Atmospheric pressure ionization in a miniature mass spectrometer

A miniature cylindrical ion trap mass spectrometer featuring an atmospheric pressure interface allowing atmospheric pressure chemical ionization and electrospray ionization is described together with its analytical performance characteristics. The vacuum system, ion optics, mass analyzer, control electronics system, and detection system have all been designed and built in-house. The design is based upon a three-stage, differentially pumped vacuum system with the instrument capable of being interfaced to many types of atmospheric pressure ionization sources. Ions are transferred through home-built ion optics, and instrument control is achieved through custom-designed electronics and LabView control software. Corona discharge ionization and electrospray ionization sources are implemented and used to allow the analysis of both gaseous- and solution-phase samples during the characterization of the instrument. An upper mass/charge limit of approximately 450 Th with unit resolution was achieved using a 2.5-mm-internal radius cylindrical ion trap as the mass analyzer. The specificity of the instrument can be increased by employing the MS/MS capabilities of the ion trap and has been demonstrated for nitrobenzene. Limits of detection for the trace analysis in air of the chemical warfare agent simulant methyl salicylate (1.24 ppb) and for nitrobenzene (629 pptr) are achieved. The dynamic range of the instrument is currently limited to approximately 2 orders of magnitude by saturation of the detection electronics. Isolation and collision-induced dissociation efficiencies in MS/MS experiments both greater than 50% are reported. Electrospray/nanospray data are presented on solutions including 100 microM (D,L)-arginine, 10 microM (-)-ephedrine, and 10 microM lomefloxacin.     

Handheld rectilinear ion trap mass spectrometer

A shoebox-sized, 10-kg, handheld mass spectrometer, Mini 10, based on a rectilinear ion trap mass analyzer has been designed, built, and characterized. This instrument has evolved from a decade-long experimental and simulation program in mass spectrometer miniaturization. The rectilinear ion trap has a simplified geometry and high trapping capacity, and when used with a miniature and ruggedized pumping system, it allows chemical analysis while the instrument is being carried. Compact electronics, including an air core RF drive coil, were developed to control the instrument and to record mass spectra. The instrument runs on battery power, consuming less than 70 W, similar to a laptop computer. Wired and wireless networking capabilities are implemented. The instrument gives unit resolution and a mass range of over m/z 500. Tandem mass spectrometry capabilities are implemented using collision-induced dissociation, and they are used to provide confirmation of chemical structure during in situ analysis. Continuous monitoring of air and solution samples is demonstrated, and a limit of detection of 50 ppb was obtained for toluene vapor in air and for an aqueous naphthalene solution using membrane sample introduction.     

Direct analysis of semivolatile organic compounds in air by atmospheric pressure chemical ionization mass spectrometry.

Atmospheric pressure chemical ionization is employed for direct air analysis, without ion source modification, by using the sheath gas as the sample transport agent. A simple modification of the sheath gas inlet line allows introduction of gaseous samples into a commercial atmospheric pressure chemical ionization source. Optimization and testing of this novel air sampling method are described and detection of semivolatile compounds is shown. The analytical performance of the technique is established with methyl salicylate, including a limit of quantification of 100 pptr, a limit of detection of 50 pptr, a linear response from 100 pptr to 20 ppb, and rise and fall times of 12 and 20 s, respectively. Using reagent ion monitoring, it is shown that the protonated methanol dimer is the principal CI reagent ion leading to protonated dimethyl methylphosphonate, while the monomer is mainly responsible for protonating methyl salicylate. Since the formation of the CI reagent (methanol clusters) can be controlled by simple variation of experimental parameters, the selectivity of the method can be easily adjusted to suit the targeted analyte. Performance is found to be independent of the choice of air or nitrogen as the sheath gas (and thus as the sample matrix) and this, together with the sensitivity and speed of the technique, make it promising for field studies.     

