Browsing by Subject "Ambient ionization"
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Item Advanced development of ambient ionization mass spectrometry imaging methods and their utilization towards the understanding of metabolic diseases(2020-07-06) Feider, Clara Leigh; Eberlin, Livia Schiavinato; Brodbelt, Jennifer S; Crooks, Richard; Milner, ThomasAmbient ionization mass spectrometry (MS) technologies offer a unique opportunity to bring the specificity and sensitivity of MS into clinics, potentially allowing rapid analyses of biospecimens without need for sample preparation or highly trained personnel. As these technologies offer significant advantages over current technologies in terms of speed and suitability for a hospital environment, ambient ionization methods have been applied to a wide variety of clinical applications such as disease diagnosis, therapeutic drug monitoring, and biomarker discovery. Despite these successes, there remain challenges for these methods to overcome before they can be relied upon for routine analysis of patient samples. Prior to their use by physicians to inform decisions regarding patient care, ambient ionization MS technologies must be robust, versatile, and be shown to improve patient outcomes by providing information that is lacking in current standard of care procedures. This dissertation serves to outline recent advancements made towards the improvements of ambient ionization MS technologies as well as the application of these techniques towards disease indications that have yet to be explored. Chapter 2 provides data and discussion about how relative humidity can contribute to variability and poor data quality during desorption electrospray ionization (DESI) MS experiments, providing essential information about how atmospheric conditions can contribute to the robustness of the technique. Chapters 3 and 4 present methods for integration of new separation and fragmentation techniques with ambient ionization methods in order to increase the amount of information that can be gathered from a biological specimen. Finally, Chapter 5 presents results from the utilization of DESI-MS imaging towards understanding endometriosis, a chronic gynecological condition that has limited diagnosis and treatment options for patients. The entirety of this work aims to discuss how further improvements to ambient ionization MS technologies can make them useful for understanding a wider variety of disease processes and the progress that is being made to this end.Item Advancements in ambient ionization and MALDI mass spectrometry imaging methods and their application in disease diagnosis and characterization(2023-07-10) Lin, Monica; Eberlin, Livia Schiavinato; Brodbelt, Jennifer S.; Webb, Lauren J; Breen, Michael TDirect analysis using mass spectrometry (MS) techniques provide a powerful approach to investigate the molecular composition and spatial distribution of complex samples with high sensitivity and specificity. In particular, these techniques have been widely applied to achieve rapid molecular analysis of complex clinical samples including native tissue samples and biospecimens. Several types of direct analysis MS techniques have been developed for tissue analysis including a variety of ambient ionization MS techniques and matrix-assisted laser desorption ionization (MALDI) MS. Notably, both approaches are highly capable of performing molecular imaging of endogenous metabolites, lipids, and proteins to characterize tissue samples. Furthermore, through applying ambient ionization and MALDI MS imaging techniques, new insights into disease state can be learned by investigating the correlation between spatially resolved molecular information with histological evaluation in tissue samples. Although several other types of direct analysis MS techniques have been developed, this dissertation focuses on advancements using solvent-based ambient ionization MS (e.g. desorption electrospray ionization (DESI)) and MALDI MS imaging methods for tissue analysis and disease characterization. In Chapter 2, a fundamental and systematic investigation of the affect of solvent properties on molecular extraction processes in solvent-based ambient ionization was performed. In Chapter 3, the performance of DESI MS imaging for the analysis and statistical classification of thyroid fine needle aspiration (FNA) biopsies using different solvents, sources, and high-performance MS systems was evaluated. Next, Chapter 4 describes the development of a sample preparation method for MALDI MS imaging to improve detection of various endogenous proteins by selectively reducing signal from hemoglobin proteins in blood-rich tissues. Lastly, in Chapter 5, various MALDI imaging MS methods were applied to characterize the protein and N-glycan molecular signatures in endometriosis tissues and provide new insights into possible mechanisms of endometriosis development and progression. Collectively, this dissertation provides insights into the fundamental aspects, method developments, and applications of direct analysis MS techniques including solvent-based ambient ionization MS and MALDI MS imaging for tissue analysis. Furthermore, this dissertation showcases the exciting and significant potential of direct analysis MS techniques to solve current challenges in the clinic and provide new insights in healthcare and medicine.Item Development of transmission mode desorption electrospray ionization (TM-DESI)(2009-12) Chipuk, Joseph Eugene; Brodbelt, Jennifer S.; Stevenson, Keith J.; Willets, Katherine A.; Webb, Lauren J.; Lane, Michelle A.A new era of high-throughput mass spectrometry emerged with the nearly simultaneous introduction of two ambient ionization techniques: desorption electrospray ionization (DESI) and direct analysis in real time (DART). The ability to integrate near instantaneous sample analysis with the specificity of mass spectrometry opened up a broad range of applications. While some of these involve the direct analysis of bulk materials, many others require the collection and deposition of samples onto suitable substrates. This dissertation details the development of a new mode of operation for DESI. Instead of depositing a sample onto a continuous surface, the sample is either collected by or deposited onto a mesh substrate. Analytes either adsorb to the mesh strands or become suspended within the confines of the mesh in macroscale droplets. The samples are then analyzed by scrolling the mesh orthogonally into the path of an electrospray plume positioned coaxial to the inlet capillary of the mass spectrometer, thereby resulting in the transmission of the ionizing plume directly through the material. The transmission mode results in desorption and ionization typical of DESI, but with the added benefits of a simpler experimental geometry and the convenient analysis of both dry (i.e., following evaporation of the deposition solvent) and wet (i.e., solvated) samples. The simplification of the experimental arrangement increases method robustness and reproducibility, while the inclusion of a mesh substrate introduces new possibilities for sample collection and introduction, due to the intricate chemistry between the mesh material, analytes, and deposition/electrospray solvent system. However, the most important benefit lies in the development of surface-enhanced TM-DESI, whereby mesh substrates are derivatized to specifically capture and concentrate targeted analytes directly from solution. Following removal of matrix interferences by sample rinsing and subsequent cleavage of a photolabile linker, the mesh is analyzed directly by TM-DESI-MS. The technique has the potential to overcome interferences that have typically required chromatographic separations using LC-MS or have been insurmountable using ambient ionization methods. The impact of the surface-enhanced method could be tremendous as it may ultimately unite the competing metrics of analytical speed and specificity for ambient ionization mass spectrometry.