Advanced development of ambient ionization mass spectrometry imaging methods and their utilization towards the understanding of metabolic diseases
Ambient 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.