Micro Ion Mobility Spectrometry for Gas-phase Detection

En un món ideal, podríem ser capaços de detectar ràpidament i classificar qualsevol tipus de substància química i biològica que es trobés en baixes concentracions, utilitzant instruments petits i de fàcil ús. És en aquest escenari on va aparèixer l'espectrometria de mobilitat iònica (IMS). Es tracta d'una tècnica de mesura i anàlisi, on els analits ionitzats es separen per diferències de mobilitat sota la influència d’un camp elèctric en un flux de gas neutre o d'aire a pressió i temperatura ambient. Els avantatges de l'IMS inclouen instrumentació compacte i portàtil, un temps de separació curt (escala de mili-segons), i uns límits de detecció baixos, i permeten una àmplia gamma d'aplicacions. En aquest sentit, un esforç intens de recerca s'ha enfocat cap a la miniaturització dels dispositius d'IMS disponibles vers als micro- espectròmetres de mobilitat iònica de forma d’ona asimètrica i d’alt camp (FAIMS). En aquesta tesi es presenten els primers desenvolupaments i contribucions tecnològiques als FAIMS en el IMB-CNM (CSIC). En particular, aquest treball està dedicat a la simulació, disseny, i fabricació d'un micro FAIMS planar (p-FAIMS) per a aplicacions de seguretat. El treball s'organitza en cinc capítols dividits en dues seccions. La primera secció consta de tres capítols. El primer capítol és introductori i en el segon capítol s'introdueix al lector en l'actual estat de la tècnica de l'espectrometria de mobilitat iònica en general i en particular per als micro- espectròmetres de mobilitat iònica de forma d’ona asimètrica i d’alt camp. El tercer capítol descriu el modelatge d'un tipus de FAIMS planar per a diferents camps elèctrics i condicions de flux. La segona part consta de dos capítols. El quart capítol presenta un resum dels diferents dissenys i materials considerats per a la implementació del p-FAIMS: estructures Vidre-Si-Vidre i PCB-PMMA-PCB, les tasques tecnològiques fetes per cada un i les estratègies de solució que hi han conduit. La fotoionització UV ha estat l'escollida com a mètode de ionització en tots els casos per raons de seguretat. També es presenta la caracterització amb toluè del nou prototip de p-FAIMS de baix cost fabricat a l'IMB-CNM. El cinquè capítol es presenta un resum de l'estudi de la viabilitat del monitoratge d'un fàrmac analgèsic (remifentanil) en l’alè de pacients sota anestèsia. Un espectròmetre de mobilitat iònica comercial s'utilitza per a aquesta aplicació mèdica en col·laboració amb el KIST-Europe i la Chirurgische Universitätsklinik d'Homburg (Alemanya).In an ideal world, we might be able to rapidly detect and classify any type of chemical and biological that is found in low concentrations, using instruments of small size and easy implementation. Is in that scenario where the Ion mobility spectrometry (IMS) appeared. It is a technique of measurement and analysis, where ionized analytes are separated by mobility differences under electric field in a flow of neutral gas or air at ambient pressure and temperature. The advantages of IMS include compactness and portability of instrumentation, short separation time (milliseconds scale), and low detection limits, and allow a wide range of applications. In this sense, an intense research effort has been focused towards miniaturization from the available IMS’s devices to the micro high-Field Asymmetric waveform Ion Mobility Spectrometers (FAIMS). This thesis presents the first developments and technological contributions to the FAIMS at IMB-CNM (CSIC). Particularly, this work is dedicated to the simulation, design, and fabrication of a micro planar FAIMS (p-FAIMS) for security applications. The work is organized in five chapters divided in two sections. The first section consists of three chapters. Chapter one is introductory, and on Chapter two introduces the lector to the actual state-of-the-art of the Ion Mobility Spectrometry in general and in particular for the micro high-Field Asymmetric waveform Ion Mobility Spectrometry. Chapter three described the modeling of a planar type of FAIMS for different electric fields and flow conditions. The second section consists of two chapters. Chapter four provides a summary of the different designs and materials considered for the p-FAIMS implementation: Glass-Si-Glass and PCB-PMMA-PCB structures; the technological tasks done for each one and the solving strategies that have leaded to it. UV photoionization has been the chosen as ionization method for safety reasons in all cases. It also presents the characterization with toluene of the new low-cost p-FAIMS prototype fabricated in the IMB-CNM. Chapter five provides a summary of the feasibility study of an online-monitoring of an analgesic drug (remifentanil) in patients breath under anesthesia. A commercial Ion Mobility Spectrometer is used for this medical application in collaboration with the KIST-Europe and the Chirurgische Universitätsklinik from Homburg (Germany)

Chemical Analysis of Whale Breath Volatiles: A Case Study for Non-Invasive Field Health Diagnostics of Marine Mammals