Ultrasensitive methyl salicylate gas sensing determined by Pd-doped SnO2

Efficient chemical warfare agents (CWAs) detection is required to protect people from the CWAs in war and terrorism. In this work, a Pd-doped SnO₂ nanoparticles-based gas sensor was developed to detect a nerve agent simulant named methyl salicylate. The sensing measurements of methyl salicylate under different Pd doping amounts found that the 0.5 at.% Pd-doped SnO₂ exhibited a significant improvement in the detection of methyl salicylate at the ppb (1 ppb = 10⁻⁹) level, and the response value to 160 ppb methyl salicylate is 0.72 at 250 °C. Compared with the pure SnO₂, the response value is increased by 4.5 times, which could be attributed to the influence of the noble metal Pd on the oxygen state and its catalytic effect. In addition, the 0.5 at.% Pd-doped SnO₂ sensor still has an obvious response to 16 ppb methyl salicylate with a response value of 0.13, indicating the lower detection limit of the sensor.     

Mass spectrometer characterization of halogen gases in air at atmospheric pressure

We have developed a new interface for a commercial ion trap mass spectrometer equipped with APCI capable of real-time measurements of gaseous compounds with limits of detection on the order of pptv. The new interface has been tested using the detection of Br2 and Cl2 over synthetic seawater ice at atmospheric pressure as a model system. A mechanical pump is used to draw gaseous mixtures through a glass manifold into the corona discharge area, where the molecules are ionized. Analysis of bromine and chlorine in dry air show that ion intensity is affected by the pumping rate and the position of the glass manifold. The mass spectrometer signals for Br2 are linear in the 0.1-10.6 ppbv range, and the estimated 3sigma detection limit is 20 pptv. The MS signals for Cl2 are linear in the 0.2-25 ppbv range, and the estimated 3sigma detection limit is 1 ppbv. This new interface advances the field of analytical chemistry by introducing a practical modification to a commercially available ion trap mass spectrometer that expands the available methods for performing highly specific and sensitive measurements of gases in air at atmospheric pressure.     

Determination of water vapor by microwave spectroscopy withapplication to quality control of natural gas

The design and construction of a microwave spectrometer is reported. The aim of this instrument is to detect water vapor at low levels. Sinusoidal Stark field modulation is used in order to amplitude modulate the absorption of microwave energy by the water molecule, thus enhancing the sensitivity of the instrument. A semiconfocal Fabry-Perot resonator is used to hold the sample under test. The fourth harmonic of the Stark modulation frequency was used to show the quantitative presence of water in the sample gas. Both atmospheric air, and liquified natural gas (LNG) were used as carrier gases. The peak-to-peak intensity of the fourth harmonic was used to calibrate the instrument against different amounts of water present in atmospheric air. The observed limit of this prototype is around 300 p.p.m. water. No attempt was made to lower the detection limit at this point since the aim of this project was to examine the feasibility of using the fourth harmonic to determine water content reliably     

Single-photon ionization quadrupole mass spectrometry with an electron beam pumped excimer light source

The application of soft ionization methods for mass spectrometry (MS), such as single-photon ionization (SPI) using vacuum ultraviolet (VUV) light, provides powerful analytical instrumentation for real-time on-line monitoring of organic substances in gaseous matrixes. A compact and mobile quadrupole mass spectrometer (QMS) system using a novel electron beam pumped rare gas VUV lamp for SPI has been developed for on-line analysis of organic trace compounds (ppb concentrations). The VUV radiation of the light source is employed for SPI in the ion source of the QMS. The concept of the interfacing of the VUV light source with the QMS is described and the SPI-QMS is characterized. On-line detection limits down to 50 ppb for benzene, toluene, and m-xylene were achieved. The instrument is well suited for continuous measurements of aromatic and aliphatic trace compounds and can therefore be used for on-line monitoring of trace compounds in dynamically fluctuating process gases. First measurements of gas standards, petrochemical samples, and on-line monitoring of automotive exhaust are presented.     

