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2. Monitoring Neural Activities in the VTA in Response to Nicotine Intake Using a Novel Implantable Microimaging Device

Author

Sunaga, Yoshinori, Ohta, Yasumi, Akay, Yasemin M, Ohta, Jun, Akay, Metin, Sunaga, Yoshinori, Ohta, Yasumi, Akay, Yasemin M, Ohta, Jun, and Akay, Metin

Abstract

Measurements of the deep brain area of rodents has been one of the most important methods to study deep brain activities, in part due to limited access of this region. In order to address this problem, we have designed and fabricated an implantable microimaging device for fluorescence imaging in the deep brain of rodents. In this study, we established a new fabrication method of a flat and uniformed fluorescence filter for an implantable microimaging device which obtained higher quality images, and aimed to show the performance of the device in the ventral tegmental area (VTA) of rats. We introduced GCaMP6s in the VTA of rats by adeno-associated viral (AAV) injection. The change in the fluorescence intensity was associated with nicotine administration and was observed by using our custom implantable microimaging device. We showed that nicotine administration significantly affected the excitation of DA neurons in different sub-regions of the VTA, reaching a maximum activation between 6-10 minutes following nicotine exposure, followed by a decrease after 31-35 minutes. Therefore, we believe our implantable microimaging device can potentially be used to monitor the neural activation within the sub-regions of the VTA in response to acute nicotine exposure by using GCaMP.

Published
2023

13. Polarization Image Sensor for Highly Sensitive Polarization Modulation Imaging Based on Stacked Polarizers.

Author

Sasagawa, Kiyotaka, Okada, Ryoma, Haruta, Makito, Takehara, Hironari, Tashiro, Hiroyuki, and Ohta, Jun

Subjects
CMOS image sensors, IMAGE sensors, POLARIZERS (Light), COMPLEMENTARY metal oxide semiconductors, DETECTION limit
Abstract

In this article, We demonstrated an image sensor for detecting changes in polarization with high sensitivity. For this purpose, we constructed an optical system with a two-layer structure, comprising an external polarizer and polarizers on a pixel array. An external polarizer is used to enhance the polarization rotation while reducing the intensity to avoid pixel saturation of the image sensor. Using a two-layer structure, the two polarizers can be arranged under optimal conditions and the image sensor can achieve high polarization-change detection performance. We fabricated the polarization image sensor using a 0.35- $\mu \text{m}$ CMOS process and, by averaging 50 ${\times }\,\,50$ pixels and 96 frames, achieved a polarization rotation detection limit of 5.2 ${\times }\,\,10^{-4^{\circ}} $ at a wavelength of 625 nm. We also demonstrated the applicability of electric-field distribution imaging using an electrooptic crystal (ZnTe) for weak-polarization-change distribution measurements. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Monitoring Neural Activities in the VTA in Response to Nicotine Intake Using a Novel Implantable Microimaging Device

Author

Sunaga, Yoshinori, Ohta, Yasumi, Akay, Yasemin M, Ohta, Jun, Akay, Metin, Sunaga, Yoshinori, Ohta, Yasumi, Akay, Yasemin M, Ohta, Jun, and Akay, Metin

Abstract

Measurements of the deep brain area of rodents has been one of the most important methods to study deep brain activities, in part due to limited access of this region. In order to address this problem, we have designed and fabricated an implantable microimaging device for fluorescence imaging in the deep brain of rodents. In this study, we established a new fabrication method of a flat and uniformed fluorescence filter for an implantable microimaging device which obtained higher quality images, and aimed to show the performance of the device in the ventral tegmental area (VTA) of rats. We introduced GCaMP6s in the VTA of rats by adeno-associated viral (AAV) injection. The change in the fluorescence intensity was associated with nicotine administration and was observed by using our custom implantable microimaging device. We showed that nicotine administration significantly affected the excitation of DA neurons in different sub-regions of the VTA, reaching a maximum activation between 6-10 minutes following nicotine exposure, followed by a decrease after 31-35 minutes. Therefore, we believe our implantable microimaging device can potentially be used to monitor the neural activation within the sub-regions of the VTA in response to acute nicotine exposure by using GCaMP., identifier:2169-3536

