Application and uses of electronic noses for clinical diagnosis on urine samples: A review

The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents

Ion mobility spectrometry-mass spectrometry (IMS-MS) of small molecules: separating and assigning structures to ions

The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early 20th Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods, and theory together with contributions from computational chemistry and gas-phase ion chemistry, which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS-mass spectrometry (IMS-MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi-/cross-disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilized for "small molecule" species. This review focuses on the application of IMS-MS to "small molecule" species typically used in drug discovery (100-500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods, and applications are addressed. The typical application of IMS-MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (3-100) and the differences in collision cross-sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS-MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, "small molecule" separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS-MS, not solely IMS, and small molecule applications. © 2012 Wiley Periodicals, Inc

A review

Funding Information: PhD grant PD/BDE/150627/2020 was financed by Fundação para a Ciência e Tecnologia (FCT - Portugal) and Volkswagen Autoeuropa. Funding Information: The authors would like to thank Fundação para a Ciência e Tecnologia (FCT - Portugal), and Volkswagen Autoeuropa for co-financing the doctoral grant PD/BDE/150627/2020. Publisher Copyright: © 2023 The AuthorsIon Mobility Spectrometry (IMS) has gained relevance in the field of analytical techniques over the past decades. If compared with well-established techniques like mass spectrometry or infrared spectroscopy, IMS is considerably less developed or employed in specific fields but presents promising results and a substantial margin for improvements. Its outstanding sensitivity and selectivity, analytical flexibility, instrumental versatility and almost real-time results capacity have contributed to elevate IMS among the main analytical techniques for the detection of volatile organic compounds. Due to its growth potential, it is mandatory to assess in which scientific fields IMS has played a relevant role in the past years of academic research and understand in which areas it can become equally important in the near future. For this purpose, hundreds of scientific works from the past ten years were addressed and the most relevant were reviewed in this work. Three main categories of IMS applications were defined to group the reviewed articles: Environmental and Safety Research, Health Research and Food Research. In addition, some original studies were specifically developed for this review paper, to act as elucidative examples. The working principle of the IMS is included for clarification purposes. A glossary of all the mentioned compounds was also included. Throughout the text, it is clear how relevant IMS has become and how diverse its applicability can be, ranging from simpler topics like fraud detection to more complex ones like pathologies diagnosis. It is safe to say that IMS has been, step by step, gaining relevance as an analytical technique and its potential for supporting many diverse scientific fields is evident.publishersversionpublishe

Ultra-high-resolution ion mobility spectrometry : current instrumentation, limitations, and future developments

With recent advances in ionization sources and instrumentation, ion mobility spectrometers (IMS) have transformed from a detector for chemical warfare agents and explosives to a widely used tool in analytical and bioanalytical applications. This increasing measurement task complexity requires higher and higher analytical performance and especially ultra-high resolution. In this review, we will discuss the currently used ion mobility spectrometers able to reach such ultra-high resolution, defined here as a resolving power greater than 200. These instruments are drift tube IMS, traveling wave IMS, trapped IMS, and field asymmetric or differential IMS. The basic operating principles and the resulting effects of experimental parameters on resolving power are explained and compared between the different instruments. This allows understanding the current limitations of resolving power and how ion mobility spectrometers may progress in the future

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

Analysis and Treatment of Emerging Polar Contaminants

Two major classes of polar compounds have recently become a major focus as sources of contamination of water systems. Pharmaceuticals and personal care products (PPCPs) enter water through wastewater streams, and many of these compounds survive current wastewater treatment processes. High production volume chemicals (HPVCs), defined as chemicals produced in excess of one million pounds per year have numerous entries into surface and drinking waters due to their ubiquity. The commonality between many of these compounds is their polarity, which makes them water-soluble. While both PPCPs and HPVCs have been entering into the environment for decades, advances in analyte detection have increased the ability of scientists to identify these compounds in surface, waste and drinking waters. Methods for polar compound suites have been developed using a number of technologies, however these processes are often time consuming and require specialized instrumentation. In this study, a fast, robust method for the detection and treatment of emerging polar contaminants was developed with accompanying instrumentation. A liquid chromatography system, hyphenated to a universal gas phase detector, flame ionization detector (FID), was designed. By using pure subcritical water as a mobile phase, temperature was used to control chromatographic retention. This instrument may be used for rapid screening of environmental samples with minimal preparation. Using subcritical water chromatography allowed for testing of mass transfer between subcritical water and organic phases, which provides data on the transport of polar contaminants between solvent phases. A second component of the work in this dissertation was to test a treatment protocol for waste streams, which demonstrated the reduction of selected analytes within the PPCP and HPVC classes. Subcritical water wet oxidation allowed for the breakdown of all polar organic molecules dissolved in a water sample. As a thermochemical process, the oxidation reaction further reduced select compounds that remain after current biological waste removal processes, and provided a value-added process to current wastewater treatment, in which a needed process, disinfection, can be coupled to additional contaminant removal

