Improved design for high resolution electrospray ionization ion mobility spectrometry

An improved design for high resolution electrospray ionization ion mobility spectrometry (ESI-IMS) was developed by making some salient modifications to the IMS cell and its performance was investigated. To enhance desolvation of electrospray droplets at high sample flow rates in this new design, volume of the desolvation region was decreased by reducing its diameter and the entrance position of the desolvation gas was shifted to the end of the desolvation region (near the ion gate). In addition, the ESI source (both needle and counter electrode) was positioned outside of the heating oven of the IMS. This modification made it possible to use the instrument at higher temperatures, and preventing needle clogging in the electrospray process. The ion mobility spectra of different chemical compounds were obtained. The resolving power and resolution of the instrument were increased by about 15-30% relative to previous design. In this work, the baseline separation of the two adjacent ion peaks of morphine and those of codeine was achieved for the first time with resolutions of 1.5 and 1.3, respectively. These four ion peaks were well separated from each other using carbon dioxide (CO₂) rather than nitrogen as the drift gas. Finally, the analytical parameters obtained for ethion, metalaxyl, and tributylamine indicated the high performance of the instrument for quantitative analysis.     

Coupling of capillary electrophoresis with electrospray ionization multiplexing ion mobility spectrometry

In this work, ion mobility spectrometry (IMS) function as a detector and another dimension of separation was coupled with CE to achieve two‐dimensional separation. To improve the performance of hyphenated CE‐IMS instrument, electrospray ionization correlation ion mobility spectrometry is evaluated and compared with traditional signal averaging data acquisition method using tetraalkylammonium bromide compounds. The effect of various parameters on the separation including sample introduction, sheath fluid of CE and drift gas, data acquisition method of IMS were investigated. The experimental result shows that the optimal conditions are as follows: hydrodynamic sample injection method, the electrophoresis voltage is 10 kilo volts, 5 mmol/L ammonium acetate buffer solution containing 80% acetonitrile as both the background electrolyte and the electrospray ionization sheath fluid, the ESI liquid flow rate is 4.5 μL/min, the drift voltage is 10.5 kilo volts, the drift gas temperature is 383 K and the drift gas flow rate is 300 mL/min. Under the above conditions, the mixture standards of seven tetraalkylammoniums can be completely separated within 10 min both by CE and IMS. The linear range was 5–250 μg/mL, with LOD of 0.152, 0.204, 0.277, 0.382, 0.466, 0.623 and 0.892 μg/mL, respectively. Compared with traditional capillary electrophoresis detection methods, the developed CE‐ESI‐IMS method not only provide two sets of qualitative parameters including electrophoresis migration time and ion drift time, ion mobility spectrometer can also provide an additional dimension of separation and could apply to the detection ultra‐violet transparent compounds or none fluorescent compounds.     

A critical review of ion mobility spectrometry for the detection of explosives and explosive related compounds

Ion mobility spectrometry has become the most successful and widely used technology for the detection of trace levels of nitro-organic explosives on handbags and carry on-luggage in airports throughout the US. The low detection limits are provided by the efficient ionization process, namely, atmospheric pressure chemical ionization (APCI) reactions in negative polarity. An additional level of confidence in a measurement is imparted by characterization of ions for mobilities in weak electric fields of a drift tube at ambient pressure. Findings from over 30 years of investigations into IMS response to these explosives have been collected and assessed to allow a comprehensive view of the APCI reactions characteristic of nitro-organic explosives. Also, the drift tube conditions needed to obtain particular mobility spectra have been summarized. During the past decade, improvements have occurred in IMS on the understanding of reagent gas chemistries, the influence of temperature on ion stability, and sampling methods. In addition, commercial instruments have been refined to provide fast and reliable measurements for on-site detection of explosives. The gas phase ion chemistry of most explosives is mediated by the fragile CONO(2) bonds or the acidity of protons. Thus, M(-) or M.Cl(-) species are found with only a few explosives and loss of NO(2), NO(3) and proton abstraction reactions are common and complicating pathways. However, once ions are formed, they appear to have stabilities on time scales equal to or longer than ion drift times from 5-20 ms. As such, peak shapes in IMS are suitable for high selectivity and sensitivity.     

