In addition to the CH3COCH3 + ion, CH3CO+ and CH3 + fragments were observed. The laser power dependences suggest that the CH3COCH3 +, CH3CO+ and CH3 + ions are produced in three-, four-, and four-photon processes, respectively. Production of CH3CO+ and CH3 +involves excitation of the ground state acetone cation by an additional photon and subsequent decomposition of the excited acetone ion. The average translational energies of CH3CO+ and CH3 + from dissociation in CH3COCH3 +(X) + hv → CH3CO+ + CH3 and CH3COCH3 +(X) + hv → CH3 + + CH3CO, respectively, were derived from the ion TOF peak profiles.

Analysis of Quinapril by Two Solvent-Saving Methods: Application of Capillary Column High-Performance Liquid Chromatography with Ultraviolet Absorbance Detection and LDI-TOF-MS

A capillary column high-performance liquid chromatography (CapLC) method and a laser desorption ionization-time of flight (LDI-TOF)-MS method are described for the determination of quinapril, an angiotensin-converting enzyme inhibitor. Effective separation was achieved by using a C18 capillary column at a flow rate of 10 microL/min. For CapLC, quinapril and 7-hydroxycoumarin (internal standard) were detected at 210 and 320 nm, respectively. Phenformin replaced 7-hydroxycoumarin as the internal standard for the LDI-TOF-MS method successfully developed to detect quinapril. The calibration curves showed good linearity in the range of 1-100 micro/mL in these two methods. For high throughput purposes, the LDI-TOF-MS method was simpler and faster than the CapLC method. Both green methods were suitably validated and successfully applied to determine quinapril in commercial tablets.

Pulsed ion extraction diagnostics in a quadrupole ion trap linear time-of-flight mass spectrometer

Pulsed extraction techniques are investigated for a quadrupole ion trap (QIT) interfaced to a linear time-of-flight (TOF) mass analyzer. A nonfocusing short-pulse mode of operation is developed and characterized. The short-pulse mode creates a near-monoenergetic ion packet, which is useful for reaction kinetics experiments and for making diagnostic measurements of the ion cloud size in the trap. Monopolar and bipolar pulsing modes, with the voltage pulses applied to one or both QIT endcaps to extract the ions into the TOF region, are compared. Ion TOF peak distributions are characterized experimentally and by ion trajectory simulations. Also, first-order spatial (Wiley-McLaren) focusing of ions is characterized for the conventional long-pulse extraction mode. The nonparallel fields in the QIT, which serves as the first acceleration region in the linear-TOF mass spectrometer, are shown to degrade spatial focusing and mass resolution.

Measuring the extraction time of negative ions from the ionization chamber of a static mass spectrometer

A technique for measuring the time of extraction of negative ions from the ionization chamber of the ion source of an MИ-1201“B” static mass spectrometer is described. The time of extraction of SF6 negative molecular ions equal to ∼(8.5 ± 1.0) μs is comparable to the ion time of flight in the tube of the analyzer.

Abstract 4580: Detection of early-stage pancreatic cancer by mass spectrometry: a multi-institutional validation study

Abstract Background Invasive ductal carcinoma of the pancreas is one of the worst prognoses among common human malignancies. The poor outcome of pancreatic cancer patients seems to be attributable to difficulty in early detection. Methods Mass spectra of peptide were obtained from a total of 1314 plasma/serum samples, consisting 4 cohorts (namely Cohorts 1-4) obtained from 7 medical institutions participating in the “Third-Term Comprehensive Control Research for Cancer” conducted by the Ministry of Health, Labor and Welfare of Japan and one institute in Germany using orthogonal matrix assisted laser/desorption ionization time of flight (oMALDI-qQTOF-MS). The amino acid sequences and posttranslational modifications of marker proteins were identified by tandem mass spectrometry (MS/MS). Results Plasma apolipoprotein AII heterodimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summated value differed between 112 pancreatic cancer patients and 103 healthy controls (Cohort 1) with high statistical significance [P = 1.36 × 10−21, P = 4.35 × 10−14, and P = 1.83 × 10−24 (Mann-Whitney U-test)] and area-under-curve (AUC) values of 0.877, 0.798, and 0.903, respectively. The significance was further verified in 2 retrospective cohorts [Cohort 2 (n = 103) and Cohort 3 (n = 163)] and a hospital-based prospective cohort [Cohort 4 (n = 833)]. Patients with invasive ductal adenocarcinoma of the pancreas, including those with stage-I disease, could be discriminated from healthy controls with the sensitivity of 97.6% (243/249) and specificity of 95.3% (122/128) by the combination of DUPAN-2, CA19-9, ApoAII-2, and ApoCIII-0. Interpretation Although the reduction of the 2 modified forms of plasma/serum apolipoproteins was not pancreatic cancer-specific, the accurate measurement of plasma/serum proteins had a high capability in detecting pancreatic cancer. This test is essentially safe and might be applicable to the primary mass screening of pancreatic cancer in asymptomatic populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4580.

Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectral Analysis of Marine Lipopeptides with Potential Therapeutic Implications

Marine Bacillus circulans DMS-2 (MTCC 8281) was found to produce lipopeptides, which reduced the surface tension of the medium from 69 to 28 mNm−1. The methanol extracts of the lipopeptides were resolved in RP-HPLC, which resulted in the presence of two major surface active fractions corresponding to the peaks E and F were eluted at the retention times of 16.8 and 18 min, respectively. Fourier transform infrared spectroscopy and matrix assisted laser desorption ionization time of flight (MALDI-ToF) mass spectral analysis showed that the produced lipopeptides belonged to surfactin family. In the MALDI-ToF spectrum, the major molecular mass of the HPLC purified isoforms were identified at m/z 1,044 and 1,058 Da, respectively. In addition, this marine strain also produced new variants of surfactins with molecular weights ranging from m/z 1,066 to 1,098 Da, which have not been reported earlier. Both surface-active fractions were found to have potent antimicrobial activity against the Gram-positive and Gram-negative bacterial strains.

Spatial investigations of ion and electron time of flight in laser ablated ZnO plasma

The time of flight (TOF) spectra of ions and electrons of laser ablated ZnO:Ga plasma plume were recorded. The laser fluence was varied from 2.55 Jcm-2 to 17.85 Jcm-2 and the ablation was carried out in vacuum and N2O ambient pressure ranging from 0.0001 mbar to 0.1 mbar. The TOF spectra were recorded at positions 10 mm to 50 mm from the target surface along the direction normal to the surface. Ion acceleration and corresponding electron deceleration were detected in the plasma due to the formation of electric double layer during plasma expansion. Twin peaks were recorded in the ion TOF spectra-corresponding to accelerated and thermal ions, while two categories of thermal electrons were detected in electron TOF spectra. The behaviour of these ions and electrons is studied as a function of laser fluence, ambient gas pressure and distance from the target surface.

Nuclear Proteome Analysis of Monkey Embryonic Stem Cells During Differentiation

The nuclear proteome enables, manages, and regulates the genome by the collective actions and interactions of proteins found in the nucleus. We applied a proteomic approach to analyze a nuclear proteome during embryonic stem cell (ESC) proliferation, and 3 and 9 days after initiation of differentiation. The nuclei were isolated from cells and their proteins were separated using 2-DE. Out of about 560 protein spots reproducible detected on any give gel, 49 differentially expressed proteins were identified by Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI TOF/TOF) mass spectrometry. Of them, several nuclear located proteins involved in chromatin remodeling, transcription regulation, apoptosis, cell proliferation, and differentiation were identified including CTBP1, MM-1, RUVBL1, HCC-1, SGTA, SUMO2, and Galectin-1. Functional interaction analysis of differentially expressed proteins revealed that most of nuclear proteins had a direct interaction with c-Myc and p53.

Theoretical calculations for mass resolution of a quadrupole ion trap reflectron time‐of‐flight mass spectrometer

We have developed a theoretical method of predicting the mass resolution for a quadrupole ion trap reflectron time-of-flight (QIT-reTOF) mass spectrometer as a function of the spatial and velocity distributions of ions, voltages applied to the electrodes, and dimensions of the instrument. The flight times of ions were calculated using theoretical equations derived with an assumption of uniform electric fields inside the QIT and with the analytical description of the potential including the monopole, dipole, and quadrupole components. The mass resolution was then estimated from the flight-time spread of the ions with finite spatial and velocity distributions inside the QIT. The feasibility of the theoretical method was confirmed by the reasonable agreement of the theoretical resolution with the experimental one measured by varying the extraction voltage of the QIT or the deceleration voltage of the reflectron. We found that the theoretical resolution estimated with the assumption of the uniform electric fields inside the QIT reproduced the experimental one better than that with the analytical description of the potential. The possible applications of this theoretical method include the optimization of the experimental parameters of a given QIT-reTOF mass spectrometer and the design of new instruments with higher mass resolution.