Advances in High Field Asymmetric Ion Mobility Spectrometry (FAIMS) Analyzers and FAIMS-Mass Spectrometry Interfaces

High field asymmetric ion mobility spectrometry (FAIMS) is a gas phase separation technique that separates ions by the ratio of high to low electric field mobility, which is a characteristic of the three dimensional structure of ions. FAIMS separation in front of mass spectrometric analysis has the ability to reduce chemical noise thereby increasing signal-to-noise ratios and limits of detection; it can also be used to separate isobaric and isomeric compounds. FAIMS analyzers are simple to construct and are easily integrated into the atmospheric pressure ion source of current mass spectrometers without major modifications. The motivation of developing FAIMS analyzers in the Glish lab has been for the study of three dimensional gas phase ion structure of biological molecules, as well as to improve separation of compounds which are irresolvable using low resolution mass spectrometry and liquid chromatography. This dissertation does not focus on the application of FAIMS for structural elucidation, but instead on the development of a FAIMS device that combines excellent speed, resolution, and sensitivity in a simple to use small package. Described in the following chapters are the background for selection of gas phase ions by shape to charge, the development of a high amplitude asymmetric waveform power supply, modifications made the planar FAIMS device designed by the Pacific Northwest National Lab and the development of four generations of planar FAIMS devices. For each device limitations and flaws in the design are discussed along with proposed solutions and data demonstrating the results of modifications to analyzer design, and the successful construction of a planar FAIMS device with high speed, high sensitivity, and resolving power equal to much larger and more expensive devices

Development of a Portable Mass Spectrometer for Operation at 1 Torr

Portable mass spectrometers have obtained increased interests because they show great potential in different fields such as the industrial process analysis, forensics, environmental monitoring, space exploration and homeland security. Current major standard laboratory mass spectrometers have been miniaturized and their characteristics were investigated. The advantages and disadvantage of these different types of mass analyzers are also compared and examined.;Loeb-Eiber mass filter was proposed and reexamined as an alternate portable mass analyzer. Its unique paradigm makes it very suitable for development for portable mass spectrometers. The second generation Loeb-Eiber mass analyzer uses an array of short wires attached on the base instead of two long wires spooled on the base which greatly improves ion transmission to 25% from 6.25% of first generation analyzer. Also the capacitance reduced to 70 pF from 5000 pF of the first generation. The third generation Loeb-Eiber mass analyzer is fabricated based on silicon-on-insulator (SOI) using microelectromechanical system (MEMS). The electrode has square cross section that allows more ions oscillating in between adjacent electrodes compared to round electrodes. Different tuning circuits are also constructed to match the different mass filters. Glow discharge and electron ionization sources were also built and characterized

STUDY OF DETECTION OF INORGANIC IONS BY ELECTROSPRAY MASS SPECTROMETRY AND DEVELOPMENT OF ION MOBILITY SPECTROMETRY AND ITS APPLICATIONS

