During the last decade, the Denton Research Group has made significant advancements in the field of real time direct vapor detection of low volatile explosives under ambient conditions. An ion source plays a crucial role in the sensitive detection of traces of compounds in gas phase by ion mobility spectrometry, but, all the current ionization techniques have significant drawbacks and do not fully satisfy all needs. To overcome the limitations associated with either hazards from a radiogenic ion source or poor reliability from the current non-radiogenic ion sources, the author of this dissertation has undertaken the development of an entirely new ion source based on dielectric barrier discharge technologies. This dissertation describes the development, characterization, and applications of novel dielectric barrier discharge (DBD) ion sources for ion mobility spectrometry. The sources under investigation are non-radiogenic, highly reliable, and provide a high yield of ions. The difficulty of extracting ion current from a traditional dielectric barrier discharge was solved by using an array of tiny discharges formed at the crossing points of two crossed sets of glass coated wires. The relationship of the excitation voltage, frequency, and extraction field for AC excitation on the extracted ion current were studied. The dielectric barrier discharge ion source were also excited in pulse mode by fast-rising and fast-falling high voltage pulses. A high voltage switch using serial MOSFETs was specially designed for driving the dielectric barrier discharge ion source in pulse mode. Application of this dielectric barrier discharge ion source to ion mobility spectrometry was demonstrated with the measurement of limit of detection and direct vapor detection of explosives.

Glycans and their conjugates form the largest and most diverse class of biological molecules found within nature. These glycosides are vital for numerous cellular functions including recognition events, protein stabilisation and energy storage, to name a few. Additionally, abnormalities within these structures are associated with a wide range of disease states. As a result, robust analytical techniques capable of in depth characterisation of carbohydrates and their binding partners are required. Currently, liquid chromatography coupled with tandem mass spectrometry (MS2) is the 'gold standard' for characterising these species. However there are inherent challenges for 'sequencing' carbohydrates given that most structures are diastereomeric. As a result MS alone is insufficient to fully elucidate all stereochemical and often regiochemical information and alternative analytical techniques have inherent issues meaning that they are not suitable for medium/high throughput analysis. To facilitate elucidation of these structures, ion mobility spectrometry (IMS) has been used in-line with MS2. IMS of mono- and di-saccharide product ions generate by collision-induced dissociation (CID) of various glycans and their conjugates enables unambiguous identification of the monomer and the regio-/stereo-chemistry of the glycosidic bond, independent of the precursor structure. Also, given the prominence of glycans in biological recognition events, high-throughput techniques capable of elucidating and characterising carbohydrate to glycan-binding protein (GBP) interactions are highly sought after. Historically, (micro)array strategies are employed to screen large numbers of biological interactions, with detection conventionally achieved with fluorescent tagging. The major disadvantage of this approach is the requirement of a labelling step to facilitate detection of glycan-GBP binding. MS offers the ability to unambiguously identify GBPs when combined with routine bottom-up proteomics strategies, namely on-chip proteolysis followed by mass fingerprinting and MS2 analysis and subsequent comparison to protein databases. It is anticipated that these methodologies developed throughout these studies, both for carbohydrate sequencing and the characterisation of glycan-binding proteins, will greatly add to the Glycomics toolbox.

The characterization of biomolecules and biomolecular complexes represents an area of significant research activity because of the link between structure and function. Drug development relies on structural information in order to target certain domains. Many traditional biochemical techniques, however, are limited by their ability to characterize only certain stable forms of a molecule. As a result, multidimensional approaches, such as ion mobility mass spectrometry coupled to mass spectrometry (IMS-MS), are becoming very attractive tools as they provide fast separation, detection and identification of molecules, in addition to providing three-dimensional shape for structural elucidation. The present work expands the use and application of trapped ion mobility spectrometry-coupled to mass spectrometry (TIMS-MS) by analyzing a range of biomolecules (including proteoforms, intrinsically disordered peptides, DNA and molecular complexes). The aim is to i) evaluate the TIMS platform measuring sensitivity, selectivity, and separation of targeted compounds, ii) pioneer new applications of TIMS for a more efficient and higher throughput methodologies for identification and characterization of biomolecular ions, and iii) characterize the dynamics of selected biomolecules for insight into the folding pathways and the intra-or intermolecular interactions that define their conformational space.

The drift time spectra of polycyclic aromatic hydrocarbons (PAH), alkylbenzenes and alkylphenylethers were recorded with a laser-based ion mobility (IM) spectrometer. The ion mobilities of all compounds were determined in helium as drift gas. This allows the calculation of the diffusion cross sections (Omegacalc) on the basis of the exact hard sphere scattering model (EHSSM) and their comparison with the experimentally determined diffusion cross sections (Omegaexp). These Omegaexp/Omegacalc-correlations are presented for molecules with a rigid structure like PAH and prove the reliability of the theoretical model and experimental method. The increase of the selectivity of IM spectrometry is demonstrated using resonance enhanced multiphoton ionisation (REMPI) at atmospheric pressure, realized by tuneable lasers. The REMPI spectra of nine alkylbenzenes and alkylphenylethers are investigated. On the basis of these spectra, the complete qualitative distinction of eight compounds in a mixture is shown. These experiments are extended to alkylbenzene isomer mixtures.

