Particle discriminator interface for nanoflow ESI-MS

An atmosphere to vacuum interface was designed to exploit the different mobility and momentum characteristics of ions, and charged and neutral particles in electrospray ionization-mass spectrometry. The purpose of this device is to transmit with high efficiency the ions created at atmospheric pressure into the mass analyzer and to deflect the large charged and neutral particles prior to entrance into the vacuum system, thereby maintaining system cleanliness and stability. This interface is particularly suitable for low flow rate electrospray ionization-mass spectrometry where the close proximity of the electrospray emitters to the vacuum entrance, and near total consumption of the entire spray, leads to the production of large quantities of non-desolvated droplets and large charged and neutral particles. The improvement involves the application of potential gradients to a particle discriminator space located between the gas restricting ion entrance orifice of the mass spectrometer and the exit of a heated laminar flow chamber to divert large particles from the gas conductance limiting orifice. A counter-current flow of drying gas is used to deflect neutral particles and solvent vapor. Two stages of desolvation are achieved with the combined effects of the curtain gas and heated laminar flow chamber. This enhances the efficiency of desolvation and ion production, and stabilizes the resulting ion current under a wide variety of solvent compositions. In addition, this system eliminates the problems associated with the boiling of solution in nanospray tips when operated in close proximity to a heated mass spectrometer inlet. The particle discriminator interface gives approximately a 2-fold improvement in ion count rates, and a 3-fold improvement in stability (as measured by the signal relative standard deviation).     

Air flow assisted ionization for remote sampling of ambient mass spectrometry and its application

Ambient ionization methods are an important research area in mass spectrometry (MS) analysis. Under ambient conditions, the gas flow and atmospheric pressure significantly affect the transfer and focusing of ions. The design and implementation of air flow assisted ionization (AFAI) as a novel and effective, remote sampling method for ambient mass spectrometry are described herein. AFAI benefits from a high extracting air flow rate. A systematic investigation of the extracting air flow in the AFAI system has been carried out, and it has been demonstrated not only that it plays a role in the effective capture and remote transport of charged droplets, but also that it promotes desolvation and ion formation, and even prevents ion fragmentation during the ionization process. Moreover, the sensitivity of remote sampling ambient MS analysis was improved significantly by the AFAI method. Highly polar and nonpolar molecules, including dyes, pharmaceutical samples, explosives, drugs of abuse, protein and volatile compounds, have been successfully analyzed using AFAI-MS. The successful application of the technique to residue detection on fingers, large object analysis and remote monitoring in real time indicates its potential for the analysis of a variety of samples, especially large objects. The ability to couple this technique with most commercially available MS instruments with an API interface further enhances its broad applicability.     

Investigation of chromatographic peak broadening in supercritical fluid chromatography/atmospheric pressure chemical ionization mass spectrometry

Multimode ionization source allows for switching between different ionization techniques, for example, electrospray and atmospheric pressure chemical ionization, within a single analysis. Supercritical fluid chromatography can handle a wide polarity range of substances from hydrophilic to lipophilic in a single run and can undoubtedly benefit from versatility of this ion source. Nevertheless, we observed a significant chromatographic peak broadening effect in atmospheric pressure chemical ionization mode during supercritical fluid chromatography‐mass spectrometry analysis of volatile flavor compounds with a dual ion source named ESCi (Waters). Surprisingly, this effect was not related to the separation process but was triggered solely by the ion source conditions. Neither of photodiode array detector, electrospray mode nor a dedicated atmospheric pressure chemical ionization source suffered from such a phenomenon. Chromatographic peak profiles of ten test substances obtained with the dual ion source were compared with photodiode array detector data as a reference. The broadening effect was more pronounced for volatile compounds with low polarity. Dependence of peak broadening on the ion source settings was systematically investigated. Tuning of desolvation gas flow and its temperature dramatically reduced peak distortion and increased detection sensitivity.     

