Pressure Drift Tube Ion Mobility Research Articles

Separations of Carbohydrates with Noncovalent Shift Reagents by Frequency-Modulated Ion Mobility-Orbitrap Mass Spectrometry.

An increased focus on characterizing the structural heterogeneity of carbohydrates has been driven by their many significant roles in extant life and potential roles in chemical evolution and the origin of life. In this work, multiplexed drift tube ion mobility-Orbitrap mass spectrometry methods were developed to analyze mixtures of disaccharides modified with noncovalent shift reagents. Since traditional coupling of atmospheric pressure drift tube ion mobility cells with Orbitrap mass analyzers suffers from low duty cycles (<0.1%), a frequency modulation scheme was applied to improve the signal-to-noise ratios (SNR). Several parameters such as the resolution setting and maximum injection time of the Orbitrap analyzer and the magnitude and duration of the frequency sweep were investigated for their impact on the sensitivity gains and resolution of disaccharide-shift reagent adducts. The sweep time and disaccharide concentration had a positive correlation with SNR. The magnitude of the frequency sweep had a negative correlation with SNR. However, increasing the frequency sweep improved the resolution of mixtures of disaccharide analytes. Application of frequency-modulated ion mobility-Orbitrap mass spectrometry to four noncovalently modified glucose dimers allowed for the differentiation of three out of these four analytes.

Atmospheric Pressure Drift Tube Ion Mobility Spectrometry Coupled with Two-Dimensional Tandem Mass Spectrometry.

Atmospheric pressure drift tube ion mobility was coupled with two-dimensional tandem mass spectrometry (2D MS/MS) in a linear ion trap to simultaneously collect ion mobility and the entire MS/MS data domain. Utilizing ion intensities from precursor ion and neutral loss scan lines, ion mobility spectra of multiple compounds with particular functional groups were acquired in a single experiment. Functional group-specific ion mobility spectra were demonstrated for a standard mixture of lipids. Additionally, ion mobility was used to separate isobaric ions prior to 2D MS/MS. The combination of these two methods offers improvements for the analysis of complex mixtures.

Deducing Proton-Bound Heterodimer Association Energies from Shifts in Ion Mobility Arrival Time Distributions.

Through vapor modification of the counter-current drift gas in an atmospheric pressure drift tube ion mobility spectrometer (IMS), we demonstrate measurement of gas-phase association enthalpies and entropies for select proton-bound heterodimers formed from a phosphonic acid with 2-propanol. Previous efforts to determine gas-phase association thermodynamic properties have relied largely upon lower pressure systems and inference of the relative concentrations of m/ z isolated species. In contrast, the drift tube IMS based approach developed and applied in this study leverages the explicit gas-phase equilibrium that is established within an ion mobility drift cell. The inferred enthalpies and entropies of association are based solely upon monitoring a shift in the arrival time of an ion at different temperatures (and not on the signal intensity or on external instrument drift time calibration). We specifically report the gas-phase Gibbs free energy, enthalpy, and entropy changes for the association of 2-propanol with protonated methyl, ethyl, and propyl phosphonic acid ions (MPA, EPA, PPA) across the 100-175 °C temperature range. For all of these proton-bound heterodimers, the standard enthalpies and entropies of 2-propanol association were negative and positive, respectively. These data indicate that proton-bound heterodimer formation is both enthalpically and entropically favorable, though we find that the magnitude of the standard enthalpy change for vapor association is small (near 1 kcal/mol for all examined heterodimers). Though many prior results (largely obtained with high pressure mass-spectrometry) for other proton-bound organic heterodimer complexes show larger enthalpic favorability and an entropic barrier, our results qualitatively conform to the bulk Kelvin-Thomson-Raoult (KTR) model, which is commonly utilized in describing ion-induced nucleation of a vapor onto a soluble, nanometer scale ion. The KTR model suggests that heterodimer formation due to vapor binding to an ion should be slightly enthalpically favored (due to a larger Thomson effect than the Kelvin effect) and entropically favored because of ion solvation (Raoult's effect). The method presented in this study can be applied to any static-field ion mobility spectrometer and to a wide variety of heterodimers. Due to the ease of implementation and broad applicability, this approach may find consistent use in determining the thermodynamic properties of weakly bound gas-phase heterodimer complexes which are difficult to probe via alternative techniques. Moreover, this renewed implementation of the IMS experiment is directly compatible with soft ionization sources which will enable the characterization of vapor modifier-induced mobility shift experiments for larger molecular complexes.

