A 512-Pixel, 51-kHz-Frame-Rate, Dual-Shank, Lens-Less, Filter-Less Single-Photon Avalanche Diode CMOS Neural Imaging Probe

Choi, Jaebin; Taal, Adriaan J.; Pollmann, Eric H.; Lee, Changhyuk; Kim, Kukjoo; Moreaux, Laurent; Roukes, M. L.; Shepard, Kenneth L.

doi:10.1109/jssc.2019.2941529

Cited by 17 publications

(22 citation statements)

References 40 publications

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“…For MIMAS, the spectral sensitivity and added orthogonality between both color channels provide a 95% higher separability value. A 25% transmission efficiency over all angles, compared with 3% previously reported for metal gratings 9 , improves signal photon count by over 8×.…”

Section: Resultsmentioning

confidence: 57%

“…To achieve imaging at depth, these instruments also require implantation of their requisite GRIN lenses (typically, with 0.3–2 mm diameter); this results in even greater displacement of brain tissue while still delivering only restricted fields of view. 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 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Resultsmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Beyond LSFM imaging, these neural probes can also be used for laminar optogenetic neural stimulation, e.g., for addressing individual cortical layers. When combined with a new class of implantable neural probes containing photodetector arrays that is now emerging, 43 they can enable complex image reconstruction realized by means of a complete, implantable lensless imaging system.…”

Section: Discussionmentioning

confidence: 99%

Implantable photonic neural probes for light-sheet fluorescence brain imaging

et al. 2021

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. Significance: Light-sheet fluorescence microscopy (LSFM) is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. We demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200-mm-diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed, in vitro , and in vivo mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses for propagation distances up to in free space. Imaging areas were as large as in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of LSFM for deep brain imaging and experiments in freely moving animals.

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“…• D-pixels yielded discrete photon counts with quantum efficiency η = 0.6 and an additive dark noise level of ν = 300 s −1 , which corresponds to the performance of stateof-the-art single photon avalanche diode (SPAD) detectors [9].…”

Section: Simulated Light Emission Transport Fluorescence and Detecmentioning

confidence: 99%

Signal separability in integrated neurophotonics

Yatsenko

Moreaux

Choi

et al. 2020

Preprint

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Photonic probes record fluorescent signals by using arrays of light emitters and detectors embedded in neural tissue. Neither the emitted nor collected light fields are focused. Instead, in proposed configurations, hundreds of emitters will form rapid sequences of structured illumination patterns—providing sufficient spatial and temporal differentiation of neural signals for computational demixing. Here we define criteria for evaluating probe designs for achieving better signal separability. We find that probe geometry has profound, often unintuitive, effects on the separability of neural signals, providing initial design guidelines to achieve separation of individual cells in densely labeled populations.

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A 512-Pixel, 51-kHz-Frame-Rate, Dual-Shank, Lens-Less, Filter-Less Single-Photon Avalanche Diode CMOS Neural Imaging Probe

Cited by 17 publications

References 40 publications

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

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

Implantable photonic neural probes for light-sheet fluorescence brain imaging

Signal separability in integrated neurophotonics

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