Selective generation of charge-cependent/independent ion energy distributions from a heated capillary electrospray source

Retarding grid and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry variable trap potential measurements are performed to determine factors that contribute to the kinetic energy distribution of ions formed in an electrospray source that uses a heated capillary for desolvation. The control of ion kinetic energies is achieved by manipulating the skimmer position in the postcapillary expansion and by varying the potential appEed to the skimmer. The selective generation of either charge-dependent or charge-independent ion energy distributions is demonstrated. Charge-dependent energy distributions of electro-sprayed ions are created by sampling ions near the Mach disk of the supersonic expansion and by using a larger diameter skimmer orifice; the FTICR spectra acquired under these conditions exhibit mass-to-charge ratio-dependent mass discrimination determined by the potential used to trap the ions. Charge-independent energies of electrosprayed ions are created by positioning the capillary adjacent to the skimmer to sample thermal ions and by using a smaller skimmer orifice to reduce expansion cooling; under these conditions ion kinetic energy is determined primarily by the skimmer potential and no mass-to-charge ratio-dependence is observed in the selection of optimum FTICR trapping conditions. The ability to select between proteins of different conformation on the basis of kinetic energy differences is demonstrated. For example, a 0.4 V difference in trap potential is observed in the selective trapping of open and closed forms of the +10 charge state of lysozyme. Finally, it is demonstrated that by operating the source under conditions which deliver a beam of ions with charge-independent energies to the cell, it is possible to obtain precursor and product ion signal magnitudes in FTTCR spectra without charge-dependent mass discrimina-tion.     

Flow injection of liquid samples to a mass spectrometer with ionization under vacuum conditions: a combined ion source for single-photon and electron impact ionization

Electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo-ionization (APPI) are the most important techniques for the ionization of liquid samples. However, working under atmospheric pressure conditions, all these techniques involve some chemical rather than purely physical processes, and therefore, side reactions often yield to matrix-dependent ionization efficiencies. Here, a system is presented that combines both soft single-photon ionization (SPI) and hard 70 eV electron impact ionization (EI) of dissolved compounds under vacuum conditions. A quadrupole mass spectrometer was modified to enable direct EI, a technique developed by Cappiello et al. to obtain library-searchable EI mass spectra as well as soft SPI mass spectra of sample solutions. An electron beam-pumped rare gas excimer lamp working at 126 nm was used as well as a focusable vacuum UV light source for single-photon ionization. Both techniques, EI and SPI, were applied successfully for flow injection experiments providing library-matchable EI fragment mass spectra and soft SPI mass spectra, showing dominant signals for the molecular ion. Four model compounds were analyzed: hexadecane, propofol, chlorpropham, and eugenol, with detection limits in the picomolar range. This novel combination of EI and SPI promises great analytical benefits, thanks to the possibility of combining database alignment for EI data and molecular mass information provided by SPI. Possible applications for the presented ionization technology system are a matrix-effect-free detection and a rapid screening of different complex mixtures without time-consuming sample preparation or separation techniques (e.g., for analysis of reaction solutions in combinatorial chemistry) or a switchable hard (EI) and soft (SPI) MS method as detection step for liquid chromatography.

Detection mass bias in atmospheric pressure ionization mass spectrometry

A previously uncharacterized source of detection mass bias is shown to be associated with atmospheric pressure ionization mass spectrometry (APIMS), and is attributed to a mass dependence in the sampling of ions from the supersonic free jet expansion of gas emerging from the ion source. The halide ions Cl ^?, Br^?, and I^? are shown to be transported from the ion source aperture to a quadrupole mass filter with efficiencies that increase linearly with increasing mass of the ion. While the polyatomic anions SF ₆ ^- and C₇F ₁₄ ^- are detected with even greater efficiencies than would be expected for monatomic anions of the same mass, this additional sensitivity to the polyatomic anions is thought to be related to ion loss processes occurring within the ion source. The experimental conditions under which these mass bias effects can be minimized or enhanced in APIMS are described.     