Coupling of a High-Resolution Ambient Pressure Drift Tube Ion Mobility Spectrometer to a Commercial Time-of-flight Mass Spectrometer.

Ion mobility spectrometry provides information about molecular structures of ions. Hence, high resolving power allows separation of isomers which is of major interest in several applications. In this work, we couple our high-resolution ion mobility spectrometer (IMS) with a resolving power of Rp = 100 to a time-of-flight mass spectrometer (TOF-MS). Besides, the benefit of an increased resolving power such an IMS-MS also helps analyzing and understanding the ionization processes in IMS. Usually, the coupling between IMS and TOF-MS is realized by synchronizing data acquisition of the IMS and MS resulting in two-dimensional data containing ion mobility and mass spectra. However, due to peak widths of less than 100μs in our high-resolution IMS, this technique is not practicable due to significant peak broadening during the ion transfer into the MS and an insufficient data acquisition rate of the MS. Thus, a novel but simple interface between the IMS and MS has been designed which minimizes ion losses, allows recording of ion mobility at full IMS resolving power, and enables a shuttered transmission of ions into the MS. The interface is realized by replacing the Faraday plate used in IMS by a Faraday grid that is shielded by two additional aperture grids. For demonstration, positive product ions of benzene, toluene, and m-xylene in air are investigated. The IMS is equipped with a radioactive 3H source. Besides the well-known product ions M+ and M·NO+, a dimer ion is also observed for benzene and toluene, consisting of two molecules and three further hydrogen atoms. Graphical Abstract ᅟ.

Atmospheric Pressure Drift Tube Ion Mobility–Orbitrap Mass Spectrometry: Initial Performance Characterization

Atmospheric pressure drift tube ion mobility spectrometry (AP-DTIMS) was coupled with Fourier transform Orbitrap mass spectrometry. The performance capabilities of this versatile new arrangement were demonstrated for different DTIMS ion gating operation modes and Orbitrap mass spectrometer parameters with regard to sensitivity and resolving power. Showcasing the optimized AP-DTIMS-Orbitrap MS system, isobaric peptide and sugar isomers were successfully resolved and the identities of separated species validated by high-energy collision dissociation experiments.

Ambient Pressure Inverse Ion Mobility Spectrometry Coupled to Mass Spectrometry.

Although higher resolving powers are often achieved using ambient pressure drift tube ion mobility mass spectrometry (DT-IMMS) systems, lower duty cycles are often required which directly impacts sensitivity. Moreover, the mechanism of ion gating using Bradbury-Nielsen or Tyndall-Gate configurations routinely results in ion gate depletion effects which discriminate against low mobility ions. This paper reports a new method of ambient pressure ion mobility operation in which inverse ion mobility spectrometry is coupled to a time-of-flight mass spectrometer to improve sensitivity and minimize the effects of ion gate depletion. In this mode of operation, the duty cycle is improved to approximate 99% from a typical value of less than 1%, improving the signal intensity by over 2 orders of magnitude. Another advantage of inverse ion mobility mass spectrometry is a reduction of the impact of ion gate depletion on low mobility molecules that translates into higher sensitivity for this class of analytes. To demonstrate these benefits afforded by this instrumental mode of operation differences in sensitivity, resolving power, and ion discrimination are compared between the inverse and normal modes of operation using tetraalkylammonium standards. These results show that the ion throughput is significantly increased for analytes with a broad range of mobilities with little impact on resolving power. While the mobility-based discrimination is minimized using the inverse mode of operation, the noise level in the inverse mode is highly dependent upon the stability of ionization source.

Determination of the transfer function of an atmospheric pressure drift tube ion mobility spectrometer for nanoparticle measurements.