In the new era of drug abuse, the proliferation of new psychoactive substances (NPS), commonly referred to as designer drugs or legal highs, has been a global concern. These substances are produced to circumvent current legislation for controlled substances with minor modifications in their chemical structure. Although many efforts have been made previously, the characterization of such substances are still challenging because of (1) the continual emergence of newly identified substances, (2) the lack of a universal screening test for NPS that are structurally similar to each other, and (3) the complex and time-consuming chromatographic techniques currently used. Therefore, it is necessary to develop novel analytical methods that can be readily adapted by forensic laboratories to overcome these challenges. In this dissertation, various analytical techniques have been evaluated for qualitative analysis of these emerging NPS. For rapid screening purposes, a commercial ion mobility spectrometry with a 63Ni ion source (63Ni-IMS) and also direct analysis in real time coupled to a quadrupole time-of-flight mass spectrometer (DART-QTOF-MS) were investigated first. The results showed that rapid detection by 63Ni-IMS and identification by DART-QTOF-MS can be achieved with sub-nanogram detection capability and high speed total analysis time less than two minutes. In recent developments of gas chromatography mass spectrometry (GC-MS), gas chromatography (GC) has been coupled to state-of-the-art mass spectrometers, including triple quadrupole (MS/MS) and quadrupole time-of-flight (QTOF). It was revealed that the application of GC-MS/MS and GC-QTOF facilitates the unambiguous identification of emerging NPS with a chemical ionization (CI) source. In addition, constitutional isomers of NPS were differentiated with the capabilities of product ion scan and multiple reaction monitoring (MRM) modes. Finally, the coupling of IMS with a mass spectrometer (IMS-MS) was investigated as an alternative confirmatory technique. With the development of an optimal solvent system in the electrospray ionization (ESI) process, the rapid analysis and identification of synthetic cathinone was successfully achieved less than five minutes. As a proof-of-concept, seized drugs samples provided by a local forensic laboratory were analyzed using these developed methods by various analytical techniques. The results from these seized samples are also presented in this evaluation.

Smokeless powder additives are usually detected by their extraction from post-blast residues or unburned powder particles followed by analysis using chromatographic techniques. This work presents the first comprehensive study of the detection of the volatile and semi-volatile additives of smokeless powders using solid phase microextraction (SPME) as a sampling and pre-concentration technique. Seventy smokeless powders were studied using laboratory based chromatography techniques and a field deployable ion mobility spectrometer (IMS). The detection of diphenylamine, ethyl and methyl centralite, 2,4-dinitrotoluene, diethyl and dibutyl phthalate by IMS to associate the presence of these compounds to smokeless powders is also reported for the first time. A previously reported SPME-IMS analytical approach facilitates rapid sub-nanogram detection of the vapor phase components of smokeless powders. A mass calibration procedure for the analytical techniques used in this study was developed. Precise and accurate mass delivery of analytes in picoliter volumes was achieved using a drop-on-demand inkjet printing method. Absolute mass detection limits determined using this method for the various analytes of interest ranged between 0.03 - 0.8 ng for the GC-MS and between 0.03 - 2 ng for the IMS. Mass response graphs generated for different detection techniques help in the determination of mass extracted from the headspace of each smokeless powder. The analyte mass present in the vapor phase was sufficient for a SPME fiber to extract most analytes at amounts above the detection limits of both chromatographic techniques and the ion mobility spectrometer. Analysis of the large number of smokeless powders revealed that diphenylamine was present in the headspace of 96% of the powders. Ethyl centralite was detected in 47% of the powders and 8% of the powders had methyl centralite available for detection from the headspace sampling of the powders by SPME. Nitroglycerin was the dominant peak present in the headspace of the double-based powders. 2,4-dinitrotoluene which is another important headspace component was detected in 44% of the powders. The powders therefore have more than one headspace component and the detection of a combination of these compounds is achievable by SPME-IMS leading to an association to the presence of smokeless powders.

Indiana University-Purdue University Indianapolis (IUPUI) / Ion mobility spectrometry is a powerful technique for the study related to molecule. The work of tow major applications are introduced in this paper. The first application is the optimization of parameters in CCS. The accurate calculation of the collision cross section for multiple molecules is a long-time interested topic in the research for substances detection in micro scale. No reliable analytical approach to calculate the collision cross section has been established to date. Different approaches rely on different mechanism will provide different results in significant extent. This work introduce a method for the determination of parameters in the Lennard Jones potential. Experimental data combined with numerical computation was the fundamental strategy during the optimization of the parameters. In the experiment, electrospray is used as the ion source of IMS while a nebulizer was utilized to electrify the aromatic compounds. New parameters show no less accuracy and equal efficiency while can explain the physical meaning of the collision more clearly. The second application is the trace detection of explosives with very low concentration. The detection of explosives is an important topic in security, while the detection will be difficult due to the low vapor pressure of explosives. In this work, two types of devices are designed for the trace detection of explosives at an extremely low concentration. TNT is selected as the explosives in the experiment. The experiment succeed to reach a sensitivity of 1 part per quintillion, and even find out a linear relationship between the logarithm of TNT concentration and TNT vapor pressure.

