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 demonstrate an image sensor pixel with dual-layer metal grid polarizer with extinction ratio over 80 in 65-nm standard CMOS technology. By recent advanced CMOS technology, it is feasible to design sub-wavelength metal layer patterns in the visible wavelengths. Fine metal grid has high polarization characteristics. Its extinction ratio depends on the grid pitch. Thus, high extinction ratio can be realized by using deep sub-micron CMOS technology. As the grating pitch decreases, extinction ratio becomes high. On the other hand, multiple metal layers can be designed in usual CMOS technology. It is expected that improvement of extinction ratio is also achieved by utilizing this feature. In this work, we compare the extinction ratios of dual-layer polarizers with different spacing and demonstrate high extinction ratio can be achieved by optimizing the spacing.

Dual-layer metal-grid polarizer for polarization image sensor in 65-nm CMOS technology

We describe a retinal prosthesis device that uses an image sensor based on a pulse frequency modulation (PFM) photosensor array. A PFM-based photosensor converts light intensity into the frequency of an output electrical pulse stream, and thus is suitable for stimulating retinal cells. We demonstrate various circuit improvements for image preprocessing and packaging techniques and present the results of an electrophysiology experiment.

Retinal prosthesis device based on pulse-frequency-modulation vision chip

We review recently obtained results for CMOS (Complementary Metal Oxide Semiconductor) imaging devices used in biomedical applications. The topics include dish type image sensors, deep-brain implantation devices for small animals, and retinal prosthesis devices. Fundamental device structures and their characteristics are described, and the results of in vivo experiments are presented.

/pdf/cmos-imaging-devices-for-biomedical-applications-1bfh51thl8.pdf

CMOS Imaging Devices for Biomedical Applications

Electrode materials for neural stimulation have been widely investigated for implantable devices. Among them, iridium and iridium oxide are attractive materials for bio-interface applications due to their desirable stability, electrochemical performance, and biocompatibility. In this study, iridium oxide/platinum (IrOx/Pt) composite films were successfully fabricated on titanium substrates by chemical bath deposition and these films are expected to be used as biocompatible stimulation electrodes. We modified the film compositions to optimize the performances. In addition, these IrOx/Pt composite films were characterized before and after annealing by SEM and XRD. We also identified the hydrophilicity of these iridium oxide/platinum composite films by measuring contact angles. Finally, the charge storage capacities of these iridium oxide/platinum composite films were evaluated by an electrochemical workstation. As a result, the charge storage capacities of the iridium oxide/platinum composite films are largely increased, and this leads to a very efficient neurostimulation electrode. Additionally, we successfully demonstrated the chemical bath deposition of IrOx film on the surface of the bullet-shaped titanium microelectrode.

https://www.mdpi.com/2079-6412/8/12/420/pdf

Fabrication of Iridium Oxide/Platinum Composite Film on Titanium Substrate for High-Performance Neurostimulation Electrodes

A chronic brain blood-flow imaging device was developed for cerebrovascular disease treatment. This device comprises a small complementary metal-oxide semiconductor image sensor and a chronic fiber-optic plate window on a mouse head. A long-term cerebral blood-flow imaging technique was established in a freely moving mouse. Brain surface images were visible for one month using the chronic FOP window. This device obtained brain surface images and blood-flow velocity. The blood-flow changes were measured in behavioral experiments using this device. The chronic brain blood-flow imaging device may contribute to determining the cause of cerebrovascular disease and the development of cerebrovascular disease treatment.

Takashi Tokuda

Papers

Dual-layer metal-grid polarizer for polarization image sensor in 65-nm CMOS technology

Retinal prosthesis device based on pulse-frequency-modulation vision chip

CMOS Imaging Devices for Biomedical Applications

Fabrication of Iridium Oxide/Platinum Composite Film on Titanium Substrate for High-Performance Neurostimulation Electrodes

Chronic brain blood-flow imaging device for a behavioral experiment using mice.