This thesis focuses on the development of a novel drift tube and novel pulse circuit design for ion mobility spectrometry in combination with different ionization methods for various applications, as well as aspect of electrospray mass spectrometry of inorganic ions. The first project was the study of the measurement of a mixture of inorganic cations using an electrospray ion-trap mass-spectrometry normally used for neutral organic compounds. The mass spectra showed the production of solvent clusters, which could be minimized by making use of the collision-induced dissociation capability of the instrument as well as by heating of the inlet tube. The collision-induced dissociation (CID) voltages were optimized to reduce adduct and cluster formation. The use of an internal standard for construction of linear calibration lines was studied. The work showed potential for quantitation of mixtures of inorganic ions using the electrospray mass spectrometer. In the second project, a gas sensor based on a field asymmetric ion mobility spectrometer was constructed in-house, coupled with a Krypton lamp as ionization source. A rectangular pulse was employed as the separation waveform for the drift tube instead of the commonly used but less efficient bi-sinusoidal waveform. The device was used for qualitative and quantitative measurement of ethylene gas that is emitted by climacteric fruit. For selectivity in the detection of ethylene, a Krypton lamp with a specific radiation energy (eV) was employed, leading to high ionization efficiency of ethylene and with other compounds having higher ionization energies not being ionized. The device was applied to the determination of ethylene given off by 6 types of climacteric fruits, namely apples, bananas, kiwi fruit, nectarines, pears and plums. In the third project, the novel use of flexible printed circuit board material for the construction of drift tubes for ion mobility spectrometry was developed. The circuit board was etched out to give narrow copper stripes which when rolled up produced a tube with a series of circular electrodes, equivalent to the ring electrodes of a conventional ion-mobility spectrometer. One- on-one comparison in terms of performance was evaluated between a conventional stacked ring set-up and the flexible PCB set-up. Its analytical capability was demonstrated with the determination of the C12, C14 and C16 benzalkonium ions (BACs) in commercial cleaning products. The fourth project was the development and construction of an ion shutter which is the key factor in an ion mobility spectrometer. The ion shutter controls the injection of pulses of ions into the drift tube. A very short injection time is required to achieve high resolution. Theoretically, ion shutters depend on the design of suitable electronic circuits to create a narrow pulse for the ion injection. A new design of circuitry for pulse generation applicable for an ion mobility spectrometer is reported. The design is based on an optocoupler for the gate or through the trimmer resistor, for switching a pulse with amplitude of 40-70 V at high voltage up to 10 kV. The optocoupled pulser was compared to those of MOSFET-based pulser by comparison of the detection of tetraalkylammonium ions. To the best of our knowledge, this is the first use of an optocoupler-based pulser for ion injection in the ion mobility spectrometer. The fifth project was the coupling of a plasma source to an ion mobility spectrometer for direct testing of pharmaceutical tablets. The miniature plasma source is mounted at an oblique angle at the injection gate of the ion mobility spectrometer. A helium plasma is created by using a high alternating voltage of 8 kV at 28 kHz and is employed for the desorption and ionization of solid or liquid samples, which are placed on an electrically isolated sample holder. The instrument was built in-house at low cost and with a design that can be easily constructed by other laboratories. The instrument was tested with the rapid identification of drugs in pharmaceutical tablets such as acetaminophen, caffeine, loratadine, norfloxacin, tadalafil, and thiamine. The sixth project was the application of an ion mobility spectrometer coupled with an electrospray ionization source for the determination of the antibiotic tobramycin in ophthalmic solution. This method allows the direct analysis of tobramycin in the solution. The ion mobility spectrometry uses the developed printed circuit board as the drift tube. In order to ensure that the benzalkonium ions used as preservative in the sample did not interfere with the tobramycin detection a solution of benzalkonium salts was also measured using the electrospray – ion mobility spectrometer. To the best of our knowledge, this is the first time of the ESI-IMS for direct determination of tobramycin in eye drops. The last project was the determination of the ethylene gas by ion mobility spectrometry in combination with a Krypton lamp as photoionization source. Such a UV lamp with a specific excitation energy of 10.6 eV, the ethylene can be selectively ionized for measurement. The device makes use of stacked printed circuit board material for the construction of the drift tube, which can be easily built in-house. The effect of a field strength and a flow rate of drift gas on the peak area and resolving power of ethylene peak was investigated. One possibility of interference, which was ethanol, was studied for possible overlapping of the peaks. The novel method was developed and validated for ethylene gas liberated from five fruits. i.e. apples, avocados, bananas, kiwi fruit and pears. The analysis time was 20 s for one measurement

High Resolution Ion Mobility Spectrometry with Increased Ion Transmission: Exploring the Analytical Utility of Periodic-Focusing DC Ion Guide Drift Cells

