Time-of-flight ion mobility spectrometry and differential mobility spectrometry: A comparative study of their efficiency in the analysis of halogenated compounds

The ion mobilities of halogenated aromatics which are of interest in environmental chemistry and process monitoring were characterized with field-deployable ion mobility spectrometers and differential mobility spectrometers. The dependence of mobility of gas-phase ions formed by atmospheric-pressure photoionization (APPI) on the electric field was determined for a number of structural isomers. The structure of the product ions formed was identified by investigations using the coupling of ion mobility spectrometry with mass spectrometry (APPI-IMS-MS) and APPI-MS. In contrast to conventional time-of-flight ion mobility spectrometry (IMS) with constant linear voltage gradients in drift tubes, differential mobility spectrometry (DMS) employs the field dependence of ion mobility. Depending on the position of substituents, differences in field dependence were established for the isomeric compounds in contrast to conventional IMS in which comparable reduced mobility values were detected for the isomers investigated. These findings permit the differentiation between most of the investigated isomeric aromatics with a different constitution using DMS.     

Influence of structural features of isomeric hydrocarbons on ion formation at atmospheric pressure

Ion mobility spectrometry (IMS) in combination with different techniques of atmospheric pressure ionization (⁶³Ni ionization, photoionization, Corona discharge ionization) was applied to determine the influence of structural features of aromatic and cyclic hydrocarbons on ion mobility spectra. For this purpose, different sets of isomeric hydrocarbons were investigated using the above-mentioned ionization techniques. We found different structural features of these isomeric non-polar compounds which cause distinct differences in ion mobility spectra. These differences result from the formation of different product ions or a different relative abundance of ions formed depending on the occurrence of certain structural features (position of the double bond, arrangement of double bonds within the carbon ring, configuration of aliphatic side chain in the space, position of aliphatic side chain on the carbon ring and the number of carbon atoms in the aliphatic side chain). The nature of product ions formed was determined using a coupling of IMS with mass spectrometry (MS).     

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.     

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.     

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.     

Ion mobility spectra of cyclic and aliphatic hydrocarbons with different substituents

We investigated the influence of structural differences on the ionization pathways and drift behavior in ion mobility spectrometry for cyclic and aliphatic hydrocarbons with different functional groups. The sets of cyclic and aliphatic compounds had an identical mass or a mass difference of 2 Da. Therefore, mass effects can be neglected during the investigation of these compounds. Depending on the functional group, considerable differences were found in the detectable concentration ranges and in the number and position of product ion peaks in ion mobility spectra. The spectra of chlorinated compounds and hydrocarbons show no correlation to their calculated collisional cross sections. Differences in collisional cross section between cyclic and aliphatic substances investigated were only found to influence the drift times detected for amines and aliphatic aldehydes while complex ion chemistry was observed for the other substances.     

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.     

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.     

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.     

Hydrocarbon detection using laser ion mobility spectrometry

A Laser Ion Mobility Spectrometer has been set up and trace detection experiments have been performed. We find that laser ionization almost selectively ionizes aromatic hydrocarbons. Aliphatic hydrocarbons are only laser-ionized in case these contain conjugated double bonds. As, in contrast to radioactive ion mobility spectrometry, background air constituents and air contaminants cannot be ionized, drift spectra are inherently simple and easily interpretable. We show that a laser ion mobility spectrometer can be operated in two basically different modes, either using tunable or fixed-frequency laser sources. In the tunable laser mode, aromatic hydrocarbons can be detected in the positive mode and distinguished from each other on account of their different excitation wavelengths and ion drift times. In the fixed-frequency mode, specially chosen and intentionally admitted aromatic hydrocarbons are laser ionized and the primary ionization is transferred to non-aromatic species by means of atmospheric pressure chemical ionization. In this latter mode of operation nitroglycerin and triacetone triperoxide, two non-aromatic high explosives, could be detected.     

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.     