Quantification of VX vapor in ambient air by liquid chromatography isotope dilution tandem mass spectrometric analysis of glass bead filled sampling tubes

An analysis method has been developed for determining low parts-per-quadrillion by volume (ppqv) concentrations of nerve agent VX vapor actively sampled from ambient air. The method utilizes glass bead filled depot area air monitoring system (DAAMS) sampling tubes with isopropyl alcohol extraction and isotope dilution using liquid chromatography coupled with a triple-quadrupole mass spectrometer (LC/MS/MS) with positive ion electrospray ionization for quantitation. The dynamic range was from one-tenth of the worker population limit (WPL) to the short-term exposure limit (STEL) for a 24 L air sample taken over a 1 h period. The precision and accuracy of the method were evaluated using liquid-spiked tubes, and the collection characteristics of the DAAMS tubes were assessed by collecting trace level vapor generated in a 1000 L continuous flow chamber. The method described here has significant improvements over currently employed thermal desorption techniques that utilize a silver fluoride pad during sampling to convert VX to a higher volatility G-analogue for gas chromatographic analysis. The benefits of this method are the ability to directly analyze VX with improved selectivity and sensitivity, the injection of a fraction of the extract, quantitation using an isotopically labeled internal standard, and a short instrument cycle time.     

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.     

Delta34S measurements of sulfur by multicollector inductively coupled plasma mass spectrometry

An accurate and precise method for the determination of delta34S measurements by multicollector inductively coupled plasma mass spectrometry has been developed. Full uncertainty budgets, taking into consideration all the uncertainties of the measurement process, have been calculated. The technique was evaluated by comparing measured values with a range of isotopically enriched sulfur solutions prepared by gravimetric addition of a 34S spike. The gravimetric and measured results exhibited a correlation of R2 >0.999. Repeat measurements were also made after adding Na (up to 420 microg g(-1)) and Ca (up to 400 microg g(-1)) salts to the sulfur standard. No significant deviations in the delta34S values were observed. The Russell correction expression (Ingle, C.; Sharp, B.; Horstwood, M.; Parrish, R.; Lewis, D. J. J. Anal. At. Spectrom. 2003, 18, 219) was used to correct for mass bias on the 34S/32S isotope amount ratio from the mass bias observed for the 30Si/28Si isotope amount ratio. Consistent compensation for instrumental mass bias was achieved. Resolution of the measured delta34S values was better than 1 per thousand after consideration of all uncertainty components. The technique was evaluated for practical applications by measurement of delta34S for a range of mineral waters by pneumatic nebulization sample introduction and the analysis of genuine and counterfeit pharmaceuticals using both laser ablation sample introduction and liquid chromatography. For the former two cases polyatomic interferences were resolved by operating the MC-ICPMS in medium resolution, while for the chromatographic analyses polyatomic interferences were minimized by the use of a membrane desolvator, allowing the instrument to be operated at a resolution of 400.     

Analysis of phosphorylated peptides by ion mobility-mass spectrometry

An ion mobility-mass spectrometry technique for rapid screening of phosphopeptides in protein digests is described. A data set of 43 sequences (ranging in mass from 400 to 3000 m/z) of model and tryptic peptides, including serine, threonine, and tyrosine phosphorylation, was investigated, and the data support our previously reported observation (Ruotolo, B. T.; Verbeck, G. F., IV; Thomson, L. M.; Woods, A. S.; Gillig, K. J.; Russell, D. H. J. Proteome Res. 2002, 1, 303.) that the drift time-m/z relationship for singly charged phosphorylated peptide ions is different from that for nonphosphorylated peptides. The data further illustrate that a combined data-dependent IM-MS/MS approach for phosphopeptide screening would have enhanced throughput over conventional MS/MS-based methodologies.     

