Atmospheric-pressure ionization studies and field dependence of ion mobilities of isomeric hydrocarbons using a miniature differential mobility spectrometer

The ionization pathways and ion mobility were determined for sets of structural isomeric and stereoisomeric non-polar hydrocarbons (saturated and unsaturated cyclic hydrocarbons and aromatic hydrocarbons) using a novel miniature differential mobility spectrometer with atmospheric-pressure photoionization (APPI) to assess how structural and stereochemical differences influence ion formation and ion mobility. The analytical results obtained using the differential mobility spectrometry (DMS) were compared with the reduced mobility values measured using conventional time-of-flight ion mobility spectrometry (IMS) with the same ionization technique.The majority of differences in DMS ion mobility spectra observed among isomeric cyclic hydrocarbons can be explained by the formation of different product ions. Comparable differences in ion formation were also observed using conventional IMS and by investigations using the coupling of ion mobility spectrometry with mass spectrometry (APPI-IMS-MS) and APPI-MS. Using DMS, isomeric aromatic hydrocarbons can in the majority of cases be distinguished by the different behavior of product ions in the strong asymmetric radio frequency (rf) electric field of the drift channel. The different peak position of product ions depending on the electric field amplitude permits the differentiation between most of the investigated isomeric aromatics with a different constitution; this stands in contrast to conventional IMS in which comparable reduced mobility values were detected for the isomeric aromatic compounds.     

Ion mobility-mass spectrometry

This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided.     

Investigation of isomeric flavanol structures in black tea thearubigins using ultraperformance liquid chromatography coupled to hybrid quadrupole/ion mobility/time of flight mass spectrometry

Ultra performance liquid chromatography (UPLC) when coupled to ion mobility (IMS)/orthogonal acceleration time of flight mass spectrometry is a suitable technique for analyzing complex mixtures such as the black tea thearubigins. With the aid of this advanced instrumental analysis, we were able to separate and identify different isomeric components in the complex mixture which could previously not be differentiated by a conventional high performance liquid chromatography/tandem mass spectrometry. In this study, the difference between isomeric structures theasinensins, proanthocyanidins B‐type and rutin (quercetin‐3O‐rutinoside) were studied, and these are present abundantly in many botanical sources. The differentiation between these structures was accomplished according to their acquired mobility drift times differing from the traditional investigations in mass spectrometry, where calculation of theoretical collisional cross sections allowed assignment of the individual isomeric structures. The present work demonstrates UPLC–IMS‐MS as an efficient technology for isolating and separating isobaric and isomeric structures existing in complex mixtures discriminating between them according to their characteristic fragment ions and mobility drift times. Therefore, a rational assignment of isomeric structures in many phenolic secondary metabolites based on the ion mobility data might be useful in mass spectrometry‐based structure analysis in the future. Copyright © 2014 John Wiley & Sons, Ltd.     

Chemical standards for ion mobility spectrometry: a review

Ion mobility spectrometry (IMS), using stand-alone instrumentation and hyphenated with mass spectrometry (IM-MS), has recently undergone significant expansion in the numbers of users and applications, particularly in sectors outside its established user base; predominantly military and security applications. Although several IMS reference standards have been proposed, there are no currently universally recognised reference standards for the calibration and evaluation of mobility spectrometers. This review describes current practices and the literature on chemical standards for validating IMS systems in positive and negative ion modes. The key qualities and requirements an ‘ideal’ reference standard must possess are defined, together with the instrumental and environmental factors such as temperature, electric field, humidity and drift gas composition that may need to be considered. Important challenges that have yet to be resolved are also identified and proposals for future development presented.     

