This Small Business Innovation Research (SBIR) Phase II project will enhance the capabilities of imaging biomolecular ions from solid tissue samples using matrix assisted laser desorption time-of-flight imaging mass spectrometry (MALDI-IMS). Currently, organic acid matrices are used to promote the desorption and ionization of biomolecules from the tissue surface, however, these types of matrices have a number of limitations. Specifically, extensive fragmentation can interfere with the analysis of lipids, peptides and pharmaceuticals in the low mass region (m/z < 500), and organic matrices tend to form large crystals upon drying which can limit imaging resolution and repeatability. NanoComposix is developing a new matrix that utilizes gold nanoparticles to efficiently ionize biomolecules from tissue samples. This gold nanoparticle matrix has much lower background ion signal, has improved imaging resolution, and specifically ionizes molecules not observed using traditional organic matrices. MALDI-IMS will be used to validate optimized nanoparticle formulations and application methods using hepatic and neuronal tissue slices.
The broader impacts of this research are the potential for profound affects on the scientific communities understanding of disease, capabilities for early disease diagnosis, and our ability to find new drug targets. Information on the content and spatial distribution of biomarkers in tissue will accelerate the development of ?personalized medicine? where drugs can be selected based on individual patient characteristics. The current organic matrices used for MALDI-IMS are limited and there is an immediate need for new matrices with unique specificity and sensitivity towards biomarkers that are not observed using standard matrices.
Mass spectrometry is a powerful tool for identifying molecules in research studies and clinical samples. A recent scientific advance is the development of Matrix Assisted Laser Desorption Imaging Mass Spectrometry (MALDI-IMS) that creates images of molecular expression for use in the fields of metabalomics, proteomics, cell biology and drug target discovery. Histology performed with MALDI-IMS provides orders of magnitude more information about the molecular structure of tissue compared to traditional tissue staining and labeling. Information on both the content and spatial distribution of biomarkers in tissue will accelerate the development of "personalized medicine" where drugs can be selected based on individual patient characteristics. The current organic matrices used for MALDI-IMS are limited, and there is an immediate need for new matrices with unique specificity and sensitivity towards biomarkers that are not observed using standard matrices. In this project we developed gold nanoparticle based matrices that have the potential to unlock the ability to visualize biomarkers not currently observed using standard matrices. The developed GNP matrix is highly effective for the identification of lipids and other small molecules and has much lower background signal compared to organic matrices such as DHB. The new information garnered by these nanoparticle based matrices will further accelerate the acceptance and use of MALDI-IMS techniques and could have profound effects on the scientific community’s understanding of disease, capabilities for early disease diagnosis, and our ability to find new drug targets.
