Journal of Biological Physics

, Volume 41, Issue 4, pp 339–347 | Cite as

Graphene microelectrode arrays for neural activity detection

  • Xiaowei Du
  • Lei Wu
  • Ji Cheng
  • Shanluo Huang
  • Qi Cai
  • Qinghui Jin
  • Jianlong Zhao
Original Paper


We demonstrate a method to fabricate graphene microelectrode arrays (MEAs) using a simple and inexpensive method to solve the problem of opaque electrode positions in traditional MEAs, while keeping good biocompatibility. To study the interface differences between graphene–electrolyte and gold–electrolyte, graphene and gold electrodes with a large area were fabricated. According to the simulation results of electrochemical impedances, the gold–electrolyte interface can be described as a classical double-layer structure, while the graphene–electrolyte interface can be explained by a modified double-layer theory. Furthermore, using graphene MEAs, we detected the neural activities of neurons dissociated from Wistar rats (embryonic day 18). The signal-to-noise ratio of the detected signal was 10.31 ± 1.2, which is comparable to those of MEAs made with other materials. The long-term stability of the MEAs is demonstrated by comparing differences in Bode diagrams taken before and after cell culturing.


Microelectrode arrays MEA Graphene Neural activity detection 



This work was supported by grants from the National Basic Research Program of China (973 Program) (Nos. 2011CB707505 and 2012CB933303), the National Science Foundation of China (Nos. 21275153 and 61271161), the Scientific Equipment Research Project of the Chinese Academy of Sciences (No. YZ201337), the CAS-Helmholtz joint research team (No. GJHZ1306) and the Science and Technology Project of Jiangsu Province, China (No. BE2012049).


