Toward implantable devices for angle-sensitive, lens-less, multifluorescent, single-photon lifetime imaging in the brain using Fabry-Perot and absorptive color filters

Implantable image sensors have the potential to revolutionize neuroscience. Due to their small form factor requirements; however, conventional filters and optics cannot be implemented. These limitations obstruct high-resolution imaging of large neural densities. Recent advances in angle-sensitive image sensors and single-photon avalanche diodes have provided a path toward ultrathin lens-less fluorescence imaging, enabling plenoptic sensing by extending sensing capabilities to include photon arrival time and incident angle, thereby providing the opportunity for separability of fluorescence point sources within the context of light-field microscopy (LFM). However, the addition of spectral sensitivity to angle-sensitive LFM reduces imager resolution because each wavelength requires a separate pixel subset. Here, we present a 1024-pixel, 50 mu m thick implantable shank-based neural imager with color-filter-grating-based angle-sensitive pixels. This angular-spectral sensitive front end combines a metal-insulator-metal (MIM) Fabry-Perot color filter and diffractive optics to produce the measurement of orthogonal light-field information from two distinct colors within a single photodetector. The result is the ability to add independent color sensing to LFM while doubling the effective pixel density. The implantable imager combines angular-spectral and temporal information to demix and localize multispectral fluorescent targets. In this initial prototype, this is demonstrated with 45 mu m diameter fluorescently labeled beads in scattering medium. Fluorescent lifetime imaging is exploited to further aid source separation, in addition to detecting pH through lifetime changes in fluorescent dyes. While these initial fluorescent targets are considerably brighter than fluorescently labeled neurons, further improvements will allow the application of these techniques to in-vivo multifluorescent structural and functional neural imaging.

Automated summary

Implantable image sensors have the potential to revolutionize neuroscience by overcoming limitations in high-resolution imaging. Recent advances in technology have enabled ultra-thin lens-less fluorescence imaging, extending sensing capabilities to include photon arrival time and incident angle. A new implantable neural imager with angular-spectral sensitive pixels has been developed, combining metal-insulator-metal (MIM) Fabry-Perot color filters and diffractive optics to enable independent color sensing while doubling the effective pixel density. This imager utilizes angular-spectral and temporal information to demix and localize multispectral fluorescent targets, demonstrating its potential for in-vivo multifluorescent neural imaging.