Ion mobility spectrometer—field asymmetric ion mobility spectrometer-mass spectrometry

Since the development of electrospray ionization (ESI) for ion mobility spectrometry mass spectrometry (IMMS), IMMS have been extensively applied for characterization of gas-phase bio-molecules. Conventional ion mobility spectrometry (IMS), defined as drift tube IMS (DT-IMS), is typically a stacked ring design that utilizes a low electric field gradient. Field asymmetric ion mobility spectrometry (FAIMS) is a newer version of IMS, however, the geometry of the system is significantly different than DT-IMS and data are collected using a much higher electric field. Here we report construction of a novel ambient pressure dual gate DT-IMS coupled with a FAIMS system and then coupled to a quadrupole ion trap mass spectrometer (QITMS) to form a hybrid three-dimensional separation instrument, DT-IMS-FAIMS-QITMS. The DT-IMS was operated at ~3 Townsend (electric field/number density (E/N) or (Td)) and was coupled in series with a FAIMS, operated at ~80 Td. Ions were mobility-selected by the dual gate DT-IMS into the FAIMS and from the FAIMS the ions were detected by the QITMS for as either MS or MSⁿ. The system was evaluated using cocaine as an analytical standard and tested for the application of separating three isomeric tri-peptides: tyrosine-glycine-tryptophan (YGW), tryptophan-glycine-tyrosine (WGY) and tyrosine-tryptophan-glycine (YWG). All three tri-peptides were separated in the DT-IMS dimension and each had one mobility peak. The samples were partially separated in the FAIMS dimension but two conformation peaks were detected for the YWG sample while YGW and WGY produced only one peak. Ion validation was achieved for all three samples using QITMS.     

Qualitative analysis of trace constituents by ion mobility increment spectrometer

Ion mobility increment spectrometry (IMIS) is a high sensitive selective ionization technology for detection and identification of ultra-trace constituents, including toxic compounds, CW-agents, drugs and explosives in ambient air or liquid sample. Like an ion mobility spectrometry (IMS), this technology rests on sampling air containing a mixture of trace constituents, its ionization, spatial separation of produced ions and separated ions detection. Unlike IMS, ions of different types in IMIS are separated by ion mobility increment, α. Value α, is a function of the parameters: electric field strength and form, atmospheric pressure. To exclude the influence of these parameters on an α, the method of explosives identification by a standard compound was suggested. As a standard compound iodine was used. The relationship among the mobility coefficient increments equal to the relationship among the compensation voltage α_i/α_iodine=U_i/U_iodine is determined, where i are ions of 1,3-dinitrobenzene, 1,3,5-trinitrobenzene, p-mononitrotoluene, 2,4-dinitrotoluene and 2,4,6-trinitrotoluene This relationship is practically independent of the above mentioned parameters in the range 25<E/N<90 Td. The limits of the relative error of this relationship are determined both from spectra of individual compounds and nitrocompound-iodine mixtures.     

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.     

Profiling and imaging of tissues by imaging ion mobility-mass spectrometry

Molecular profiling and imaging mass spectrometry (IMS) of tissues can often result in complex spectra that are difficult to interpret without additional information about specific signals. This report describes increasing data dimensionality in IMS by combining two-dimensional separations at each spatial location on the basis of imaging ion mobility-mass spectrometry (IM-MS). Analyte ions are separated on the basis of both ion-neutral collision cross section and m/z, which provides rapid separation of isobaric, but structurally distinct ions. The advantages of imaging using ion mobility prior to MS analysis are demonstrated for profiling of human glioma and selective lipid imaging from rat brain.     

