Structure selective ion molecule interactions (SSIMI) in ion mobility spectrometry

The overall objective of this project was to develop an analytical method that utilizes structure selective ion molecule interactions (SSIMI) in ion mobility spectrometry (IMS) to shift the mobility of a targeted analyte through the addition of a gas phase modifier to the buffer gas. IMS is a sensitive, rapid method for the detection of harmful chemicals; however false alarm responses do occur and a reduction in their frequency decrease both the cost and time required for detection. The investigation reported here probed the effects of a series of buffer gas modifiers on the mobilities of chemical warfare agent simulants (CWAs), toxic industrial chemicals (TICs) and a known interference (butyl carbitol) found in fire extinguishing agents. The major finding of this research was that a modifier with a proton affinity similar to, but not greater than, the target analyte produced the greatest changes in mobilities due to the formation of an ion cluster between the neutral modifier and target analyte ion. Mass spectrometry was utilized to confirm the formation of ion-neutral clusters that caused the target ion to shift its mobility. While a number of modifiers were screened, acetonitrile and isobutyronitrile were found to have sufficiently selective SSIMI with the target compound. For example, in the presence of acetonitrile modifier, the protonated response ion of the CWA simulant DMMP, [DMMP]H⁺, had a mobility shift of 10.8 %, but the mobility was unchanged for the interferent, butyl carbitol. The mobility of the simulant DMMP decreased with the introduction of modifiers, while the mobility of the interference did not change, demonstrating the potential of the SSIMI technique for reducing false alarm rates.     

The adduction behavior of water reactant ions with mobility shift reagents in ion mobility spectrometry is determined by the number of locations for adduction,interaction energies,proton affinities,and steric hindrance of these species

The introduction of mobility shift reagents (SRs) into the buffer gas of mobility spectrometers yields SR-ion clusters that decrease ion mobilities and allow the separation of overlapping ions. With a large amount of papers on the introduction of SRs in ion mobility spectrometry (IMS) few investigations explain the behavior of the adducts of reactant ions with SRs and it is not clear what type of peaks to expect which obscures the interpretation of spectra. Electrospray-ionization IMS was coupled to quadrupole mass spectrometry, and 2-butanol (B), ethyl lactate (L), and methanol were introduced as SRs into the buffer gas. The hybrid functional X3LYP/6–311++(d,p) with Gaussian 09 was used for theoretical calculations of SR-ion interaction energies. Adducts of the reactant ions with B and L presented different behaviors; even at low flow rates, L consumed all sodium, reactant ions, and water by adduction, because a) in the experimental conditions, SRs were more concentrated in the buffer gas than reactant ions, b) L’s high proton affinity and c) L’s three electron-donor oxygens, increases adduction. Therefore, chemical equilibria in the buffer gas were only between L and L_nH⁺, L_mH₃O⁺, or L_xNa⁺ adducts and, consequently, these sets of adducts had different mobilities. The lower mobility of L_mH₃O⁺ compared to L_nH⁺ was explained on the base of the lower steric hindrance in LH₃O⁺ for attachment of L molecules. The behavior of reactant ions with B was different: B_nH₃O⁺ and B_nH⁺ overlapped because the relatively low proton affinity and the single and weaker interaction site in B allowed protons and water to be exchanged between species. Finally, L₄H⁺, L₄H₃O⁺, B₄H⁺ and B₅H⁺ ions, not reported before, were seen for large SR concentrations. This study explains two different behaviors of the adducts of SRs with reactant ions using interaction energies, proton affinities, steric hindrance, and the number of locations for adduction.     

