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

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.

Subdural CMOS optical probe (SCOPe) for bidirectional neural interfacing

“…A variety of lens-less computational imaging optical metasurfaces have been demonstrated to avoid these limitations of refraction optics ( Fig. S16 ), such as angle-sensitive pixels( 18, 49 ), random diffuser masks( 50 ), micro-lens arrays( 14, 15 ), coded-aperture amplitude masks( 16, 51 ), and phase-masks( 17, 52 ). We choose to use a separable coded-aperture amplitude mask( 16, 51 ) because of small working distances required.…”

“…(A) We evaluated various types of computational imaging masks on the basis of working distance, reconstruction with LED blocks, light collection efficiency, flexibility, 3D capabilities, and ease of integration. (B) Comparison of working distances of the angle pixel( 49 ), amplitude mask( 16, 19 ), phase mask( 17 ), and fiber optic plate. (C) Numerical aperture, comparing amplitude and phase masks.…”

An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation

“…Out of its many strengths as an imaging tool, what emerged to be particularly relevant from the perspective of this study was the insensitivity of the fluorescence lifetime of a fluorophore toward its concentration, emission intensity, and bleaching effect. − As a dye, FITC was a stable pH-sensitive marker for microscopy. The fluorescence lifetime of FITCor other fluorescein derivatives per se, such as C-SNARF-4 or Oregon Green 488decreases with pH. − For example, the lifetime of FITC is 1.6 ns at pH 3, 4.5 ns at pH 5.8, and 7.8 ns at pH 9. However, FITC is often incompatible with super-resolution microscopic techniques, such as stimulated emission depletion microscopy, which might be one of its limitations in further studies.…”

WS2–Flake-Sandwiched, Au-Nanodisk-Enabled High-Quality Fabry–Pérot Nanoresonators for Photoluminescence Modulation

“…They offer powerful tools for light manipulation and have been widely employed in studies of light–matter interaction from weak to strong coupling regimes. They have also found wide potential applications in the development of lasers, , color filters, , and ultrasensitive sensors. − The FP resonator, developed by Fabry and Pérot in 1899 based on the interference phenomenon of light circulating between two parallel silver plates, is one of the most widely studied optical resonators. FP resonators can give ultrahigh quality ( Q ) factors with a rather simple structure, offering great flexibility in integrating various types of materials, including gas, semiconductor quantum dots, two-dimensional (2D) materials, and molecules, into the cavities for sensing, lasing, and polaritonic studies. − FP resonators can also couple directly with light along the cavity axis without the momentum-matching requirement, which is highly desirable in practical applications.…”

“…They offer powerful tools for light manipulation and have been widely employed in studies of light−matter interaction from weak to strong coupling regimes. They have also found wide potential applications in the development of lasers, 1,2 color filters, 3,4 and ultrasensitive sensors. 5−8 The FP resonator, developed by Fabry and Peŕot in 1899 based on the interference phenomenon of light circulating between two parallel silver plates, 9 is one of the most widely studied optical resonators.…”