Drift tube ion mobility spectrometry (IMS) is a powerful, post-ionization separation that yields structural information of ions through an ion-neutral collision cross section. The ion-neutral collision cross section is governed by the collision frequency of the ion with the neutral drift gas. Consequently, ions of different size will have different collision frequencies with the gas and be separated in the drift cell. A significant challenge for IMS, however, is to separate ions with very similar collision cross sections, requiring higher resolution ion mobility spectrometers. Resolution in IMS is of utmost importance for the separation of complex mixtures, e.g. crude oil samples, proteolytic digests, positional isomers, and ion conformers. However, most methods employed to increase mobility resolution significantly decrease ion transmission through the mobility device. Herein, a periodic-focusing DC ion guide drift cell (PDC IG) is presented to display its potential capabilities for higher mobility resolution with increased ion transmission. The PDC IG utilizes unique electrode geometry compared to the conventional uniform field electrode design. Electrode geometry can be defined by the electrode inner diameter (d), thickness (t), and spacing (s). Specifically, the ratio of d : t : s is equal to, or very near, 1:1:1. The PDC IG electrode design creates a non-uniform (fringing) electric field-especially near the electrode walls. The design also causes variations in the radial electric field which provides an effective RF as ions move through the device and a radially confining effective potential that improves ion transmission through the device. In this dissertation the analytical utility of the PDC IG drift cell for ion mobility separations will be explored. The radial focusing properties of the device will be presented along with studies of electrode geometry and its effect on ion mobility resolution and ion transmission through the drift cell. PDC IG drift cell length is also examined to determine its effect on mobility resolution and ion transmission. Finally, the PDC IG drift cell device is coupled to an orthogonal-acceleration time-of-flight mass spectrometer as well as a modular, PDC IG drift cell being adapted to a commercial qTOF mass spectrometer for IM-MS experiments

A low cost gas phase analysis system for the diagnosis of bacterial infection

Drug resistance is becoming a major concern in both the western world and in developing countries. The over use of common anti-bacterial drugs has resulted in a plethora of multi-drug resistant diseases and an ever reducing number of effective treatments - and is now of major concern to the UK government. One of the major reasons behind this is the difficulty in identifying bacterial infections from viral infections, especially in primary care where patients have an expectation of receiving medication. For most viral conditions, there is no effective treatment and the body fights off the disease, thus prescribing anti-bacterial drugs simply results in the proliferation of drugs within the community - increasing the rate of drug resistance. Increasing drug resistance contributed to the rise of superbugs (drug resistant bacteria) which are expected to kill an about 10 million people a year worldwide by the year 2050 and could result to an economic loss of $63 trillion. Increasing drug resistance contributed to the rise of superbugs (drug resistant bacteria) which are expected to kill an about 10 million people a year worldwide by the year 2050 and could result to an economic loss of$63 trillion. Therefore, there is a strong medical and economic need to develop tools that can diagnose bacterial diseases from viral infections, focused towards primary care. One means of achieving this is through the detection of gas-phase biomarkers IX of disease. It is well known that the metabolic activity of bacteria is significantly different from its host. Many studies have shown that it is possible to detect a bacterial infection, identify the strain and its current life-cycle stage simply by measuring bacterial metabolic emissions. In addition, the human body's response to a bacterial infection is significantly different from a viral infection the human body's response to a bacterial infection is significantly different from a viral infection, allowing human stress markers to also be used for differentiating these conditions. Thus, there is evidence that these bio-markers exist and could be detected. However, a major limiting factor inhibiting the wide-spread deployment of this concept is the unit cost of the analytical instrumentation required for gas analysis. Currently, the main preferred methods are GCMS (gas chromatography/mass spectrometry), TOF-MS (time of flight - MS) and SIFT-MS (selective ion flow tube - MS). Though excellent at undertaking this role, the typical unit cost of these instruments is in excess of $100k, making them out of reach of current GP budgets. Therefore, what is required is a low-cost, portable instrument that can detect bacterial infections from viral infections and be applicable to primary care

