Implantable Fluorescence Imager for Deep Neuronal Imaging

This thesis describes the design, fabrication, and characterization of the Implantable Fluorescence Imager (IFI): a camera chip with a needle-like form factor designed for imaging neuronal activity in the deep brain. It is fabricated with a complementary metal oxide semiconductor (CMOS) process, allowing for hundreds or thousands of single- photon-sensitive photodetectors to be densely packed onto a device width comparable to a single-channel fiber optic cannula (~100 μm). The IFI uses a combination of spectral and temporal filters as a fluorescence emission filter, and per-pixel Talbot gratings for 3D light-field imaging. The IFI has the potential to overcome the imaging depth limit of multi-photon microscopes imposed by the scattering and absorption of photons in brain tissue, and the resolution limit of noninvasive imaging techniques, such as functional magnetic resonance imaging and photoacoustic imaging. It competes with graded index lens-based miniaturized microscopes in imaging depth, but offers several comparative advantages. First, its cross sectional area is at least an order of magnitude smaller for an equal field of view. Second, the distribution of pixels along its entire length allows the study of multi- layer or multi-region dynamics. Finally, the scalability advantage of silicon integrated circuit technology in system miniaturization and data bandwidth may allow thousands of such imaging shanks to be simultaneously deployed for large-scale volumetric recording

Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS

Funding: This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) under contract N6600117C4012, by the National Institutes of Health under grant U01NS090596, by the Leverhulme Trust (RPG-2017-231) and by the Alexander von Humboldt Stiftung (Humboldt-Professorship to M.C.G.). This work was performed in part at the Columbia Nano Initiative cleanroom facility, at the CUNY Advanced Science Research Center Nanofabrication Facility, and at the Singh Center for Nanotechnology, part of the National Nanotechnology Coordinated Infrastructure Program, which is supported by the National Science Foundation grant NNCI-2025608. C.-K.M. acknowledges funding from the European Commission through a Marie-Skłodowska Curie Individual Fellowship (101029807).The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type and subcellular specificity—is a powerful tool in neuroscience. However, to interface with the opsins, deep-brain light delivery systems are required that match the scale of the spatial and temporal control offered by the molecular actuators. Here we show that organic light-emitting diodes can be combined with complementary metal–oxide–semiconductor technology to create bright, actively multiplexed emissive elements. We create implantable shanks in which 1,024 individually addressable organic light-emitting diode pixels with a 24.5 µm pitch are integrated with active complementary metal–oxide–semiconductor drive and control circuitry. This integration is enabled by controlled electrode conditioning, monolithic deposition of the organic light-emitting diodes and optimized thin-film encapsulation. The resulting probes can be used to access brain regions as deep as 5 mm and selectively activate individual neurons with millisecond-level precision in mice.Publisher PDFPeer reviewe

Customers\u27 perception of the attributes of different formats of menu labeling: a comparison between Korea and the U.S

Background/objectives: This study compared the perception of customers from Korea and the U.S. on the attributes of different formats of menu labeling The specific objectives were 1) to compare the customers\u27 perceived usefulness, ease-of-understanding, clarity, and attractiveness of different formats of menu labeling between Korea and the U.S.; and 2) to compare the customers\u27 use intention to different formats of menu labeling between Korea and the U.S. Subjects/methods: A survey was conducted in Korea and the U.S. The participants were allocated randomly to view 1 of the 7 restaurant menus that varied according to the following types of menu labeling formats: (type 1) kcal format, (type 2) traffic-light format, (type 3) percent daily intake (%DI) format, (type 4) kcal + traffic-light format, (type 5) kcal + %DI format, (type 6) traffic-light + %DI format, and (type 7) kcal + traffic-light + %DI format. A total of 279 Koreans and 347 Americans were entered in the analysis. An independent t-test and 1-way analysis of variance were performed. Results: Koreans rated type 4 format (kcal + traffic light) the highest for usefulness and attractiveness. In contrast, Americans rated type 7 (kcal + traffic light + %DI) the highest for usefulness, ease-of-understanding, attractiveness, and clarity. Significant differences were found in the customers\u27 perceived attributes to menu labeling between Korea and the U.S. Americans perceived higher for all the 4 attributes of menu labeling than Koreans. Conclusions: The study is unique in identifying the differences in the attributes of different formats of menu labeling between Korea and the U.S. Americans rated the most complicated type of menu labeling as the highest perception for the attributes, and showed a higher use intention of menu labeling than Koreans. This study contributes to academia and industry for practicing menu labeling in different countries using different formats

A 512-Pixel 3kHz-Frame-Rate Dual-Shank Lensless Filterless Single-Photon-Avalanche-Diode CMOS Neural Imaging Probe