Nuevas contribuciones de las técnicas de movilidad iónica ambiental y clínico

Enmarcada dentro de las técnicas de vanguardia se encuentran las técnicas de movilidad iónica o IMS atendiendo a sus siglas en inglés. Entre sus ventajas cabe destacar, su rapidez, su sensibilidad a nivel de trazas y su simplicidad de análisis, las cuales han contribuido al creciente interés para su desarrollo y aplicación en áreas tales como farmacéutica, análisis forense, biomedicina y análisis ambiental [1]. La aplicación directa de las técnicas de IMS para la determinación de compuestos de interés en matrices complejas tales como muestras ambientales y biológicas constituye todavía un reto que resulta difícil de abordar debido a que muchos métodos analíticos y las herramientas necesarias para poder usarlos de forma rutinaria se encuentran actualmente en fase de desarrollo. Existiendo además el compromiso de mejorar los problemas asociados a la baja selectividad y en algunas ocasiones de sensibilidad, los cuales pueden solucionarse mediante el acoplamiento a columnas de cromatografía de gases y módulos de extracción para la separación y preconcentración de los analitos de interés. Como consecuencia de lo anteriormente expuesto, el objetivo principal de esta Tesis Doctoral ha sido el desarrollo de metodologías analíticas mediante el uso de IMS en el campo ambiental y clínico

Estudio teórico y aplicado del potencial de la espectrometría de movilidad iónica