Quantitative ion mobility spectroscopy based on molecular collision rate theory

Atmospheric pressure chemical ionization and ion mobility spectrometry (IMS) have traditionally been viewed as a qualitative analytical technique for identifying specific chemicals in the atmosphere. This work employs a nonlinear model based on molecular collision rate theory for quantitative modeling of chemical analyte concentrations. The collision rate between any two molecules depends on the relative populations of each chemical species in the volume of air analyzed where most collisions between ions, or neutral molecules and ions, result in no charge transfer. The rate constants for formation of product ions and consumption of source ions are estimated using empirical data over a wide concentration range for several analytes and reagent gases. The rate constants are unique to the analyte and the reagent gas as well as the sensitivity of the particular IMS instrument and provide a quantitative model to relate the mobility peak amplitudes to the analyte concentration. The rate constants can also be normalized by the reaction ion consumption rate constant to remove the IMS instrument sensitivity and provide a qualitative metric for analyte identification independent of a particular IMS instrument. A quantitative example is given for an acetic acid plume measured by a hand-held IMS detector outdoors has the plume passes. The quantitative rate constants provide a reasonable basis for estimating analyte concentration from the ion mobility spectra over a wide range of analyte concentrations.     

The effect of humidity on sensitivity of amine detection in ion mobility spectrometry

Vaporized water molecules are unavoidably present in every ion mobility spectrometry (IMS) measurement. In general, this humidity is seen in positive mode IMS-spectra as protonated water clusters producing reactant ions. Clusters containing water molecules are also abundant among ions generated by an analyte. In this paper the influence of humidity on IMS-spectra was systematically investigated and determined by measuring different concentrations of a selected amine at various levels of humidity. The selected amine, trimethylamine (TMA), was chosen as the model analyte due to its atmospheric importance. During the measurements, surplus water vapor was introduced into the drift section inside the IMS instrument; the concentrations of both amine and water were adjusted by controlling the gas flows. The simultaneous presence of water vapor and analyte at various predefined concentrations revealed the sensitivity of the IMS-technique to water and the effect of moisture on the ion mobility distribution. The results indicated that the existence, positions and shapes of the peaks are strongly dependent on the amount of moisture. However, the sensitivity of detection is weakly dependent on humidity if this detection is based on monomer ion peak or the sum of peaks generated by the analyte, In addition, the main principles of the adjustment of sample and water concentrations are presented here.     

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.     

Caffeine and glucosamine mobility shifts by adduction with 2‐butanol depended on interaction energy,charge delocalization,and steric hindrance in ion mobility spectrometry

Ion mobility spectrometry (IMS) is an analytical technique that separates gas‐phase ions drifting under an electric field according to their size to charge ratio. We used electrospray ionization‐drift tube IMS coupled to quadrupole mass spectrometry to measure the mobilities of glucosamine (GH⁺) and caffeine (CH⁺) ions in pure nitrogen or when the shift reagent (SR) 2‐butanol was introduced in the drift gas at 6.9 mmol m⁻³. Binding energies of 2‐butanol‐ion adducts were calculated using Gaussian 09 at the CAMB3LYP/6‐311++G(d,p) level of theory. The mobility shifts with the introduction of 2‐butanol in the drift gas were −2.4% (GH⁺) and −1.7% (CH⁺) and were due to clustering of GH⁺ and CH⁺ with 2‐butanol. The formation of GBH⁺ was favored over that of CBH⁺ because GBH⁺ formed more stable hydrogen bonds (83.3 kJ/mol) than CBH⁺ (81.7 kJ/mol) for the reason that the positive charge on CH⁺ is less sterically available than on GH⁺ and the charge is stabilized by resonance in CH⁺. These results are a confirmation of the arguments used to explain the drift behavior of these ions when ethyl lactate SR was used (Bull Kor Chem Soc 2014, 1023–1028). This study is a step forward to predict IMS separations of overlapping peaks in IMS spectra, simplifying a procedure that is trial and error by now.     

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.     

Ion characterisation by comparison of ion mobility spectrometry and mass spectrometry data