Monte Carlo simulation of ion transport in non-linear ion mobility spectrometry

A program for Monte Carlo simulation of ion transport in non-linear ion mobility spectrometry, also known as field asymmetric ion mobility spectrometry (FAIMS) or differential mobility spectrometry (DMS), has been developed. Simulations are based on elastic collisions between the ions and the gas particles, and take into account the effects of flow dynamics and asymmetric electric fields. Using this program, the separation and diffusion of the ions moving in a planar DMS filtration gap are demonstrated. Ion focusing in a cylindrical filtration gap is also confirmed. A characteristic compensation voltage is found to provide insight for understanding separation in non-linear ion mobility spectrometry. The simulation program is used to study the characteristics of non-linear ion mobility spectrometry, the effect of the carrier gas flow, and the dependence of the compensation voltage and nonlinear mobility coefficient (α) on the applied asymmetric electric field.     

Ion mobility-mass spectrometry analysis of isomeric carbohydrate precursor ions

The rapid separation of isomeric precursor ions of oligosaccharides prior to their analysis by mass spectrometry to the nth power (MS ⁿ ) was demonstrated using an ambient pressure ion mobility spectrometer (IMS) interfaced with a quadrupole ion trap. Separations were not limited to specific types of isomers; representative isomers differing solely in the stereochemistry of sugars, in their anomeric configurations, and in their overall branching patterns and linkage positions could be resolved in the millisecond time frame. Physical separation of precursor ions permitted independent mass spectra of individual oligosaccharide isomers to be acquired to at least MS³, the number of stages of dissociation limited only practically by the abundance of specific product ions. IMS–MS ⁿ analysis was particularly valuable in the evaluation of isomeric oligosaccharides that yielded identical sets of product ions in tandem mass spectrometry experiments, revealing pairs of isomers that would otherwise not be known to be present in a mixture if evaluated solely by MS dissociation methods alone. A practical example of IMS–MSⁿ analysis of a set of isomers included within a single high-performance liquid chromatography fraction of oligosaccharides released from bovine submaxillary mucin is described.     

Nanoclusters formation in ion mobility spectrometry and change separation selectivity of picoline isomers

Ion mobility spectrometry (IMS) was applied to determine the influence of structural features of nanocluster formation of picoline isomers in ion mobility spectrometry. Since the results of our studies show that different isomers have the same mobilities in pure nitrogen buffer gas and their corresponding peaks are totally overlapped, 2-butanol vapor was introduced into buffer gas by means of an online system from 0 to 300 mL min^?1. We found different structural features of these isomeric compounds which cause distinct differences in ion mobility spectra. These differences result from the formation of different nanocluster product ions (~1 nm³) with different cross section areas formed depending on the occurrence of certain structural features (position of the methyl group on the pyridine ring). The size of cluster product ions formed was determined using cross section area measurements. The effects of temperature in the range from 80 to 200 °C and electric field strength have also been investigated. At 140–160 °C and 636 V cm^?1, optimum peak-to-peak resolution can be obtained.     

Resistively heated temperature programmable silicon micromachined gas chromatography with differential mobility spectrometry

A microfabricated electromechanical system based on radio frequency modulated ion mobility spectrometry (MEMS-RFIMS), also known as differential ion mobility spectrometry (DMS) has been successfully interfaced to a custom-fabricated resistively heated temperature programmable micromachined gas chromatograph. In contrast to a conventional time-of-flight ion mobility spectrometer, the DMS uses the non-linear mobility dependence in strong radio frequency electric fields for ion filtering. Selective and sensitive detection of targeted analytes of interest can be achieved by using different transport gases, radio frequencies, and associated compensation voltages. In addition, the detection of both positive and negative ions, depending on the ionization mechanism favorable to the analytes involved is achieved. When compared to a stand-alone GC with a non spectrometric detector or a stand-alone DMS, GC-DMS as a hyphenated technique offers two competitive advantages; two orthogonal separating methods in a single analytical system and the resolving power of gas chromatography to minimize charge exchange in the ionization chamber of the detector. In this article, a portable, resistively heated temperature programmable silicon machined gas chromatograph with differential mobility detection is introduced. The performance of the instrument is illustrated with examples of difficult industrial applications.     

