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Unlocking the brain with novel graphene technology

Researchers of NANBIOSIS U8 Micro– Nano Technology Unit of CIBER-BBN at the Barcelona Institute of Microelectronics have participated in the recent developments of a new graphene-based detection platform that could be the gateway to unlock superior understanding of the brain by providing a measure of high brain activity resolution and in real time. This research has been developed within the framework of the EU BrainCom project.

The European Union’s Horizon 2020 research project, BrainCom, is coordinated by the ICN2 Advanced Electronic Materials and Devices Group led by Professor José A. Garrido and the CIBER BBN GBIO Group and the Nanbiosis U8 platform participate. (Anton Guimera, Xavier Illa, Ana Moya, Elisabet Prats and Rosa Villa)

Arguably, a better understanding of the working principles of the human brain remains one of the major scientific challenges of our time. Despite significant advances made in the field of neurotechnology in recent years, neural sensing interfaces still fall short of equally meeting requirements on biocompatibility, sensitivity, and high spatio-temporal resolution. The European Union Horizon 2020 research project BrainCom, coordinated by the ICN2 Advanced Electronic Materials and Devices Group led by ICREA Prof. José A. Garrido, is tackling these problems. BrainCom brings together experts from the fields of neurotechnology, neuroscience, and ethics to develop novel technologies capable of overcoming these limitations and shed light onto the mechanisms of information encoding and processing in the brain.

In four research articles published between March and April 2020 — featured in Elsevier’s Carbon, IOP’s 2D Materials, Wiley’s Small, and American Chemical Society’s Nano Letters — researchers from the BrainCom consortium present the technological advances achieved in the project, discuss in-depth methodology, and demonstrate novel capabilities for high resolution sensing of the brain’s electrical activity. The recent developments exploit the unique properties of graphene, an atom-thick layer of carbon, which conforms with the soft and convoluted surface of the brain providing an excellent neural sensing interface. Graphene sensors have an additional advantage that represents a turning point in neural engineering: the sensing mechanism of these graphene active sensors (so-called transistors) is compatible with  electronic multiplexing, a technology that enables transmitting the signals detected by multiple sensors through a single micrometric wire. This implies that the number of sensors on the neural implants can be increased while minimizing the footprint of the connectors required to link the implants to external electronic equipment.

This technology, developed in close collaboration with Dr Anton Guimerà at the CSIC Institute of Microelectronics of Barcelona (IMB-CNM, CSIC), has been evaluated in pre-clinical studies at the laboratory of neuroscientist Prof. Anton Sirota at Ludwig-Maximilians Universität (LMU, Munich). A collaborative and multidisciplinary approach is crucial for the success of the project, which aims at addressing a very hard scientific and technological challenge. The human brain has an astonishing complexity, consisting out of as many as 100 billion neurons. To fully understand the underlying principles of such a convoluted system requires the simultaneous detection of the electrical activity of large neural populations with a high spatial and temporal resolution. Unfortunately, current neural sensing technologies present a trade-off between spatial resolution and large-area coverage of the brain surface. The work carried out by the BrainCom project’s researchers shows how graphene-based sensors represent an outstanding building block for such large scale and highly sensitive neural interfaces. As explained in the recently published papers, graphene sensors can be reduced in size to the dimension of about one single neuron, while maintaining a high signal quality. In addition, their sensitivity expands over a wide range of frequencies; from infra-slow oscillations to very fast signals elicited by individual cells.

These findings clear the path for a scale-up of graphene sensor technology towards arrays with an ultra-high-count of sensors. Such biocompatible and high bandwidth neural interfaces can have a great impact on the development of neuroprosthesis, which enable a direct communication between the brain and a computer. These results represent the fruition of long-term EU research initiatives, which pursue the ambitious goal of restoring speech to impaired patients by reading the signals in their brains, which are related to their intentional speech. The research consortium will now focus on upscaling the production of these neural interfaces and testing their performance in safe human clinical trials. This and other applications of graphene sensors are also supported by the EU Graphene Flagship within the Biomedical Technologies work package.

Reference Articles:

Garcia-Cortadella R, Schaefer N, Cisneros-Fernández J, Re L, Illa X, Moya-Lara A ,Santiago S, Guirado G, Villa R, Sirota A, Serra-Graells F, Garrido JA, Guimerà-Brunet A Switchless Multiplexing of Graphene Active Sensor Arrays for Brain Mapping Nano Letters (2020) DOI: 10.1021/acs.nanolett.0c00467

Garcia-Cortadella R, Masvidal-Codina E, de la Cruz J, Schaefer N, Schwesig G, Jeschke C, Martínez-Aguilar J, Sánchez-Vives MV, Villa R, Illa X, Sirota A, Guimerà-Brunet A, Garrido JA Distortion‐Free Sensing of Neural Activity Using Graphene Transistors Small (2020) 1906640, March 2020. DOI: 10.1002/smll.201906640