  1. 1.
    Jimbo, Y., Kawana, A.: Electrical-stimulation and recording from cultured neurons using a planar electrode array. Bioelectrochem. Bioenerg. 29(2), 193–204 (1992). doi: 10.1016/0302-4598(92)80067-Q CrossRefGoogle Scholar
  2. 2.
    Egert, U., Schlosshauer, B., Fennrich, S., Nisch, W., Fejtl, M., Knott, T., Muller, T., Hammerle, H.: A novel organotypic long-term culture of the rat hippocampus on substrate-integrated multielectrode arrays. Brain Res. Protoc. 2(4), 229–242 (1998). doi: 10.1016/S1385-299x(98)00013-0 CrossRefGoogle Scholar
  3. 3.
    Fofonoff, T.A., Martel, S.M., Hatsopoulos, N.G., Donoghue, J.P., Hunter, I.W.: Microelectrode array fabrication by electrical discharge machining and chemical etching. IEEE Trans. Biomed. Eng. 51(6), 890–895 (2004). doi: 10.1109/Tbme.2004.826679 CrossRefGoogle Scholar
  4. 4.
    Gross, G.W., Rhoades, B.K., Reust, D.L., Schwalm, F.U.: Stimulation of monolayer networks in culture through thin-film indium-tin oxide recording electrodes. J. Neurosci. Meth. 50(2), 131–143 (1993). doi: 10.1016/0165-0270(93)90001-8 CrossRefGoogle Scholar
  5. 5.
    Geim, A.K., Novoselov, K.S.: The rise of graphene. Nat. Mater. 6(3), 183–191 (2007). doi: 10.1038/Nmat1849 CrossRefADSGoogle Scholar
  6. 6.
    Hess, L.H., Jansen, M., Maybeck, V., Hauf, M.V., Seifert, M., Stutzmann, M., Sharp, I.D., Offenhausser, A., Garrido, J.A.: Graphene transistor arrays for recording action potentials from electrogenic cells. Adv. Mater. 23(43), 5045–5049 (2011). doi: 10.1002/adma.201102990 CrossRefGoogle Scholar
  7. 7.
    Cohen-Karni, T., Qing, Q., Li, Q., Fang, Y., Lieber, C.M.: Graphene and nanowire transistors for cellular interfaces and electrical recording. Nano Lett. 10(3), 1098–1102 (2010). doi: 10.1021/Nl1002608 CrossRefADSGoogle Scholar
  8. 8.
    Chen, C.H., Lin, C.T., Chen, J.J., Hsu, W.L., Chang, Y.C., Yeh, S.R., Li, L.J., Yao, D.J.: A graphene-based microelectrode for recording neural signals. In: 16th Int. Conf. on Solid-State Sensors, Actuators and Microsystems, Beijing, China, 5-9 Jun. 2011, pp. 1883–1886Google Scholar
  9. 9.
    Bendali, A., Hess, L.H., Seifert, M., Forster, V., Stephan, A.F., Garrido, J.A., Picaud, S.: Purified neurons can survive on peptide-free graphene layers. Adv. Healthcare Mater. 2(7), 929–933 (2013). doi: 10.1002/adhm.201200347 CrossRefGoogle Scholar
  10. 10.
    Park, D.-W., Schendel, A.A., Mikael, S., Brodnick, S.K., Richner, T.J., Ness, J.P., Hayat, M.R., Atry, F., Frye, S.T., Pashaie, R., Thongpang, S., Ma, Z., Williams, J.C.: Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications. Nat. Commun. 5, 5258 (2014). doi: 10.1038/ncomms6258 CrossRefADSGoogle Scholar
  11. 11.
    Kuzum, D., Takano, H., Shim, E., Reed, J.C., Juul, H., Richardson, A.G., de Vries, J., Bink, H., Dichter, M.A., Lucas, T.H., Coulter, D.A., Cubukcu, E., Litt, B.: Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging. Nat. Commun. 5, 5259 (2014). doi: 10.1038/ncomms6259 CrossRefADSGoogle Scholar
  12. 12.
    Kim, K.S., Zhao, Y., Jang, H., Lee, S.Y., Kim, J.M., Kim, K.S., Ahn, J.-H., Kim, P., Choi, J.-Y., Hong, B.H.: Large-scale pattern growth of graphene films for stretchable transparent electrodes. Nature 457(7230), 706–710 (2009). doi: 10.1038/nature07719 CrossRefADSGoogle Scholar
  13. 13.
    Bae, S., Kim, H., Lee, Y., Xu, X., Park, J.-S., Zheng, Y., Balakrishnan, J., Lei, T., Ri Kim, H., Song, Y.I., Kim, Y.-J., Kim, K.S., Ozyilmaz, B., Ahn, J.-H., Hong, B.H., Iijima, S.: Roll-to-roll production of 30-inch graphene films for transparent electrodes. Nat. Nanotechnol. 5(8), 574–578 (2010). doi: 10.1038/nnano.2010.132 CrossRefADSGoogle Scholar
  14. 14.