Mass spectrometry has frequently been employed in the analysis of biologically relevant molecules; however, mass spectrometry alone may not always be sufficient for the differentiation and characterization of isomeric and isobaric ions. In this work, infrared multiple photon dissociation (IRMPD) spectroscopy and ion mobility spectrometry (IMS) were evaluated as complementary techniques for the characterization and separation of isomeric and isobaric ions of biological relevance. In the first project, analysis of experimental IRMPD spectroscopy data shows that this technique is useful in the differentiation of hydroxyproline isomers. Absorption bands allow for the differentiation of three isomeric species: 1640 cm-1 (trans-4-hydroxyproline), 1718 cm-1 (cis-4-hydroxyproline), and 1734 cm-1 (cis-3-hydroxyproline). In the second project, theoretical CCS and IR spectroscopy predictions of isobaric modified amino acids and isomeric drugs have been carried out as predictions of IMS and IRMPD spectroscopy suitability. Preliminary IMS measurements suggest that the CCS predictions are at least qualitatively useful.

No description available.

The use of laser desorption as a sample introduction method for solid phase microextraction (SPME) has been investigated in this research project. Three different types of analytical instruments, mass spectrometry (MS), ion mobility spectrometry (IMS) and gas chromatography (GC) were employed as detectors. The coupling of laser desorption SPME to these three instruments was constructed and described in here. <br /><br /> Solid phase microextraction/surface enhanced laser desorption ionization fibers (SPME/SELDI) were developed and have been coupled to two IMS devices. SPME/SELDI combines sampling, sample preparation and sample introduction with the ionization and desorption of the analytes. Other than being the extraction phase for the SPME fiber, the electro-conductive polymer coatings can facilitate the ionization process without the involvement of a matrix assisted laser desorption/ionization (MALDI) matrix. The performance of the SPME coatings and the experimental parameters for laser desorption SPME were investigated with the SPME/SELDI IMS devices. The new SPME/SELDI-IMS 400B device has a faster data acquisition system and a more powerful data analysis program. The optimum laser operation parameters were 250 <em>&mu;J</em> laser energy and 20 <em>Hz</em> repetition rate. Three new SPME coatings, polypyrrole (PPY), polythiophene (PTH) and polyaniline (PAN) were developed and evaluated by an IMS and a GC. The PPY coating was found to have the best performance and was used in most of the experiments. The characteristics of the PPY and the PTH SPME/SELDI fiber were then assessed with both IMS and MS. Good linearity could be observed between the fiber surface area and the signal intensity, and between the concentration and the signal intensities. <br /><br /> The ionization mechanism of poly(ethylene glycol) 400 (PEG) was studied with the SPME/SELDI-IMS 400B device. It was found that the potassiated ions and sodiated ions were both present in the ion mobility spectra. The results obtained with quadrupole time-of-flight (QTOF) MS confirmed the presence of both potassiated and sodiated ions. This result suggested that cationization is the main ionization process when polymers are directly ionized from the PPY coated silica surface. Four PEGs with different average molecular weights and poly(propylene glycol) 400 were also tested with this SPME/SELDI device. The differences between the ion mobility spectra of these polymers could be used for the fast identification of synthetic polymers. <br /><br /> The SPME/SELDI fibers were then coupled to QTOF MS and hybrid quadrupole linear ion trap (QqLIT) MS, respectively. Improved sensitivity could be achieved with QqLIT MS, as the modified AP MALDI source facilitated the ion transmission. The application of method for analysis of urine sample and the bovine serum albumin (BSA) digest were demonstrated with both PPY and PTH fibers. The LOD for leucine enkephalin in urine was determined to be 40 <em>fmol &mu;L^-1</em> with PTH coated fiber; and the LOD for the BSA digest was 2 <em>fmol &mu;L^-1</em> obtained with both PTH and PPY fibers. <br /><br /> A new multiplexed SPME/AP MALDI plate was designed and evaluated on the same QqLIT MS to improve the throughput, and the performance of this technique. The experimental parameters were optimized to obtain a significant improvement in performance. The incorporation of diluted matrix to the extraction solution improved the absolute signal and S/N ratio by 104X and 32X, respectively. The incorporation of reflection geometry for the laser illumination improved the S/N ratio by more than two orders of magnitude. The fully optimized high throughput SPME/AP MALDI configuration generated detection limit improvements on the order of 1000-7500X those achieved prior to these modifications. This system presents a possible alternative for qualitative proteomics and drug screening. <br /><br /> Laser desorption SPME as a sample introduction method for the fast analysis of non-volatile synthetic polymers was also demonstrated here. The coupling of laser desorption SPME to GC/FID and GC/MS was performed, and the advantage of laser desorption over traditional thermal desorption was demonstrated in this research. Laser desorption PEG 400 was observed more effcient than thermal desorption. Good separation was obtained even with a 1-m or 2-m column. These results demonstrate the potential of laser desorption SPME as a sample introduction method for the fast GC analysis of non-volatile compounds such as synthetic polymers.