A study recently published in "Nature Communication" demonstrates that graphene-based active sensor arrays are a mature technology for large-scale application in wide frequency band neural sensing interfaces. This work was developed by researchers from various institutes and a company that are part of the EU Graphene Flagship – including the ICN2.
The study of the brain aiming at comprehending its workings requires a thorough analysis of cerebral electrophysiology, as well as investigating the relation between neural activity patterns and behaviour. In order to perform these studies, researchers need to have access to and record brain activity – i.e. the signals produced in it – over a long period of time and across different states. This translates in the need for neural sensing interfaces able to detect signals from different channels, over a wide frequency range, and with high spatial resolution and sensitivity. In addition, the sensors should be integrated in flexible substrates and, of course, be biocompatible. Meeting these requirements is not an easy task.
Graphene-based active sensors are promising candidate for this application, thanks to the flexibility of graphene, its electronic properties, as well as its high stability and biocompatibility. In particular, graphene solution-based field-effect transistors (g-SGFET) have shown very good performance, especially in terms of sensitivity to cortical signals in the infra-slow (<0.5 Hz) frequency band. For graphene active sensors arrays to be used as reliable tools for neuroscientific research, the maturity of this technology and its large-scale applicability needed to be demonstrated.
A team of researchers from the European Graphene Flagship – specifically, from the ICN2 Advanced Electronic Materials and Devices group, led by ICREA Prof. José A. Garrido, and the ICN2 Nanomedicine group, led by Prof. Kostas Kostarelos, from the Bernstein Center for Computational Neuroscience Munich (Germany), the Multi Channel Systems company (Reutlingen, Germany), the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC) and the University of Manchester (UK) –conducted a systematic study on a 64-channel g-SGFET array, proving that this technology is ready for application in wide frequency band neural sensing interfaces. This work has been recently published in Nature Communications.
As a first step, the authors verified the applicability of commercially available single-layer graphene, produced by chemical-vapour-deposition and transferred onto a flexible polymeric substrate. The g-SGFET array fabricated from this material presented good performance both in terms of homogeneity and sensitivity. Then, the biocompatibility of graphene-based epicortical devices was investigated in-vivo by implanting different types of devices onto the brain cortex of laboratory mice. The monitoring of the immunohistochemical response of the animals and of potential effects on their behaviour showed no significant issues, proving the adequate biocompatibility of graphene-based neural interfaces. A dedicated wireless headstage – an electronic device attached to the head of the laboratory animal – was also developed, meeting specific requirements of signal amplification without introducing disturbance.
This device was built on the basis of a sensing technology developed by the ICN2 and the IMV-CNM-CSIC, in the frame of both the Graphene Flagship and the BrainCom European project. Using this 64-channel g-SGFET array, the researchers were able to record epicortical brain activity in freely behaving rats over long periods of time (up to 24 hours). By combining it with the tracking of the animals’ motion, they could classify brain states and explore the relation between neural activity patterns and behaviour. The excellent results of this study demonstrate that graphene active-sensors array can be effectively applied in neuroscience research. Thanks to their stability and biocompatibility, these neural interfaces are powerful tools to record brain activity over a wide frequency band during spontaneous behaviour of the animals under test.
"It is very remarkable to see that we can properly identify and correlate the animals’ brain states with the measured infra-slow activity," Prof. Garrido comments. The next step will be to explore commercial applications: "We are already collaborating with some companies interested in this technology and we aim to translate it into a product and, beyond that, to introduce it into clinics and hospitals," he concludes.
For more information: News by the Graphene Flagship.
Reference article:
Garcia-Cortadella, G. Schwesig, C. Jeschke, X. Illa, Anna L. Gray, S. Savage, E. Stamatidou, I. Schiessl, E. Masvidal-Codina, K. Kostarelos, A. Guimerà-Brunet, A. Sirota & J. A. Garrido, Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity. Nature Communications 12, 211 (2021). DOI: 10.1038/s41467-020-20546-w