Paper spray ionization with ion mobility spectrometry at ambient pressure

A paper spray ion source was combined with a drift tube operating at ambient pressure for mobility measurements of ions derived from pharmaceutical solutions. Paper spray ionization with solvent alone resulted in a mixture of ions convolved to a single peak with a reduced mobility of 2.19 cm²/Vs in the mobility spectrum. These were mass-identified principally as m/z 157, (MeOH)₂(HCOOH)₂H⁺ and m/z 129, (MeOH)₄(H₂O)H⁺ while pharmaceuticals with nitrogen bases formed MH⁺ product ions. The duration of response was governed by the volume of liquid added to the paper source and was limited by evaporation of solvent in gas at 58 °C venting the drift tube. Quantitative variation was attributed in part to morphologic changes in the tip of the paper spray source. This was associated with mass flow in the electrical discharge and not due alone to cycles of wetting and drying of the paper. Mobility spectra of chlorpromazine in urine, exhibited a single product ion peak and linear response was 30 to 500 ng with an estimated limit of detection of 1.5 ng. Ion flux could be prolonged by continuous addition of liquid and findings portend a combination of paper spray ionization IMS with paper chromatography.     

Investigation of drift gas selectivity in high resolution ion mobility spectrometry with mass spectrometry detection

Recent studies in electrospray ionization (ESI)/ion mobility spectrometry (IMS) have focussed on employing different drift gases to alter separation efficiency for some molecules. This study investigates four structurally similar classes of molecules (cocaine and metabolites, amphetamines, benzodiazepines, and small peptides) to determine the effect of structure on relative mobility changes in four drift gases (helium, nitrogen, argon, carbon dioxide). Collision cross sections were plotted against drift gas polarizability and a linear relationship was found for the nineteen compounds evaluated in the study. Based on the reduced mobility database, all nineteen compounds could be separated in one of the four drift gases, however, the drift gas that provided optimal separation was specific for the two compounds.     

Monte Carlo simulation of ion transport in ion mobility spectrometry

A program for simulation of ion trajectories in ion mobility spectrometry (IMS) instruments has been developed and incorporated into SIMION 7.0 [Int. J. Mass Spectrom. 200 (2000) 3–25]. Simulations were based on elastic collisions between ions and gas particles and conducted for an IMS drift tube. The program was validated by comparing the reduced mobility of helium ions derived from the simulation with the experimental data for helium ions in neon drift gas in low electric fields. Typical IMS parameters, including pressure, temperature, and flow rate of the drift gas were taken into account in the simulations. The program demonstrates capabilities of generating IMS spectra and predicting ion transport efficiency and separating ions. For the IMS drift tube studied, a correlation between imperfection of the electric field distribution and low resolution has been observed.     

Development and evaluation of a nano-electrospray ionisation source for atmospheric pressure ion mobility spectrometry

A nano-electrospray ionisation source has been designed and constructed for a high temperature ion mobility spectrometer. The drift cell was modified by replacement of the 63Ni atmospheric pressure chemical ionisation source with a tube lens/desolvation region and operated using commercial nano-electrospray capillaries. Ions were introduced into the drift region via a Bradbury-Nielson gate (pulse width 50 micros, repetition period 20 ms). A unidirectional flow of nitrogen was used as the drift gas at temperatures in the range 100-150 degrees C to aid desolvation. The performance of the nano-electrospray ion source has been demonstrated for analytes including crown ethers, amino acids and peptides. Reduced mobilities determined by nano-ESI were consistent with those reported using a 63Ni ion source.     

Evaluation of micro- versus nano-electrospray ionization for ambient pressure ion mobility spectrometry

