Project Summary The goal of this project is to demonstrate a bench-top system that can interface with individual axons in the cervical vagus nerve through an implanted, all-optical instrument. Addressing individual axons requires single micron spatial resolution at a depth of several mm. Reporting and modulation are achieved through multiphoton absorption of incident infrared light and detection of fluorescence in the visible spectrum. The optical system must be precisely focused on individual axons and maintain this alignment with one micron tolerance as the animal breaths and, in eventual experiments, moves. Movement of the animal must not cause damage or initiate rejection, which in turn requires that the mechanical properties of the implant match the surrounding soft tissue. No existing bioimaging technology can meet these requirements. Thus, this supplement will support and advance the aim of the parent grant to create a new class of soft gradient index optics that deform under strain of implantation or animal movement. These will be created from soft solid polymers that are optically patterned with a permanent refractive index gradient that focuses light in the same manner as existing glass micro-endoscopes but with improved performance such as aberration correction. The proposed bio-imaging technology will improve the performance of existing glass micro-endoscopes for deep, broad-bandwidth, high-resolution neuromodulation while also matching tissue modulus to enable chronic implantation. To extend the performance of these lenses during bending, we propose to incorporate stress relaxation chemistry into the solid matrix of the polymer. Covalent adaptable networks plastically deform in response to strain such as that caused by implantation or movement. We have shown these eliminate stress-induced birefringence that typically limits the performance of polymer optics. We hypothesize this scheme, when applied to these soft polymer optics, will also improve performance under strain. Here we request funds for three years of graduate training for Mr. Arlo Marquez-Grap, who is pursuing his doctorate in Materials Science and Engineering at the University of Colorado Boulder. Mr. Marquez-Grap has a strong background in optics and materials and is keenly interested in materials for biomedicine. This work will provide him broad training in optical imaging, neuroscience, biomaterials and independent research. A comprehensive mentoring plan will provide professional development and training to launch his career as an independent researcher.