Novel ion mobility setup combined with collision cell and time-of-flight mass spectrometer

An ion mobility cell of a novel type was coupled to an orthogonal injection time-of-flight (TOF) mass spectrometer. The mobility cell operates at low-pressure and contains a segmented RF ion guide providing an axial electric field that drives the ions towards the exit. A flow of gas is arranged inside the ion guide in such a way that the gas drag counteracts the force exerted by the axial field. Ions with different mobility coefficients can be scanned out of the ion guide by ramping the axial field strength. The ions can be analyzed intact or fragmented in a collision cell before introduction into an orthogonal TOF mass spectrometer. An ion source with matrix assisted laser desorption/ionization (MALDI) was attached to the instrument. The setup was evaluated for the analysis of peptide and protein mixture, with sequential fragmentation of multiple precursor ions from a protein digest and with mobility separation of fragment ions formed by in-source fragmentation of pure peptides. The mobility resolution for peptides was observed to be three times higher than the theoretical resolution predicted for a classical mobility setup with similar operating conditions (pressure, field strength, and length).     

Numerical simulation of Monte Carlo ion transport at atmospheric pressure within improved air amplifier geometry

A computational fluid dynamics (CFD) software package ANSYS Fluent was employed for simulation of ion transport at atmospheric pressure between a nano-electrospray ionization (nano-ESI) emitter and the mass spectrometer (MS) sampling inlet tube inside an improved air amplifier device incorporating a radiofrequency ion funnel. The flow field, electric field and the ion trajectory calculations were carried out in separate steps. Parallelized user-defined functions were written to accommodate the additional static and transient electric fields and the elastic ion-gas collisions with the Monte Carlo hard-sphere simulation abilities within Fluent’s environment. The ion transmission efficiency from a nano-ESI emitter to the MS sampling inlet was evaluated for different air amplifier and ion funnel operating conditions by tracking 250 sample reserpine ions. Results show that the high velocity gas stream and the external electric field cause a rapid acceleration of the ion beam and its dispersion along the centreline of the air amplifier which leads to reduction of the space-charge effect and the beam divergence. The radiofrequency potential applied to the ion funnel contributed to additional ion focusing.     

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.     

Super‐atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis

Ion source pressure plays a significant role in the process of ionization and the subsequent ion transmission inside a mass spectrometer. Pressurizing the ion source to a gas pressure greater than atmospheric pressure is a relatively new approach that aims to further improve the performance of atmospheric pressure ionization sources. For example, under a super‐atmospheric pressure environment, a stable electrospray can be sustained for liquid with high surface tension such as pure water, because of the suppression of electric discharge. Even for nano‐electrospray ionization (nano‐ESI), which is known to work with aqueous solution, its stability and sensitivity can also be enhanced, particularly in the negative mode when the ion source is pressurized. A brief review on the development of super‐atmospheric pressure ion sources, including high‐pressure electrospray, field desorption and superheated ESI, and the strategies to interface these ion sources to a mass spectrometer will be given. Using a recent ESI prototype with an operating temperature at 220 °C under 27 atm, we also demonstrate that it is possible to achieve an online Asp‐specific protein digestion analysis in which the whole processes of digestion, ionization and MS acquisition could be completed on the order of a few seconds. This method is fast, and the reaction can even be monitored on a near‐real‐time basis. Copyright © 2016 John Wiley & Sons, Ltd.     

On-line characterization of gaseous and particulate organic analytes using atmospheric pressure chemical ionization mass spectrometry

A modified atmospheric pressure chemical ionization ion source is applied for direct analysis of volatile or low volatile organic compounds in air. The method is based on the direct introduction of the analytes in the gas phase and/or particle phase into the ion source of a commercial ion-trap mass spectrometer. Two methods are employed for the production of primary ions at atmospheric pressure, photoionization and corona discharge. It is shown that in the presence of a dopant, photoionization can be a highly efficient ionization method also for real-time analysis with detection limits for selected analytes in the lower ppt-range. Using corona discharge for the production of primary ions, which is instrumentally easier since no additional chemicals have to be added to the sample flow, we demonstrate the analytical potential of on-line atmospheric pressure chemical ionization mass spectrometry for reaction monitoring experiments. To do so, an atmospherically relevant gas phase reaction is carried out in a 500 l reaction chamber and gaseous and particulate compounds are monitored in the positive and negative ion mode of the mass spectrometer.     