Metabolic profiling of Escherichia coli by ion mobility-mass spectrometry with MALDI ion source

Comprehensive metabolome analysis using mass spectrometry (MS) often results in a complex mass spectrum and difficult data analysis resulting from the signals of numerous small molecules in the metabolome. In addition, MS alone has difficulty measuring isobars and chiral, conformational and structural isomers. When a matrix-assisted laser desorption ionization (MALDI) source is added, the difficulty and complexity are further increased. Signal interference between analyte signals and matrix ion signals produced by MALDI in the low mass region (<1500 Da) cause detection and/or identification of metabolites difficult by MS alone. However, ion mobility spectrometry (IMS) coupled with MS (IM-MS) provides a rapid analytical tool for measuring subtle structural differences in chemicals. IMS separates gas-phase ions based on their size-to-charge ratio. This study, for the first time, reports the application of MALDI to the measurement of small molecules in a biological matrix by ion mobility-time of flight mass spectrometry (IM-TOFMS) and demonstrates the advantage of ion-signal dispersion in the second dimension. Qualitative comparisons between metabolic profiling of the Escherichia coli metabolome by MALDI-TOFMS, MALDI-IM-TOFMS and electrospray ionization (ESI)-IM-TOFMS are reported. Results demonstrate that mobility separation prior to mass analysis increases peak-capacity through added dimensionality in measurement. Mobility separation also allows detection of metabolites in the matrix-ion dominated low-mass range (m/z < 1500 Da) by separating matrix signals from non-matrix signals in mobility space.     

迁移管的电场强度对真空紫外电离-离子迁移谱仪性能的影响

离子迁移管是离子迁移谱仪的核心部分,它用来产生均匀的电场,以使不同迁移率的离子进行分离。本研究以丙酮为例,详细研究了本课题组所研制的真空紫外电离源-离子迁移谱仪中迁移管的电场参数对离子的灵敏度和分辨率的影响,发现电压的增大灵敏度增大,但是分辨率存在一个最佳的电压,这些结果可用于迁移谱的优化设计。     

单向气流负电晕放电离子迁移谱的研究及其在爆炸物检测中的应用

基于离子迁移谱的爆炸物探测仪多采用放射性电离源,发展非放射性电离源一直是该技术的研究热点。本研究基于电晕放电原理设计了一种新型负电晕放电电离源结构,结合自行研制的离子迁移谱仪,应用于痕量爆炸物的快速、高灵敏检测。单向气流模式下,对此电离源的气流、放电电压等运行参数进行了系统优化,得到最佳实验条件为：电晕放电电离源结构的电极环孔直径为3 mm,针-环距离为2 mm,放电电压为2400 V,漂气流速为1200 mL/min。在此条件下,避免了放电副产物氮氧化物和臭氧等引发的一系列复杂反应,得到了单一的反应试剂离子O-2(H2O)n。将其应用于爆炸物,如2,4,6-三硝基甲苯(TNT)、硝酸铵(AN)、硝化甘油( NG)、太安( PETN)、黑索金( RDX)等的高灵敏快速直接检测,对TNT的检测限达到200 pg/μL。结果表明,此负电晕放电电离源具有灵敏度高、结构简单、无辐射性、反应试剂离子单一等优点,在爆炸物快速高灵敏检测、公共安全保障等方面具有广阔的应用前景。     

Feasibility of higher-order differential ion mobility separations using new asymmetric waveforms

Technologies for separating and characterizing ions based on their transport properties in gases have been around for three decades. The early method of ion mobility spectrometry (IMS) distinguished ions by absolute mobility that depends on the collision cross section with buffer gas atoms. The more recent technique of field asymmetric waveform IMS (FAIMS) measures the difference between mobilities at high and low electric fields. Coupling IMS and FAIMS to soft ionization sources and mass spectrometry (MS) has greatly expanded their utility, enabling new applications in biomedical and nanomaterials research. Here, we show that time-dependent electric fields comprising more than two intensity levels could, in principle, effect an infinite number of distinct differential separations based on the higher-order terms of expression for ion mobility. These analyses could employ the hardware and operational procedures similar to those utilized in FAIMS. Methods up to the 4th or 5th order (where conventional IMS is 1st order and FAIMS is 2nd order) should be practical at field intensities accessible in ambient air, with still higher orders potentially achievable in insulating gases. Available experimental data suggest that higher-order separations should be largely orthogonal to each other and to FAIMS, IMS, and MS.