The work presented in this thesis describes the improvement and application of on-tissue chemistry for in-situ biomolecular analysis using matrix assisted-laser desorption/ionization mass... Show moreThe work presented in this thesis describes the improvement and application of on-tissue chemistry for in-situ biomolecular analysis using matrix assisted-laser desorption/ionization mass spectrometry imaging (MALDI-MSI). We have proposed new methodologies, applying on-tissue (enzymatic) chemistry, to increase the molecular information obtained in a MALDI-MSI analysis. We have also developed an automated histology-guided MSI platform, based on state-of-the-art image processing tools, to facilitate high mass and spatial resolution MALDI-MSI while maintaining reasonable data loads and acquisition times. We have shown the importance of these methods in a clinical biomarker discovery study on myxoid liposarcoma tissues. Show less