Ultra-high resolution imaging mass spectrometry (MS), using matrix-assisted laser desorption ionization (MALDI) MS coupled to a Fourier transform ion cyclotron resonance (FT-ICR) mass analyzer, provides a powerful technology for visualization of diverse endogenous molecules and assessment of their tissue distribution in a native anatomical context. This capability of MALDI-FT-ICR imaging is unprecedented in its ultra-high resolution (>10,000,000), sensitivity, molecular specificity, and breadth of coverage, using a single analytical platform. The ability to visualize the distribution of large numbers of molecules of diverse molecular classes (metabolites, lipids, nucleotides, peptides) in tissues on microscopic slides, overlayed with relevant histological/pathology information, now paves the way for massively synergistic knowledge of human health and disease states. NIH-supported researchers at Weill Cornell Medical (WCM) and the greater New York City biomedical research community (including Cornell Ithaca, NYU School of Medicine, Albert Einstein School of Medicine, Memorial Sloan-Kettering Cancer Center, New York Presbyterian Hospital, Hospital for Special Surgery) have an urgent unmet need for high-resolution MALDI imaging to elucidate the tissue distributions of diverse molecules of biomedical importance. This instrumentation is needed by a group of 10 NIH-supported Major Users who request funds to purchase an ultra-high resolution Bruker 7 Tesla SolariX XR MALDI-FT-ICR imaging system with integrated dual MALDI/ESI source, computer and operating/analytical software. The requested MALDI imaging system will be housed in a newly-expanded Mass Spectrometry Core Facility on the 16th floor of the Belfer Building at Weill Cornell Medicine, and address the needs of WCM biomedical investigators, along with the broader New York City and State research community. Our MS Facility Core Staff and user's group seek to not only apply existing MALDI imaging technology for advancement of ongoing NIH- supported research, but also intend to expand and significantly advance MS imaging capabilities for isotope flux measurements, redoxome analysis, and assessment of newly-discovered RNA modifications that impact the efficiency of protein translational. We are currently unaware of any ultra-high-resolution MALDI-MS imaging instrumentation in the whole of NYS that duplicates the capabilities of the requested instrumentation. Consequently, availability of MALDI-FT-ICR is anticipated to have great value to a diverse research neighborhood and high demand. We have established a solid plan for making the requested instrumentation available to users and WCM is fully-committed to long-term financial support for the useful lifetime of the instrumentation.
Mass spectrometry (MS) is a fundamental analytical tool used for biomedical investigations to identify and quantify molecules of interest. Until now, biological MS-based analyses has typically been limited to studies of tissue extracts and tissue homogenates, stripped of potentially important information on where the quantified molecules actually reside within a given tissue source. This grant application seeks funds to purchase a state- of-the-art high-resolution imaging MS platform that will enable 10 Major Users with the unprecedented capability to visualize the microscopic distribution of diverse molecules of interest for advancement of their ongoing NIH-supported research goals.