Possible conformational change within the desolvated and cationized sBBI/trypsin non-covalent complex during the collision-induced dissociation process

Electrospray ionization mass spectrometry (ESI-MS) has become an analytical technique widely used for the investigation of non-covalent protein-protein and protein-ligand complexes due to the soft desolvation conditions that preserve the stoichiometry of the interacting partners. Dissociation studies of solvated or desolvated complexes (in the source and in the collision cell, respectively) allow access to information on protein conformation and localization of the metal ions involved in protein structure stabilization and biological activity. The complex of bovine trypsin and small soybean Bowman-Birk inhibitor (sBBI) was studied by ESI-MS to determine changes occurring within the complex during its transfer from droplets to the gas phase independently of the ion polarity. Under collision-induced dissociation (CID) conditions, unexpected binding of the Ca(2+) ion (cofactor of native trypsin) to the inhibitor molecule was observed within the desolvated sBBI/trypsin/Ca(2+) complex (with a 1:1:1 stoichiometry). This formal gas-phase migration of the calcium ion from trypsin to the inhibitor may be related to conformational rearrangements in the solvent-free and likely collapsed complex. However, under conditions leading to the increase in complex charge state, the appearance of the cationized trypsin molecule was detected during complex dissociation, thus reflecting different pathways of the evolution of complex conformation.     

Characterization of a glow discharge ion source for the mass spectrometric analysis of organic compounds

A glow discharge ion source has been constructed for the mass spectrometric analysis of organic compounds. Characterization of the source has been made by studying the effect of pressure and discharge current on ionic distributions by anodic ion sampling along the discharge axis. Ion and electron densities and electronic temperatures have been calculated by using the single Langmuir probe technique to correlate the extraction efficiency with measured ion distributions and gain some insight into the ionization of organic molecules. The spectra obtained for several classes of organic compounds show that formation of parent-molecular ions by proton transfer, resulting partly from the background water molecules, is a major low energy process while charge transfer, Penning ionization, and electron ionization ace probably responsible for the fragmentation observed. The spectra result from the simultaneous occurrence of high and low energy reactions, and their structural information content is very high, yielding both molecular and extensive fragment ion information. The glow discharge ion source has proved to be essentially maintenance-free, easy to operate, stable, and can be used at reasonable mass resolution (up to 70001. The source also provides picogram range detection limits and has a linear response range of about six orders of magnitude, which makes it an interesting ion source for routine analysis. Preliminary work conducted with chromatographic interfaces indicates that its use can be easily extended to both gas and liquid chromatography.     

Inline pneumatically assisted atmospheric pressure matrix‐assisted laser desorption/ionization ion trap mass spectrometry

Atmospheric pressure (AP) matrix‐assisted laser desorption/ionization (MALDI) is known to suffer from poor ion transfer efficiencies as compared to conventional vacuum MALDI (vMALDI). To mitigate these issues, a new AP‐MALDI ion source utilizing a coaxial gas flow was developed. Nitrogen, helium, and sulfur hexafluoride were tested for their abilities as ion carriers for a standard peptide and small drug molecules. Nitrogen showed the best ion transport efficiency, with sensitivity gains of up to 1900% and 20% for a peptide standard when the target plate voltage was either continuous or pulsed, respectively. The addition of carrier gas not only entrained the ions efficiently but also deflected background species and declustered analyte–matrix adducts, resulting in higher absolute analyte signal intensities and greater signal‐to‐noise (S/N) ratios. With the increased sensitivity of pneumatically assisted (PA) AP‐MALDI, the limits of detection of angiotensin I were 20 or 3 fmols for continuous or pulsed target plate voltage, respectively. For analyzing low‐mass analytes, it was found that very low gas flow rates (0.3–0.6 l min^?1) were preferable owing to increased fragmentation at higher gas flows. The analyte lability, type of gas, and nature of the extraction field between the target plate and mass spectrometer inlet were observed to be the most important factors affecting the performance of the in‐line PA‐AP‐MALDI ion source. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparison of the internal energy deposition of venturi-assisted electrospray ionization and a venturi-assisted array of micromachined ultrasonic electrosprays (AMUSE)

The internal energy deposition of a Venturi-assisted array of micromachined ultrasonic electrosprays (AMUSE), with and without the application of a DC charging potential, is compared with equivalent experiments for Venturi-assisted electrospray ionization (ESI) using the "survival yield" method on a series of para-substituted benzylpyridinium salts. Under conditions previously shown to provide maximum ion yields for standard compounds, the observed mean internal energies were nearly identical (1.93-2.01 eV). Operation of AMUSE without nitrogen flow to sustain the air amplifier focusing effect generated energetically colder ions with mean internal energies that were up to 39% lower than those for ESI. A balance between improved ion transfer, adequate desolvation, and favorable ion energetics was achieved by selection of optimum operational ranges for the parameters that most strongly influence the ion population: the air amplifier gas flow rate and API capillary temperature. Examination of the energy landscapes obtained for combinations of these parameters showed that a low internal energy region (相似文献   