Published
2020

15. Monitoring Neural Activities in the VTA in Response to Nicotine Intake Using a Novel Implantable Microimaging Device

Author

40807640, Sunaga, Yoshinori, Ohta, Yasumi, Akay, Yasemin M, 80304161, Ohta, Jun, Akay, Metin, 40807640, Sunaga, Yoshinori, Ohta, Yasumi, Akay, Yasemin M, 80304161, Ohta, Jun, and Akay, Metin

Abstract

Measurements of the deep brain area of rodents has been one of the most important methods to study deep brain activities, in part due to limited access of this region. In order to address this problem, we have designed and fabricated an implantable microimaging device for fluorescence imaging in the deep brain of rodents. In this study, we established a new fabrication method of a flat and uniformed fluorescence filter for an implantable microimaging device which obtained higher quality images, and aimed to show the performance of the device in the ventral tegmental area (VTA) of rats. We introduced GCaMP6s in the VTA of rats by adeno-associated viral (AAV) injection. The change in the fluorescence intensity was associated with nicotine administration and was observed by using our custom implantable microimaging device. We showed that nicotine administration significantly affected the excitation of DA neurons in different sub-regions of the VTA, reaching a maximum activation between 6-10 minutes following nicotine exposure, followed by a decrease after 31-35 minutes. Therefore, we believe our implantable microimaging device can potentially be used to monitor the neural activation within the sub-regions of the VTA in response to acute nicotine exposure by using GCaMP.

Published
2020

19. Precise Temporal Control of Interferential Neural Stimulation via Phase Modulation.

Author

Terasawa, Yasuo, Tashiro, Hiroyuki, Ueno, Tokio, and Ohta, Jun

Subjects
PHASE modulation, NEURAL stimulation, AMPLITUDE modulation, NERVE tissue, ELECTRIC stimulation
Abstract

Objective: Noninvasive neural stimulation via temporally interferential (TI) electrical field is currently an area of interest as a noninvasive method of brain stimulation. The major limitation of TI stimulation is the difficulty of precise temporal control of the stimulation, due to the nature of the sinusoidal envelope generated by the interference. The purpose of this study was to investigate the possibility of improving interferential stimulation by introducing precise temporal control using phase modulation. Methods: In conventional TI, a sinusoidal current is applied to two electrode pairs with slightly different frequencies, to cause interference. In this paper we describe phase modulation interference (PMI). Instead of shifting frequency, the phase of a sinusoidal wave was partially modulated, causing a transient increase or decrease of the envelope. The spatial distribution of envelope modulation amplitude by TI and PMI was visualized using both electromagnetic simulation and actual measurement using tissue phantom. Results: The measured voltage transient in the tissue phantom produce a precise, temporally controlled pulse-like envelope using PMI. The spatial distributions of the amplitude of the envelope modulation by TI and PMI did not differ significantly, and were consistent with electromagnetic simulation. Conclusion: PMI allows precise temporal control of interferential stimulation, thus increasing the practical utility of interferential stimulation. Significance: PMI improves interferential stimulation, allowing more temporally precise stimulation to neural tissue located distantly from the stimulating electrodes. [ABSTRACT FROM AUTHOR]

Published
2022
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24. Wearable and Battery-Free Health-Monitoring Devices With Optical Power Transfer.

