Super-resolution Workstation for Imaging Live Biological Nanostructures. A novel research instrument will be developed for visualizing and measuring living biological structures that are below the resolution limit of conventional light microscopy. This super-resolution microscope does not require any mechano-optical adjustments during image acquisition and will thus allow for fast imaging of sub-resolution structures free of inherent mechanical artifacts. The instrument will combine two established techniques -- the spatial resolution enhancement of Standing Wave Microscopy with the temporal resolution enhancement of Acousto-Optic Laser Scanning. The proposed instrument will be unique in its performance and will be of particular advantage in applications where the dynamics of sub-resolution living biological structures are to be studied. The PI has previously conceived and constructed a series of advanced imaging instruments necessary for his long-term biological research goal to understand information processing in single neurons and small neuronal populations. All developed instruments utilized the PI's expertise with Diffractive Optical Elements, specifically Acousto-Optic Devices. The optical properties of these elements are rapidly adjustable, i.e. with electronically produced sound waves in the radio frequency range, making acousto-optic devices unique building blocks for advanced imaging instrumentation. The proposed imaging workstation will be developed in a two-step approach, resulting in improved spatial resolution in three dimensions. The inertia-free control of the necessary illumination patterns by acousto-optic devices will result in a highly versatile instrument with superior mechanical stability and imaging speed. The proposed workstation for fast super-resolution imaging would be of high importance in biomedical research. It would vastly improve the way important intracellular structures can be visualized and their function monitored, including mitochondria, endoplasmic reticulum, and microtubules. Specifically in experimental Neuroscience such an instrument would support the study of various aspect of synaptic transmission, including presynaptic vesicle clusters and postsynaptic dendritic spine necks. For example, the fragile sub-resolution structure of spine necks is susceptible to changes during development and plasticity, but also to a number of neurological diseases. In general, the availability of the proposed super-resolution imaging capability would be transformational and benefit large communities in the biomedical field.

Public Health Relevance

(provided by the applicant): Although the proposed imaging workstation was conceived for Biomedical Research, it has also great potential as a diagnostic tool. Changes in subcellular structure and function often coincide with various states of numerous diseases. The proposed instrument will allow microscopic inspection and functional testing of subcellular structures in live, non-fixed cellular specimen at unparalleled spatio- temporal resolution.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRR1-BT-7 (01))
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Friedman, Fred K
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Baylor College of Medicine
Schools of Medicine
United States
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