This Small Business Innovation Research Phase I project will enhance the capabilities of 2D spatial mapping of expression levels of biomolecules from tissue samples using matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Current MALDI imaging protocols use organic acid matrices to promote desorption and ionization of biomolecules from the tissue surface. These organic matrices limit the analysis of small biomolecules due to the extensive fragmentation and interference in the low mass region of the mass spectrum. Furthermore, no one matrix is currently capable of desorbing and ionizing all types of biomolecules. New matrices are needed to fill this void and this research is developing a new matrix that utilizes gold nanoparticles (AuNP) to efficiently ionize biomolecules from tissue samples. A series of well characterized AuNPs with different sizes and surface chemistries will determine the mechanism of the AuNP induced ionization. Optimal formulations will be tested on tissue samples to determine their effectiveness as a matrix for tissue imaging. <br/><br/>The broader impacts of this research are to supply new matrices that are well characterized which will lead to new insightful information about the spatial expression of specific biomarkers thereby leading to better drug discovery and improved health outcomes. Gold nanoparticle matrices have unique specificity, good sensitivity and the potential to unlock the 2D spatial imaging of biomolecules that cannot currently be observed using standard methods. These types of new information could have profound affects on the scientific community?s ability to understand/diagnose disease and find novel drug targets.