Multifunctional Fibers for Volumetric Imaging and Electrical Recording of Neuronal Activity In Vivo

While electrophysiology has traditionally been used to capture neuronal firing dynamics via electrodes implanted in the brain, optical sensing methods leveraging genetically-encoded fluorescent indicators offer unique advantages for neural sensing, including the ability to monitor specific cell types and detect neurotransmitter release. Endoscopic optical imaging also enables longitudinal tracking of many individual neurons within a wide field of view, but temporal sensitivity remains poor compared to electrophysiology, thus motivating the complementary usage of these techniques in tandem. However, expanding the functionality of neural implants stands to increase damage to surrounding tissue; large, stiff devices provoke inflammatory responses, attenuating recording capabilities and limiting long-term use of devices in vivo. Recent advances using thermal drawing to fabricate multifunctional fibers have yielded soft, flexible, polymer-based probes potentiating bidirectional electrical and optical sensing and stimulation in the brain, while minimizing foreign body response. Optical sensing capabilities of these probes have so far been limited to fiber photometry, which uses a single waveguide channel to relay a bulk fluorescence readout, and lacks the spatial signal discrimination offered by implantable endoscopic lenses. In this work, we advance the optical capabilities of multifunctional fibers to incorporate multicore waveguide bundles capable of relaying spatially-resolved fluorescent signals as analogues of neural activity. Our thermally-drawn fiber bundles feature hundreds to thousands of individual waveguide cores, each acting as a single pixel of an image with customizable resolution and field of view depending on the bundle design. We demonstrate imaging through polymer optical fiber bundles at a spatial resolution of 3 microns, sufficient for visualizing individual neurons. We further apply signal processing methods to leverage spatially-variant light modes captured within each individual waveguide core to achieve 3D imaging without demanding additional hardware. Finally, we show preliminary deployment of our multifunctional devices in vivo, interfaced with custom, miniaturized, head-mounted microscopes to capture fast calcium transients in the mouse brain. Compared to conventional endoscopic brain imaging, multifunctional imaging fiber bundles offer superior materials compatibility with surrounding brain tissue, volumetric imaging capabilities, and complementary electrical stimulation and recording. Overall, our fiber-based platform offers unique opportunities to probe neural signaling across spatiotemporal scales and diverse experimental paradigms.