Quantitative analysis of protein phosphorylation in mouse brain by hypothesis-driven multistage mass spectrometry

Determination of site-specific changes in the levels of protein phosphorylation in mammals presents a formidable analytical challenge. Here, we demonstrate a strategy for such analyses utilizing a combination of stable isotope chemical labeling and tandem mass spectrometry. Phosphoproteins of interest are isolated from two sets of animals that have undergone differential drug treatments, separated by SDS-PAGE, excised, and subjected to in-gel enzymatic digestion. Using a simple chemical labeling step, we introduce stable, isotopically distinct mass tags into each of the two sets of peptides that originate from the samples under comparison, mix the samples, and subject the resulting mixture to a procedure based on our previously reported hypothesis-driven multistage MS (HMS-MS) method (Chang, E. J.; Archambault, V.; McLachlin, D. T.; Krutchinsky, A. N.; Chait, B. T. Anal. Chem. 2004, 76, 4472-4483). The method takes advantage of the dominant loss of H3PO4 during MS/MS from singly charged phosphopeptide ions produced by matrix-assisted laser desorption/ionization (MALDI) in the ion trap mass spectrometer. In the present work, quantitation is achieved by isolating the range of m/z values that include both isotopic forms of the putative phosphopeptide and measuring the relative intensities of the two resulting -98-Da fragment ion peaks. This MS/MS measurement can be repeated on the same MALDI sample for all potential phosphopeptide ion pairs that we hypothesize might be produced from the protein under study. Use of MS/MS for quantitation greatly increases the sensitivity of the method and allows us to measure relatively low levels of phosphorylation, phosphopeptides, or both that are not easily observable by single-stage MS. We apply the current method to the determination of changes in the levels of phosphorylation in DARPP-32 from the mouse striatum upon treatment of animals with psychostimulant drugs.     

Chemical agent identification by field-based attenuated total reflectance infrared detection and solid-phase microextraction

Attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy is used to identify liquid and solid-phase chemicals. This research examines the feasibility of identifying vapor-phase chemicals using a field-portable ATR-FT-IR spectrometer (TravelIR) combined with solid-phase microextraction (SPME). Two nerve agent simulants, diisopropyl methylphosphonate (DIMP) and di-methyl methylphosphonate (DMMP), and three sorbent polymers were evaluated. Each polymer was deposited as a thin film on the instrument's sampling interface to partition and concentrate the simulants from air samples prepared in Tedlar bags. The lowest vapor concentrations identified were 50 ppb (v/v) (DIMP) and 250 ppb (v/v) (DMMP). The ATR-FT-IR instrument demonstrated a linear response at concentrations of 1 ppm (v/v) and below. Increasing the sample exposure time, the sample air velocity, and the film thickness was demonstrated to increase the amount of analyte extracted from the air sample. This research demonstrates that it is feasible to use a portable ATR-FT-IR spectrometer with SPME sampling to detect and identify vapor-phase chemicals.     

Demonstration of proton-transfer reaction time-of-flight mass spectrometry for real-time analysis of trace volatile organic compounds

A proton-transfer reaction mass spectrometer based on time-of-flight mass spectrometry is described. This instrument couples a radioactive ion source and drift tube with a reflectron time-of-flight mass spectrometer. Volatile organic compounds in the gas phase with concentrations at the parts per billion by volume level can be detected in a matter of seconds, and crucially, the multichannel data acquisition in TOF-MS means that this detection sensitivity is available in all mass channels simultaneously. The typical mass resolution (m/Deltam) is in excess of 1000. The performance of the instrument is demonstrated using urban air measurements and a linear response/calibration test.     