Super-Atmospheric Pressure Electrospray Ion Source: Applied to Aqueous Solution

This is a follow-up paper of our previous report on an ion source, which was operated at an operating pressure higher than the atmospheric pressure. Besides having more working gas for desolvation, the reduction of mean free path of electrons in a higher pressure environment increases the threshold voltage for gaseous breakdown, thus enabling a stable electrospray for the sample solution with high surface tension without the occurrence of electric discharge. In our previous work, the ion source was not coupled directly to the mass spectrometer and significant amount of ions were lost before entering the vacuum of the mass spectrometer. In this paper, we report the new design of our second prototype in which, by using a modified ion transport capillary, the pressurized ESI ion source was coupled directly to the first pumping stage of the mass spectrometer without additional modification on the vacuum pumping system. Demonstrations of the new ion source on the sensitive detection of native proteins from aqueous solution in both positive and negative ion modes are presented.     

Mechanisms of repeller-induced effects in thermospray liquid chromatography/mass spectrometry

The application of a high potential at the repeller electrode, positioned opposite to the sampling cone in order to increase the sampling efficiency, can induce fragmentation in thermospray mass Spectrometry. Until now, this fragmentation has been attributed to collision-induced dissociation. As a result of studies on the changes in the reagent gas composition in the thermospray buffer ionization mode as a function of the repeller potential in the positive-ion mode, it appears that three different processes are occurring. At low repeller potentials, the thermospray mass spectra of the eluent are determined by the proton affinities and the concentrations of the various solvent constituents, and the stabilities of the formed cluster ions under the ion source conditions. With an increase in the repeller potential, collision-induced dissociation of the background ions starts to occur. When the kinetic energy of the ions and cluster ions becomes high enough, endothermic proton transfer and solvent-switching reaction pathways are opened. For the relatively volatile analytes studied, e.g. aniline, acetophenone, benzaldehyde and benzoic acid, similar effects are observed.     

Analysis of protein mixtures by electrospray mass spectrometry: Effects of conformation and desolvation behavior on the signal intensities of hemoglobin subunits

The determination of solution-phase protein concentration ratios based on ESI-MS intensity ratios is not always straightforward. For example, equimolar mixtures of hemoglobin alpha- and beta-subunits consistently result in much higher peak intensities for the alpha-chain. The current work explores the origin of this effect. Under mildly acidic conditions (pH 3.4) alpha-globin is extensively unfolded, whereas beta-globin retains residual structure. Because of its greater nonpolar character, the more unfolded alpha-subunit can more effectively compete for charge. This leads to suppression of beta-globin signals under conditions where the protein ion yield is limited by the charge concentration on the initially formed ESI droplets. More balanced intensities are observed when operating under charge excess conditions and/or in a solvent environment where both proteins are unfolded to a similar degree (pH 2.2). However, even in these cases the overall alpha-globin peak intensity is still twice as high as that of the beta-subunit. The persistent imbalance under these conditions originates from the different declustering behaviors of the two proteins. A considerable fraction of beta-globin undergoes incomplete desolvation during ESI, thereby reducing the intensity of bare [beta + zH](z+) ions. When including the contributions of incompletely desolvated species, the overall alpha:beta ion intensity ratio is close to unity. The alpha:beta intensity imbalance can also be eliminated by a strongly elevated declustering potential in the ion sampling interface. In conclusion, important factors that have to be considered for the ESI-MS analysis of protein mixtures are (1) conformational effects, resulting in differential surface activities, and (2) dissimilarities in the protein desolvation behavior.     

