Graphene and microelectronics to decipher the unfathomable of neuronal diseases

Graphene, with its high conductivity, flexibility and biocompatibility, is the perfect ally for deciphering the electrical activity of the brain and exploring therapies for neurological diseases, as experts in the field have shown in recent years, including researchers from the Institute of Microelectronics. of Barcelona (IMB), attached to the National Center for Microelectronics (CNM) of the Higher Council for Scientific Research (CSIC), in Spain.

Applying these advances to the diagnosis and treatment of diseases such as epilepsy and Parkinson’s is getting closer, since now the technology-based company Inbrain Neuroelectronics, co-founded by CSIC researchers, is developing graphene transistors in the White Room of Micro and IMB nanofabrication.

The scientific community had spent years developing materials to advance knowledge of the brain and the signals involved in diseases such as epilepsy or Parkinson’s, which cannot be known with the electrode technology used to date. “To better understand brain diseases, we need to reliably record and map a wide range of frequencies, including ultra-slow ones, using the same array of sensors,” explains Anton Guimerà, a scientist at the IMB.

European projects such as Graphene Flagship and BrainCom have shaped the international collaboration of leading research institutions to deepen this knowledge and the application of graphene. These consortia have brought together the IMB, the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and the Networked Biomedical Research Center, among others. His most recent success has been the development of graphene transistors capable of detecting extremely low brain frequencies (research that was covered in the journal Nature Materials).

From here, graphene transistors managed to get out of the scientific field and capture the interest of the industry. On the one hand, these collaborations have given rise to three patents and one industrial secret, of which the CSIC is the majority owner together with the ICN2. On the other, in 2020 the technology-based company Inbrain Neuroelectronics was created to develop revolutionary technologies in the treatment of neurological diseases. It was co-founded by Guimerà, and two ICN2 researchers, José A. Garrido and Kostas Kostarelos. Now, the company is manufacturing graphene transistors in the CSIC’s White Room for Micro and Nanofabrication.

“We want to carry out the first clinical trial in humans in 2023 to achieve brain mapping for the resection of tumors and epileptic foci,” says Carolina Aguilar, an executive at Inbrain Neuroelectronics, about the next objectives of the company, which has already carried out tests in mice and large animals. “The tests will be carried out at a center associated with the University of Manchester, with whom we collaborate, and it will be the first time that graphene has been used in the brain of a human being,” she adds. Subsequently, “we will focus on the development of the platform at the chronic level for the decoding and treatment of brain diseases.”

Graphene microtransistors in direct contact with brain tissue

Existing brain interfaces are based on metals, such as platinum or iridium, and can have multiple side effects. The technology developed consists of nanostructured graphene electrodes with micrometric dimensions and, due to their properties, they provide numerous advantages over metallic electrodes.

Microtransistors are a sheet of graphene in direct contact with brain tissue connected by two metal tracks to the recording electronics. These devices “take advantage of the field effect property of graphene to implement a local amplification of neural signals”, adds Guimerà. The electrical activity of the brain thus modulates the conductivity of the two-dimensional material, allowing the recording of brain activity.

Simulated composition where the adaptation of a neural interface based on graphene transistors with the cerebral convolutions is reflected. (Image: Inbrain)

Graphene, whose development began to be studied a little over a decade ago, thus enables interfaces with fewer restrictions on the miniaturization and resolution of brain signals. In addition, through multiplexing techniques (combining two or more signals and transmitting them through a single medium), it facilitates the increase in recording channels without increasing the number of connections and simplifies its handling. The acquisition of these signals is based on integrated circuits or chips designed in the IMB, which makes it possible to process the large volume of information that is extracted from brain activity.

“Thanks to the biocompatibility and electrochemical stability it offers, the transistor records a wide range of frequencies, including ultra-slow ones, with the same fidelity as glass micropipettes, overcoming their limitations of use and allowing, for the first time, the recording of these signals at multiple points in the brain and simultaneously. This fact facilitates the study of ultra-slow signals in the functioning of the brain and its pathologies”, explains the IMB researcher. “The goal is to exceed the current standard,” he adds.

More than a third of the European population suffers from some type of brain disease, with a high social and health cost. It is necessary to develop new diagnostic tools and more efficient therapies. With graphene implants, the possibility of giving a therapeutic response adapted to the clinical condition of each patient opens up. (Source: Sabela Rey Cao / IMB / CSIC)