This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/ This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/ACCESS.2021.3111666, IEEE Access VOLUME XX, 2017 1 DATE OF PUBLICATION XXXX 00, 0000, DATE OF CURRENT VERSION XXXX 00, 0000. Digital Object Identifier 10.1109/ACCESS.2017.Doi Number Micro-LED Array-Based Photo-Stimulation Devices for Optogenetics in Rat and Macaque Monkey Brains Yasumi Ohta 1 , Mark Christian Guinto 1 , Takashi Tokuda 2 , Member, IEEE, Mamiko Kawahara 1 , Makito Haruta 1 , Hironari Takehara 1 , Hiroyuki Tashiro 1,3 , Kiyotaka Sasagawa 1 , Member, IEEE, Hirotaka Onoe 4 , Reona Yamaguchi 5 , Yoshinori Koshimizu 6 , Kaoru Isa 6 , Tadashi Isa 4,5,6 , Kenta Kobayashi 7 , Yasemin M. Akay 8 , Senior Member, IEEE, Metin Akay 8 , Fellow, IEEE, and Jun Ohta 1 , Fellow, IEEE 1 Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, Japan 2 Institute of Innovative Research, Tokyo Institute of Technology, Meguro-Ku, Tokyo, Japan 3 Department of Health Sciences, Faculty of Medical Sciences, Kyusyu University, Higashi-Ku, Fukuoka, Japan 4 Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan 5 Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan 6 Department of Neuroscience, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Sakyo-Ku, Kyoto, Japan 7 Department of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, Aichi, Japan 8 Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA Corresponding author: Jun Ohta (e-mail: ohta@ms.naist.jp). This work was supported in part by the JST CREST, Grant Number JPMJCR1651, and the JSPS KAKENHI Grant Number JP18H03780. ABSTRACT Optogenetics is a powerful tool for controlling biological functions using light. Optical fibers have been extensively utilized in optical stimulation devices for optogenetics. However, the use of optical fibers results in a small photo-stimulation region. In this study, micro-LED array devices were developed to achieve large-area photo-stimulation in the brain of a large animal, such as macaque monkeys. Planar and linear micro-LED array devices were designed and fabricated to photo-stimulate the prefrontal cortex (PFC) and ventral tegmental area (VTA) of the brain and induce a neurochemical response. Device operation, optical intensity, and safety were first characterized using rats. Subsequently, the devices were used to photo- stimulate the brain of macaque monkeys. In addition, microdialysis in the PFC was performed. The devices detected modulated levels of dopamine in the brains. Thus, the photo-stimulation of both the PFC and VTA were successfully achieved, and the effectiveness of the developed micro-LED array devices was demonstrated. The study will help facilitate further studies on micro-LED array stimulation for system-wide optogenetic manipulation in large animals. INDEX TERMS Brain, Dopamine, Implantation, Light Emitting Diodes, Macaque Monkeys, Microdialysis, Optogenetics, Photo-stimulation