Optical functional neural imaging has revolutionized neuroscience with optical reporters that enable single-cell-resolved monitoring of neuronal activity in vivo. State-of-the-art microscopy methods, however, are fundamentally limited in imaging depth by absorption and scattering in tissue even with the use of the most sophisticated two-photon microscopy techniques [1]. To overcome this imaging depth problem, we develop a lens-less, optical-filter-less, shank-based image sensor array that can be inserted into the brain, allowing cellular-resolution recording at arbitrary depths with excitation provided by an external laser light source (Fig. 11.5.1). Lens-less imaging is achieved generally by giving each pixel a spatial sensitivity function, which can be introduced by near-field or far-field, phase or amplitude masking. Since probe thickness must be less than 70μm to limit tissue damage and far-field masks are characterized by distances on the order of 200μm between the mask and the detector [2], we employ a near-field amplitude mask formed by Talbot gratings in the back-end metal of the CMOS process, which gives each pixel a diffraction-grating-induced angle-sensitivity [3]. Filter-less fluorescence imaging is achieved with time-gated operation in which the excitation light source is pulsed and pixel-level time-gated circuitry collects photons only after the excitation source has been removed

Customers' perception of the attributes of different formats of menu labeling: a comparison between Korea and the U.S

Background/objectives: This study compared the perception of customers from Korea and the U.S. on the attributes of different formats of menu labeling The specific objectives were 1) to compare the customers' perceived usefulness, ease-of-understanding, clarity, and attractiveness of different formats of menu labeling between Korea and the U.S.; and 2) to compare the customers' use intention to different formats of menu labeling between Korea and the U.S. Subjects/methods: A survey was conducted in Korea and the U.S. The participants were allocated randomly to view 1 of the 7 restaurant menus that varied according to the following types of menu labeling formats: (type 1) kcal format, (type 2) traffic-light format, (type 3) percent daily intake (%DI) format, (type 4) kcal + traffic-light format, (type 5) kcal + %DI format, (type 6) traffic-light + %DI format, and (type 7) kcal + traffic-light + %DI format. A total of 279 Koreans and 347 Americans were entered in the analysis. An independent t-test and 1-way analysis of variance were performed. Results: Koreans rated type 4 format (kcal + traffic light) the highest for usefulness and attractiveness. In contrast, Americans rated type 7 (kcal + traffic light + %DI) the highest for usefulness, ease-of-understanding, attractiveness, and clarity. Significant differences were found in the customers' perceived attributes to menu labeling between Korea and the U.S. Americans perceived higher for all the 4 attributes of menu labeling than Koreans. Conclusions: The study is unique in identifying the differences in the attributes of different formats of menu labeling between Korea and the U.S. Americans rated the most complicated type of menu labeling as the highest perception for the attributes, and showed a higher use intention of menu labeling than Koreans. This study contributes to academia and industry for practicing menu labeling in different countries using different formats.This article is published as Bosselman R, Choi HM, Lee KS, Kim E, Cha J, Jeong JY, Jo M, Ham S. Customers' perception of the attributes of different formats of menu labeling: a comparison between Korea and the U.S. Nutr Res Pract. 2020 Jun;14(3):286-297. doi: 10.4162/nrp.2020.14.3.286. </p

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

We present an implantable single-photon shank-based imager, monolithically integrated onto a single CMOS IC. The imager comprises of 512 single-photon avalanche diodes distributed along two shanks, with a 6-bit depth in-pixel memory and an on-chip digital-to-time converter. To scale down the system to a minimally invasive form factor, we substitute optical filtering and focusing elements with a time-gated, angle-sensitive detection system. The imager computationally reconstructs the position of fluorescent sources within a 3-D volume of 3.4 mm × 600 μm× 400 μm

A 512-Pixel 3kHz-Frame-Rate Dual-Shank Lensless Filterless Single-Photon-Avalanche-Diode CMOS Neural Imaging Probe

Optical functional neural imaging has revolutionized neuroscience with optical reporters that enable single-cell-resolved monitoring of neuronal activity in vivo. State-of-the-art microscopy methods, however, are fundamentally limited in imaging depth by absorption and scattering in tissue even with the use of the most sophisticated two-photon microscopy techniques [1]. To overcome this imaging depth problem, we develop a lens-less, optical-filter-less, shank-based image sensor array that can be inserted into the brain, allowing cellular-resolution recording at arbitrary depths with excitation provided by an external laser light source (Fig. 11.5.1). Lens-less imaging is achieved generally by giving each pixel a spatial sensitivity function, which can be introduced by near-field or far-field, phase or amplitude masking. Since probe thickness must be less than 70μm to limit tissue damage and far-field masks are characterized by distances on the order of 200μm between the mask and the detector [2], we employ a near-field amplitude mask formed by Talbot gratings in the back-end metal of the CMOS process, which gives each pixel a diffraction-grating-induced angle-sensitivity [3]. Filter-less fluorescence imaging is achieved with time-gated operation in which the excitation light source is pulsed and pixel-level time-gated circuitry collects photons only after the excitation source has been removed