Determination of several pesticides in water by solid-phase extraction, liquid chromatography and electrospray tandem mass spectrometry

The analysis of pesticides in water samples is a problem of primary concern for quality control laboratories due to the toxicity level of these compounds and their public health risk. In order to evaluate the impact of pesticides in the Lisbon drinking water supply system, following the requirements of the European Union Directive 98/83/EC, we developed and validated an analytical method based on the combination of solid-phase extraction with liquid chromatography and tandem mass spectrometry. In this work, several pesticides were studied: imidacloprid, dimethoate, cymoxanil, carbendazime, phosmet, carbofuran, isoproturon, diuron, methidathion, linuron, pyrimethanil, methiocarbe, tebuconazole and chlorpyrifos. Several parameters of the electrospray source were optimized in order to get the best formation conditions of the precursor ion for each pesticide, namely capillary and extractor voltage, cone voltage, cone gas flow rate and desolvation gas flow rate. After optimization of the collision cell energy of the triple quadrupole, two different precursor ion-product ion transitions were selected for each pesticide, one for quantification and one for qualification, and these ions were monitored under time-scheduled multiple reaction monitoring (MRM) conditions. The selection of specific fragment ions for each pesticide guarantees a high degree of selectivity as well as additional sensitivity to quantify trace levels of these pesticides in water samples. This method showed excellent linearity ranges for all pesticides, with correlation coefficients greater than 0.9989. Determination limits (between 0.0041 and 0.0480 microg/L), precision (RSD <9.18%), accuracy and recovery studies in several water samples using solid-phase extraction were also performed.     

Experimental and simulation investigation of ion transfer in different sampling capillaries

Atmospheric pressure interfaces were a fundamental structure for transferring air generated ions into the vacuum manifold of a mass spectrometer. This work is devoted to the characterization of ion transfer in metal capillaries through both experimental and simulated investigations. The impact of capillary configurations on ion transmission efficiency was evaluated using an electrospray mass spectrometer with various bent capillaries as the transfer devices. In addition, a numerical model has been set up by coupling the SIMION 8.0 and the computational flow dynamics for simulation study of ion migration in the complex atmospheric system. The transfer efficiency was found to be highly affected by the variation in electric field and the capillary geometry, revealing that the hydrodynamic and electric force were both dominant and interactional during the transmission process. The consistency of the results from the experimental analysis and simulation modeling proved the validity of the model, which was helpful for understanding ion activity in transfer capillaries. Copyright © 2015 John Wiley & Sons, Ltd.     

Biases in ion transmission through an electrospray ionization-mass spectrometry capillary inlet

A heated capillary inlet for an electrospray ionization mass spectrometry (ESI-MS) interface was compared with shorter versions of the inlet to determine the effects on transmission and ionization efficiencies for low-flow (nano) electrosprays. Five different inlet lengths were studied, ranging from 6.4 to 1.3 cm. As expected, the electrospray current transmission efficiency increased with decreasing capillary length due to reduced losses to the inside walls of the capillary. This increase in transmission efficiency with shorter inlets was coupled with reduced desolvation of electrosprayed droplets. Surprisingly, as the inlet length was decreased, some analytes showed little or no increase in sensitivity, while others showed as much as a 15-fold gain. The variation was shown to be at least partially correlated with analyte mobilities, with the largest gains observed for higher mobility species, but also affected by solution conductivity, flow rate, and inlet temperature. Strategies for maximizing sensitivity while minimizing biases in ion transmission through the heated capillary interface are proposed.     

Coupling of an atmospheric-samling ion source with an ion-trap mass spectrometer

An atomospheric-sampling glow-discharge ionization source has been interfaced with an ion-trap mass spectrometer. Under optimum conditions, the efficiency of ion injection is 1–5%. Several factors have a significant effect on the ion injection efficiency, including the voltages on the three-element lens system situated between the ion-source exit and the ion-trap entrance end-cap, the pressure of the bath gas present in the ion-trap vacuum housing, the nature of the bath gas and the amplitude of the radiofrequency voltage applied to the ring electrode during ion injection. Collision-induced dissociation (and electron detachment from anions) is also observed for some ions on injection, depending on the conditions. The most important experimental variables in determining the extent to which dissociation (or electron detachment) occurs are the nature of the bath gas, the bath gas presure and the radiofrequency voltage applied to the ring electrode during injection. These effects are illustrated with data obtained for polyatomic anions injected from the golw-discharge ion source.     

