Saturday, November 23, 2024
11/23/2024
Project Summary This is a re-submission of the proposal “High-End Fluorescence Biological Atomic Force Microscope” of 2020 NIH S10 program (Application Number: 1 S10 OD030401-01) focusing on mechanobiological studies, a rapidly growing field of research on the influence of mechanics in biological systems. To study mechanobiology at the molecular, cellular, and tissue levels, researchers need a tool that can measure and control the mechanics of samples while monitoring biological activities within the samples. The instrument requested in this proposal is an integrated system that positions an atomic force microscope (AFM) on top of a fluorescence microscope, providing unique capabilities to precisely measure and apply forces and simultaneously visualize biological phenomena. The AFM platform offers force measurements, high-resolution mechanical property mapping, video- rate imaging, and a nano-fluidics integrated probe system. The fluorescence microscope includes a spinning disk confocal, total internal -reflection fluorescence (TIRF), and differential interference contrast (DIC). The PI and the respective manufacturers will integrate the two systems to set up a combined platform (Bio-AFM) that can perform advanced and simultaneous mechanical and optical measurements in real time, providing novel approaches for mechanobiological studies of a broad variety of target bio-systems. Access to the Bio-AFM will immediately advance the research of 16 users (10 major and 6 minor) from 5 universities and 11 departments, including 9 users funded by the NIH (> $12M in the past 5 years) and 6 users funded by NSF, Air Force, Navy, and Army research programs. Progress in those initial projects will advance research on neuron disorders (6 projects), the biophysics of atheroma and microvascular disease (3 projects), biomedical materials (3 projects), mechano-sensing and its application in immunology (2 projects), bone-related disorders (1 project), and bio-sensing for diagnostics (1 project). The Bio-AFM will be housed in a well-established core facility where it will be accessible to everyone that needs it. The Surface Science Core Facility currently serves more than 230 end users from more than 70 research groups. The existing infrastructure for instrument training, operation, and management is easily adaptable to accommodate the Bio-AFM. The PI is the Surface Science Core Facility’s founding Director (with more than 20 years of AFM research experience) and will be responsible for overseeing all Bio-AFM activities at the facility. The Bio-AFM, like all other instruments in the Surface Science Core Facility, will be fully supported by the institution with regard to finances, safety, outreach, IT, grant management, and administration. Given the expertise, infrastructure, and institutional supports, the requested Bio-AFM will not only benefit the initial 14 users, but also provide new opportunities to countless future users and new projects for biomedical research extending far beyond the end of the grant period.
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