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 CMOS LSI-based flexible neural stimulation device application with new fabrication technologies has been developed. The device was designed for application in retinal prosthesis. The device is based on multichip architecture, which enables the LSI-based stimulation device to be flexible. A fabrication process of arrayed bulk Pt electrodes, and a packaging structure of LSI chips with flip-chip bonding technology have been developed. These features provide the fabricated device with a lifetime of ten days in saline solution.

CMOS LSI-based multichip flexible neural stimulation device with embedded bulk Pt electrodes

This work presents the concept of a battery-free, sticker-like, device for a non-invasive health-monitoring sensor. The device consists of two functional blocks: an optical power-transfer block and an amperometric measurement block. The former accumulates power from a series-connected photovoltaic cell in a capacitor and intermittently supplies the power to the amperometric measurement circuit. This circuit is driven by powering pulses and displays the amperometric current as the durations of the light pulses from a light-emitting diode. The function of the circuit was successfully demonstrated through simulations, in which the equivalent circuit of an electrochemical glucose sensor was used as an example. The simulation results showed that the proposed device would work as expected for a variety of glucose concentrations at an oxidation voltage of 0.8 V.

Battery-Free. Sticker-Like, Device for Health Monitoring, Operated by Optical Power Transfer

Inspired by biological information scheme, pulse frequency modulation (PFM) technique is robust for noise sources due to its digital encode of analog signals. In a viewpoint of image sensors, PFM is also useful for a wide dynamic range and has already been demonstrated over 60 dB. We have designed a pixel circuit of a CMOS image sensor using PFM for the next generation architecture of vision chips. The chip is fabricated using a standard 0.35 micrometers double poly, triple metal CMOS technology. The photodiode is a parasitic pn diode between p-well and n-diffusion with the size of 2 micrometers squares. The top of the photodiode is covered with third metal and 1 micrometers square hole is open for aperture. Feedback circuits consist of a Schmitt trigger and two inverters. We have demonstrated by introducing PFM the chip works well under the power supply voltage of 0.55V with 50 dB. Such a low voltage operation suggests deep sub-micron technologies, for example, 0.18 micrometers technologies could be applied to the sensor. The other important point in our chip is that the photodiode is very small in size of 2 micrometers by 2 micrometers with the aperture size of 1 micrometers by 1 micrometers . This enables us to realize an image sensor with a small fill factor, which is very useful for vision chips where functional circuits are integrated in each pixel.

Low-voltage operation of a CMOS image sensor based on pulse frequency modulation

Recent development of biomedical devices based on microelectronics technologies are reviewed. Implantable biomedical devices are focused and discussed in detail. Two typical devices are demonstrated; one is for retinal prosthesis and the other is a deep brain implantable device. Future issues for implantable biomedical devices are addressed.

Takashi Tokuda

Papers

CMOS LSI-based multichip flexible neural stimulation device with embedded bulk Pt electrodes

Battery-Free. Sticker-Like, Device for Health Monitoring, Operated by Optical Power Transfer

Low-voltage operation of a CMOS image sensor based on pulse frequency modulation

Biomedical Devices based on Semiconductor Microelectronics Technologies

Planer Multi Electrode Array Coupled CMOS Image Sensor for in vitro Electrophysiology