We explored the feasibility of collecting exhaled breath from a moribund gray whale (Eschrichtius robustus) for potential non-invasive health monitoring of marine mammals. Biogenic volatile organic compound (VOC) profiling is a relatively new field of research, in which the chemical composition of breath is used to non-invasively assess the health and physiological processes on-going within an animal or human. In this study, two telescopic sampling poles were designed and tested with the primary aim of collecting whale breath exhalations (WBEs). Once the WBEs were successfully collected, they were immediately transferred onto a stable matrix sorbent through a custom manifold system. A total of two large volume WBEs were successfully captured and pre-concentrated onto two Tenax®-TA traps (one exhalation per trap). The samples were then returned to the laboratory where they were analyzed using solid phase micro extraction (SPME) and gas chromatography/mass spectrometry (GC/MS). A total of 70 chemicals were identified (58 positively identified) in the whale breath samples. These chemicals were also matched against a database of VOCs found in humans, and 44% of chemicals found in the whale breath are also released by healthy humans. The exhaled gray whale breath showed a rich diversity of chemicals, indicating the analysis of whale breath exhalations is a promising new field of research

Micro Ion Mobility Spectrometry for Gas-phase Detection

En un món ideal, podríem ser capaços de detectar ràpidament i classificar qualsevol tipus de substància química i biològica que es trobés en baixes concentracions, utilitzant instruments petits i de fàcil ús. És en aquest escenari on va aparèixer l'espectrometria de mobilitat iònica (IMS). Es tracta d'una tècnica de mesura i anàlisi, on els analits ionitzats es separen per diferències de mobilitat sota la influència d'un camp elèctric en un flux de gas neutre o d'aire a pressió i temperatura ambient. Els avantatges de l'IMS inclouen instrumentació compacte i portàtil, un temps de separació curt (escala de mili-segons), i uns límits de detecció baixos, i permeten una àmplia gamma d'aplicacions. En aquest sentit, un esforç intens de recerca s'ha enfocat cap a la miniaturització dels dispositius d'IMS disponibles vers als micro- espectròmetres de mobilitat iònica de forma d'ona asimètrica i d'alt camp (FAIMS). En aquesta tesi es presenten els primers desenvolupaments i contribucions tecnològiques als FAIMS en el IMB-CNM (CSIC). En particular, aquest treball està dedicat a la simulació, disseny, i fabricació d'un micro FAIMS planar (p-FAIMS) per a aplicacions de seguretat. El treball s'organitza en cinc capítols dividits en dues seccions. La primera secció consta de tres capítols. El primer capítol és introductori i en el segon capítol s'introdueix al lector en l'actual estat de la tècnica de l'espectrometria de mobilitat iònica en general i en particular per als micro- espectròmetres de mobilitat iònica de forma d'ona asimètrica i d'alt camp. El tercer capítol descriu el modelatge d'un tipus de FAIMS planar per a diferents camps elèctrics i condicions de flux. La segona part consta de dos capítols. El quart capítol presenta un resum dels diferents dissenys i materials considerats per a la implementació del p-FAIMS: estructures Vidre-Si-Vidre i PCB-PMMA-PCB, les tasques tecnològiques fetes per cada un i les estratègies de solució que hi han conduit. La fotoionització UV ha estat l'escollida com a mètode de ionització en tots els casos per raons de seguretat. També es presenta la caracterització amb toluè del nou prototip de p-FAIMS de baix cost fabricat a l'IMB-CNM. El cinquè capítol es presenta un resum de l'estudi de la viabilitat del monitoratge d'un fàrmac analgèsic (remifentanil) en l'alè de pacients sota anestèsia. Un espectròmetre de mobilitat iònica comercial s'utilitza per a aquesta aplicació mèdica en col·laboració amb el KIST-Europe i la Chirurgische Universitätsklinik d'Homburg (Alemanya).In an ideal world, we might be able to rapidly detect and classify any type of chemical and biological that is found in low concentrations, using instruments of small size and easy implementation. Is in that scenario where the Ion mobility spectrometry (IMS) appeared. It is a technique of measurement and analysis, where ionized analytes are separated by mobility differences under electric field in a flow of neutral gas or air at ambient pressure and temperature. The advantages of IMS include compactness and portability of instrumentation, short separation time (milliseconds scale), and low detection limits, and allow a wide range of applications. In this sense, an intense research effort has been focused towards miniaturization from the available IMS's devices to the micro high-Field Asymmetric waveform Ion Mobility Spectrometers (FAIMS). This thesis presents the first developments and technological contributions to the FAIMS at IMB-CNM (CSIC). Particularly, this work is dedicated to the simulation, design, and fabrication of a micro planar FAIMS (p-FAIMS) for security applications. The work is organized in five chapters divided in two sections. The first section consists of three chapters. Chapter one is introductory, and on Chapter two introduces the lector to the actual state-of-the-art of the Ion Mobility Spectrometry in general and in particular for the micro high-Field Asymmetric waveform Ion Mobility Spectrometry. Chapter three described the modeling of a planar type of FAIMS for different electric fields and flow conditions. The second section consists of two chapters. Chapter four provides a summary of the different designs and materials considered for the p-FAIMS implementation: Glass-Si-Glass and PCB-PMMA-PCB structures; the technological tasks done for each one and the solving strategies that have leaded to it. UV photoionization has been the chosen as ionization method for safety reasons in all cases. It also presents the characterization with toluene of the new low-cost p-FAIMS prototype fabricated in the IMB-CNM. Chapter five provides a summary of the feasibility study of an online-monitoring of an analgesic drug (remifentanil) in patients breath under anesthesia. A commercial Ion Mobility Spectrometer is used for this medical application in collaboration with the KIST-Europe and the Chirurgische Universitätsklinik from Homburg (Germany)