Monitoring of toxic compounds in air using a handheld rectilinear ion trap mass spectrometer

A miniature, handheld mass spectrometer, based on the rectilinear ion trap mass analyzer, has been applied to air monitoring for traces of toxic compounds. The instrument is battery-operated, hand-portable, and rugged. We anticipate its use in public safety, industrial hygiene, and environmental monitoring. Gaseous samples of nine toxic industrial compounds, phosgene, ethylene oxide, sulfur dioxide, acrylonitrile, cyanogen chloride, hydrogen cyanide, acrolein, formaldehyde, and ethyl parathion, were tested. A sorption trap inlet was constructed to serve as the interface between atmosphere and the vacuum chamber of the mass spectrometer. After selective collection of analytes on the sorbent bed, the sorbent tube was evacuated and then heated to desorb analyte into the instrument. Sampling, detection, identification, and quantitation of all compounds were readily achieved in times of less than 2 min, with detection limits ranging from 800 parts per trillion to 3 parts per million depending on the analyte. For all but one analyte, detection limits were well below (3.5-130 times below) permissible exposure limits. A linear dynamic range of 1-2 orders of magnitude was obtained over the concentration ranges studied (sub-ppbv to ppmv) for all analytes.     

Chip-based capillary electrophoresis/mass spectrometry determination of carnitines in human urine

A chip-based capillary electrophoresis/mass spectrometry (CE/MS) system is described for the CE separation and on-line electrospray detection of carnitine and selected acylcarnitines from mixtures of analytical standards as well as extracts of fortified human urine. Chip-based CE/MS experiments in two different laboratories were carried out using a triple-quadrupole mass spectrometer and a quadrupole time-of-flight (QTOF) mass spectrometer, respectively. The glass chips used with both systems were comparably equipped with a microfabricated capillary electrophoresis (CE) channel but with different electrosprayers. The quadrupole chip-based CE/MS experiments employed a miniature coupled microsprayer, which allowed coupling of the microelectrospray process via a micro liquid junction at the exit of the CE capillary channel. Selected ion monitoring (SIM) CE/MS experiments were employed for all of the quadrupole CE/MS work. The QTOF CE/MS full-scan single MS and MS/MS experiments were carried out in another laboratory using accurate mass measurement TOF mass spectrometry techniques. The electrospray process that was employed with the QTOF system differed in that an inserted nanoelectrospray capillary needle was carefully affixed into a flat-bottomed hole that was aligned with the CE channel exit orifice. SIM CE/MS using the described quadrupole system provided acceptable ion current electropherograms from fmole levels from analytical standard solutions of carnitine and acylcarnitines that were manually injected (loaded) onto the chip. In addition, the corresponding electropherograms for human urine fortified with the target carnitine and acylcarnitines at a 10-20 microg/mL (35-124 microM) level were obtained via SIM CE/MS techniques. The measured CE separation efficiency for the SIM CE/MS electropherograms was determined to be 2860 plates (peak width at half-height method or N = 5.54(T/WO.5(2)), and carnitine and three acylcarnitines were separated in less than 48 s. In contrast, using quadrupole-TOF technologies, the same samples could be diluted by a factor of 2-4 to obtain a comparable detector response for the target compounds. In the full-scan, single mass analyzer mode (m/z 150-500), the CE separation efficiency was measured to be 2600 plates, but mass measurement accuracy was less than 5.0 ppm for the quaternary cations. In the CE/MS/MS mode, full-scan collision-induced dissociation (CID) mass spectra were obtained with a mass accuracy of < or =10 ppm for the higher mass ions and < or =27 ppm for the lower mass product ions. These results demonstrate the feasibility for on-chip CE separation and electrospray mass spectrometric detection for these important compounds in synthetic mixtures, as well as in human urine extracts.     

Experimental upgrades of membrane introduction mass spectrometry for water and air analysis

