Tissue Metabolomics by Advanced Mass Spectrometry and Separation Techniques
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Leontyev, Dmitry
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Abstract
Metabolomics is the comprehensive study of small molecule alterations in biological systems and is widely used to investigate metabolic disorders, diseases, and conditions such as cancer. As the final layer in the ‘omics cascade following genomics, transcriptomics, and proteomics, metabolomics is closest to phenotypic changes, making it a powerful tool for understanding disease pathology and identifying biomarkers. Unlike other ‘omics fields, which primarily analyze molecules assembled from amino acids or nucleotides, metabolomics encompasses an immense structural diversity, making it impossible for a single analytical platform to capture the full metabolic profile. High-resolution mass spectrometry (MS) is particularly well-suited for metabolomics due to its ability to differentiate species with similar m/z values, especially when coupled with liquid chromatography (LC) for enhanced separation and metabolite coverage.
Mass spectrometry imaging (MSI) is another key approach in non-targeted metabolomics, enabling the spatial mapping of metabolites directly in tissues without requiring liquid extraction, which can disrupt their native distributions. Many MSI platforms utilize time-of-flight (ToF) mass analyzers, which can be coupled with ion mobility spectrometry (IMS) to provide additional front-end separation, improving metabolite coverage and enhancing MSI’s capabilities.
This thesis focuses on characterizing metabolomic and lipidomic alterations in brain tissue following traumatic brain injury and in renal cell carcinoma tissues using a combination of MSI, LC-MS, and IMS. Additionally, it explores the application of high-accuracy collision cross-section measurements to improve metabolite identification and details the development of a triboelectric nanogenerator-powered laser ablation electrospray ion source for MSI.
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Date
2025-04-23
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Dissertation