Dataset of "A Metabolites Merging Strategy (MMS): Harmonization to enable studies intercomparison"

<p>Metabolomics encounters challenges in cross-study comparisons due to diverse metabolite nomenclature and reporting practices. To bridge this gap, we introduce the Metabolites Merging Strategy (MMS), offering a systematic framework to harmonize multiple metabolite datasets for enhanced interstudy comparability. MMS has three steps. Step 1: Translation and merging of the different datasets by employing InChIKeys for data integration, encompassing the translation of metabolite names (if needed). Followed by Step 2: Attributes' retrieval from the InChIkey, including descriptors of name (title name from PubChem and RefMet name from Metabolomics Workbench), and chemical properties (molecular weight and molecular formula), both systematic (InChI, InChIKey, SMILES) and non-systematic identifiers (PubChem, CheBI, HMDB, KEGG, LipidMaps, DrugBank, Bin ID and CAS number), and their ontology. Finally, a meticulous three-step curation process is used to rectify disparities for conjugated base/acid compounds (optional step), missing attributes, and synonym checking (duplicated information). The MMS procedure is exemplified through a case study of urinary asthma metabolites, where MMS facilitated the identification of significant pathways hidden when no dataset merging strategy was followed. This study highlights the need for standardized and unified metabolite datasets to enhance the reproducibility and comparability of metabolomics studies.</p&gt

Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis

To increase compliance with colorectal cancer screening programs and to reduce the recommended screening age, cheaper and easy non-invasiveness alternatives to the fecal immunochemical test should be provided. Following the PRISMA procedure of studies that evaluated the metabolome and volatilome signatures of colorectal cancer in human urine samples, an exhaustive search in PubMed, Web of Science, and Scopus found 28 studies that met the required criteria. There were no restrictions on the query for the type of study, leading to not only colorectal cancer samples versus control comparison but also polyps versus control and prospective studies of surgical effects, CRC staging and comparisons of CRC with other cancers. With this systematic review, we identified up to 244 compounds in urine samples (3 shared compounds between the volatilome and metabolome), and 10 of them were relevant in more than three articles. In the meta-analysis, nine studies met the criteria for inclusion, and the results combining the case-control and the pre-/post-surgery groups, eleven compounds were found to be relevant. Four upregulated metabolites were identified, 3-hydroxybutyric acid, L-dopa, L-histidinol, and N1, N12-diacetylspermine and seven downregulated compounds were identified, pyruvic acid, hydroquinone, tartaric acid, and hippuric acid as metabolites and butyraldehyde, ether, and 1,1,6-trimethyl-1,2-dihydronaphthalene as volatiles

Review on ion mobility spectrometry. Part 2: hyphenated methods and effects of experimental parameters

Ion Mobility Spectrometry (IMS) is a widely used and ‘well-known’ technique of ion separation in the gaseous phase based on the differences of ion mobilities under an electric field. This technique has received increased interest over the last several decades as evidenced by the pace and advances of new IMS devices available. In this review we explore the hyphenated techniques that are used with IMS, specifically mass spectrometry as an identification approach and a multi-capillary column as a pre-separation approach. Also, we will pay special attention to the key figures of merit of the ion mobility spectrum and how data sets are treated, and the influences of the experimental parameters on both conventional drift time IMS (DTIMS) and miniaturized IMS also known as high Field Asymmetric IMS (FAIMS) in the planar configuration. The present review article is preceded by a companion review article which details the current instrumentation and contains the sections that configure both conventional DTIMS and FAIMS devices. These reviews will give the reader an insightful view of the main characteristics and aspects of the IMS technique

Review on ion mobility spectrometry. Part 1: current instrumentation

Ion Mobility Spectrometry (IMS) is a widely used and `well-known’ technique of ion separation in the gaseous phase based on the differences in ion mobilities under an electric field. All IMS instruments operate with an electric field that provides space separation, but some IMS instruments also operate with a drift gas flow that provides also a temporal separation. In this review we will summarize the current IMS instrumentation. IMS techniques have received an increased interest as new instrumentation and have become available to be coupled with mass spectrometry (MS). For each of the eight types of IMS instruments reviewed it is mentioned whether they can be hyphenated with MS and whether they are commercially available. Finally, out of the described devices, the six most-consolidated ones are compared. The current review article is followed by a companion review article which details the IMS hyphenated techniques (mainly gas chromatography and mass spectrometry) and the factors that make the data from an IMS device change as a function of device parameters and sampling conditions. These reviews will provide the reader with an insightful view of the main characteristics and aspects of the IMS technique