Author

Wuthibenjaphonchai, Nattakarn, Haruta, Makito, Sasagawa, Kiyotaka, Tokuda, Takashi, Carrara, Sandro, and Ohta, Jun

Abstract

Wireless epidermal wearable devices attract interests and expectations as a tool for personalized, low-cost health monitoring technology. The concept of the wireless attachable personal health monitoring devices has been more widely considered by combining them with biosensors. To bring the most advantage out of the structure of the epidermal attachable device, a battery-free approach was introduced to reduce the volume and extend the lifetime of the device. In this work, an energy harvesting technology and noninvasive sensor were applied with the attachable battery-free devices as a wireless power system and painless measuring system. A glucose sensor was used as an example to develop the wireless wearable device for diabetes-monitoring. The device consists of two functional parts: an optical power transfer and an electrochemical sensing part. The operation starts when the optical power transfer part accumulates power from series-connected photovoltaic cells and intermittently supplies the power to the electrochemical sensing part. In the electrochemical sensing part, an amperometric method was used for controlling the oxidation voltage and measuring a faraday current from the noninvasive sensor and current as brightness and duration of light pulses from a light-emitting diode (LED). The experiment results show that the device works as expected for a variety of glucose concentrations. [ABSTRACT FROM AUTHOR]

Published
2021
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25. Improved Charge Pump Design and Ex Vivo Experimental Validation of CMOS 256-Pixel Photovoltaic-Powered Subretinal Prosthetic Chip.

Author

Kuo, Po-Han, Wong, Oi-Ying, Tzeng, Chi-Kuan, Wu, Pu-Wei, Chiao, Chuan-Chin, Chen, Po-Hung, Chen, Po-Chun, Tsai, Yueh-Chun, Chu, Fang-Liang, Ohta, Jun, Tokuda, Takashi, Noda, Toshihiko, and Wu, Chung-Yu

Subjects
ON-chip charge pumps, RETINAL ganglion cells, CMOS image sensors, POWER resources, ELECTRIC power, SOLAR cells
Abstract

An improved design of CMOS 256-pixel photovoltaic-powered implantable chip for subretinal prostheses is presented. In the proposed subretinal chip, a high-efficiency fully-integrated 4× charge pump is designed and integrated with on-chip photovoltaic (PV) cells and a 256-pixel array with active pixel sensors (APS) for image light sensing, biphasic constant current stimulators, and electrodes. Thus the PV voltage generated by infrared (IR) light can be boosted to above 1V so that the charge injection is increased. The proposed chip adopts the 32-phase divisional power supply scheme (DPSS) to reduce the required supply current and thus the required area of the PV cells. The proposed chip is designed and fabricated in 180-nm CMOS image sensor (CIS) technology and post-processed with biocompatible IrOx electrodes and silicone packaging. From the electrical measurement results, the measured stimulation frequency is 28.3 Hz under the equivalent electrode impedance load. The measured maximum output stimulation current is 7.1 μA and the amount of injected charges per pixel is 7.36 nC under image light intensity of 3200 lux and IR light intensity of 100 mW/cm2. The function of the proposed chip has been further validated successfully with the ex vivo experimental results by recording the electrophysiological responses of retinal ganglion cells (RGCs) of retinas from retinal degeneration (rd1) mice with a multi-electrode array (MEA). The measured average threshold injected charge is about 3.97 nC which is consistent with that obtained from the patch clamp recording on retinas from wild type (C57BL/6) mice with a single electrode pair. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Next-generation Fundus Camera with Full Color Image Acquisition in 0-lx Visible Light by 1.12-micron Square Pixel, 4K, 30-fps BSI CMOS Image Sensor with Advanced NIR Multi-spectral Imaging System

Author

Sumi, Hirofumi, primary, Takehara, Hironari, additional, Miyazaki, Shunsuke, additional, Shirahige, Daiki, additional, Sasagawa, Kiyotaka, additional, Tokuda, Takashi, additional, Watanabe, Yoshihiro, additional, Kishi, Norimasa, additional, Ohta, Jun, additional, and Ishikawa, Masatoshi, additional

Published
2018
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38. CMOS 256-Pixel/480-Pixel Photovoltaic-Powered Subretinal Prosthetic Chips With Wide Image Dynamic Range and Bi/Four-Directional Sharing Electrodes and Their Ex Vivo Experimental Validations With Mice.

