Sensitivity Analysis of an Optical Interferometric Surface Stress Ethanol Gas Sensor with a Freestanding Nanosheet.

Ethanol (EtOH) gas detection has garnered considerable attention owing to its wide range of applications in industries such as food, pharmaceuticals, medical diagnostics, and fuel management. The development of highly sensitive EtOH-gas sensors has become a focus of research. This study proposes an optical interferometric surface stress sensor for detecting EtOH gas.

Real-time simultaneous visualization of lactate and proton dynamics using a 6-μm-pitch CMOS multichemical image sensor.

Multi-analyte detection and imaging of extracellular chemical signaling molecules are crucial for understanding brain function and molecular pathology. In this work, we present a 6-μm-pitch, CMOS-based multichemical image sensor that enables the simultaneous visualization and spatiotemporal multimodal analysis of the lactate and proton (H) dynamics without any labeling. Using semiconductor lithography, gold electrode patterns functioning as lactate-sensing regions were formed on a potentiometric sensor array.

Demonstrating a Filter-Free Wavelength Sensor with Double-Well Structure and Its Application.

This study proposed a filter-free wavelength sensor with a double-well structure for detecting fluorescence without an optical filter. The impurity concentration was optimized and simulated to form a double-well-structured sensor, of which the result was consistent with the fabricated sensor. Furthermore, we proposed a novel wavelength detection method using the current ratio based on the silicon absorption coefficient.

A Multimodal Sensing Device for Simultaneous Measurement of Dissolved Oxygen and Hydrogen Ions by Monolithic Integration of FET-Based Sensors.

We examined the possibility of measuring dissolved oxygen by using a potentiometric solid-state semiconductor sensor. Thin films of tin (IV) oxide (SnO) are widely used in oxygen gas sensors. However, their ability to detect dissolved oxygen (DO) in solutions is still unknown.

Bio-Interface on Freestanding Nanosheet of Microelectromechanical System Optical Interferometric Immunosensor for Label-Free Attomolar Prostate Cancer Marker Detection.

Various biosensors that are based on microfabrication technology have been developed as point-of-care testing devices for disease screening. The Fabry-Pérot interferometric (FPI) surface-stress sensor was developed to improve detection sensitivity by performing label-free biomarker detection as a nanomechanical deflection of a freestanding membrane to adsorb the molecules. However, chemically functionalizing the freestanding nanosheet with excellent stress sensitivity for selective molecular detection may cause the surface chemical reaction to deteriorate the nanosheet quality.

CMOS-Based Redox-Type Label-Free ATP Image Sensor for In Vitro Sensitive Imaging of Extracellular ATP.

Adenosine 5'-triphosphate (ATP) plays a crucial role as an extracellular signaling molecule in the central nervous system and is closely related to various nerve diseases. Therefore, label-free imaging of extracellular ATP dynamics and spatiotemporal analysis is crucial for understanding brain function. To decrease the limit of detection (LOD) of imaging extracellular ATP, we fabricated a redox-type label-free ATP image sensor by immobilizing glycerol-kinase (GK), L-α-glycerophosphate oxidase (LGOx), and horseradish peroxidase (HRP) enzymes in a polymer film on a gold electrode-modified potentiometric sensor array with a 37.

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

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.

Chronic brain blood-flow imaging device for a behavioral experiment using mice.

A chronic brain blood-flow imaging device was developed for cerebrovascular disease treatment. This device comprises a small complementary metal-oxide semiconductor image sensor and a chronic fiber-optic plate window on a mouse head. A long-term cerebral blood-flow imaging technique was established in a freely moving mouse.

Highly sensitive lens-free fluorescence imaging device enabled by a complementary combination of interference and absorption filters.

We report a lens-free fluorescence imaging device using a composite filter composed of an interference filter and an absorption filter, each applied to one side of a fiber optic plate (FOP). The transmission of angled excitation light through the interference filter is absorbed by the absorption filter. The auto-fluorescence of the absorption filter is reduced by the reflection from the interference filter of normally incident excitation light.

Compact Lensless Fluorescence Counting System for Single Molecular Assay.

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.

CMOS-based opto-electronic neural interface devices for optogenetics.

CMOS-based opto-electronic neural interface devices are presented. The devices are designed with target application of in vitro and in vivo optogenetics. Two types of the opto-electronic neural interface devices are presented.

"Optical communication with brain cells by means of an implanted duplex micro-device with optogenetics and Ca(2+) fluoroimaging".

To better understand the brain function based on neural activity, a minimally invasive analysis technology in a freely moving animal is necessary. Such technology would provide new knowledge in neuroscience and contribute to regenerative medical techniques and prosthetics care. An application that combines optogenetics for voluntarily stimulating nerves, imaging to visualize neural activity, and a wearable micro-instrument for implantation into the brain could meet the abovementioned demand.

Fabrication and functional demonstration of a smart electrode with a built-in CMOS microchip for neural stimulation of a retinal prosthesis.

