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.

This paper reviews recent advancement of micro CMOS imaging devices to measure brain neural activities in an un-tethered mouse. Three types of imaging devices have been developed: a fiber endoscope, a head-mountable imaging device, and a brain-implantable imaging device. Among them, a brain-implantable imaging device can realize to observe neural activity in deep brain regions of the brain, such as hippocampus. The detail device structure and characteristics are presented.

Implantable micro CMOS imaging devices for biomedical applications

We have developed a multimodal CMOS sensing device to detect fluorescence image and electrical potential for neural activities in a mouse deep brain. The device consists of CMOS image sensor with on-chip electrodes and excitation light sources, all of which are integrated on a polyimide substrate. The novel feature of this device is its embedded on-chip electrodes which are partially transmit incident light so that the whole image can be acquired by the sensor. We have demonstrated the CMOS sensor device successfully operates in hippocampus area of an anesthetized mouse.

A multimodal sensing device for fluorescence imaging and electrical potential measurement of neural activities in a mouse deep brain

We have fabricated a CMOS image sensor which can simultaneously capture optical and on-chip potential images. The target applications of the sensor are; 1) on-chip DNA (and other biomolecular) sensing 
and 2) on-chip neural cell imaging. The sensor was fabricated using a 0.35μm 2-poly, 4-metals standard CMOS process. The sensor has a pixel array that consists of alternatively aligned optical sensing pixels (88×144) and potential sensing pixels (88×144). The total size of the array is QCIF (176×144). The size of the pixel is 7.5μm×7.5μm. The potential sensing pixel has a sensing electrode which capacitively couples with the measurement target on the sensor. It can be operated either in a wide-range (over 5V) mode or in a high-sensitivity (1.6mV/LSB) mode. Two-dimensional optical and potential imaging function was also demonstrated. Probes with gel tips were placed on the sensor surface and potential was applied. A potential spot with diameter smaller than 50μm was successfully observed in the dual imaging operation.

An optical and potential dual-image CMOS sensor for bioscientific applications

We have developed an on-chip image sensor with target applications of on-chip biomolecular and neural imaging. The sensor pixel can sense not only intensity of incident light, but also on-chip electric potential. The light shield structure on the pixel circuit was used as a sensing electrode. Once the passivation layer on the sensing electrode was removed, one can perform on-chip voltammetric measurement, which will be a powerful solution for on-chip biosensing applications. To realise the on-chip voltammetric measurement, we used a column reset line as a current path. Basic characteristics of the sensor was characterized in either optical / potential image sensor operation or optical / voltammetric image sensor operation.

An Optical/Potential/Voltammetric Multifunctional CMOS Image Sensor for On-chip Biomolecular/Neural Sensing Applications

An LSI-based cooperative multi-chip neural stimulation/recording device is proposed and fabricated. The proposed multi-chip device consists of small (600 /spl mu/m /spl times/ 600 /spl mu/m in the present design) intelligent neural stimulation/recording chips (unit chip). The unit chip has a neural stimulation/recording electrode array and individual control circuit. It can work with other unit chips cooperatively. One can configure any number of the unit chips as the multi-chip neural stimulation/recording device. Compared to conventional single-chip architecture, the proposed multi-chip architecture has advantages in thinness, mechanical strength and flexibility, and extendibility. That makes the multi-chip neural stimulation/ recording device more suitable for in vivo applications than conventional single-chip devices. Packaging technology for cooperative multi-chip device is also discussed. We developed a thin, flexible packaging technique for the multi-chip neural stimulation/recording device and LSI-compatible Pt/Au stacked biocompatible bump electrode.

Takashi Tokuda

Papers

Implantable micro CMOS imaging devices for biomedical applications

A multimodal sensing device for fluorescence imaging and electrical potential measurement of neural activities in a mouse deep brain

An optical and potential dual-image CMOS sensor for bioscientific applications

An Optical/Potential/Voltammetric Multifunctional CMOS Image Sensor for On-chip Biomolecular/Neural Sensing Applications

Flexible and extendible neural stimulation/recording device based on cooperative multi-chip CMOS LSI architecture