Thermal desorption counter‐flow introduction atmospheric pressure chemical ionization for direct mass spectrometry of ecstasy tablets

A novel approach to the analysis of ecstasy tablets by direct mass spectrometry coupled with thermal desorption (TD) and counter‐flow introduction atmospheric pressure chemical ionization (CFI‐APCI) is described. Analytes were thermally desorbed with a metal block heater and introduced to a CFI‐APCI source with ambient air by a diaphragm pump. Water in the air was sufficient to act as the reactive reagent responsible for the generation of ions in the positive corona discharge. TD‐CFI‐APCI required neither a nebulizing gas nor solvent flow and the accompanying laborious optimizations. Ions generated were sent in the direction opposite to the air flow by an electric field and introduced into an ion trap mass spectrometer. The major ions corresponding to the protonated molecules ([M + H]⁺) were observed with several fragment ions in full scan mass spectrometry (MS) mode. Collision‐induced dissociation of protonated molecules gave characteristic product‐ion mass spectra and provided identification of the analytes within 5 s. The method required neither sample pretreatment nor a chromatographic separation step. The effectiveness of the combination of TD and CFI‐APCI was demonstrated by application to the direct mass spectrometric analysis of ecstasy tablets and legal pharmaceutical products. Copyright © 2009 John Wiley & Sons, Ltd.     

Ion internal energy distributions validate the charge residue model for small molecule ion formation by spray methods

This paper reports a detailed study of the internal energy distribution of ions formed by four electrospray ionization (ESI)-related ionization methods, with particular emphasis on electrosonic spray ionization (ESSI). Substituted benzylpyridinium ions were used as thermometer ions to probe the internal energy distribution. The influence of different instrumental parameters was studied. Cone and skimmer voltages as well as the collision energy were found to strongly affect the ion internal energy distribution, whereas the distance between the emitter and the inlet of the mass spectrometer, the nebulizing gas pressure or the flow rate showed no influence. The internal energy distribution obtained with an ESSI source was compared with those obtained for electrospray (ESI), nanoelectrospray (nanoESI) and sonic spray ionization (SSI) on the same mass spectrometer with the same instrumental parameters. No clear differences were observed. As the charge residue model is the only ion formation mechanism possible for SSI, we conclude that benzylpyridinium ions are formed by the pathway suggested by this model.     

Collision-induced dissociation of bradykinin ions in the interface region of an ESI-MS

By applying different electric field strengths to the orifice-skimmer region of an electrospray ionization mass spectrometer, the rate of dissociation can be varied based on the amount of internal energy acquired by an ion through collisions with the curtain gas molecules. Both the Arrhenius equation and Rice-Ramsperger-Kassel (RRK) theory can be used to predict the rate of dissociation of internally excited molecules. A previously determined model for collision-induced dissociation is tested by comparison of predicted and experimentally observed orifice-skimmer potential differences for dissociation of ions. The rate of collision-induced dissociation of bradykinin ions is determined by monitoring the fragments produced in a mass spectrometer. The semi-quantitative model is found to yield effective predictions when accurate Arrhenius and RRK parameters are utilized.     

Ionization of Volatile Organics and Nonvolatile Biomolecules Directly from a Titanium Slab for Mass Spectrometric Analysis

Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) and electrospray ionization (ESI)-MS can cover the analysis of analytes from low to high polarities. Thus, an ion source that possesses these two ionization functions is useful. Atmospheric surface-assisted ionization (ASAI), which can be used to ionize polar and nonpolar analytes in vapor, liquid, and solid forms, was demonstrated in this study. The ionization of analytes through APCI or ESI was induced from the surface of a metal substrate such as a titanium slab. ASAI is a contactless approach operated at atmospheric pressure. No electric contacts nor any voltages were required to be applied on the metal substrate during ionization. When placing samples with high vapor pressure in condensed phase underneath a titanium slab close to the inlet of the mass spectrometer, analytes can be readily ionized and detected by the mass spectrometer. Furthermore, a sample droplet (~2 μL) containing high-polarity analytes, including polar organics and biomolecules, was ionized using the titanium slab. One titanium slab is sufficient to induce the ionization of analytes occurring in front of a mass spectrometer applied with a high voltage. Moreover, this ionization method can be used to detect high volatile or polar analytes through APCI-like or ESI-like processes, respectively.     

