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 have developed a CMOS vision chip, an image sensor with pixel-level signal processing, to replace photoreceptor cells in the retina. In this paper, we describe a pixel-level signal processing, which is to control on the stimulus waveform and the amount of the electrical injection charge.
Our CMOS vision chip is an array of a pixel, which consists of a photo detector, a pulse shaper, and a current stimulus circuit. The photo detector circuit generates a pulse frequency modulated (PFM) pulse, which frequency is proportional to the intensity of the incoming light. The PFM photo detector is also modified to restrict the maximum frequency of PFM pulse signal for safety neural stimulation.
The PFM pulse signal should be converted into suitable waveform for efficient neural stimulation. We have employed a pulse shaper to generate one stimulus pulse from one PFM pulse. The pulse parameters (i.e., pulse duration, polarity, etc) of the output pulse signal are controlled by the external signal.
For the electrical neural stimulus, the stimulus intensity is given by the amount of the electrical injection charge. The amount of the injection charge should be enough to evoke a phosphene but should be low to avoid the damage of the retinal tissue caused by the excess charge injection. In our prototyped CMOS vision chip, the stimulus current amplitude is used to control the amount of charge. The 6-bit binary-weighted digital-to-analog converter (DAC) with 2μA resolution is used to control the stimulus current amplitude.

System implementation of a CMOS vision chip for visual recovery

Implementation of Eye-Safe Imaging Capability onto CMOS Image Sensors with Reverse-Carrier-Injection

CMOS-based miniaturized and distributed implantable brain interface device architecture is proposed and demonstrated. Optical-powering is the key feature of the system. Based on the concept, an ultra-small optical stimulator for freely-moving experiments is realized. Architecture, CMOS design, device packaging, and device functionality will be described.

CMOS-based distributed implantable brain interface device

The development of image sensors that incorporate metal-wiregrid polarizers is being explored with CMOS technologies. Although this approach shows promise for on-chip polarization image sensing, the sensors have yet to match the performance of those that use off-chip polarizers. This is because conventional CMOS fabrication techniques do not allow a sufficiently fine grid design. The recently developed, deep-submicron forms of CMOS-integrated circuits could potentially address this problem, since the metal wire structures made from this advanced form of technology are smaller than the wavelengths of visible light. As such, it is possible to directly integrate a nanophotonic wire structure onto a CMOS image-sensing chip for the purpose of detecting light in the visible to near-IR regions. The production of image-sensing circuits with directly integrated imaging devices is achieved via established CMOS fabrication processes. A particular advantage of such mixed-signal circuits is that they enable real-time signal processing of polarized images: this a feature that off-chip polarizers cannot offer.1, 2 On-chip polarizers are also well suited to conducting large-scale optical measurements in parallel. Using a 65nm CMOS process, we designed and fabricated a image sensor that contained a polarizer composed of a grid of metal wire arranged in a parallel array. The metal grid was positioned on top of the image-sensing pixel (see Figure 1).3–5 With a pixel size of 20 20 m2 and a photodiode area of 13:2 13:2 m2, the fill factor corresponded to 43.6%. Others have reported that the extinction ratio of polarizers constructed from similar metal wire grids increases with decreasing grid pitch. The extinction ratio relates the transmission of the unwanted component to the wanted component. For the metal wire Figure 1. Conceptual diagram of image sensor pixel with a single-layer, on-chip polarizer.4 TE: Transverse-electric wave. TM: Transversemagnetic wave.

A high-extinction-ratio optical polarizer based on advanced CMOS technology

A CMOS-based neural interface device with on-chip localized optical stimulation capability was proposed and demonstrated. A multifunctional CMOS image sensor with an addressable on-chip electrode array was integrated with a GaInN light emitting diode (LED) array formed on a sapphire substrate. The basic functionality of the device was evaluated, and optical stimulation on ChR2-expressed Neuro-2A cells was successfully performed. A variation of the device with electric neural accessibility is also proposed.

Takashi Tokuda

Papers

System implementation of a CMOS vision chip for visual recovery

Implementation of Eye-Safe Imaging Capability onto CMOS Image Sensors with Reverse-Carrier-Injection

CMOS-based distributed implantable brain interface device

A high-extinction-ratio optical polarizer based on advanced CMOS technology

CMOS-based on-chip neural interface devices for optogenetics