Electronic nose implementation for biomedical applications

The growing rate of diabetes and undiagnosed diabetes related diseases is becoming a worldwide major health concern. The motivation of this thesis was to make use of a technology called the ‘electronic nose’ (eNose) for diagnosing diseases. It presents a comprehensive study on metabolic and gastro-intestinal disorders, choosing diabetes as a target disease. Using eNose technology with urinary volatile organic compounds (VOCs) is attractive as it allows non-invasive monitoring of various molecular constituents in urine. Trace gases in urine are linked to metabolic reactions and diseases. Therefore, urinary volatile compounds were used for diagnosis purposes in this thesis. The literature on existing eNose technologies, their pros and cons and applications in biomedical field was thoroughly reviewed, especially in detecting headspace of urine. Since the thesis investigates urinary VOCs, it is important to discover the stability of urine samples and their VOCs in time. It was discovered that urine samples lose their stability and VOCs emission after 9 months. A comprehensive study with 137 diabetic and healthy control urine samples was done to access the capability of commercially available eNose instruments for discrimination between these two groups. Metal oxide gas sensor based commercial eNose (Fox 4000, AlphaMOS Ltd) and field asymmetric ion mobility spectrometer (Lonestar, Owlstone Ltd) were used to analyse volatiles in urinary headspace. Both technologies were able to distinguish both groups with sensitivity and specificity of more than 90%. Then the project moved onto developing a Non-dispersive infrared (NDIR) sensor system that is non-invasive, low-cost, precise, rapid, simple and patient friendly, and can be used at both hospitals and homes. NDIR gas sensing is one of the most widely used optical gas detection techniques. NDIR system was used for diagnosing diabetes and gastro related diseases from patient’s wastes. To the best of the authors’ knowledge, this is the first and only developed tuneable NDIR eNose system. The developed optical eNose is able to scan the whole infrared range between 3.1μm and 10.5 μm with step size of 20 nm. To simulate the effect of background humidity and temperature on the sensor response, a gas test rig system that includes gas mixture, VOC generator, humidity generator and gas analyser was designed to enable the user to have control of gas flow, humidity and temperature. This also helps to find out system’s sensitivity and selectivity. Finally, after evaluating the sensitivity and selectivity of optical eNose, it was tested on simple and complex odours. The results were promising in discriminating the odours. Due to insufficient sample batches received from the hospital, synthetic urine samples were purchased, and diabetic samples were artificially made. The optical eNose was able to successfully separate artificial diabetic samples from non-diabetic ones