The comparison of nanospray and microspray ionizations for detecting mixtures of compounds by ion mobility spectrometry has been investigated for sensitivity, ion transmission through a drift tube, and ion suppression effects when used as an ionization source for ambient pressure ion mobility spectrometry (IMS). Several articles have demonstrated that nano-electrospray ionization mass spectrometry (n-ESI-MS) has improved sensitivity, provides less background noise, and lower limits of detection than micro-electrospray ionization (μ-ESI) for IMS. Most importantly, data from n-ESI-MS is concentration-sensitive. Our laboratory previously published an article that observed a striking result when μ-ESI-IMS was investigated for a single compound in the positive ion mode. The data reported was mass-sensitive. In this new investigation, we have investigated mixtures, and experiments were designed to evaluate the effect of sensitivity, ion transmission and ion suppressions in μ-ESI-IMS and n-ESI-IMS. At an electrospray flow rate in the μL min⁻¹ range, compounds with higher proton affinities responded best while at the nanospray flow rates of nL min⁻¹, relative responses were more equal. This study observed that a decreased ESI flow rate resulted in a decreased ion signal. These trends demonstrated less sensitivity for ESI-IMS at reduced flow rates but suggest better quantification. At higher flow rates, relative ionization efficiencies were still uniform for all the components studied individually and in mixtures and sensitivity improved by about 78%. Concentration studies showed that at high concentrations, ion detection efficiencies were uniform at about 33% for all compounds studied individually and in mixtures. At low concentrations, the detection efficiency varied from 31% to 86%, depending on the proton affinity of the component in the mixture. Ion transmission through the IMS tube measured with a segmented Faraday detector that was incorporated into the IMS design indicated that most of the ion current for mixtures was transported through the IMS tube with a radius of less than 18 mm for both positive and negative ion modes.     

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.     

Separation of benzodiazepines by electrospray ionization ion mobility spectrometry-mass spectrometry

Benzodiazepines are a commonly abused class of drugs; requiring analytical techniques that can separate and detect the drugs in a rapid time period. In this paper, the two-dimensional separation of five benzodiazepines was shown by electrospray ionization (ESI) ion mobility spectrometry (IMS)-mass spectrometry (MS). In this study, both the two dimensions of separation (m/z and mobility) and the high resolution of our IMS instrument enabled confident identification of each of the five benzodiazepines studied. This was a significant improvement over previous IMS studies that could not separate many of the analytes due to low instrumental resolution. The benzodiazepines that contain a hydroxyl group in their molecular structure (lorazepam and oxazepam) were found to form both the protonated molecular ion and dehydration product as predominant ions. Experiments to isolate the parametric reasons for the dehydration ion formation showed that it was not the result of corona discharge processes or the potential applied to the needle. However, the potential difference between the needle and first drift ring did influence both the relative intensity ratios of the two ions and the ion sensitivity.     

Liquid chromatography/electrospray ionization/ion mobility spectrometry of chlorophenols with full flow from large bore LC columns

Chlorophenols (CPs) as a mixture of fourteen congeners from mono- to pentachlorophenol were determined using liquid chromatography/electrospray ionization/ion mobility spectrometry (LC/ESI/IMS) to describe the response and analytical performance of a mobility spectrometer as a detector for liquid chromatography. The mobility spectrometer was equipped with an interface so that flows from a large bore column could be electrosprayed directly into the drift tube at flow rates up to 500 μL/min without splitting of flow. A linear gradient of the mobile phase from 40% to 90% methanol and 60% to 10% acetic acid (AcOH)–ammonium acetate buffer solution over 40 min with a C18 column provided baseline separations though mobility spectra for CPs were influenced by mobile phase composition. Product ions formed from CPs with ESI included phenoxide anions CPO^?, AcOH·CPO^?, CPOH·CPO^?, and Na⁺·(CPO^?)₂ and were found to be governed by the drift gas temperature. Ions were identified using LC/ESI/mass spectrometry (MS) and supported by results from computational modeling. Quantitative response was affected by congener structure through the acidities of the OH moiety and by the composition of the mobile phase. Limits of detection ranged from 0.135 mg/L for 2,3,5-trichlorophenol and pentachlorophenol to 2.23 mg/L for 2-chlorophenol; corresponding linear ranges were 20 and 70.     

Ion mobility spectrometry as flow-injection detector and continuous flow monitor for aniline in hexane and water

Ion mobility spectrometry (IMS) was used as a flow-injection detector to quantitatively examine the ionization chemistry of aniline in hexane. A 5-microl sample was vaporized at 15-90-sec intervals in a flowing air stream and analyzed with an IMS equipped with acetone reactant ion chemistry, ambient temperature drift tube and membrane-based inlet. Precision was 3-11% relative standard deviation for 1-100 ppm aniline in hexane with 90-sec injection intervals and detection limits were ca. 0.5 ppm with 5-microl injections. Matrix effects with amine and organic solvent mixtures were observed and corrected for low and medium proton affinity interferences with standard addition methods. Pronounced fouling of the IMS occurred when a continuous water flow was introduced for aqueous flow injection-IMS. Continuous water monitoring without degraded IMS performance was possible by sampling air flow through a Silastic tube immersed in an aqueous sample.     