Transformation of the gas‐phase favored O‐protomer of p‐aminobenzoic acid to its unfavored N‐protomer by ion activation in the presence of water vapor: An ion‐mobility mass spectrometry study

An ion‐mobility mass spectrometry study showed that the preferred O‐protonated form of p‐aminobenzoic in the gas phase can be converted to the thermodynamically less favored N‐protomer by in‐source collision‐induced ion activation during the ion transfer process from the atmospheric region to the first vacuum region if the humidity is high in the ion source. Upon the addition of water vapor to the nitrogen gas used to promote the solid analyte to the gas phase under helium‐plasma ionization conditions, the intensity of the ion‐mobility arrival‐time peak for the N‐protomer increased dramatically. Evidently, the ion‐activation process in the first vacuum region is able to provide the energy required to surmount the barrier to isomerize the O‐protomer to the more energetic N‐protomer. The transfer of the proton attached to the carbonyl oxygen atom of the O‐protomer to the amino group takes place by a water‐bridge mechanism. Apparently, the postionization transformations that take place during the transmission of ions from the atmospheric‐pressure ion source to the detector, via different physical compartments of low to high vacuum, play an eminent role in determining the population ratios eventually manifested at the detector.     

Development of an ion mobility spectrometer for use in an atmospheric pressure ionization ion mobility spectrometer/mass spectrometer instrument for fast screening analysis

An ion mobility spectrometer that can easily be installed as an intermediate component between a commercial triple-quadrupole mass spectrometer and its original atmospheric pressure ionization (API) sources was developed. The curtain gas from the mass spectrometer is also used as the ion mobility spectrometer drift gas. The design of the ion mobility spectrometer allows reasonably fast installation (about 1 h), and thus the ion mobility spectrometer can be considered as an accessory of the mass spectrometer. The ion mobility spectrometer module can also be used as an independently operated device when equipped with a Faraday cup detector. The drift tube of the ion mobility spectrometer module consists of inlet, desolvation, drift, and extraction regions. The desolvation, drift and extraction regions are separated by ion gates. The inlet region has the shape of a stainless steel cup equipped with a small orifice. Ion mobility spectrometer drift gas is introduced through a curtain gas line from an original flange of the mass spectrometer. After passing through the drift tube, the drift gas serves as a curtain gas for the ion-sampling orifice of the ion mobility spectrometer before entering the ion source. Counterflow of the drift gas improves evaporation of the solvent from the electrosprayed sample. Drift gas is pumped away from the ion source through the original exhaust orifice of the ion source. Initial characterization of the ion mobility spectrometer device includes determination of resolving power values for a selected set of test compounds, separation of a simple mixture, and comparison of the sensitivity of the electrospray ionization ion mobility spectrometry/mass spectrometry (ESI-IMS/MS) mode with that of the ESI-MS mode. A resolving power of 80 was measured for 2,6-di-tert-butylpyridine in a 333 V/cm drift field at room temperature and with a 0.2 ms ion gate opening time. The resolving power was shown to be dependent on drift gas flow rate for all studied ion gate opening times. Resolving power improved as the drift gas flow increased, e.g. at a 0.5 ms gate opening time, a resolving power of 31 was obtained with a 0.65 L/min flow rate and 47 with a 1.3 L/min flow rate for tetrabutylammonium iodide. The measured limits of detection with ESI-MS and with ESI-IMS/MS modes were similar, demonstrating that signal losses in the IMS device are minimal when it is operated in a continuous flow mode. Based on these preliminary results, the IMS/MS instrument is anticipated to have potential for fast screening analysis that can be applied, for example, in environmental and drug analysis.     

Mass spectrometric behavior of levoglucosan under different ionization conditions and implications for studies of cellulose pyrolysis

Pyrolysis-mass spectrometric studies of cellulose indicate low abundances of levoglucosan in the product spectrum compared to the yield values determined in more conventional types of pyrolysis studies. To examine the reason for these conflicting observation, levoglucosan was examined under different ion source conditions and ionization modes to ascertain the relative contributions of thermal degradation and ionization fragmention to the low abundances of the levoglucosan molecular ion. Low-energy electron ionization using conventional sample volatilization and molecular-beam sampling is compared to chemical ionization using methane, isobutane, and ammonia as reagent gases, and to field ionization and desorption. The mass spectrometric fragmentation patterns under the various systems indicate that studies of cellulose pyrolysis underestimate the amount of levoglucosan formed due to ionization fragmentation and thermal rearrangement reactions in the ion source. Several peaks, including m/z 126 and 144, are dominated by the contribution from the fragmentation of levoglucosan.