    Mailly-Giacchetti, B., Hsu, A., Wang, H., Vinciguerra, V., Pappalardo, F., Occhipinti, L., Guidetti, E., Coffa, S., Kong, J., Palacios, T.: pH sensing properties of graphene solution-gated field-effect transistors. J. Appl. Phys. 114(8), 084505 (2013). doi: 10.1063/1.4819219 CrossRefADSGoogle Scholar
  15. 15.
    Wang, Y.Y., Burke, P.J.: A large-area and contamination-free graphene transistor for liquid-gated sensing applications. Appl. Phys. Lett. 103(5), 052103 (2013). doi: 10.1063/1.4816764 CrossRefADSGoogle Scholar
  16. 16.
    Zhuo, H., Peng, F.C., Lin, L.M., Qu, Y., Lai, F.C.: Optical properties of porous anodic aluminum oxide thin films on quartz substrates. Thin Solid Films 519(7), 2308–2312 (2011). doi: 10.1016/j.tsf.2010.11.024 CrossRefADSGoogle Scholar
  17. 17.
    Blake, P., Hill, E.W., Castro Neto, A.H., Novoselov, K.S., Jiang, D., Yang, R., Booth, T.J., Geim, A.K.: Making graphene visible. Appl. Phys. Lett. 91(6), 063124 (2007). doi: 10.1063/1.2768624 CrossRefADSGoogle Scholar
  18. 18.
    Reina, A., Jia, X.T., Ho, J., Nezich, D., Son, H.B., Bulovic, V., Dresselhaus, M.S., Kong, J.: Large area, few-layer graphene films on arbitrary substrates by chemical vapor deposition. Nano Lett. 9(1), 30–35 (2009). doi: 10.1021/Nl801827v CrossRefADSGoogle Scholar
  19. 19.
    Ferrari, A.C., Meyer, J.C., Scardaci, V., Casiraghi, C., Lazzeri, M., Mauri, F., Piscanec, S., Jiang, D., Novoselov, K.S., Roth, S., Geim, A.K.: Raman spectrum of graphene and graphene layers. Phys. Rev. Lett. 97(18), 187401 (2006). doi: 10.1103/Physrevlett.97.187401 CrossRefADSGoogle Scholar
  20. 20.
    Malard, L.M., Pimenta, M.A., Dresselhaus, G., Dresselhaus, M.S.: Raman spectroscopy in graphene. Phys. Rep. 473(5–6), 51–87 (2009). doi: 10.1016/j.physrep.2009.02.003 CrossRefADSGoogle Scholar
  21. 21.
    Piela, B., Wrona, P.K.: Capacitance of the gold electrode in 0.5 M H2SO4 solution: a.c. impedance studies. J. Electroanal. Chem. 388(1–2), 69-79 (1995). doi: 10.1016/0022-0728(94)03848-W
  22. 22.
    Wang, H.N., Pilon, L.: Accurate simulations of electric double layer capacitance of ultramicroelectrodes. J. Phys. Chem. C 115(33), 16711–16719 (2011). doi: 10.1021/Jp204498e CrossRefGoogle Scholar
  23. 23.
    Xia, J.L., Chen, F., Li, J.H., Tao, N.J.: Measurement of the quantum capacitance of graphene. Nat. Nanotechnol. 4(8), 505–509 (2009). doi: 10.1038/Nnano.2009.177 CrossRefADSGoogle Scholar
  24. 24.
    Casero, E., Parra-Alfambra, A.M., Petit-Domínguez, M.D., Pariente, F., Lorenzo, E., Alonso, C.: Differentiation between graphene oxide and reduced graphene by electrochemical impedance spectroscopy (EIS). Electrochem. Commun. 20, 63–66 (2012). doi: 10.1016/j.elecom.2012.04.002 CrossRefGoogle Scholar
  25. 25.
    Chen, Z., Appenzeller, J.: Mobility extraction and quantum capacitance impact in high performance graphene field-effect transistor devices. In: Electron Devices Meeting, San Francisco, CA, 15-17 Dec. 2008, pp. 1-4Google Scholar
  26. 26.
    Fang, T., Konar, A., Xing, H., Jena, D.: Carrier statistics and quantum capacitance of graphene sheets and ribbons. Appl. Phys. Lett. 91(9), 092109 (2007). doi: 10.1063/1.2776887 CrossRefADSGoogle Scholar
  27. 27.
    Cheng, J., Zhu, G., Wu, L., Du, X., Zhang, H., Wolfrum, B., Jin, Q., Zhao, J., Offenhausser, A., Xu, Y.: Photopatterning of self-assembled poly (ethylene) glycol monolayer for neuronal network fabrication. J. Neurosci. Meth. 213(2), 196–203 (2013). doi: 10.1016/j.jneumeth.2012.12.020 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Xiaowei Du
    • 1
    • 2
  • Lei Wu
    • 1
  • Ji Cheng
    • 1
    • 2
  • Shanluo Huang
    • 1
    • 2
  • Qi Cai
    • 1
    • 2
  • Qinghui Jin
    • 1
  • Jianlong Zhao
    • 1
  1. 1.State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghaiChina
  2. 2.University of Chinese Academy of SciencesBeijingChina

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