Ion mobility spectrometry detection for gas chromatography

The hyphenated analytical method in which ion mobility spectrometry (IMS) is coupled to gas chromatography (GC) provides a versatile alternative for the sensitive and selective detection of compounds after chromatographic separation. Providing compound selectivity by measuring unique gas phase mobilities of characteristic analyte ions, the separation and detection process of gas chromatography-ion mobility spectrometry (GC-IMS) can be divided into five individual steps: sample introduction, compound separation, ion generation, ion separation and ion detection. The significant advantage of a GC-IMS detection is that the resulting interface can be tuned to monitor drift times/ion mobilities (as a mass spectrometer (MS) can be tuned to monitor ion masses) of interest, thereby tailoring response characteristics to fit the need of a given separation problem. Because IMS separates ions based on mobilities rather than mass, selective detection among compounds of the same mass but different structures are possible. The most successful application of GC-IMS to date has been in the international space station. With the introduction of two-dimensional gas chromatography (2D-GC), and a second type of mobility detector, namely differential mobility spectrometry (DMS), GC prior to mobility measurements can now produce four-dimensional analytical information. Complex mixtures in difficult matrices can now be analyzed. This review article is intended to provide an overview of the GC-IMS/DMS technique, recent developments, significant applications, and future directions of the technique.     

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.     

In situ isobaric lipid mapping by MALDI–ion mobility separation–mass spectrometry imaging

The highly diverse chemical structures of lipids make their analysis directly from biological tissue sections extremely challenging. Here, we report the in situ mapping and identification of lipids in a freshwater crustacean Gammarus fossarum using matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) in combination with an additional separation dimension using ion mobility spectrometry (IMS). The high‐resolution trapped ion mobility spectrometry (TIMS) allowed efficient separation of isobaric/isomeric lipids showing distinct spatial distributions. The structures of the lipids were further characterized by MS/MS analysis. It is demonstrated that MALDI MSI with mobility separation is a powerful tool for distinguishing and localizing isobaric/isomeric lipids.     

Enhancement of mass spectrometry performance for proteomic analyses using highfield asymmetric waveform ion mobility spectrometry (FAIMS)

Remarkable advances in mass spectrometry sensitivity and resolution have been accomplished over the past two decades to enhance the depth and coverage of proteome analyses. As these technological developments expanded the detection capability of mass spectrometers, they also revealed an increasing complexity of low abundance peptides, solvent clusters and sample contaminants that can confound protein identification. Separation techniques that are complementary and can be used in combination with liquid chromatography are often sought to improve mass spectrometry sensitivity for proteomics applications. In this context, high‐field asymmetric waveform ion mobility spectrometry (FAIMS), a form of ion mobility that exploits ion separation at low and high electric fields, has shown significant advantages by focusing and separating multiply charged peptide ions from singly charged interferences. This paper examines the analytical benefits of FAIMS in proteomics to separate co‐eluting peptide isomers and to enhance peptide detection and quantitative measurements of protein digests via native peptides (label‐free) or isotopically labeled peptides from metabolic labeling or chemical tagging experiments. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of terpenes in humid ambient air using ultraviolet ion mobility spectrometry

Atmospheric humidity causes the major problem using ion mobility spectrometers (IMS) under ambient conditions. Significant changes of the spectra are decreasing sensitivity as well as selectivity. Therefore, the influence of humidity on the IMS signal was investigated in case of direct introduction of the analyte into the ionisation chamber and in case of pre-separation by help of a multi-capillary column (MCC). For direct analyte introduction, a significant decrease of the total number of ions in the range of 28-42% with increasing relative humidity was found. Simultaneously additional peaks in the spectra were formed, thus complicating the identification of the analytes. In case of pre-separation of the analyte, the spectra do not change with increasing relative humidity, due to the successive appearance of the analyte and the water molecules in the ionisation chamber. Detection limits were found in the range of 5 μg/m³ (about 1 ppbv) for selected terpenes and—with pre-separation—independent on relative humidity of the analyte. Without pre-separation, detection limits are in the same range for dry air as carrier gas but in the range of 200-600 μg/m³ when relative humidity reaches 100%. Thus, MCC-UV ion mobility spectrometry is optimally capable for the detection of trace substances in ambient air (e.g. indoor air quality control, process control, odour detection) without further elaborate treatment of the carrier gas containing the analyte and independent on relative humidity.     