Drift tube-ion mobility spectrometers (DT-IMSs) are used to separate and characterize the structures of gas phase ions. Recent work in coupling an atmospheric pressure DT-IMS to a condensation particle counter (CPC) has extended the application of drift tube ion mobility spectrometry to nanoparticle analysis, with measurements possible for singly charged particles up to 20 nm in diameter. In examining systems with such large analytes, often of interest is not only separation, but also determination of the nanoparticle size or mobility distribution function, defined as the nanoparticle concentration per unit mobility/size. Distribution function determination requires a priori knowledge of the DT-IMS transfer function, i.e. the DT-IMS combined transmission and detection efficiency as a function of both mobility and drift/arrival time. The transfer function completely describes analyte transport through an instrument; unfortunately, it has not been experimentally determined in previous work for a DT-IMS. Here, we develop and apply a new method to infer the transfer function of a DT-IMS-CPC system, wherein the system is used to measure particles which are first transmitted through a well-characterized differential mobility analyzer (DMA). The DMA acts as a mobility filter, and only transmits particles within a narrow, well-defined mobility range. From a series of measurements at fixed drift/arrival time (up to 12 seconds) but variable DMA transmission window, DT-IMS-CPC transfer functions are inverted via a Twomey-Markowski algorithm. Transfer function inversion reveals that the DT-IMS-CPC system has a resolving power in excess of 10 and upwards of 20. Such resolving powers are in good agreement with model predictions, and are higher than commercially available DMAs in the nanoparticle size range.

Rapid identification of triphenylmethane dyes by ion mobility time-of-flight mass spectrometry.

An ion mobility time-of-flight mass spectrometry (IM-TOFMS)-based method has been preliminarily investigated for the identification of triphenylmethane ballpoint pen dyes on paper. The dyes were sampled from one-year-old ballpoint pen ink entries. The entries were written on paper documents stored in the dark in a bookcase. Sample solutions were prepared by extraction of dyes in a vial. Basic violet 2, Methyl violet 6B, Methyl violet 2B and Crystal violet were characterized by IM-TOFMS. Since the ballpoint ink dyes contain ionic compounds, the studied compounds were expected to form stable peaks in the atmospheric pressure drift tube ion mobility spectrometry, and this was experimentally verified. The studied dyes produce [M - Cl]+ ions in electrospray and form stable individual mass-selective reduced mobility peaks. The values of the characteristic reduced mobility are: 1.187 cm2/(V·s) for Basic violet 2 (m/z 330.20), 1.165 cm2/(V·s) for Methyl violet 6B (m/z 344.21), 1.156 cm2/(V·s) for Methyl violet 2B (m/z 358.23), 1.123 cm2/(V·s) for Crystal violet (m/z 372.24). IM-TOFMS is expected to be a promising tool for fast and reliable analysis of dyes in complex matrixes.

Multidimensional Separation of Natural Products Using Liquid Chromatography Coupled to Hadamard Transform Ion Mobility Mass Spectrometry.

A high performance liquid chromatograph (HPLC)was interfaced to an atmospheric drift tube ion mobility time of flight mass spectrometry. The power of multidimensional separation was demonstrated using chili pepper extracts. The ambient pressure drift tube ion mobility provided high resolving powers up to 166 for the HPLC eluent. With implementation of Hadamard transform (HT), the duty cycle for the ion mobility drift tube was increased from less than 1% to 50%, and the ion transmission efficiency was improved by over 200 times compared with pulsed mode, improving signal to noise ratio 10 times. HT ion mobility and TOF mass spectrometry provide an additional dimension of separation for complex samples without increasing the analysis time compared with conventional HPLC. Graphical Abstract ᅟ.

IMS-MS and IMS-IMS investigation of the structure and stability of dimethylamine-sulfuric acid nanoclusters.

