Abstract
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 µm 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 μm 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.
Highlights
Optical imaging has revolutionized neuroscience by allowing recording of neural function in vivo
We demonstrate how the combination of angular and spectral sensing allows for simultaneous source separation and localization of multispectral fluorescent sources
We begin with two MIM filters, green and red bandpass filters designed with HfO2 dielectric thicknesses of d1 = 70 nm and d2 = 100 nm, respectively, sandwiched between two 30 nm thick silver layers (Fig. 1a)
Summary
Optical imaging has revolutionized neuroscience by allowing recording of neural function in vivo. Light scattering and absorption in tissue fundamentally limits the depth at which fluorescence microscopes can detect labeled neurons. The limitations with existing state-of-the-art imaging approaches at depth have led to the search for alternatives in which the imager itself is given a shank form factor and directly inserted into the tissue[9,10]. In this case, minimizing the thickness of the device is of prime importance to reduce displaced tissue volume. While implantable lens-less methods lack the light gathering capabilities of lenses, they can image sources close to the device to compensate for diminished photon yield, not limited by the working distances associated with refractive optics
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