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化学进展 2021, Vol. 33 Issue (4): 568-580 DOI: 10.7536/PC200811 前一篇   后一篇

• 综述 •

石墨烯在神经电信号检测中的应用

吕苏叶1,2,3, 邹亮1,2,3, 管寿梁1,2,3, 李红变1,2,*()   

  1. 1 中国科学院纳米科学卓越创新中心 国家纳米科学中心 北京 100190
    2 中国科学院纳米生物效应与安全性重点实验室 国家纳米科学中心 北京 100190
    3 中国科学院大学 北京 100049
  • 收稿日期:2020-08-04 修回日期:2020-09-14 出版日期:2021-04-20 发布日期:2020-12-28
  • 通讯作者: 李红变
  • 基金资助:
    国家自然科学基金项目(51972073)
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Application of Graphene in Neural Activity Recording

Suye Lv1,2,3, Liang Zou1,2,3, Shouliang Guan1,2,3, Hongbian Li1,2()   

  1. 1 CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology,Beijing 100190, China
    2 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology,Beijing 100190, China
    3 University of Chinese Academy of Sciences,Beijing 100049, China
  • Received:2020-08-04 Revised:2020-09-14 Online:2021-04-20 Published:2020-12-28
  • Contact: Hongbian Li
  • Supported by:
    the National Natural Science Foundation of China(51972073)

神经电极是监测大脑活动的重要工具,在理解大脑运行机制和治疗神经系统疾病等领域发挥着重要作用。实现神经电极对神经电信号的长期稳定检测,构筑可靠的电极-神经界面是关键。传统的神经电极多采用刚性材料,与柔软的神经组织力学性能不匹配,限制了其对神经电信号的长期稳定记录。石墨烯是一种具有单原子层厚度的二维碳纳米材料,具有高的导电性、力学柔性和良好的生物相容性,可以与神经细胞/组织构筑稳定的电极-神经界面,从而实现神经电信号的长期稳定记录。本文梳理了石墨烯在神经电信号检测中的应用,包括石墨烯-细胞的相互作用及利用石墨烯神经电极进行体外和在体神经电信号的检测和记录等。最后,对石墨烯在神经电信号检测方面的未来发展方向进行了展望。

关键词： 石墨烯, 神经电极, 电生理, 界面, 长期稳定记录

As a powerful tool for monitoring brain activities, neural electrodes have been playing a crucial role in the understanding of brain functions and the treatment of neurological disorders. In particular, the construction of a stable electrode-neural interface is critical for the stable chronic neural recording. However, conventional neural electrodes are mainly constructed with rigid materials, whose Young’s moduli are several orders of magnitude higher than that of the brain tissue. This large mechanical mismatch causes the micromotion of the neural electrodes, which elicits inflammatory response of the brain tissue and thus limits the stable chronic neural recording. With the one-atom thickness, graphene has been considered as a promising active material for neural electrodes with stable electrode-neural interfaces for its high conductivity, excellent flexibility and good biocompatibility. In this review, we provide an overview of graphene for neural activity recording, from their modulation on the growth of neurons to applications in bothin vitro and in vivo neural activity recording. At last, challenges and prospects of graphene for neural activity recording are proposed.