Ion mobility spectrometry (IMS) is an analytical technique based on the separation of gaseous ions under the influence of an electric field through an inert gas atmosphere. Some of the main limitations of IMS, depending on the context, may be the limited quantification capacity of compounds in real samples since narrow linear quantification ranges are normally obtained; the low selectivity due to the low resolution power of this type of equipment; and the difficulty of unequivocally identifying compounds in real samples since the existing databases are not as up-to-date as for other technologies such as mass spectrometry (MS). Therefore, it is evident that there is a demand for more selective methodologies and that provide greater analyte detection and quantification capacity. With these premises, it can be said that the greatest current challenge of the IMS is to maximize the detection capacity of the technique in order to achieve the unambiguous identification of a high number of analytes. This challenge is currently utopian when working with complex samples. For this reason, the main motivation of this Doctoral Thesis was to seek solutions for the different challenges that the IMS currently faces in a theoretical and applied context. The basic objective of the research was to explore the potential of IMS by using theoretical and applied strategies to improve the detection and identification coverage of the analysis carried out with this technology. These new strategies were applied throughout the main steps of the analytical process and allowed improving basic analytical features such as the selectivity and sensitivity of optimized analysis methods and their detection capacity. The achievement of this basic objective leaded to analysis methods of standards and real samples, such as explosives, drugs, soil, rosemary plant, olives and mainly different types of olive oils. This basic objective was divided into three general objectives according to the different research topics to address in this Doctoral Thesis: a) To take benefits derived from the study of theoretical aspects of IMS for improving the interpretation of IMS spectra and from the use of additional features such as structural information to enhance qualitative analysis; b) To develop approaches to improve the detection and identification capacity in IMS analysis; and c) To exploit the opportunities of gas chromatography (GC)-IMS and IMS devices for food analysis as an expanding application area in IMS based on untargeted analysis methods. In this context, the Thesis has included the following studies: (i) To study about the fundamentals of the formation of product ions through the modeling of ions stability using ab initio computations to math these results with the spectral patterns and structure of ions [1]. (ii) To explore the fragmentation of ions using an external electric field and the potential of the extra information of these fragments to enhance the rates of categorization by chemical class using neural networks [2]. (iii) To explore a thermal desorption (TD)-IMS device to obtain spectral fingerprints of Cannabis herbal samples, with and without pretreatment for rapid assignment to their different chemotypes by using principal component análisis (PCA) and linear discriminant analysis (LDA) [3]. (iv) To achieve the selectivity in response to trinitrotoluene (TNT) through reactive removal of interfering ions following mobility isolation using a tandem IMS with reactive stage as detection system [4]. (v) To develop a pioneer online coupling of supercritical fluid extraction (SFE) as sample introduction system (SIS) prior IMS using a column filled with Tenax TA material as sorbent trap to coupled both devices to improve analytical properties such as sensitivity and selectivity of future IMS methods [5]. (vi) To carry out a bibliographical study which gather and critically discuss recent publications related to analytical techniques to distinguish olive oils according to their quality as extra virgin (EVOO), virgin (VOO) or lampante (LOO) [6]. (vii) To investigate and compare different chemometric approaches for olive oil classification as EVOO, VOO or LOO using GC-IMS to get the most robust model over time [7]. (viii) To evaluate the combination of the results of orthogonal instrumental techniques to differentiate EVOO, VOO or LOO to imitate the expert panels [8]. (ix) To analyze olive and olive oil samples according with their production system to classify them as organic or conventional using ultraviolet (UV)-IMS, GC-IMS, GC-MS and/or capillary electrophoresis (CE)-UV [9].La espectrometría de movilidad iónica (IMS en inglés) es una técnica analítica que se basa en la separación de iones gaseosos bajo la influencia de un campo eléctrico a través de una atmósfera de gas inerte. Algunas de las principales limitaciones de la IMS, dependiendo del contexto, pueden ser la limitada capacidad de cuantificación de compuestos en muestras reales ya que se obtienen normalmente rangos lineales de cuantificación muy estrechos; la escasa selectividad debido al bajo poder de resolución de este tipo de equipos; y la dificultad de identificación de forma inequívoca de compuestos en muestras reales ya que las bases de datos existentes no están tan actualizadas como para otras tecnologías como la espectrometría de masas (MS en inglés). Por tanto, resulta evidente que existe una demanda de metodologías más selectivas y que proporcionen mayor capacidad de detección y cuantificación de analitos. Con estas premisas, se puede decir que el mayor reto actual de la IMS es maximizar la capacidad de detección de la técnica con el fin de conseguir la identificación inequívoca de un alto número de analitos. Este reto es actualmente utópico cuando se trabaja con muestras complejas. Por ello, la principal motivación de esta Tesis Doctoral fue buscar soluciones para los distintos retos a los que se enfrenta actualmente la IMS en un contexto teórico y aplicado. El objetivo básico de la investigación fue explorar el potencial de la IMS mediante el uso de estrategias teóricas y aplicadas para mejorar la capacidad de detección e identificación de los análisis realizados con esta tecnología. Estas nuevas estrategias se aplicaron a lo largo de las etapas principales del proceso analítico y permitieron mejorar características analíticas básicas, como la selectividad y la sensibilidad, de los métodos de análisis optimizados y su capacidad de detección. El logro de este objetivo básico condujo a métodos de análisis de estándares y muestras reales, como explosivos, drogas, suelo, plantas de romero, aceitunas y principalmente diferentes tipos de aceites de oliva. Este objetivo básico se dividió en tres objetivos generales de acuerdo con los diferentes temas de investigación para abordar en esta Tesis Doctoral: a) aprovechar los beneficios derivados del estudio de los aspectos teóricos de la IMS para mejorar la interpretación de los espectros de IMS y del uso de características adicionales como información estructural para mejorar el análisis cualitativo; b) desarrollar herramientas para mejorar la capacidad de detección e identificación en los análisis de IMS; y c) aprovechar las oportunidades de los instrumentos de cromatografía de gases (GC en inglés)-IMS e IMS para el análisis de alimentos como un área de aplicación en expansión en IMS basado en métodos de análisis no dirigidos. En este contexto, la Tesis ha incluido los siguientes estudios: (i) Estudiar los fundamentos de la formación de iones producto a través del modelado computacional de la estabilidad de los iones utilizando cálculos ab initio para combinarlos con los patrones espectrales y la estructura de los iones [1]. (ii) Explorar la fragmentación de iones utilizando un campo eléctrico externo y el potencial de la información adicional de estos fragmentos para mejorar las tasas de categorización por clase química utilizando redes neuronales [2]. (iii) Explorar un equipo de desorción térmica (TD en inglés)-IMS para obtener huellas espectrales de muestras de plantas de cannabis, con y sin pretratamiento, para la rápida asignación de los diferentes quimiotipos mediante análisis de componentes principales (PCA en inglés) y análisis discriminante lineal (LDA en inglés) [3]. (iv) Lograr la respuesta selectiva del trinitrotolueno (TNT en inglés) a través de la eliminación con etapa reactiva de iones interferentes usando el aislamiento de iones con un IMS en tándem con etapa reactiva como sistema de detección [4]. (v) Desarrollar un acoplamiento on-line pionero de la extracción con fluidos supercríticos (SFE en inglés) como sistema de introducción de muestra previo a la IMS utilizando una columna rellena con el material Tenax TA como trampa sorbente para acoplar ambos dispositivos para mejorar propiedades analíticas como la sensibilidad y la selectividad de futuros métodos IMS [5]. (vi) Realizar un estudio bibliográfico que reúna y discuta críticamente las publicaciones recientes relacionadas con técnicas analíticas para distinguir los aceites de oliva según su calidad como virgen extra (AOVE), virgen (AOV) o lampante (AOL) [6]. (vii) Investigar y comparar diferentes estrategias quimiométricas para la clasificación del aceite de oliva como AOVE, AOV o AOL utilizando la GC-IMS para obtener el modelo más robusto con el tiempo [7]. (viii) Evaluar la combinación de los resultados de técnicas instrumentales ortogonales para diferenciar AOVE, AOV o AOL para imitar los paneles de expertos [8]. (ix) Analizar muestras de aceitunas y aceite de oliva de acuerdo con su sistema de producción para clasificarlas como ecológicas o convencionales usando ultravioleta (UV)-IMS, GC-IMS, GC-MS y/o electroforesis capilar (CE en inglés)- UV [9]