The proportional relationship between the efficiency of a DC ion source and atom mass

The efficiency of ion extraction from a DC ion source has been found by experiment to bear a close correlation to atomic mass. The factors influencing this efficiency are examined theoretically in terms of the mechanisms of extraction, that is, by gas flow, electric field and bulk diffusion. It is found that while charged material is extracted by the electric field, the transport mechanism to the region influenced by the extraction electrode is dominated by gas flow and is therefore dependent on atomic mass. Close agreement with theory and experiment can be seen.The practical application of this approximately linear dependence of ion yield and mass is demonstrated in the VG 9000 glow discharge mass spectrometer. The simple ratio of matrix ion current to contamination ion current gives a direct quantitative reading of weight-% impurity levels down to ppt levels.Presented in part at the 1989 European Winter Conference on Plasma Spectrochemistry, Reutte, Austria     

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.     

Precursor ion scan profiles of acylcarnitines by atmospheric pressure thermal desorption chemical ionization tandem mass spectrometry

The fatty acyl esters of L-carnitine (acylcarnitines) are useful biomarkers for the diagnosis of some inborn errors of metabolism analyzed by liquid chromatography/tandem mass spectrometry. In this study the acylcarnitines were analyzed by atmospheric pressure thermal desorption chemical ionization using a commercial tandem mass spectrometer (APTDCI-MS/MS). The method is based on the precursor ion scan mode determination of underivatized acylcarnitines desorbed from samples by a hot desolvation gas flow and ionized by a corona pin discharge. During desorption/ionization step the temperature induces the degradation of acylcarnitines; nevertheless, the common fragment to all acylcarnitines [MH-59](+) is useful for analyzing their profile. APTDCI parameters, including angle of collection and incidence, gas flows and temperatures, were optimized for acylcarnitines. The experiments were performed drying 2 microL of an equimolar mixture of acylcarnitine standards on a glass slide. The specificity was evaluated by comparing product ion spectra and the precursor ion spectra of 85 m/z of acylcarnitines obtained by the APTDCI method and by electrospray ionization flow injection analysis (ESI-FIA). The method was also employed to analyze acylcarnitines extracted from a pathological dried blood spot and a control. The method enables analysis of biological samples and recognition of some acylcarnitines that are diagnostic markers of inherited metabolic diseases. The intrinsic high-throughput analysis of the ambient desorption ionization methods offers a new opportunity either for its potential application in clinical chemistry and for the expanded screening of some inborn errors of metabolism.     

Mass spectrometry of N-linked oligosaccharides using atmospheric pressure infrared laser ionization from solution

An atmospheric pressure (AP) infrared (IR) laser ionization technique, implemented on a quadrupole ion trap mass spectrometer, was used to analyze underivatized, N-linked oligosaccharides in solution. Experiments were conducted on an atmospheric pressure infrared ionization from solution (AP-IRIS) ion source which differed from previous AP IR matrix-assisted laser desorption/ionization (MALDI) interfaces in that the ion source operated in the absence of an extraction electric field with a higher power 2.94 microm IR laser. The general term 'IRIS' is used as the mechanism of ionization differs from that of MALDI, and is yet to be fully elucidated. The AP-IRIS ion source demonstrated femtomole-level sensitivity for branched oligosaccharides. AP-IRIS showed approximately 16 times improved sensitivity for oligomannose-6 and the core-fucosylated glycan M3N2F over optimal results obtainable on a AP UV-MALDI with a 2,4,6-trihydroxyacetophenone matrix. Comparison between IR and UV cases also showed less fragmentation in the IR spectrum for a glycan with a conserved trimannosyl core, core-substituted with fucose. A mixture of complex, high-mannose and sialylated glycans resulted in positive ion mass spectra with molecular ion peaks for each sugar. Tandem mass spectrometry of the sodiated molecular ions in a mixture of glycans revealed primarily glycosidic (B, Y) cleavages. The reported results show the practical utility of AP-IRIS while the ionization mechanism is still under investigation.     