Buffer gas additives (modifiers/shift reagents) in ion mobility spectrometry: Applications,predictions of mobility shifts,and influence of interaction energy and structure

Ion mobility spectrometry (IMS) is an analytical technique used for fast and sensitive detection of illegal substances in customs and airports, diagnosis of diseases through detection of metabolites in breath, fundamental studies in physics and chemistry, space exploration, and many more applications. Ion mobility spectrometry separates ions in the gas‐phase drifting under an electric field according to their size to charge ratio. Ion mobility spectrometry disadvantages are false positives that delay transportation, compromise patient's health and other negative issues when IMS is used for detection. To prevent false positives, IMS measures the ion mobilities in 2 different conditions, in pure buffer gas or when shift reagents (SRs) are introduced in this gas, providing 2 different characteristic properties of the ion and increasing the chances of right identification. Mobility shifts with the introduction of SRs in the buffer gas are due to clustering of analyte ions with SRs. Effective SRs are polar volatile compounds with free electron pairs with a tendency to form clusters with the analyte ion. Formation of clusters is favored by formation of stable analyte ion‐SR hydrogen bonds, high analytes' proton affinity, and low steric hindrance in the ion charge while stabilization of ion charge by resonance may disfavor it. Inductive effects and the number of adduction sites also affect cluster formation. The prediction of IMS separations of overlapping peaks is important because it simplifies a trial and error procedure. Doping experiments to simplify IMS spectra by changing the ion‐analyte reactions forming the so‐called alternative reactant ions are not considered in this review and techniques other than drift tube IMS are marginally covered.     

Differential mobility spectrometry of chlorocarbons with a micro-fabricated drift tube

Chlorocarbons were ionized through gas phase chemistry at ambient pressure in air and resultant ions were characterized using a micro-fabricated drift tube with differential mobility spectrometry (DMS). Positive and negative product ions were characterized simultaneously in a single drift tube equipped with a 3 mCi (63)Ni ion source at 50 degrees C and drift gas of air with 1 ppm moisture. Scans of compensation voltage for most chlorocarbons produced differential mobility spectra with Cl(-) as the sole product ion and a few chlorocarbons produced adduct ions, M (.-) Cl(-). Detection limits were approximately 20-80 pg for gas chromatography-DMS measurements. Chlorocarbons also yielded positive ions through chemical ionization in air and differential mobility spectra showed peaks with characteristic compensation voltages for each substance. Field dependence of mobility was determined for positive and negative ions of each substance and confirmed characteristic behavior for each ion. A DMS analyzer with a membrane inlet was used to continuously monitor effluent from columns of bentonite or synthetic silica beads to determine breakthrough volumes of individual chlorocarbons. These findings suggest a potential of DMS for monitoring subsurface environments either on site or perhaps in situ.     

Atmospheric pressure chemical ionization studies of non-polar isomeric hydrocarbons using ion mobility spectrometry and mass spectrometry with different ionization techniques

The ionization pathways were determined for sets of isomeric non-polar hydrocarbons (structural isomers, cis/trans isomers) using ion mobility spectrometry and mass spectrometry with different techniques of atmospheric pressure chemical ionization to assess the influence of structural features on ion formation. Depending on the structural features, different ions were observed using mass spectrometry. Unsaturated hydrocarbons formed mostly [M - 1]+ and [(M - 1)2H]+ ions while mainly [M - 3]+ and [(M - 3)H2O]+ ions were found for saturated cis/trans isomers using photoionization and 63Ni ionization. These ionization methods and corona discharge ionization were used for ion mobility measurements of these compounds. Different ions were detected for compounds with different structural features. 63Ni ionization and photoionization provide comparable ions for every set of isomers. The product ions formed can be clearly attributed to the structures identified. However, differences in relative abundance of product ions were found. Although corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra detected are complex and differ from those obtained with 63Ni ionization and photoionization.     