Comparison of the internal energy deposition of direct analysis in real time and electrospray ionization time-of-flight mass spectrometry

The internal energy (E_int) distributions of a series of p-substituted benzylpyridinium ions generated by both direct analysis in real time (DART) and electrospray ionization (ESI) were compared using the “survival yield” method. DART mean E_int values at gas flow rates of 2, 4, and 6 L min⁻¹, and at set temperatures of 175, 250, and 325 °C were in the 1.92–2.21 eV range. ESI mean E_int at identical temperatures in aqueous and 50% methanol solutions ranged between 1.71 and 1.96 eV, and 1.53 and 1.63 eV, respectively. Although the results indicated that ESI is a “softer” ionization technique than DART, there was overlap between the two techniques for the particular time-of-flight mass spectrometer used. As a whole, there was an increase in E_int with increasing reactive and drying gas temperatures for DART and ESI, respectively, indicating thermal ion activation. Three dimensional computational fluid dynamic simulations in combination with direct temperature measurements within the DART ionization region revealed complex inversely coupled fluid-thermal phenomena affecting ion E_int values during atmospheric transport. Primarily, that DART gas temperature in the ionization region was appreciably less than the set gas temperature of DART due to the set gas flow rates. There was no evidence of E_int deposition pathways from metastable-stimulated desorption, but fragmentation induced by high-energy helium metastables was observed at the highest gas flow rates and temperatures.     

Coupling laser ablation/desorption electrospray ionization to atmospheric pressure drift tube ion mobility spectrometry for the screening of antimalarial drug quality

Significant developments in the field of ambient desorption/ionization mass spectrometry (MS) have led to high-throughput direct analysis and imaging capabilities. However, advances in coupling ambient ionization techniques with standalone drift tube ion mobility spectrometry (DTIMS) have been comparatively slower, despite the attractive ruggedness and simplicity of IMS. In this study, we have developed and characterized a laser ablation/desorption electrospray ionization (LADESI) DTIMS platform, and applied it to the detection of active pharmaceutical ingredients (APIs) in antimalarial tablets collected in developing countries. The overarching goal of this work was to perform an initial evaluation of LADESI DTIMS as a technique with the potential for constituting the core of a portable drug quality-testing platform. The set-up consisted of an IR laser for desorption and an electrospray ionizer for capturing the ablated plume coupled to a high-resolution monolithic resistive glass drift tube ion mobility spectrometer. For more confident API identification, tablet extracts were also investigated via electrospray IM MS to correlate LADESI DTIMS reduced mobility (K(0)) values to m/z values. Overall, it was found that the IR LADESI DTIMS platform provided distinct ion mobility spectral fingerprints that could be used to detect the presence of the expected APIs, helping to distinguish counterfeit drugs from their genuine counterparts.     

Letter: A simple ion source set-up for desorption/ionization on silicon with ion mobility spectrometry and ion mobility spectrometry-mass spectrometry

Using a simple ion source set-up, laser desorption/ionization on silicon (DIOS) was demonstrated with the use of a custom-made drift tube ion mobility spectrometer (IMS), mounted on a commercial triple quadrupole mass spectrometer, and with an IMS equipped with a Faraday plate detector. DIOS was tested by mobility measurement of tetrapropylammonium iodide, tetrabutylammonium iodide and tetrapentylammonium iodide, whilst 2,6-di-tert- butylpyridine was used as a standard. The reduced mobilities measured for the test halides are in concordance with previously obtained ion mobility spectrometry-mass spectrometry data.     