Ion mobility-mass spectrometry studies of organic and organometallic complexes and reaction monitoring

Ion mobility (IM) spectrometry is a gas-phase electrophoretic technique in which ions are separated on the basis of their relative mobility in the presence of a weak electric field gradient and a buffer gas. Ion mobility-mass spectrometry (IM-MS) has the capability of separating ions based on m/z, size and shape, providing additional structural information compared to using mass spectrometry on its own. In this thesis, IM-MS has been used to investigate organic and organometallic complexes and identify reactants, intermediates and products in reaction mixtures. Collision cross sections (CCS) have been measured for three salen ligands, and their complexes with copper and zinc using travelling-wave ion mobility-mass spectrometry (TWIMS) and drift tube ion mobility-mass spectrometry (DTIMS), allowing a comparative size evaluation of the ligands and complexes. CCS measurements using TWIMS were determined using peptide and TAAH calibration standards with good intra-day and inter-day reproducibility. TWIMS measurements gave significantly larger CCS than DTIMS derived data in helium, indicating that the choice of calibration standards is important in ensuring the accuracy of TWIMS derived CCS measurements. The CCS data obtained from IM-MS measurements have been compared to CCS values obtained from X-ray coordinates and modelled structures. The analysis of small organic and organometallic molecules has been extended to investigations of the potential of IM-MS for reaction monitoring and structural studies of the components of catalytic cycles. Reaction mixtures of an organocatalysed Diels-Alder cycloaddition reaction have been monitored using IM-MS and high-field asymmetric waveform ion mobility-mass spectrometry (FAIMS-MS). Reactant, product, catalyst and reaction intermediates, including an intermediate not previously detected, were identified and the catalyst and intermediates monitored over time. An organometallic catalytic cycle using a palladium catalyst has been analysed using IM-MS and the CCS of reactants, intermediates and products have been measured and compared to theoretical CCS calculations. Good agreement was observed between measured and calculated data. Species not amenable to electrospray ionisation were covalently bound to an ionisable tag containing a quaternary ammonium ion allowing the tagged molecules to be detected by IM-MS