Non‐vacuum field desorption ion source implemented under super‐atmospheric pressure

Standard field desorption (FD) ionization is implemented under high vacuum condition. In this paper, non‐vacuum FD is performed under a super‐atmospheric pressure environment using untreated tungsten wires as FD emitter, and the ion source was coupled to a commercial linear ion trap mass spectrometer. The operating pressure of the ion source was 6 bars which was high enough to provide sufficient dielectric strength to the working gas so that the high voltage that was required for FD could be applied to the emitter without occurrence of electrical discharge. Non‐volatile sample deposited on the bare tungsten wire FD emitter was heated by flowing direct current through the emitter. Similar to vacuum FD, the formation of conical protrusion of the liquefied sample layer under the strong electric field was also observed. Using the present ion source, high pressure field‐desorption of polar neutral compounds, organic salts and ionic liquids is demonstrated. Copyright © 2012 John Wiley & Sons, Ltd.     

Thin‐layer chromatography and mass spectrometry coupled using proximal probe thermal desorption with electrospray or atmospheric pressure chemical ionization

An atmospheric pressure proximal probe thermal desorption sampling method coupled with secondary ionization by electrospray or atmospheric pressure chemical ionization was demonstrated for the mass spectrometric analysis of a diverse set of compounds (dyestuffs, pharmaceuticals, explosives and pesticides) separated on various high‐performance thin‐layer chromatography plates. Line scans along or through development lanes on the plates were carried out by moving the plate relative to a stationary heated probe positioned close to or just touching the stationary phase surface. Vapors of the compounds thermally desorbed from the surface were drawn into the ionization region of a combined electrospray ionization/atmospheric pressure chemical ionization source where they merged with reagent ions and/or charged droplets from a corona discharge or an electrospray emitter and were ionized. The ionized components were then drawn through the atmospheric pressure sampling orifice into the vacuum region of a triple quadrupole mass spectrometer and detected using full scan, single ion monitoring, or selected reaction monitoring mode. Studies of variable parameters and performance metrics including the proximal probe temperature, gas flow rate into the ionization region, surface scan speed, read‐out resolution, detection limits, and surface type are discussed. Published in 2010 by John Wiley & Sons, Ltd.     

Polarization induced electrospray ionization mass spectrometry for the analysis of liquid,viscous and solid samples

In this study, a polarization‐induced electrospray ionization mass spectrometry (ESI‐MS) was developed. A micro‐sized sample droplet was deposited on a naturally available dielectric substrate such as a fruit or a stone, and then placed close to (~2 mm) the orifice of a mass spectrometer applied with a high voltage. Taylor cone was observed from the sample droplet, and a spray emitted from the cone apex was generated. The analyte ion signals derived from the droplet were obtained by the mass spectrometer. The ionization process is similar to that in ESI although no direct electric contact was applied on the sample site. The sample droplet polarized by the high electric field provided by the mass spectrometer initiated the ionization process. The dielectric sample loading substrate facilitated further the polarization process, resulting in the formation of Taylor cone. The mass spectral profiles obtained via this approach resembled those obtained using ESI‐MS. Multiply charged ions dominated the mass spectra of peptides and proteins, whereas singly charged ions dominated the mass spectra of small molecules such as amino acids and small organic molecules. In addition to liquid samples, this approach can be used for the analysis of solid and viscous samples. A small droplet containing suitable solvent (5–10 µl) was directly deposited on the surface of the solid (or viscous) sample, placed close the orifice of mass spectrometer applied with a high voltage. Taylor cone derived from the droplet was immediately formed followed by electrospray processes to generate gas‐phase ions for MS analysis. Analyte ions derived from the main ingredients of pharmaceutical tablets and viscous ointment can be extracted into the solvent droplet in situ and observed using a mass spectrometer. Copyright © 2015 John Wiley & Sons, Ltd.     

