timsTOF fleX MALDI-2 for Spatial Molecular Imaging

PROJECT SUMMARY/ABSTRACT This shared instrumentation proposal seeks funding for the purchase of a Bruker ‘timsTOF fleX MALDI-2 for Spatial Molecular Imaging’ including a bundled HTX M3+ sprayer. This new mass spectrometry (MS) platform will facilitate ongoing and future scientific research to spatially resolve molecular signatures, even in a multi-omic workflow monitoring proteins, glycans, lipids, and metabolites all within the same tissue down to a spatial resolution of ~5-10 µM. All costs will be accounted for with this proposal. We propose to operate this integrated timsTOF fleX MALDI-2 mass spectrometry system exclusively for spatially resolved molecular imaging of human and animal tissues and organoids as part of large group of 18 independent principal investigators from the Buck Institute and seven other institutions or universities. These researchers bring together 19 NIH-funded grants (including P01, U54, U01, R01, P30, UG3 activity codes) and one R01 supplement, all of which have significant needs for state-of-the-art mass spectrometry for spatially resolved proteomics, metabolomics, lipidomics and glycan analysis – even in a multi-omic systems approach. The most critical features of this new instrumentation will be the 1) second post-ionization laser (MALDI-2) to greatly reduce noise and to improve ionization and sensitivity substantially, 2) full MS Imaging workflow solutions with workflows using the HTX M3+ Sprayer Bundle for sample preparation and matrix application required for MS Imaging, 3) high spatial resolution to reveal small distinct architectural features in tissues, 4) dual TIMS ion mobility for reduction of complexity, separation of isobaric features and increased sensitivity and selectivity for improved MS Imaging, 5) lipid and metabolite MS Imaging using ion mobility cross section (CCS) measurements as additional identifier (CCS) using the MetaboScape Databases and SCiLS (combination of m/z and CCS in spectral libraries and databases), and 6) true multi-omic approach for MS Imaging. Overall, the acquisition of this instrument to the Mass Spectrometry Core at the Buck Institute for Research on Aging will provide unique and novel features that will bring innovation and totally novel capabilities (spatial molecular MS Imaging) for our 18 proposed user projects that are examining key issues of human health and health span, including the this innovative mass spectrometry molecular imaging technology to study the biology of aging including differential aging of specific organs and to investigate age-related diseases, including Alzheimer’s and Huntington’s disease, a Parkinsonism, osteoarthritis, kidney diseases and metabolic disorders.