PFI:AIR - TT: Proof-of-concept fiber-based miniature multiphoton microscope using adaptable optics

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This PFI: AIR Technology Translation project focuses on combining miniature adaptable optics with multiphoton laser scanning microscopy to fill the need for a versatile, implantable, three-dimensional imaging system for studying brain activity in awake behaving animals. The fiber-coupled miniature multiphoton microscope is important because it allows neuroscientists an unprecedented ability to study dynamics of complex neuronal circuits while animals are undergoing different behavior tasks. The project will result in a proof-of-concept demonstration of our product operating in freely moving animals. The fiber-coupled miniature multiphoton microscope will allow full three-dimensional scanning through active focusing with no mechanically moving parts in a compact, light weight design. The product can be readily connected to a commercial-laser scanning microscope. These features allow for reduced cost, flexibility in configuration of the wavelength or imaging modality to be performed, and can provide imaging over larger brain volumes when compared to the leading head-mounted microscope systems in this market space.This project addresses the following technology gaps as it translates from research discovery toward commercial application. Although light microscopy has rapidly advanced for studies of biological systems, one major gap is the ability to use these advanced imaging tools for dynamic studies in the brain in freely moving animals. We propose to combine the advantages of two-photon excitation with depth scanning using adaptive optics in a compact fiber-coupled design. Current commercially available miniature microscopes only allow for single imaging planes, do not enable active focusing during imaging and do not allow both targeted imaging and optogenetic stimulation. The miniature multiphoton fiber-coupled microscope will use a fiber-bundle to translate the laser-scanned signal to the distal microscope head and miniature adaptable optical elements to provide fast active focusing. This will accomplish high versatility for applications such as fast region-of-interest imaging, optogenetic stimulation, and depth imaging with multiphoton techniques. Personnel involved in this project including undergraduate and graduate students, will receive experience in technology translation through meetings with business partners, attending technology conferences, and participating in outreach events.This project engages 3i (Intelligent Imaging Innovations), an international company that specializes in delivering advanced optical microscope systems. This collaboration will allow implementation of this fiber-coupled microscope into commercial systems and speed delivery to a global commercial market.