Continuous full filling capillary electrochromatography-electrospraying chromatographic nanoparticles

The influence of instrumental parameters affecting the ionization in continuous full filling capillary electrochromatography/electrospray ionization mass spectrometry (CFF‐CEC/ESI‐MS) was investigated. The investigated parameters were the BGE and sheath liquid ion strength and organic modifier content, the nebulizer gas pressure, and the concentration of nanoparticles in the BGE. It was found that the nebulizer pressure had the largest influence on the separation efficiency and apparent retention. It was shown that even the lowest pressure investigated was sufficient to guide the nanoparticle flow away from the mass spectrometer inlet. A nebulizer pressure of 5 psi was found to be optimal; increasing the pressure significantly decreased the separation efficiency due to the generation of a hydrodynamic flow. Generally, the ion strength of both the BGE and the sheath liquid were found to have very moderate effects on the separation of a homologous series of dialkyl phthalates, whereas the ionization efficiency was found to be unaffected by the nanoparticles and the separation efficiency was found to increase with increasing concentrations up to 3.8 mg/mL, whereafter it was observed to drop. The optimized method was linear over a wide concentration range and presented LOD and LOQ more than threefold lower than those previously reported using CFF‐CEC/ESI‐MS.     

Optimization of an rf-powered magnetron glow discharge for the trace analysis of glasses and ceramics

A radiofrequency (rf) powered planar magnetron glow discharge ion source has been designed and coupled to a double-focusing mass spectrometer. Superposition of the electrical field of the plasma in the cathode dark space and the magnetic field obtained from a ring-shaped magnet located directly behind the sample (cathode) form the electron traps and enhance the sputtering and ionization efficiency of the ion source. In order to establish optimum conditions for the trace analysis of nonconducting materials, mass spectrometric studies have been carried out on the ion signal intensities and energy distributions of analyte and discharge gas ions depending on pressure.     

Optimization of an rf-powered magnetron glow discharge for the trace analysis of glasses and ceramics

A radiofrequency (rf) powered planar magnetron glow discharge ion source has been designed and coupled to a double-focusing mass spectrometer. Superposition of the electrical field of the plasma in the cathode dark space and the magnetic field obtained from a ring-shaped magnet located directly behind the sample (cathode) form the electron traps and enhance the sputtering and ionization efficiency of the ion source. In order to establish optimum conditions for the trace analysis of nonconducting materials, mass spectrometric studies have been carried out on the ion signal intensities and energy distributions of analyte and discharge gas ions depending on pressure.     

Applying a dynamic method to the measurement of ion mobility

A dynamic method is applied to measure the mobility of gas-phase ions in the dual ion funnel interface of the electrospray source of a quadrupole orthogonal time-of-flight mass spectrometer. In a new operational mode, a potential barrier was formed in the second ion funnel of the mass spectrometer and then progressively increased. In this region, a flow of gas drags the ions into the mass spectrometer while the electric force applied by the potential barrier decelerates them. Ions with lower mobility can be carried by the gas flow more easily than those with high mobility. Thus, electrical forces can block the more mobile ions more easily. Hence, the electric barrier formed in the ion funnel permits only ions below a certain mobility threshold to enter the mass spectrometer. When the barrier voltage is increased, this threshold moves from high to low mobilities. Ions with mobilities above the threshold cannot enter the mass spectrometer, and their signal decreases to zero. Thus, in a barrier voltage scan, mass spectrometric signals of ions sequentially disappear. Differentiation of these decreasing ion signal curves produces peaks from which an ion mobility spectrum can be reconstructed. Blocking voltages, i.e., the positions of the peaks on the barrier voltage scale are directly related to the mobility of these ions. An internal calibration using ions with known mobility values helps determine the unknown ion mobilities and allows calculation of ionic cross sections.