Driftröhrenionenmobilitätsspektrometrie laser-induzierte Fluoreszenzdetektion

The coupling of ion mobility spectrometry (IMS) and laser-induced fluorescence spectroscopy (LIF) at atmospheric pressure was realized in this work. The construction of a module based drift tube enabled the use of different ionization techniques, as well as the implementation of a laser induced fluorescence detection system and a Faraday plate detector. With the analysis of the ionized dye Rhodamine 6G the system was characterized. For this, a “homemade” electrospray ionization source was used as ion source. At a distance of approximately 9 mm from the ESI tip to the drift tube entrance, a high desolvation rate of gaseous Rhodamine 6G was observed. The length of the drift tube was 3.2 cm. The drift time resolved laser induced fluorescence analysis of ions at ambient conditions on the example of dye Rhodamine 6G was investigated in a simplified IMS drift cell of open design. Continuous wave radiation at a wavelength of 447 nm and 462 nm was used for excitation. The maxima of the fluorescence were observed at λ = 505 nm. The drift time resolved fluorescence emission was monitored by a spectrograph in combination with a gated intensified charge coupled device. The dependencies of Rhodamine 6G fluorescence intensities (continuous ion flow) on the electric fields of both the ion gate field and the drift field were determined at the exit of the 32 mm long drift cell. With increasing gate voltage, the signal intensity decreased. With an electrospray flow rate of 300 nL min-1 and a laser diode with 462 nm used as excitation source, a gate voltage of ≥ 50 V was required to block or deflect fluorescent ions of Rhodamine 6G in the drift cell. The increase of the fluorescence intensity was proportional to the electric field strength in the range of 510 - 638 V cm-1. Drift time dependent (pulsed ion flow) LIF analysis was performed under optimized conditions (462 nm, ESI flow rate 300 nL min-1, gate voltage 80 V, ICCD integration time: 100 μs). The drift time spectra produced with both, the Faraday plate detector and the laser induced fluorescence detector showed the same trends. Significantly smaller FWHM were found with the LIF detector as compared to that found with the electrometer. Based on the findings of the experiments with Rhodamine 6G, the experimental setup for PAH analysis was designed and developed. A unidirectional flow, closed, heated (up to 200° C) drift iv tube (length: 16.8 cm) ion mobility spectrometer with photoionization source (VUV Kr, 10.0/10.6 eV) was implemented in a pulsed laser induced fluorescence detection system. With this setup it was possible to investigate the dependence of the fluorescence intensity of selected PAH (continuous ion introduction) on the experimental parameters such as: PID-lamp current, ion gate voltage, electric field strength in the drift tube. The fluorescence intensity was dependent on the PID lamp current. The rise of both the fluorescence intensity and the continuous ion current with the increase of the PID lamp current was observed. The simultaneous decrease of both the total ion current and the fluorescence intensity with the increase of the ion gate voltage was monitored. The generated by photoionization ions could be transported through the drift region and detected with the laser induced fluorescence monitoring system. The LIF signal intensities increased proportional to the drift field strength in the range of 157 – 265 V cm-1

Study of gas ionization in a glow discharge and development of a micro gas ionizer for gas detection and analysis

In the pursuit of a portable gas detector/analyser we studied the components of an ion mobility spectrometer (IMS), which is a device that lends itself well to miniaturisation. The component we focused on was the ionizer. We fabricated a series of micro ionizers with micro electromechanical systems (MEMS) technology, which had a gap spacing between 1 and 50 μm and a thickness from 0.3 to 50 μm. They were used to examine micro discharges as such and as a means of ionization. In our measurements of electrical breakdown in small gaps we confirmed the deviation from Paschen's law for breakdown voltages in gaps below 5 μm. One important result is the identification of conditions for stable DC glow discharge in micro gaps. With planar electrodes we observed stable glow for factors of pressure times gap distance pd up to 0.2 Pa×m in N2, and up to 0.14 Pa×m in Ar. With thick electrodes the glow range was extended: up to 4 Pa×m in Ar, and 10 Pa×m in laboratory air at atmospheric pressure. The advantage of using discharges in micro gaps as the ionization principle is the low voltage and power that is necessary to drive a discharge. A prerequisite for using an ionizer in an ion mobility spectrometer is the possibility to operate such an ionizer at high, up to atmospheric, pressure. Our final micro discharge devices were operated in laboratory air for several hours without significant deterioration. A miniature ion mobility spectrometer was set up, in which miniature and micro discharge ionizers were applied as the ion sources. We extracted ions from micro ionizers and measured mobility spectra of gases and mixtures of gases (air, N2, Ar). The measured peaks in the mobility spectra varied depending on the gas. In the conclusions we suggest improvements that should increase the resolution and stability of our ion mobility spectrometer, so it may become useful for gas detection. The most important improvements will be a better control of the measurement conditions and of the initial extension of the ion pulse. In addition to our experimental results we present in this work an overview of the research that has already been done in our area of interest. As the basis of our research, the involved physical theory has been worked out. Consequently, the first chapters contain a compilation of relevant subjects, from the basics of electrostatics to the theory of DC glow discharge as far as we believe it can serve the reader in understanding our results