High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors

Abstract

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.

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Fig. 1: Flexible graphene solution-gated FET array technology and characterization.
Fig. 2: Infraslow, local field potential and wide-band in vivo gSGFET recordings of CSD.
Fig. 3: Comparison of d.c.-coupled gSGFET and microelectrode recordings of CSD.
Fig. 4: Microelectrode and gSGFET recording modes: considerations for infraslow recordings.
Fig. 5: Mapping CSD with graphene transistors.
Fig. 6: Depth profile of the infralow-frequency voltage variations induced by CSD in a rat cortex.

Data availability

The experimental data that support the figures within this paper and other findings of this study can be accessed by contacting the corresponding authors. Authors can make data available on request, agreeing on data formats needed.

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Acknowledgements

This work was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 696656 (Graphene Flagship) and no. 732032 (BrainCom). This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MINECO and the ICTS ‘NANBIOSIS’, more specifically by the Micro-NanoTechnology Unit of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the IMB-CNM. E.M.C. acknowledges that this work has been done in the framework of the PhD in Electrical and Telecommunication Engineering at the Universitat Autònoma de Barcelona. E..C. thanks the Spanish Ministerio de Economía y Competitividad for the Juan de la Cierva postdoctoral grant IJCI-2015–25201. T. Durduran acknowledges support from Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad /FEDER (PHOTODEMENTIA, DPI2015–64358-C2–1-R), the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015–0522) and the Obra Social “la Caixa” Foundation (LlumMedBcn). M.V.S.V. acknowledges support from MINECO BFU2017-85048-R. ICN2 is supported by the Severo Ochoa programme fromSpanish MINECO (grant no. SEV-2017-0706).

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E.M.C. carried out most of the fabrication and characterization of the gSGFET arrays, contributed to the design and performance of the in vivo experiments, analysed the data and wrote the manuscript. X.I. designed the neural probes and fabricated the microelectrode arrays. A.B.C. contributed to the fabrication and characterization of the gSGFET arrays. M.D. performed the in vivo experiments. P.G., C.H., J.B. and E.P.A. contributed to the growth of the CVD graphene. E.P.A., E.D.C. and J.M.D.L.C. contributed to the transfer of graphene. E.P.A., E.D.C. and G.R. contributed to the characterization of CVD graphene. J.M.A. contributed to the fabrication of the custom electronic instrumentation and development of a Python-based user interface. A.C. contributed to the CSD propagation analysis. R.G.C. contributed in the noise characterization and analysis of the devices. T. Dragojević, E.E.V.R. and T. Durduran contributed to the in vivo measurements and analysis of cerebral blood flow. M.D., M.V.S.V., A.G.B., R.V. and J.A.G. participated in the design of the in vivo experiments and thoroughly reviewed the manuscript. A.G.B. contributed in the design and fabrication of the custom electronic instrumentation, development of a custom gSGFET Python library and analysis of the data. All authors read and reviewed the manuscript.

Corresponding authors

Correspondence to Jose A. Garrido or Anton Guimerà-Brunet.

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Competing interests

Patent application (no. P201831068) filled by CSIC, ICREA, CIBER, ICN2 and IDIBAPS; inventors: A.G.B., E.M.C., X.I., R.V., M.V.S.V. and J.A.G.; concerning a graphene transistor system for measuring electrophysiological signals (pending).

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Masvidal-Codina, E., Illa, X., Dasilva, M. et al. High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors. Nature Mater 18, 280–288 (2019). https://doi.org/10.1038/s41563-018-0249-4

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