In this study, we propose an advanced architecture of a smart electrode for neural stimulation of a retinal prosthesis. A feature of the proposed architecture is embedding CMOS microchips into the core of the stimulus electrodes. Microchip integration without dead space on the array is possible.

Intravital fluorescence imaging of mouse brain using implantable semiconductor devices and epi-illumination of biological tissue.

The application of the fluorescence imaging method to living animals, together with the use of genetically engineered animals and synthesized photo-responsive compounds, is a powerful method for investigating brain functions. Here, we report a fluorescence imaging method for the brain surface and deep brain tissue that uses compact and mass-producible semiconductor imaging devices based on complementary metal-oxide semiconductor (CMOS) technology. An image sensor chip was designed to be inserted into brain tissue, and its size was 1500 × 450 μm.

CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel.

A CMOS image sensor-based implantable glucose sensor based on an optical-sensing scheme is proposed and experimentally verified. A glucose-responsive fluorescent hydrogel is used as the mediator in the measurement scheme. The wired implantable glucose sensor was realized by integrating a CMOS image sensor, hydrogel, UV light emitting diodes, and an optical filter on a flexible polyimide substrate.

Functional brain fluorescence plurimetry in rat by implantable concatenated CMOS imaging system.

Measurement of brain activity in multiple areas simultaneously by minimally invasive methods contributes to the study of neuroscience and development of brain machine interfaces. However, this requires compact wearable instruments that do not inhibit natural movements. Application of optical potentiometry with voltage-sensitive fluorescent dye using an implantable image sensor is also useful.

Implantable image sensor based on intra-brain image transmission.

We developed and fabricated a micro-imager based on wireless intra-brain communication using conductive property of living tissues. An pixel array, analog-to-digital converter and transmitter are integrated on a single chip. The dimensions of the chip are 1 mm × 1mm × 0.

Image sensor pixel with on-chip high extinction ratio polarizer based on 65-nm standard CMOS technology.

In this study, we demonstrate a polarization sensitive pixel for a complementary metal-oxide-semiconductor (CMOS) image sensor based on 65-nm standard CMOS technology. Using such a deep-submicron CMOS technology, it is possible to design fine metal patterns smaller than the wavelengths of visible light by using a metal wire layer. We designed and fabricated a metal wire grid polarizer on a 20 × 20 μm(2) pixel for image sensor.

Baseband signal transmission experiment for intra-brain communication with implantable image sensor.

We demonstrate image signal transmission for wireless intra-brain communication. As a preliminary experiment, transmission characteristics of the brain phantom were measured. The baseband output signal from an implantable complementary metal-oxide-semiconductor (CMOS) image sensor is transmitted through the phantom.

Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex.

Techniques for fast, noninvasive measurement of neuronal excitability within a broad area will be of major importance for analyzing and understanding neuronal networks and animal behavior in neuroscience field. In this research, a novel implantable imaging system for fluorescence potentiometry was developed using a complementary metal-oxide semiconductor (CMOS) technology, and its application to the analysis of cultured brain slices and the brain of a living mouse is described. A CMOS image sensor, small enough to be implanted into the brain, with light-emitting diodes and an absorbing filter was developed to enable real-time fluorescence imaging.

CMOS image sensor integrated with micro-LED and multielectrode arrays for the patterned photostimulation and multichannel recording of neuronal tissue.

We developed a complementary metal oxide semiconductor (CMOS) integrated device for optogenetic applications. This device can interface via neuronal tissue with three functional modalities: imaging, optical stimulation and electrical recording. The CMOS image sensor was fabricated on 0.

Wireless intra-brain communication for image transmission through mouse brain.

We demonstrate wireless image data transmission through a mouse brain. The transmission characteristics of mouse brain is measured. By inserting electrodes into the brain, the transmission efficiency is drastically increased.

Optical and Electric Multifunctional CMOS Image Sensors for On-Chip Biosensing Applications.

In this review, the concept, design, performance, and a functional demonstration of multifunctional complementary metal-oxide-semiconductor (CMOS) image sensors dedicated to on-chip biosensing applications are described. We developed a sensor architecture that allows flexible configuration of a sensing pixel array consisting of optical and electric sensing pixels, and designed multifunctional CMOS image sensors that can sense light intensity and electric potential or apply a voltage to an on-chip measurement target. We describe the sensors' architecture on the basis of the type of electric measurement or imaging functionalities.

A multimodal sensing device for fluorescence imaging and electrical potential measurement of neural activities in a mouse deep brain.

We have developed a multimodal CMOS sensing device to detect fluorescence image and electrical potential for neural activities in a mouse deep brain. The device consists of CMOS image sensor with on-chip electrodes and excitation light sources, all of which are integrated on a polyimide substrate. The novel feature of this device is its embedded on-chip electrodes which are partially transmit incident light so that the whole image can be acquired by the sensor.

Implantable CMOS Biomedical Devices.

The results of recent research on our implantable CMOS biomedical devices are reviewed. Topics include retinal prosthesis devices and deep-brain implantation devices for small animals. Fundamental device structures and characteristics as well as in vivo experiments are presented.