中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

The role of extended and point defects, and key impurities such as C, O, and H, on the electrical and optical properties of GaN is reviewed. Recent progress in the development of high reliability contacts, thermal processing, dry and wet etching techniques, implantation doping and isolation, and gate insulator technology is detailed. Finally, the performance of GaN-based electronic and photonic devices such as field effect transistors, UV detectors, laser diodes, and light-emitting diodes is covered, along with the influence of process-induced or grown-in defects and impurities on the device physics.

Gan : processing, defects, and devices

Bound states in the continuum (BICs) are waves that remain localized even though they coexist with a continuous spectrum of radiating waves that can carry energy away. Their very existence defies conventional wisdom. Although BICs were first proposed in quantum mechanics, they are a general wave phenomenon and have since been identified in electromagnetic waves, acoustic waves in air, water waves and elastic waves in solids. These states have been studied in a wide range of material systems, such as piezoelectric materials, dielectric photonic crystals, optical waveguides and fibres, quantum dots, graphene and topological insulators. In this Review, we describe recent developments in this field with an emphasis on the physical mechanisms that lead to BICs across seemingly very different materials and types of waves. We also discuss experimental realizations, existing applications and directions for future work. The fascinating wave phenomenon of ‘bound states in the continuum’ spans different material and wave systems, including electron, electromagnetic and mechanical waves. In this Review, we focus on the common physical mechanisms underlying these bound states, whilst also discussing recent experimental realizations, current applications and future opportunities for research.

Bound states in the continuum

An apparatus may include a semiconductor chip and a fluidics assembly. The semiconductor chip has an array of wells and an array of sensors and each sensor of the array of sensors is in fluid communication with a well of the array of wells. The fluidics assembly is located on top of the semiconductor chip and is configured to deliver fluids to the semiconductor chip. The fluidics assembly includes a flow expansion chamber configured to introduce the fluids, an outlet portion configured to pipe out the fluids, and a flow chamber portion. The flow chamber portion is configured to allow the fluids to flow from the flow expansion chamber to the outlet portion and to allow the fluids to interact along the way with material in the array of wells. The flow expansion chamber has a curved wall at the top or bottom so that the height of the flow expansion chamber at the center is less than at the walls that restrict the fluids to the left and right.

Methods and apparatus for measuring analytes using large scale fet arrays

In 1929, only three years after the advent of quantum mechanics, von Neumann and Wigner showed that Schrodinger's equation can have bound states above the continuum threshold. These peculiar states, called bound states in the continuum (BICs), manifest themselves as resonances that do not decay. For several decades afterwards the idea lay dormant, regarded primarily as a mathematical curiosity. In 1977, Herrick and Stillinger revived interest in BICs when they suggested that BICs could be observed in semiconductor superlattices. BICs arise naturally from Feshbach's quantum mechanical theory of resonances, as explained by Friedrich and Wintgen, and are thus more physical than initially realized. Recently, it was realized that BICs are intrinsically a wave phenomenon and are thus not restricted to the realm of quantum mechanics. They have since been shown to occur in many different fields of wave physics including acoustics, microwaves and nanophotonics. However, experimental observations of BICs have been limited to passive systems and the realization of BIC lasers has remained elusive. Here we report, at room temperature, lasing action from an optically pumped BIC cavity. Our results show that the lasing wavelength of the fabricated BIC cavities, each made of an array of cylindrical nanoresonators suspended in air, scales with the radii of the nanoresonators according to the theoretical prediction for the BIC mode. Moreover, lasing action from the designed BIC cavity persists even after scaling down the array to as few as 8-by-8 nanoresonators. BIC lasers open up new avenues in the study of light-matter interaction because they are intrinsically connected to topological charges and represent natural vector beam sources (that is, there are several possible beam shapes), which are highly sought after in the fields of optical trapping, biological sensing and quantum information.

Lasing action from photonic bound states in continuum.