Recent studies of new particle formation events in the atmosphere suggest that nanoclusters (i.e, the species formed during the early stages of particle growth which are composed of 10(1)-10(3) molecules) may consist of amines and sulfuric acid. The physicochemical properties of sub-10 nm amine-sulfuric acid clusters are hence of interest. In this work, we measure the density, thermostability, and extent of water uptake of <8.5 nm effective diameter dimethylamine-sulfuric (DMAS) nanoclusters in the gas phase, produced via positive electrospray ionization. Specifically, we employ three systems to investigate DMAS properties: ion mobility spectrometry (IMS, with a parallel-plate differential mobility analyzer) is coupled with mass spectrometry to measure masses and collision cross sections for <100 kDa positively charged nanoclusters, two differential mobility analyzers in series (IMS-IMS) are used to examine thermostability, and finally a differential mobility analyzer coupled to an atmospheric pressure drift tube ion mobility spectrometer (also IMS-IMS) is used for water uptake measurements. IMS-MS measurements reveal that dry DMAS nanoclusters have densities of ∼1567 kg/m(3) near 300 K, independent of the ratio of dimethylamine to sulfuric acid originally present in the electrospray solution. IMS-IMS thermostability studies reveal that partial pressures of DMAS nanoclusters are dependent upon the electrospray solution concentration ratio, R = [H2SO4]/[(CH3)2NH]. Extrapolating measurements, we estimate that dry DMAS nanoclusters have surface vapor pressures of order 10(-4) Pa near 300 K, with the surface vapor pressure increasing with increasing values of R through most of the probed concentration range. This suggests that nanocluster surface vapor pressures are substantially enhanced by capillarity effects (the Kelvin effect). Meanwhile, IMS-IMS water uptake measurements show clearly that DMAS nanoclusters uptake water at relative humidities beyond 10% near 300 K, and that larger clusters uptake water to a larger extent. In total, our results suggest that dry DMAS nanoclusters (in the 5-8.5 nm size range in diameter) would not be stable under ambient conditions; however, DMAS nanoclusters would likely be hydrated in the ambient (in some cases above 20% water by mass), which could serve to reduce surface vapor pressures and stabilize them from dissociation.

A gated atmospheric pressure drift tube ion mobility spectrometer–time-of-flight mass spectrometer

Identifying the compounds of an unknown gas mixture by using an ion mobility spectrometer (IMS) is a difficult task, because several ion species can be generated in the ionization process. One method to analyze the occurring peaks in an IMS spectrum is coupling an IMS to a mass spectrometer (MS). In our setup we coupled a 3H drift tube IMS to a Bruker micrOTOF II. Therefore, the detector plate of the IMS is pierced and a transfer capillary is inserted. The ions are transferred via gas flow and electric fields into the MS. The transmission of the ions through the transfer capillary can be shuttered very precisely by increasing the electric potential of the detector generating a repulsive electric field. Thus, it is possible to transfer single ion clouds of generated IMS spectra into the mass spectrometer where a corresponding mass spectrum is generated. In this work we analyze the positive and negative IMS spectra of single analytes as well as gas mixtures and characterize the occurring ion species.

An effective approach for coupling direct analysis in real time with atmospheric pressure drift tube ion mobility spectrometry.

Drift tube ion mobility spectrometry (DTIMS) has evolved as a robust analytical platform routinely used for screening small molecules across a broad suite of chemistries ranging from food and pharmaceuticals to explosives and environmental toxins. Most modern atmospheric pressure IM detectors employ corona discharge, photoionization, radioactive, or electrospray ion sources for efficient ion production. Coupling standalone DTIMS with ambient plasma-based techniques, however, has proven to be an exceptional challenge. Device sensitivity with near-ground ambient plasma sources is hindered by poor ion transmission at the source-instrument interface, where ion repulsion is caused by the strong electric field barrier of the high potential ion mobility spectrometry (IMS) inlet. To overcome this shortfall, we introduce a new ion source design incorporating a repeller point electrode used to shape the electric field profile and enable ion transmission from a direct analysis in real time (DART) plasma ion source. Parameter space characterization studies of the DART DTIMS setup were performed to ascertain the optimal configuration for the source assembly favoring ion transport. Preliminary system capabilities for the direct screening of solid pharmaceuticals are briefly demonstrated.

Desorption electrospray ionization (DESI) with atmospheric pressure ion mobility spectrometry for drug detection

Desorption electrospray ionization (DESI) was coupled to an ambient pressure drift tube ion mobility time-of-flight mass spectrometer (IM-TOFMS) for the direct analysis of active ingredients in pharmaceutical samples. The DESI source was also coupled with a standalone IMS demonstrating potential of portable and inexpensive drug-quality testing platforms. The DESI-IMS required no sample pretreatment as ions were generated directly from tablets and cream formulations. The analysis of a range of over-the-counter and prescription tablet formations was demonstrated for amphetamine (methylphenidate), antidepressant (venlafaxine), barbiturate (Barbituric acid), depressant (alprazolam), narcotic (3-methylmorphine) and sympatholytic (propranolol) drugs. Active ingredients from soft and liquid formulations, such as Icy Hot cream (methyl salicylate) and Nyquil cold medicine (acetaminophen, dextromethorphan, doxylamine) were also detected. Increased sensitivity for selective drug responses was demonstrated through the formation of sodiated adduct ions by introducing small quantities of NaCl into the DESI solvent. Of the drugs and pharmaceuticals tested in this study, 68% (22 total samples) provided a clear ion mobility response at characteristic mobilities either as (M + H)(+), (M - H)(-), or (M + Na)(+) ions.

