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.

We present a multi-chip electric stimulator for a retinal prosthesis. The stimulator consists of small silicon devices (unit chips) molded in a thin film. It has an advantage over the conventional devices in physical flexibility and extendibility. The smart unit chip (600 μm square, in this work) is an integrated circuit (IC) that includes digital serial interface circuits, analog switch circuits and on-chip stimulus electrodes. In contrast to conventional stimulators, the present stimulator can be driven with only four wires. The multi-chip configuration enables to make the stimulator flexible and durable to bending stress. The device can be bended to place the stimulation electrodes in good contact with retinal tissue. In this paper, we present the design of the stimulator device with 0.35-μm complementary metal-oxide semiconductor (CMOS) technology. We also report a thin, flexible packaging technique for the stimulator and preliminary experimental results of a sputtered iridium oxide (IrO x ) film that can be used for chronic stimulation.

Flexible and extensible retinal prosthesis based on multi-chip architecture

This paper describes improvements in output waveform of pulse frequency modulation (PFM) photosensor to be effectively adapted for retinal prosthesis. A 32/spl times/32-pixel PFM photosensor array chip is fabricated using 0.6 /spl mu/m CMOS technology and demonstrated the improved functions. Also the output pulse pattern is displayed with 32/spl times/32-LED array to visualize the pulse output waveform. The next version of a PFM vision chip is designing for in vivo experiment, in which in-pixel image processing functions in pulse domain are employed.

Improvement of a pulse frequency modulation based photosensor for retinal prosthesis

デジタルELISAに向けた蛍光および非蛍光計測用レンズレスCMOSイメージングシステム;デジタルELISAに向けた蛍光および非蛍光計測用レンズレスCMOSイメージングシステム;Lensless CMOS Imaging Device for Fluorescent and Non-Fluorescent Imaging Dedicated to Digital ELISA

We have designed and fabricated a 16 × 16 pixel pulse frequency modulation (PFM) image sensor for retinal prosthesis. This sensor is a prototype for demonstrating application in in vitro electrophysiological experiments. Each pixel has a bonding pad on which a stimulus electrode is formed by a Pt/Au stacked biocompatible bump electrode. We have evaluated the PFM image sensor for retinal prosthesis by in vitro electrophysiological experiments using the detached frog retina, and confirmed that it can electrically stimulate the retinal cells effectively.

Electrical stimulus experiments of the frog retina using a pulse frequency modulation image sensor for retinal prosthesis

Implantable wireless fiber biophotometry is one of the most effective technique to monitor specific cell types through Ca2+ fluorescence sensing in live animals by avoiding fiber tethering and risks of breakage and injury which can occur in conventional apparatus. This demonstration will show the visitors a novel low-power, light-weight, and minimally invasive wireless optoelectronic interface enabling chronic brain fiber biophotometry in freely moving laboratory mice. The proposed device incorporates a custom integrated CMOS biosensor and off-the-shelf optical and electronic components such as a wireless transmitter, a LED as excitation light source, a microprocessor, and a miniaturized 3D-printed housing. The CMOS biosensor includes a two-step analog-to-digital converter (ADC) with a noise cancellation scheme enabling wide dynamic range and high-energy efficiency photocurrent quantization. A fiber biophotometry head-mountable 3D-printed housing holds in place the optical and electronic components and allows the utilization of a single mutlimode fiber to convey the excitation light and to collect the evoked fluorescence light.

Takashi Tokuda

Papers

Flexible and extensible retinal prosthesis based on multi-chip architecture

Improvement of a pulse frequency modulation based photosensor for retinal prosthesis

Electrical stimulus experiments of the frog retina using a pulse frequency modulation image sensor for retinal prosthesis

Live Demonstration: An Energy-Efficient CMOS Biophotometry Sensor Interface