A fork-shaped retinal stimulator for a wide viewing angle was fabricated and demonstrated. This stimulator has two flexible fork elements, each with a stimulus head. The two fork elements can be implanted at different places in the eyeball to cover a wider area of the retina. The stimulus head has stimulus electrodes with the same shape as the electrodes utilized in a clinical trial for six weeks. Complementary metal-oxide semiconductor (CMOS) microchips were integrated into the stimulator and mounted next to the stimulus electrodes. Since stimulus current generators are integrated into the microchips, no external wires for stimulus current are required. A multiplexer, which reduces the number of wirings, was also integrated into the microchips. The fabricated stimulator was evaluated through in vivo animal experiments. The stimulator was successfully implanted in two places of the eyeball. Retinal stimulation by the device evoked nerve responses from optic chiasma and produced a specific peak of evoked potential. Experimental results demonstrate the proof of concept of a fork-shaped stimulator and suggest that the same device configuration can realize multiple forkshaped stimulators for a wider viewing angle. Moreover, increasing the number of fork elements of the multifork stimulator without additional wirings becomes possible.

Fabrication of fork-shaped retinal stimulator integrated with CMOS microchips for extension of viewing angle

Intra body communication technology allows the fabrication of compact implantable biomedical sensors compared with RF wireless technology. In this paper, we report the fabrication of an implantable image sensor of 625 µm width and 830 µm length and the demonstration of wireless image-data transmission through a brain tissue of a living mouse. The sensor was designed to transmit output signals of pixel values by pulse width modulation (PWM). The PWM signals from the sensor transmitted through a brain tissue were detected by a receiver electrode. Wireless data transmission of a two-dimensional image was successfully demonstrated in a living mouse brain. The technique reported here is expected to provide useful methods of data transmission using micro sized implantable biomedical sensors.

Wireless image-data transmission from an implanted image sensor through a living mouse brain by intra body communication

A CMOS integrated flexible neural interface device has been designed and fabricated. The device enables electrical stimulation of neural tissues using an array of smart electrodes. The smart electrodes have versatile functions owing to the use of a dedicated CMOS microchip. These multiple smart electrodes also provide the array with sophisticated functions with only four wiring connections to external equipment. Moreover, the multi-chip architecture of the device is highly flexible and has low invasiveness to living body tissue. An in vivo evaluation of retinal stimulation was performed after implanting the device in the eye of an experimental animal. The stimulus function of the device was successfully demonstrated by observing responses in the visual cortex caused by the stimulation.

Smart electrode array device with CMOS multi-chip architecture for neural interface

We fabricated a device equipped with a microchannel on a complementary metal oxide semiconductor (CMOS) sensor to observe the optical polarization rotation angle during in situ monitoring. The sensor is based on the integrated wire-grid polarization detection method. The microchannel is fabricated on a Si layer by deep reactive ion etching (DRIE). Using this device, we measured the optical rotation of chiral molecules in a microfluid. This showed that the device is applicable to in situ chiral measurement. Optical rotation angles of the linearly polarized light corresponded to different concentrations of sucrose solution. Sensor output reflecting the temporal concentration change of chiral molecules was also observed. These results clearly demonstrate that the CMOS sensor has the capability of measuring chiral molecules in situ.

Microchamber Device Equipped with Complementary Metal Oxide Semiconductor Optical Polarization Analyzer Chip for Micro Total Analysis System

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Takashi Tokuda

Papers

Fabrication of fork-shaped retinal stimulator integrated with CMOS microchips for extension of viewing angle

Wireless image-data transmission from an implanted image sensor through a living mouse brain by intra body communication

Smart electrode array device with CMOS multi-chip architecture for neural interface

Microchamber Device Equipped with Complementary Metal Oxide Semiconductor Optical Polarization Analyzer Chip for Micro Total Analysis System

Lens-free Dual-color Fluorescent CMOS Image Sensor for F?rster Resonance Energy Transfer Imaging