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 propose the use of a CMOS image sensor for in vivo functional imaging of the mouse brain. A dedicated image sensor with 176 times 144 pixels array is designed, fabricated, and packaged to enable on-chip fluorescence imaging. Using this configuration, we have successfully performed imaging inside the intact mouse brain. Furthermore, we have demonstrated functional imaging inside the mouse brain. This is done in conjunction with a fluorogenic substrate, which detects the presence of serine protease inside the brain. By imaging the fluorescence signal upon injection of a stimulant, we have successfully measured the brain protease activity and accurately determined its reaction onset, which is close to 1 hr 28 min after injection of the stimulant. This method represents a new approach for neural imaging using an inexpensive CMOS imaging device

Development of a CMOS Imaging Device for Functional Imaging Inside the Mouse Brain

Real-time multifunctional optical analyzer based on polarization-analyzing CMOS image sensor for microchemical systems

Improvement of Stimulus Performance by Surface Coating of Stimulus Electrodes for Retinal Prosthesis

We have developed a prototype of battery-powered implantable image sensor unit and successfully demonstrated its operation in phosphate buffered saline (PBS) solution as simulant body solution. We have also proposed its equivalent circuit model for circuit simulation. The transmitted signal waveforms are in good agreement with the simulation result by using the model. The images taken by the implantable image sensor has been recovered from the signal received outside PBS solution.

Body channel digital pulse transmission for biometric measurement by fully implantable CMOS image sensor

A novel flexible neural interface device was proposed, designed and fabricated. The device realizes electrical stimulation and measurement of neural tissues using an array of smart electrodes. The smart electrode has intelligence by dedicated CMOS microchip. Thanks to the smart electrodes high functions of the array with large number of electrodes are obtained only with 4 wiring connected to external equipments. Moreover, the device has enough flexibility for low invasion to the living body tissues. As one of in vivo evaluations, retinal stimulation was performed with the device using an experimental animal. Stimulus function of the device implanted into the living body was demonstrated successfully, responses caused by the stimulation were observed.

Takashi Tokuda

Papers

Development of a CMOS Imaging Device for Functional Imaging Inside the Mouse Brain

Real-time multifunctional optical analyzer based on polarization-analyzing CMOS image sensor for microchemical systems

Improvement of Stimulus Performance by Surface Coating of Stimulus Electrodes for Retinal Prosthesis

Body channel digital pulse transmission for biometric measurement by fully implantable CMOS image sensor

Fabrication of a flexible neural interface device with CMOS-based smart electrodes