Some improvements to the membrane introduction mass spectrometry (MIMS) technique, resulting in low-ppt detection limits for volatile organohalogen compounds (CX) in water (namely, chloroform, bromoform, bromodichloromethane, chlorodibromomethane, tetrachloroethylene, trichloroethylene, 1,1,1-trichloroethane, and carbon tetrachloride) and low-microgram per cubic meter detection limits for benzene, toluene, ethylbenzene, and xylenes (BTEX) in gaseous samples, are shown. A static MIMS configuration was compared to a dynamic one, the former requiring longer time to obtain the analytical response. A cryotrapping preconcentration step is introduced and linearity of response, mixture effects, and detection limits are presented. The instrumental setup consists of a hollow fiber silicone membrane, a water or air container, a cryofocusing trap based on Tenax adsorbent, a Peltier cell, and a Varian ion trap benchtop mass spectrometer is described. This instrumental setup, which we named membrane extraction trap focusing mass spectrometry, allowed the detection of CX in water at a concentration as low as 8 ppt and of benzene in air at 0.1 microg/m3. The whole assembly shows great potential for on-site routine monitoring of drinking water resources and urban and indoor air under current EU and Italian regulations.     

Indirect tritium determination by an original 3He ingrowth method using a standard helium leak detector mass spectrometer

A traditional helium leak detector mass spectrometer is applied in analytical chemistry. We report its straightforward use for the precise quantification of 3He and 4He concentrations at a sub-ppb level. Repetitive external calibrations with certified gases demonstrate long-term stability, reproducibility of 3% at the ppb range, and linearity versus helium concentration over 5 orders of magnitude. The mass spectrometric determination of 3He takes into account a H3+ contribution and has a 3He detection limit of 2 ppb. Since 4He induces an attenuation effect of the mass 3 signal, this apparatus is only suitable for the measurement of 3He/4He ratio greater than 10 Ra (atmospheric ratio Ra = 1.38 x 10(-6)). This mass spectrometric technique has found novel application in the determination of tritium concentrations with an original 3He ingrowth method. Here, samples are first purified cryogenically onto activated charcoal to eliminate tritium interfering during the 3He mass spectrometric determination step. Helium is also preconcentrated, and 3He is routinely determined around 0.05 ppb with a 20% relative uncertainty. This 3He measurement technique has been successfully applied in the field of tritiated waste drums as a nondestructive method. The total amount of tritium present in these 200-L drums can be determined as low as approximately 1 GBq.     

LC/MS/MS analyses of an oleander extract for cancer treatment

An HPLC/MS/MS method has been developed for the characterization and quantification of the cardiac glycosides oleandrin, odoroside, neritaloside and the aglycone oleandrigenin, all contained in a patented-hot-water extract of Nerium oleander L (Anvirzel). Qualitative analysis of such extracts was achieved using a hybrid tandem quadrupole time-of-flight (QqTOF) mass spectrometer. Collision-induced dissociation (CID) mass spectra of oleandrin, oleandrigenin, odoroside, and neritaloside were obtained with greater than 5 ppm mass accuracy and resolution routinely in excess of 8000 (fwhm). The detection limit for oleandrin of 20 pg (injected) was realized when the precursor-to-product ion transition, m/z 577 --> 373, was monitored. We have also applied the analytical method to the determination of oleandrin, oleandrigenin, neritaloside, and odoroside in human plasma following an intramuscular injection of Anvirzel.     

Analysis of polar organic compounds using charge exchange ionization and membrane introduction mass spectrometry

Charge exchange ionization in conjunction with membrane introduction mass spectrometry provides a sensitive method for the detection of polar volatile organic compounds and semivolatile compounds in air. Sample introduction into an ion trap mass spectrometer was accomplished with a hollow fiber silicone membrane assembly. Atmospheric oxygen, which diffuses through the membrane, was used as the charge exchange reagent. Chemical ionization parameters were optimized using methyl ethyl ketone (2-butanone) standards in air. Several other oxygen-containing compounds, including acetone (2-propanone), methyl isobutyl ketone (4-methyl-2-pentanone), propanal, isopropyl alcohol (2-propanol), cyclohexanol, dimethyl sulfoxide (sulfinylbismethane), 2-(diethylamino)ethanol, and dimethyl methylphosphonate were analyzed with this technique. This method was used to obtain mass spectra for a variety of classes of compounds and produced a 4-20-fold improvement in response for all of the polar compounds we examined when compared to signal obtained from electron ionization.