植入式光电极器件发展

doi:10.3866/PKU.WHXB201912054

物理化学学报 >> 2020, Vol. 36 >> Issue (12): 1912054.doi: 10.3866/PKU.WHXB201912054

所属专题：神经界面

植入式光电极器件发展

李亚民¹^,³, 王阳¹^,², 陈弘达¹^,³, 王毅军¹^,³, 刘媛媛¹^,³, 裴为华¹^,³^,⁴^,*()

¹ 中国科学院半导体研究所，集成光电子学国家重点实验室，北京 100083
² 中国科学技术大学，微电子学院，合肥 230000
³ 中国科学院大学，北京 100083
⁴ 中国科学院脑科学与智能技术卓越创新中心，上海 200000

收稿日期:2019-12-23 录用日期:2020-01-24 发布日期:2020-03-03
通讯作者: 裴为华 E-mail:peiwh@semi.ac.cn
作者简介:裴为华，中国科学院半导体研究所研究员。2005年毕业于中国科学院半导体研究所，获微电子与固体电子学博士学位。2005–2008年在清华大学生物医学工程系和德国马普微结构与物理研究所做博士后研究。研究方向：可记录或调控神经活动的神经接口器件
基金资助:
国家重点研发计划项目(2017YFA0205903);国家重点研发计划项目(2017YFA0701100);国家重点研发计划项目(2016YFB0402405);国家自然科学基金项目(61634006);国家自然科学基金项目(61335010);国家自然科学基金项目(61671424);中国科学院战略性先导科技专项(XDB32030100);中国科学院战略性先导科技专项(XDB32040200)

Development of Implantable Optrode Devices

Yamin Li¹^,³, Yang Wang¹^,², Hongda Chen¹^,³, Yijun Wang¹^,³, Yuanyuan Liu¹^,³, Weihua Pei¹^,³^,⁴^,*()

¹ State Key Laboratory on Integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, P. R. China
² School of Microelectronics, University of Sciences and Technology of China, Hefei 230000, P. R. China
³ University of Chinese Academy of Sciences, Beijing 100049, P. R. China
⁴ CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200000, P. R. China

Received:2019-12-23 Accepted:2020-01-24 Published:2020-03-03
Contact: Weihua Pei E-mail:peiwh@semi.ac.cn
Supported by:
The project was supported by the National Key R & D Project of China(2017YFA0205903);The project was supported by the National Key R & D Project of China(2017YFA0701100);The project was supported by the National Key R & D Project of China(2016YFB0402405);National Natural Science Foundation of China(61634006);National Natural Science Foundation of China(61335010);National Natural Science Foundation of China(61671424);Strategic Priority Research Program of Chinese Academy of Science(XDB32030100);Strategic Priority Research Program of Chinese Academy of Science(XDB32040200)

摘要/Abstract

摘要：

光遗传技术为神经科学研究提供了一种可精准、快速控制单个神经元活动的手段。为了对神经元实现光遗传调控，将光安全、高效地导入脑内，需要专门的光电极(Optrode)给予支持。光电极是光遗传工具应用的重要组成部分，其功能是把光导入脑内调控神经元活动，同时记录神经元电信号在光调控下变化情况的一种植入式神经接口器件。随着光遗传技术在神经环路、认知与记忆等神经科学研究中应用的深入，以及其在癫痫、感官功能损伤等疾病治疗方面的探索，与光遗传技术相配合的光电极从材料选择、器件结构、给光方式和集成工艺等方面都呈现出百花齐放的发展态势，本文将按照现有植入式光电极的结构特点，将光电极器件分成基于波导型和基于微发光二极管型两大类，论述不同类别光电极器件优缺点及演进方向，对未来植入式光电极的理想结构形态及亟待解决的问题进行了讨论和展望。

关键词: 光遗传, 光电极, 动作电位, 光波导, 微发光二极管

Abstract:

Optogenetics transforms specific types of neurons through genetic engineering to achieve the cell membrane expression of photosensitive channel protein. When a specific wavelength of light irradiates the photosensitive channel protein, the cell is either excited or inhibited. Optogenetics provides a precise and fast method to control the activity of individual neurons for neuroscience research, which has gained increasing attention as a means of neural regulation. To realize the photogenetic regulation of neurons, light should be introduced into the brain safely and efficiently. Thus, specialized photoelectric devices are needed. Optrode plays a significant role in the application of optogenetics tools, which is the technical basis for the application of optogenetics. Optrode is a kind of implantable neural interface device. It can introduce light into the brain to regulate neural activity and record the changes of neural electrical signals under the control of lights. As the research of optogenetic technology continues, More and more optrodes are being developed and applied in the study of neuroscience and diseases, such as neural circuit, cognition and memory, epilepsy, and sensory function damage. The combination of optrode with optogenetic technologies provides various developmental modes in terms of material selection, device structure, light supply method, and integrated ways. The difficulty in fabricating optrodes lies in performing light stimulation and electrical signal recording without causing the immune rejection of the test animal and affecting its normal physiological activities simultaneously. In this study, based on structural characteristics and manufacturing process, optrodes are classified into two categories: waveguide-based and micro-light emitting diode-based. Subsequently, based on manufacturing process and light supply method, waveguide-based optrodes are further divided into optical fiber-optrode, optical waveguide-optrode based on MENS technology, and LD/LED waveguide-optrode. Similarly, micro-light emitting diode-based optrodes are divided into hard μLED optrode and soft μLED optrode. The advantages and disadvantages of different types of optrodes, as well as the evolution direction, are reviewed and summarized. Additionally, problems with existing optrodes, such as signal quality, biocompatibility, and device reliability, are discussed. Further, the ideal form of the device is presented as possessing the following characteristics: μLED and recording electrode integrated on flexible substrate, small size, high spatial resolution, high biocompatibility, wireless energy supply, wireless data transmission, etc. As optrode technologies are continuously updated, in the application of optogenetic technologies, research on brain neural circuit and functional structure will be better studied, and various nerve diseases will be gradually tamed.

Key words: Optogenetics, Optrode, Action potential, Optical waveguide, Micro-Light emitting diode

李亚民, 王阳, 陈弘达, 王毅军, 刘媛媛, 裴为华. 植入式光电极器件发展[J]. 物理化学学报, 2020, 36(12), 1912054. doi: 10.3866/PKU.WHXB201912054

Yamin Li, Yang Wang, Hongda Chen, Yijun Wang, Yuanyuan Liu, Weihua Pei. Development of Implantable Optrode Devices[J]. Acta Phys. -Chim. Sin. 2020, 36(12), 1912054. doi: 10.3866/PKU.WHXB201912054

链接本文: https://www.whxb.pku.edu.cn/CN/10.3866/PKU.WHXB201912054

https://www.whxb.pku.edu.cn/CN/Y2020/V36/I12/1912054

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Referance	Recording area/μm²	Materials	Modification Material	Impedance @1 kHz(kΩ)
24	176	Ag	/	300
32	140	Ir	/	410 ± 30
40	150	Ag	/	1000
52	5 × 10⁵	Ag	IrOx	2.96 ± 0.21
			/	38.01 ± 3.18
58	121	Ag	/	1000
			platinum black	58
			PEDOT : PSS	91

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植入式光电极器件发展

Development of Implantable Optrode Devices

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Optrodes type	Cost	Spatial resolution	Implanted damage	Light / energy supply mode
Optical fiber-optrode	low	low	big	optical fiber
optical waveguide-optrode based on MENS	high	middle	middle	optical fiber
LD/LED waveguide-optrode	high	middle	big/middle	wire
hard μLED optrode	high	high	middle	wire/wireless
soft μLED optrode	high	high	small	wire/wireless