Resolving Structural Isomers of Monosaccharide Methyl Glycosides Using Drift Tube and Traveling Wave Ion Mobility Mass Spectrometry

Monosaccharide structural isomers including sixteen methyl-D-glycopyranosides and four methyl-N-acetylhexosamines were subjected to ion mobility measurements by electrospray ion mobility mass spectrometry. Two ion mobility-MS systems were employed: atmospheric pressure drift tube ion mobility time-of-flight mass spectrometry and a Synapt G2 HDMS system which incorporates a low pressure traveling wave ion mobility separator. All the compounds were investigated as [M + Na](+) ions in the positive mode. A majority of the monosaccharide structural isomers exhibited different mobility drift times in either system, depending on differences in their anomeric and stereochemical configurations. In general, drift time patterns (relative drift times of isomers) matched between the two instruments. Higher resolving power was observed using the atmospheric pressure drift tube. Collision cross section values of monosaccharide structural isomers were directly calculated from the atmospheric pressure ion mobility experiments, and a collision cross section calibration curve was made for the traveling wave ion mobility instrument. Overall, it was demonstrated that ion mobility-mass spectrometry using either drift tube or traveling wave ion mobility is a valuable technique for resolving subtle variations in stereochemistry among the sodium adducts of monosaccharide methyl glycosides.

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.

Theoretical and experimental study of the achievable separation power in resistive‐glass atmospheric pressure ion mobility spectrometry

We present a detailed investigation of the performance of our previously reported nanoelectrospray high-resolution resistive-glass atmospheric pressure drift tube ion mobility spectrometer constructed with monolithic resistive-glass desolvation and drift regions. Using experimental spectral data and theoretical pulse width and diffusion variables, we compare theoretical and experimental resolving powers achievable under a variety of field strengths and ion gate pulse widths. The effects of instrumental and operational parameters on the resolution achievable in chromatographic terms are also discussed. Following characterization of the separation power of the instrument, experimental spectral peak width data is fitted by a least-squares procedure to a pre-existing semi-empirical model developed to study contributions to peak width other than initial pulse width and diffusional broadening. The model suggests possible contributions to the final measured peak width from electric field inhomogeneity and minor contributions from instrumental parameters such as anode size, anode-to-anode grid distance and drift gas flow rate. The model also reveals an unexpected ion gate width dependence on the final measured peak width that we attribute to non-ideal performance of the Bradbury-Nielsen ion gate and limitations in the design of our pulsing-electronics.

Digitally-Multiplexed Nanoelectrospray Ionization Atmospheric Pressure Drift Tube Ion Mobility Spectrometry

One of the shortcomings of atmospheric pressure drift tube ion mobility spectrometry (DTIMS) is its intrinsically low duty cycle (approximately 0.04-1%) caused by the rapid pulsing of the ion gate (25-400 micros) followed by a comparatively long drift time (25-100 ms), which translates into a loss of sensitivity. Multiplexing approaches via Hadamard and Fourier-type gating techniques have been reported for increasing the sensitivity of DTIMS. Here, we report an extended multiplexing approach which encompasses arbitrary binary ion injection waveforms with variable duty cycles ranging from 0.5 to 50%. In this approach, ion mobility spectra can be collected using conventional signal averaging, arbitrary, standard Hadamard and/or "extended" Hadamard operation modes. Initial results indicate signal-to-noise gains ranging from 2-7-fold for both arbitrary and "extended" Hadamard sequences. Standard Hadamard transform IMS provided increased sensitivity, with gains ranging from 9-12-fold, however, mobility spectra suffered from defects that appeared as false peaks, which were reduced or eliminated when using arbitrary or "extended" Hadamard waveforms for multiplexing. Digital multiplexing enables variation of the duty cycle in a continuous manner, minimizing the contribution of imperfect modulation on spectral defects without the need for complex spectral correction methods. By reducing the frequency of gating events employed in the variable duty cycle sequences, the contributions of factors such as ion depletion prior to gating, interaction of successively injected ion packets, and the cumulative effect of imperfect gating events were mitigated.