Phd in PHARMACEUTICAL SCIENCES

Thesis title: Spatial and Direct Profiling by MALDI Mass Spectrometry: Applications to Tissue Imaging and Food Authentication

This doctoral thesis explores the analytical versatility of Matrix-Assisted Laser Desorption/Ionization (MALDI) mass spectrometry for the investigation of small molecules across two complementary domains: food authentication and biological tissue imaging. The first part of the thesis presents the development and application of atmospheric pressure MALDI mass spectrometry (AP-MALDI-MS) for authenticating plant-derived foods. Using oregano and black pepper as model adulterated spices, AP-MALDI-MS enabled rapid molecular fingerprinting, under ambient conditions, with minimal preparation. Combined with machine learning, the method achieved high specificity in distinguishing authentic from adulterated samples, demonstrating its potential as a simple and reliable tool for routine food authenticity screening. The second part explores high-resolution mass spectrometry imaging (MALDI-MSI) for spatial mapping of metabolites and lipids in biological tissues. Using FT-ICR and Orbitrap instruments, MALDI-MSI elucidated molecular organization in complex systems. In human and reconstructed skin models, MALDI-FTICR-MSI revealed glucose accumulation and metabolic changes linked to aging, confirming reconstructed skin as a reliable and ethical alternative to human tissue. Preliminary work on mouse brain sections validated the feasibility of vacuum-sublimated NEDC matrix for sensitive metabolite detection. Furthermore, archived glioblastoma-bearing mouse brains were successfully repurposed for imaging using an AP-MALDI-Orbitrap setup, uncovering distinct molecular signatures in tumor, peritumoral, and healthy regions. This strategy supports the 3Rs principles, Replacement, Reduction, and Refinement, by maximizing the scientific value of existing biological materials. Collectively, these studies position MALDI-based mass spectrometry as a versatile platform spanning from compositional analysis to spatial molecular imaging.