Characterization of a temperature-Controlled FAIMS system

High-field asymmetric waveform ion mobility spectrometry (FAIMS) focuses and separates gas-phase analyte ions from chemical background, offering substantial improvements in the detection of targeted species in biological matrices. Ion separations have been typically performed at atmospheric pressure and ambient temperature, although routine small molecule quantitation by LC-MS (and thus LC-FAIMS-MS) is generally performed at liquid flow rates (e.g., in excess of 200 microL/min) in which atmospheric pressure ionization sources (e.g., APCI and ESI) need to be run at elevated temperatures to enhance ion desolvation. Heat from the ionization source and/or the mass spectrometer capillary interface is shown to have a significant impact on the performance of a conventional FAIMS electrode set. This study introduces a new FAIMS system that uses gas heating/cooling to quickly reach temperature equilibrium independent of the external temperature conditions. A series of equations and balance plots, which look at the effect of temperature and other variables, on the normalized field strength (E/N), are introduced and used to explain experimental observations. Examples where the ion behavior deviates from the predicted behavior are presented and explanations based on clusters or changes in ion-neutral interactions are given. Consequences of the use of temperature control, and in particular advantages of using different temperature settings on the inner and outer electrodes, for the purpose of manipulating ion separation are described.     

Evaluation of suspected interferents for TNT detection by ion mobility spectrometry

The use of ion mobility spectrometry systems to detect explosives in high security situations creates a need to determine compounds that interfere and may compromise accurate detection. This is the first study to identify possible interfering air contaminants common in airport settings by IMS. Seventeen suspected contaminants from four major sources were investigated. Due to the ionization selectivity gained by employing chloride reactant ion chemistry, only 7 of the 17 compounds showed an IMS response. Of those seven compounds, only 4,6-dinitro-o-cresol (4,6DNOC) was found to have a similar mobility to 2,4,6-trinitrotoluene (TNT) with K(o) values of 1.55 and 1.50 cm(2) V(-1) s(-1), respectively. Although baseline resolution between TNT and 4,6DNOC was not achieved, the drift time for TNT was still easily identified. Alkyl-nitrated phenols, due to acidic fog, responded the strongest in the IMS. The effect of contamination on TNT sensitivity was investigated. Charge competition between TNT and 2,4-dinitrophenol (2,4DNP) was found to occur and to effect TNT sensitivity.     

Fourier transform ion cyclotron resonance mass spectrometry using atmospheric pressure photoionization for high-resolution analyses of corticosteroids

Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) was coupled with atmospheric pressure photoionization (APPI) for the first time and used for the analysis of several corticosteroids.1 The analytes showed excellent response using APPI when compared with both electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). APPI has the advantage of requiring less heat for desolvation, resulting in less thermal degradation of the analytes and higher signal-to-noise than APCI. In terms of ultimate sensitivity, APPI is more efficient than either ESI or APCI for the analysis of corticosteroids. With some compounds, the high-resolution capability of FTICRMS was necessary to obtain an accurate mass due to contributions of the M(+.) (13)C isotope in the [M+H](+) ion peak.     

A novel surface ionization source for ion mobility spectrometer

A surface ionization (SI) source is designed and prepared for ion mobility spectrometer (IMS). The source acts not only as an emitter but also an ion injector which can inject ions periodically into the drift region of drift tube. Using the dual-role source, the dimension of the drift tube can be decreased and the circuit for high voltage can be simplified efficiently. The IMS with the SI source has a response range of ∼4 orders of magnitude and a good reproducibility to tri-ethylamine. Compared with radioactive ionization (RI), the ultra-short time for ion injection and the zero level base line of ion mobility spectrum are characteristics of the surface ionization.     

Electrospray ionization with ambient pressure ion mobility separation and mass analysis by orthogonal time-of-flight mass spectrometry.

Rapid screening and identification of drug and other mixtures are possible using a novel ambient pressure high-resolution ion mobility (APIMS) orthogonal reflector time-of-flight mass spectrometer (TOFMS). Departing ions from the APIMS drift tube traversed a pressure interface between the APIMS and TOFMS where they were subjected to numerous gas collisions that could produce selective fragmentation. By increasing the accelerating field in the pressure interface region, the ions generated using water-cooled electrospray ionization (ESI) underwent collision-induced dissociation (CID). Mixtures of ESI ions were separated by APIMS based on their respective size-to-charge (s/z) ratios while CID and analysis of mass-to-charge (m/z) ratios occurred in the pressure interface and TOFMS. Product ions that were formed in this pressure interface region could be readily assigned to precursor ions by matching the mobility drift times. This process was demonstrated by the examination of a mixture of amphetamines and the resulting fragmentation patterns of the mobility-separated precursor ion species [M + H](+).