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May 23, 2025
Malik Ebbini, Pharmsci graduate student (Li Research Group), will be defending his PhD research thesis:
Method Development and Application of MALDI Mass Spectrometry Profiling and Imaging of Biomolecules in Tissue Samples
Abstract:
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a powerful technology for acquiring spatial distribution information of biomolecules within thin tissue sections. MSI allows for simultaneous visualization of many biomolecules in situ, without requiring a priori knowledge, labels, or antibodies. Despite its strengths, MALDI MSI faces challenges in detecting biomolecules with low abundance, low ionization efficiency, or low fragmentation efficiency, particularly in complex biological samples.
This dissertation addresses these challenges by introducing novel methodologies to enhance detection sensitivity for specific biomolecules, such as lipids and proteins: Firstly, I present an innovative on-tissue chemical derivatization method that significantly improves the detection sensitivity of free fatty acids in tissue samples via MALDI MSI. Secondly, I document the development of an MSI-compatible nanoparticle co-matrix system designed to enhance both fragmentation efficiency and on-tissue enrichment for phosphoproteins. Collectively, this research develops novel methodologies in MALDI MSI and enables biological applications that provide a deeper understanding of fatty acid dynamics associated with Alzheimer’s disease pathogenesis.