Author

Wu, Chung-Yu, Tseng, Chi-Kuan, Liao, Jung-Hsing, Chiao, Chuan-Chin, Chu, Fang-Liang, Tsai, Yueh-Chun, Ohta, Jun, and Noda, Toshihiko

Subjects
ELECTRODES, PIXELS, NEUROPROSTHESES, VISIBLE spectra, CMOS image sensors, PHOTOVOLTAIC cells
Abstract

CMOS photovoltaic-powered 256-pixel/480-pixel implantable chips with a wide image dynamic range and shared electrodes are proposed and fabricated in CIS technology for subretinal prostheses. The infra-red (IR) light is incident only on photovoltaic cells of the chip whereas the visible light is mainly incident on pixels. The proposed adaptive background cancellation circuit (ABCC) is adopted to increase the image dynamic range so that the subretinal chips can adapt for different surrounding illuminances. A two-dimensional equivalent electrode model for electric crosstalk simulation is proposed to analyze the crosstalk charges and enable the stimulation pattern design with minimum crosstalk for both chips. Moreover, the bi-directional sharing electrodes (BDSEs) are used in the 256-pixel chip to increase electrode size under the same chip area and boost the stimulation charges to 11.4 nC. The four-directional sharing electrodes (FDSEs) are used to share the electrodes in both vertical and horizontal directions and achieve 480 pixels with nearly the same electrode size under the same pixel array area. The maximum stimulation charge is 9.8 nC. The dynamic range of image light is increased to 31.65 dB (24.9 dB) in the fabricated 256-pixel (480-pixel) chip. The functions of the chip have been successfully validated by both electrical measurement and ex vivo patch clamp experiments with the retinas of mice. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Needle-Type Imager Sensor With Band-Pass Composite Emission Filter and Parallel Fiber-Coupled Laser Excitation.

Author

Rustami, Erus, Sasagawa, Kiyotaka, Sugie, Kenji, Ohta, Yasumi, Haruta, Makito, Noda, Toshihiko, Tokuda, Takashi, and Ohta, Jun

Subjects
GREEN fluorescent protein, FIBER lasers, LASERS, FILTERS & filtration, OPTICAL fibers, COMPOSITE structures
Abstract

This paper presents an implantable fluorescence system with a composite emission filter and fiber-coupled laser excitation. The composite structure of the short-pass interference filter and absorption filters exhibited a band-pass spectrum between 510 and 570 nm, which is close to green fluorescent protein (GFP) emission. A high-quality excitation light was achieved by utilizing a blue laser through a low-numerical-aperture optical fiber. This coupling method is beneficial in delivering a narrow spectrum and controllable irradiation light in a specific area to minimize auto-fluorescence from the tissue. The fabricated lensless system performance is experimentally validated by imaging emission. The proposed device is capable of perceiving fluorescence emission from microspheres and GFP noticeably. [ABSTRACT FROM AUTHOR]

Published
2020
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47. Compact Lensless Fluorescence Counting System for Single Molecular Assay.

Author

Takehara, Hironari, Nakamoto, Yuta, Ikeda, Narihito, Sasagawa, Kiyotaka, Haruta, Makito, Noda, Toshihiko, Tokuda, Takashi, and Ohta, Jun

Abstract

In digital enzyme-linked immunosorbent assay, which is used for biomarker detection and diagnosis, the concentration of target biomarkers is estimated by counting the number of fluorescence chambers in the microchamber array. We propose a compact system for counting fluorescent chambers. Our system consists of three components: a micro-reaction chamber array, an absorption filter for attenuating excitation light, and a photodetector. The absorption filter has a micro-light-pipe array (m-LPA) structure. A stacked photodiode CMOS image sensor (CIS), which can discriminate color, is applied as a photodetector. This paper describes the fabrication process enabling thin m-LPA chips. The unique low-noise characteristics of the stacked photodiode CIS that attains high sensitivity by adopting the 4T-APS configuration are explained. Furthermore, a detection method using the photobleaching phenomenon is proposed for high-sensitivity fluorescence detection. This method suggests that fluorescence by a single molecular enzyme can be detected within 30 min of the start of the fluorescence reaction. [ABSTRACT FROM AUTHOR]

Published
2018
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