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HOME > No.30, Sep. 2022 > Illuminating the brain with an ultra-thin, flexible, multipoint microLED array film

Illuminating the brain with an ultra-thin, flexible, multipoint microLED array film

Development of a new optogenetic device that enables simultaneous optical stimulation at specific/multiple regions in the brainHiroto Sekiguchi
Hiroto Sekiguchi

Researchers including Associate Professor Hiroto Sekiguchi in the Department of Electrical and Electronic Information Engineering at Toyohashi University of Technology, Associate Professor Noriaki Ohkawa in the Comprehensive Research Facilities for Advanced Medical Science at Dokkyo Medical University, and Assistant Professor Izumi Fukunaga in the Sensory and Behavioural Neuroscience Unit at Okinawa Institute of Science and Technology Graduate University, have developed a flexible, multipoint microLED array film. The film can be flexibly attached to cover the brain and can illuminate specific regions of the brain using microLEDs arranged along multiple points.
In recent years, optogenetics(Note 1) has enabled the manipulation of neural activity by light. This technique requires a light-emitting device, but until now, there has been no implantable optical device that can be attached to cover the entire tissue of the brain or other organs, illuminate only the target neurons, and manipulate their activity with light at will.
To implement this device, a thin, lightweight, and flexible body is required. It was thus necessary to establish a technology to precisely arrange an LED layer a couple of micrometers thick highly on an ultra-thin biocompatible film. This time the research group has established both (1) a technology to form a hollow structure of microLEDs with high density and in minute detail, and (2) a high-precision batch transfer technology using a thermal release sheet. With these technologies, it has also successfully developed an ultra-thin, lightweight multipoint microLED array film that maintains lighting performance even when the film is bent. The application of the developed device is expected to create a new area of neuroscience research aimed at comprehensively understanding the brain information that underpins how neural activity, behaviors, and disorders are linked.

Technology to fabricate a flexible microLED film.Technology to form a hollow structure of microLED (Upper) MicroLED array batch transfer technology (Lower).
Technology to fabricate a flexible microLED film.
Technology to form a hollow structure of microLED (Upper) MicroLED array batch transfer technology (Lower).

At present, attempts are being made to use light to manipulate the activity of various functional molecules inside an organism. In particular, optogenetics - a technique to activate neural activity with light by expressing photosensitive proteins that react to a specific color of light in neurons - has a high temporal resolution and has been utilized to elucidate brain function. However, to comprehensively elucidate the complex neural network created by neurons in the brain, it is necessary to employ light stimulation that will enable free manipulation of certain regions of neurons distributed across a wide range of the brain. The application of conventional optical fibers and microscopes is not sufficient to illuminate certain or multiple regions at the same time and also restricts the free movement of animals. Although this meant high hopes for the application of an implantable LED device, the size of commercial LEDs is as large as 200 µm with thickness of tens to one hundred micrometers, so that it cannot cover a wide range of the brain. As such, it was considered unsuitable as a device to stimulate specific neurons in the regions.

A Photo of the developed microLED array. Hollow structure of a microLED array (Left) Lighting image of an ultra-thin microLED array film (Right).
A Photo of the developed microLED array. Hollow structure of a microLED array (Left) Lighting image of an ultra-thin microLED array film (Right).

Given this, the research group sought to utilize a flexible film that is thin, lightweight, and bendable, and took the challenge of fabricating microscopic and ultra-thin microLEDs less than 100µm in size and a couple of micrometers in thickness and arranging them on multiple points. To achieve this, the group adopted the anisotropic wet etching method(Note 2) using potassium hydroxide to selectively remove the bottom LED layer, which led to the formation of a hollow structure of microLEDs that are arranged at high density. Since the LED layer is separated from the substrate by the formation of the hollow structure, only the LED layer is peeled off in a batch using a thermal release sheet, and the micro-LEDs are successfully arranged on the film without damaging either the micro-LEDs or the parylene film (Note 3). By applying this technique, the group has successfully fabricated a microLED array on the film. This microLED-mounted film maintains its lighting performance even when being bent. It has also been verified that bright blue light can be obtained and used in actual optogenetic experiments with the film adhered to the surface of a mouse's brain.

Ultra-thin microLED array film adhered to the mouse's brain. Lighting LEDs targeting three points.
Ultra-thin microLED array film adhered to the mouse's brain. Lighting LEDs targeting three points.

The multipoint microLED film developed through this study has potential broader applications in neuroscience and will facilitate the control of complex brain activity freely in the spatiotemporal aspects. The brain has diverse functionalities in various regions and serves to manipulate the whole body in a complex way. It is anticipated that this technology, when combined with measuring technology, will create a new area of neuroscience research aimed at comprehensively understanding the brain information that underpins how neural activities, behaviors, and disorders are linked. Furthermore, further development of light-sensitive functional molecules in vivo is expected to lead to the application of phototherapy technology using implanted devices in vivo, in which drugs can be applied to targeted areas at desired times by irradiating them with light.
The results of this research will be published online at Applied Physics Express on March 18, 2022 (8am GMT). In addition, this work was supported by the Precursory Research for Embryonic Science and Technology Agency (JPMJPR1885) of the Strategic Basic Research Programs in Japan Science and Technology Agency (JST), under the project title "Innovation of invasive LED devices for biological optical stimulation" in the research area " Development of optical control technologies and elucidation of biological mechanisms."


Note 1: Optogenetics
Optogenetics is a technique to manipulate the activity of target neurons with light. This is achieved by gene transfer technology with which the illumination of light with specific wavelengths can express proteins that changes their activity. Channelrhodopsin-2, known as a typical protein, can introduce sodium ions into cells during neural activity when applying blue light and can artificially induce the activity of target neurons.
Note 2: Anisotropic wet etching
Anisotropic wet etching is a technique to selectively dissolve certain crystal orientations of semiconductors using chemicals. In this project, potassium hydroxide was used to selectively remove a certain crystal orientation of Si substrates.
Note 3: Parylene film
Parylene is the generic term for paraxylene-based polymers and is known as biocompatible material. The ultra-thin film can be formed by vapor deposition. It is applied as a coating material for biomedical devices such as pacemakers.


Hiroto Sekiguchi, Hayate Matsuhira, Ryota Kanda, Shuto Tada, Taiki Kitade, Masataka Tsutsumi, Atsushi Nishikawa, Alexander Loesing, Izumi Fukunaga, Susumu Setogawa, Noriaki Ohkawa (2022). Adhesionable flexible GaN-based microLED array film to brain surface for in vivo optogenetic stimulation, Applied Physics Express.



関口 寛人

豊橋技術科学大学 電気・電子情報工学系の関口寛人准教授と獨協医科大学 先端医科学統合研究施設 大川宜昭准教授、沖縄科学技術大学院大学 知覚と行動の神経科学ユニット 福永泉美准教授らは、脳を覆うように柔軟に取り付けができ、多点に配置したマイクロLEDで脳の特定部位を狙って光を照射できるフレキシブルフィルムを開発しました。




本研究成果は、2022年3月18日(GMT:8時)に「Applied Physics Express」にオンライン掲載されました。また、本研究は、科学技術振興機構(JST)戦略的創造研究推進事業 さきがけ「生命機能メカニズム解明のための光操作技術」研究領域 研究課題名「生体光刺激のための侵襲型LEDデバイスの革新」(JPMJPR1885)からの支援により行われました。



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Researcher Profile

Hiroto Sekiguchi
Name Hiroto Sekiguchi
Affiliation Department of Electrical and Electronic Information Engineering
Title Associate Professor
Fields of Research Light-Emitting Device / Semiconductor Engineering