Optimizing Mass Spectrometry Imaging for Next Generation Pharmaceutical Research

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Imaging mass spectrometry (IMS) is a label-free molecular imaging technique with emerging applications in clinical research. There are two IMS methods with cellular spatial resolution, secondary ion mass spectrometry (SIMS) and matrix assistant laser desorption ionization (MALDI) using ion beams and laser, respectively, to capture molecular snapshots of biological materials. These complementary techniques have unique advantages and different challenges. For example, sub-micron laterally resolved ion images are common in SIMS imaging owing to the nature of the ion beam and advance ion beam focusing techniques, however, the harsh bombardment of the projectile limits molecular ion yields. Together MALDI and SIMS imaging fill the analytical performance gaps for label-free biomolecular imaging and produce a comprehensive picture of the proteins, lipids, and metabolites in tissue. The research program will focus on improving the ion image quality (i.e. molecular sensitivity, quantification ability, and lateral resolution measurements) and establishing synergistic workflows that combine SIMS and MALDI IMS. The protocols and methodologies established in the research program will provide a basis for characterizing and improving ion image quality. The collective outcome of the research program will ensure progress towards the acceptance of IMS technology in clinical histopathology and clinical pharmacology by improving the detection of biomolecule and pharmaceutical compounds in tissue and cells.