Author : Monica Lin
Publisher :
Page : 0 pages
File Size : 36,78 MB
Release : 2023
Category :
ISBN :
Direct 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