The major uncertainty related to ion mobility spectrometry is the lack of knowledge about the characteristics of the ions detected. When using a radioactive atmospheric pressure ionisation source (e.g. ⁶³Ni), from theory proton bound water clusters are expected as reactant ions. When analyte ions occur, proton transfer should lead to proton-bound monomer and dimer ions. To increase the knowledge about those ionisation processes in an ion mobility spectrometer (IMS), a ß-radiation ionisation source was coupled to a mass spectrometer (MS) and an identical one to an IMS. Exemplarily, acetone, limonene and 2- and 5-nonanone were introduced into both instruments in varying concentrations. By correlating the MS and IMS spectra, conclusions about the identities of the ions detected by IMS could be drawn. Proton-bound monomer, dimer and even trimer ions (MH⁺, 2MH⁺, 3MH⁺) could be observed in the MS spectra for acetone and 5-nonanone and could be assigned to the related signals detected by IMS. The oligomers could be expected from theory for increasing concentration. Limonene and 2-nonanone yielded in a variety of different ions and fragments indicating complex gas phase ion chemistry. Those findings on the obviously different behaviour of different analytes require further research focussed on the ion chemistry in IMS including the comparison of different ionisation sources.     

Laserspray ionization (LSI) ion mobility spectrometry (IMS) mass spectrometry

A simple device is described for desolvation of highly charged matrix/analyte clusters produced by laser ablation leading to multiply charged ions that are analyzed by ion mobility spectrometry-mass spectrometry. Thus, for example, highly charged ions of ubiquitin and lysozyme are cleanly separated in the gas phase according to size and mass (shape and molecular weight) as well as charge using Tri-Wave ion mobility technology coupled to mass spectrometry. This contribution confirms the mechanistic argument that desolvation is necessary to produce multiply charged matrix-assisted laser desorption/ionization (MALDI) ions and points to how these ions can be routinely formed on any atmospheric pressure mass spectrometer.     

Ion mobility spectrometry – Mass spectrometry coupling for synthetic polymers

This review covers applications of ion mobility spectrometry (IMS) hyphenated to mass spectrometry (MS) in the field of synthetic polymers. MS has become an essential technique in polymer science, but increasingly complex samples produced to provide desirable macroscopic properties of high‐performance materials often require separation of species prior to their mass analysis. Similar to liquid chromatography, the IMS dimension introduces shape selectivity but enables separation at a much faster rate (milliseconds vs minutes). As a post‐ionization technique, IMS can be hyphenated to MS to perform a double separation dimension of gas‐phase ions, first as a function on their mobility (determined by their charge state and collision cross section, CCS), then as a function of their m/z ratio. Implemented with a variety of ionization techniques, such coupling permits the spectral complexity to be reduced, to enhance the dynamic range of detection, or to achieve separation of isobaric ions prior to their activation in MS/MS experiments. Coupling IMS to MS also provides valuable information regarding the 3D structure of polymer ions in the gas phase and regarding how to address the question of how charges are distributed within the structure. Moreover, the ability of IMS to separate multiply charged species generated by electrospray ionization yields typical IMS‐MS 2D maps that permit the conformational dynamics of synthetic polymer chains to be described as a function of their length.     

Evaluation of capillary liquid chromatography-electrospray ionization ion mobility spectrometry with mass spectrometry detection

Due to the proteomics revolution, multi-dimensional separation and detection instruments are required to evaluate many peptides and proteins in single samples. In this study, electrospray ionization (ESI) ion mobility spectrometry (IMS) was evaluated as an additional separation after HPLC separations. Common HPLC mobile phase compositions (solvents, acid modifiers, and buffers) were assessed for the effect on ESI-IMS response. Up to 5 mM sodium phosphate, a non-volatile buffer, was able to be electrosprayed into the IMS without degradation of the instrumental performance. Due to the rapid separation times of IMS, multiple IMS spectra were obtained within a single HPLC peak. A five-peptide mixture was separated in a capillary HPLC column under isocratic conditions within 3 min. Coelution of two peaks due to non-optimal HPLC conditions occurred and these two peaks could not be distinguished by HPLC with UV detection. In contrast, the single ion mobility chromatograms provided separation of each peptide as well as providing a second degree of analyte identification (HPLC retention time and IMS mobility). Furthermore, IMS-MS analysis of the five peptides and comparison with HPLC retention times showed that each peptide had a unique retention time-ion mobility-mass to charge value. This work showed that IMS could be employed for direct separation and detection of HPLC eluents and also could be combined with HPLC-MS for three unique dimensions of separation.     

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.     