Contents

1 Introduction

2 Graphene microelectrodes for cell culture and in vitro neural activity recording

2.1 Graphene for cell growth and modulation

2.2 Graphene microelectrodes for in vitro neural activity recording

3 Graphene microelectrodes for in vivo neural activity recording

3.1 Graphene-based electrocorticography(ECoG) electrodes for neural activity recording

3.2 Graphene-based intracortical electrodes for neural activity recording

4 Conclusion and prospects

Key words: graphene, neural electrodes, electrophysiology, interface, stable chronic recording
()
图1 石墨烯对神经细胞的调控。 (a) 神经干细胞在玻璃和石墨烯基底上的分化结果对照[45];(b) 图形化氟化石墨烯基底的示意图;(c) 干细胞在图形化氟化石墨烯基底上定向生长的结果[47];(d) 三维石墨烯泡沫的扫描电镜图片;(e) 神经干细胞在三维石墨烯泡沫基底和在二维石墨烯基底上的分化结果对照[54];(f) 石墨烯/聚合物微卷及其培养结果示意图;(g) 神经元轴突通过微卷与周围环境形成功能连接的示意图[58];(h) 人工神经导管的示意图;(i) 再生神经的染色图[59];(j) 不同基底上检测到的膜离子电流[61]
Fig.1 Graphene for cell culture and modulation. (a) The differentiation of hNSCs on glass(left) and graphene(right)[45]. Copyright 2011, Wiley-VCH.(b) Schematic illustration of patterned fluorinated graphene(FG) substrates;(c) Aligned growth of stem cell on patterned FG[47]. Copyright 2012, Wiley -VCH.(d) SEM image of a three-dimensional graphene foam(3D GF);(e) The results of hNSCs differentiated on 3D GF and 2D graphene film[54]. Copyright 2013, Nature Publishing Group.(f) Schematic illustration of graphene/polymer micro-roll for cell encapsulation;(g) Schematic illustration of the formation of a neuronal network connected with neuron-laden micro-rolls[58]. Copyright 2019, The Royal Society of Chemistry.(h) Schematic illustration of a graphene nerve conduit;(i) Staining image for regenerated nerves[59], Copyright 2018, Nature Publishing Group.(j) Representative traces of the spontaneous network activity of neurons grown on different substrates[61]. Copyright 2018, Nature Publishing Group.
图2 石墨烯器件对体外神经电信号的记录。(a) 60通道石墨烯微电极阵列的结构;(b) 石墨烯微电极对神经细胞电信号记录示意图;(c) 电极记录的细胞自发放信号和噪声[71];(d) Graphene-VACNT杂化电极示意图;(e)大鼠皮层神经元与三维电极界面;(f) TiN电极与VACNT电极记录信号的幅值对照[73];(g)石墨烯晶体管进行电信号记录的示意图;(h) 培养在石墨烯晶体管上的神经细胞免疫染色图;(i) 石墨烯晶体管器件记录的细胞电活动;(j) 从图i中计算出的胞外动作电位波形[75]
Fig.2 Graphene microelectrodes for in vitro neural activity recording.(a) Structure of a 60-channel graphene MEA;(b) Schematic illustration of the setup for action potential recording;(c) Spontaneous active potentials and noises recorded from graphene microelectrodes[71]. Copyright 2015, Nature Publishing Group.(d) A schematic illustration of the graphene-VACNT neural electrode;(e) FE-SEM images of the interface between rat cortical neurons and the graphene-VACNT electrode;(f) Comparison of the spike amplitude recorded with TiN electrode and VACNT electrode[73]. Copyright 2017, The Royal Society of Chemistry.(g) Schematic illustration of an inverted microscope setup using transparent graphene microelectrodes;(h) Immuno-fluorescence micrographs of the neurons cultured on the G-FETs;(i) The extracellular potentials obtained from the G-FETs;(j) The waveforms of extracellular spikes calibrated from(i)[75]. Copyright 2017, Frontiers Media S.A
图3 石墨烯神经电极阵列对大脑皮层电生理活动的记录。(a) 透明石墨烯μECoG电极阵列的分层结构示意图;(b) 透明石墨烯位点下皮质血管的荧光图像;(c) 透明石墨烯电极阵列记录的光学诱发电位[78];(d) 透明石墨烯电极的光学图片;(e) 和(f) 激光照射下,石墨烯电极不会产生光学伪迹[82];(g) 石墨烯液栅晶体管阵列光学显微镜图片;(h)石墨烯液栅晶体管电极和铂黑电极所记录的大鼠在麻醉状态下脑皮层产生的自发慢波活动对照;(i) 石墨烯液栅晶体管电极和铂黑电极记录信号的信噪比对照[88]
Fig.3 Graphene ECoG electrodes for neural activity recording.(a) Schematic of the layered structure of the transparent graphene μECoG microelectrode array.(b) Fluorescence image of the cortical vasculature under transparent graphene site.(c) Optical evoked potentials recorded by the transparent graphene μECoG microelectrode array [78]. Copyright 2014, Nature Publishing Group.(d) Optical image of the graphene microelectrode array;(e) and(f) Under the direct illumination of the graphene electrode with laser, no artifact was observed[82]. Copyright 2018, Nature Publishing Group.(g) Optical image of a graphene SGFET array;(h) Spontaneous oscillatory activity recorded by graphene SGFET and platinum black electrodes;(i) Signal-to-noise ratio versus frequency for graphene SGFETs(light redlines) and platinum black electrodes[88]. Copyright 2017, Wiley-VCH
图4 基于石墨烯的植入式神经电极。(a) G-Cu微丝电极示意图;(b) 用G-Cu微丝和裸Cu微丝培养的PC12细胞的活性对比;(c) 使用G-Cu微丝记录到的高频神经电信号[95];(d)石墨烯纤维探针的结构示意图;(e) 石墨烯纤维探针的扫描电子显微镜截面图;(f) 石墨烯纤维探针记录到的神经元放电信号[97];(g) 双模式石墨烯晶体管阵列的显微镜图片;(h) 石墨烯晶体管阵列双模式记录的示意图;(i) 双模式石墨烯晶体管阵列记录的大脑皮层表面和内部放电信号以及表面和深度峰值之间的时间间隔变化[98]
Fig.4 Graphene-based implantable electrodes.(a) Schematic illustration of the G-Cu implanted neural electrodes;(b) Comparison of the normalized viability of PC12 cells cultured with G-Cu and bare Cu microwire samples;(c) Representative acute recording of high-frequency electrophysiological signal using a G-Cu microelectrode[95]. Copyright 2016, American Chemical Society.(d) Schematic illustration of graphene fiber probe;(e) Cross-section SEM image of graphene fiber probe;(f) Neural activities recorded from the graphene fiber probe[97]. Copyright 2019, Wiley-VCH.(g) Microscope image of a dual-modality graphene SGFET electrode array;(h) Schematic and optical images of dual-modality recording setup;(i) Representative signals of surface and depth recording and time lag between surface and depth spikes[98]. Copyright 2018, Elsevier
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