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.     

Evaluation of false positive responses by mass spectrometry and ion mobility spectrometry for the detection of trace explosives in complex samples

Secondary electrospray ionization-ion mobility-time of flight mass spectrometry (SESI-IM-TOFMS) was used to evaluate common household products and food ingredients for any mass or mobility responses that produced false positives for explosives. These products contained ingredients which shared the same mass and mobility drift time ranges as the analyte ions for common explosives. The results of this study showed that the vast array of compounds in these products can cause either mass or mobility false positive responses. This work also found that two ingredients caused either enhanced or reduced ionization of the target analytes. Another result showed that an IMS can provide real-time separation of ion species that impede accurate mass identifications due to overlapping isotope peak patterns. The final result of this study showed that, when mass and mobility values were used to identify an ion, no false responses were found for the target explosives. The wider implication of these results is that the possibility exists for even greater occurrences of false responses from complex mixtures found in common products. Neither IMS nor MS alone can provide 100% assurance from false responses. IMS, due to its low cost, ease of operation, rugged reliability, high sensitivity and tunable selectivity, will remain the field method of choice for the near future but, when combined with MS, can also reduce the false positive rate for explosive analyses.     

Micro-plasma: a novel ionisation source for ion mobility spectrometry

Ion mobility spectrometry is an analytical method for identification and quantification of gas-phase analytes in the ppb_v-ppt_v range. Traditional ionisation methods suffer from low sensitivity (UV light), lack of long-term stability (partial discharge), or legal restrictions when radioactive sources are used. A miniaturised helium plasma was applied as ionisation source in an ion mobility spectrometer (IMS). Experiments were carried out to compare plasma IMS with β-radiation IMS. It could be demonstrated that the plasma IMS is characterised by higher sensitivity and selectivity than β-radiation ionisation. Plasma IMS is approximately 100 times more sensitive than the β-radiation IMS. Furthermore, variable sensitivity can be achieved by variation of the helium flow and the electric field of the plasma, and variable selectivity can be achieved by changing the electric field of the IMS. The experimental arrangement, optimisation of relevant conditions, and a typical application are presented in detail. Figure Micro-plasma used in ion mobility spectrometry     

Optimum collision energies for proteomics: The impact of ion mobility separation

Ion mobility spectrometry (IMS) is a widespread separation technique used in various research fields. It can be coupled to liquid chromatography–mass spectrometry (LC–MS/MS) methods providing an additional separation dimension. During IMS, ions are subjected to multiple collisions with buffer gas, which may cause significant ion heating. The present project addresses this phenomenon from the bottom-up proteomics point of view. We performed LC–MS/MS measurements on a cyclic ion mobility mass spectrometer with varied collision energy (CE) settings both with and without IMS. We investigated the CE dependence of identification score, using Byonic search engine, for more than 1000 tryptic peptides from HeLa digest standard. We determined the optimal CE values—giving the highest identification score—for both setups (i.e., with and without IMS). Results show that lower CE is advantageous when IMS separation is applied, by 6.3 V on average. This value belongs to the one-cycle separation configuration, and multiple cycles may supposedly have even larger impact. The effect of IMS is also reflected in the trends of optimal CE values versus m/z functions. The parameters suggested by the manufacturer were found to be almost optimal for the setup without IMS; on the other hand, they are obviously too high with IMS. Practical consideration on setting up a mass spectrometric platform hyphenated to IMS is also presented. Furthermore, the two CID (collision induced dissociation) fragmentation cells of the instrument—located before and after the IMS cell—were also compared, and we found that CE adjustment is needed when the trap cell is used for activation instead of the transfer cell. Data have been deposited in the MassIVE repository (MSV000090944).