Gas chromatography with state-of-the-art micromachined differential mobility detection: operation and industrial applications

Ion mobility spectrometry (IMS) has potential analytical applications in very diverse fields such as chemical, petrochemical, environmental, and, more recently, in drug, chemical warfare agent, and explosives detection. Commercially available IMS instruments are based on time-of-flight (TOF) mass spectrometry. IMS is inherently suitable for field operation as it uses relatively simple microfluidic devices and operates at atmospheric pressure. It is portable, highly sensitive with tunable selectivity, yet can be produced at relatively low cost. Key limitations of this analytical detection technique are low duty cycle, ion cluster formation, short linear dynamic range, and restriction to only positive or negative ion collection in a single analysis. Microelectromechanical system, radio frequency modulated IMS (MEMS RF-IMS), also known as differential mobility spectrometry, has recently been developed and commercialized. The technology is based on IMS, and MEMS RF-IMS offers substantially better performance. In this study, the strengths and limitations of the recently introduced differential mobility detector when used with gas chromatography in trace analyses are discussed and illustrated with applications of industrial significance.     

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.     

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.     

Fingerprinting bacterial strains using ion mobility spectrometry

Ion mobility spectrometry (IMS) is currently in widespread use for the detection and identification of narcotic and explosive compounds without prior sample clean-up or concentration steps. IMS analysis is rapid, less than a minute, and sensitive, with detection limits in the nanogram to picogram range, depending on the target analyte. Our studies indicate that this technique has potential for detection of specific components of bacterial cells and for identification and differentiation of bacterial strains and species within a minute, and with no specialized test kits or reagents required. When microgram quantities of whole bacterial cells are thermally desorbed, complex positive or negative ion patterns (plasmagrams) are obtained. These plasmagrams differ reproducibly for different strains and species and for different conditions of growth, and can be used for the classification and differentiation of specific strains and species of bacteria, including pathogens. Methods for improved ion peak detection, most notably sequential sample desorption at stepped increases in temperature (programmed temperature ramping), are described.     

Ion mobility spectrometry: a personal retrospective

With a background in mass spectrometric studies of gas-phase ion chemistry the atmospheric pressure technology of ion mobility spectrometry (IMS) presented me with challenges and opportunities. Fundamental studies of the parameters that influence the mobility of ions in a low electric field yielded insights about the effects of temperature, drift gas composition and the conformation of ions on the collision cross section. The inadequacy of current rigid-sphere, polarization limit and hard-core models to predict the mobility of ions particularly at low temperature and in heavy drift gases, led to inclusion of additional terms to the hard-core model to account for these effects. These studies eventually resulted in the two monographs entitled “Ion Mobility Spectrometry” and “Ion Mobility Spectrometry –Second Edition” co-authored with Prof. Gary Eiceman and published by Taylor & Francis, CRC Press in 1994 and 2005, respectively. Novel applications for biological and medical applications were developed on the basis of measurement of biogenic amines by IMS, in particular the rapid, accurate and inexpensive diagnosis of vaginal infections.     

The use of dopants in high field asymmetric waveform spectrometry

Ion mobility spectrometry (IMS) is proven core technology for the gas-phase detection of chemical warfare (CW) agents. One disadvantage of IMS technology is that ions of similar mobility cannot readily be resolved, resulting in false alarm responses and a loss of user confidence. High field asymmetric waveform spectrometry (HiFAWS) is an emerging technology for the gas-phase detection of CW agents. Of particular interest is the potential of a HiFAWS-based platform to reduce the number of false alarms by resolving ions that cannot be discriminated using IMS. It has been demonstrated that a water clustering/declustering mechanism can be a dominant process in HiFAWS. Ions that cannot be discriminated in IMS because they possess the same low field mobility value can be resolved using HiFAWS due to differences in the extent of low field ion solvation and high field ion desolvation. When operating in complex environments such as those potentially experienced in military and security arenas, IMS systems commonly employ internal dopants to reduce the number of background responses. It is possible that HiFAWS systems may also require the use of internal dopants for the same reason. It has been demonstrated that dopants employed for use in IMS may not be suitable for use in HiFAWS.     

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.     

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).