Schaefer N, Garcia-Cortadella R, Martínez-Aguilar J, Schwesig G, Illa X, Moya Lara A, Santiago S, Hébert C, Guirado G, Villa R, Sirota A, Guimerà-Brunet A, Garrido JA Multiplexed Neural Sensor Array of Graphene Solution-Gated Field-Effect Transistors 2D Materials 7(2), 2020. DOI: 10.1088/2053-1583/ab7976

Schaefer N, Garcia-Cortadella R, Bonaccini Calia A, Mavredakis N, Illa X, Masvidal-Codina E, de la Cruz J, del Corro E, Rodríguez L, Prats-Alfonso E, Bousquet J, Martínez-Aguilar J, Pérez-Marín AP, Hébert C, Villa R, Jiménez D, Guimerà-Brunet A, Garrido JA Improved metal-graphene contacts for low-noise, high-density microtransistor arrays for neural sensing Carbon 161, 647-655, 2020. DOI: 10.1016/j.carbon.2020.01.066

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Researchers from NANBIOSIS Unit 8 opt for the Cutting-Edge Science Award: How to measure brain’s hidden activity.

La Vanguardia and the Fundació Catalunya La Pedrera have jointly promoted for the tenth consecutive year the Cutting-Edge Science Award “La Vanguardia de la Ciencia”, with the objective of givin visibility to the research of excellence carried out in Spain. The prize will correspond to the proposal candidate most voted by the public.

One of the 8 selected candidates is the research led by Anton Guimerà-Brunet (NANBIOSIS Unit 8 -Institut de Microelectrònica de Barcelona-CNM-CSIC / CIBER-BBN) and Jose Garrido (Institut Català de Nanociències i Nanotecnologia / Icrea), for developing graphene implants capable of measuring the hidden activity of the brain  with more sensitivity than conventional methods.

These new devices could improve the diagnosis of epilepsy and are being used as research tool to better understand this and other diseases and develop new therapies.

Further information can be found at the Vanguardias’s website dedicated to the prize and also how to cast your vote: https://www.lavanguardia.com/ciencia/20200126/473088817129/premio-vanguardia-de-la-ciencia.html

Article of reference:

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Rosa Villa explains how New graphene implants can help to better understand the brain


A graphene implant that detects brain activity at extremely low frequencies could improve the technology of the electrodes to analyze the state of our brain, has been developed by researchers from several research institutes of the CSIC in Catalonia and the CIBER-BBN.

Last First of February , Rosa Villa, Scientific Director of NANBIOSIS U8 Micro – Nano Technology Unit was interviewed in Ágora, a program of Scientific Dissemination of Radio Aragón. Dr. Villa, researcher of the Biomedical Applications Group of the Institute of Microelectronics of Barcelona and CIBER in Bioengineering, Biomaterials and Nanomedicine, explains the relevance of the research carried out, together with several institutes of the CSIC in Catalonia, on the application of new materials to the study of brain activity.

The brain is composed of many neurons that communicate with each other. This communication occurs through electric currents that are detected with electrodes placed on the surface of the head or above the brain. Brain waves are very different if we are awake or asleep or when we have certain pathologies. The electrodes with which these electrical signals
were analyzed used to be large; thanks to the microelectronics began to make increasingly smaller electrodes that could identify communications much better but that small size also makes their limited reach, since they do not always take all the degrees of frequency.

Graphene has opened the degree of frequencies to detect the electrical signals of the brain. So far the electrodes were placed on top of the hair (for example the encephalograms) but now, although it has only been done in animals for the moment, the microelectrodes are already being placed as implants on the brain itself, which are left on the surface or they dig in to access more depth. When this is done, the brain feels invaded and isolates that electrode generating a scar, which is why more compatible materials are sought that are not rejected by the brain, such as graphene. Overcoming this technical limitation makes accessible the large amount of information that is below 0.1 Hz, while it facilitates the design of new brain-computer interfaces can register a wide range of frequency of what is occurring in a site of the brain.

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Graphene 2018 with the participation of NANBIOSIS Unit 8

Eli Prats  and Eduard Masvidal researchers of NANBIOSIS Unit 8 Micro and Nanotechnology Unit have shown their last results in ECoG recordings and biosensing using graphene based devices at the 8th edition of Graphene Conference series, the largest European Event in Graphene and 2D Materials, which is taken place in Dresden (Germany) from the 26th until the 29th of June 2018.

Eli Prats has spoken on Label-free Direct Detection of Thrombin through graphene SGFET with chemically modified aptamers and Eduard Masvidal has given a talk on Graphene transistors for ultra-slow frequency (< 0.1Hz) in vivo neural recordings showing graphene SGFETs as a promising technology for recording ultra-slow frequencies with high-spatial resolution

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Why research in micro-electronics? Neural interfaces, interaction between the nervous and the artificial system

Dra. Rosa Villa,  Scientific Director of NANBIOSIS U8. Micro – Nano Technology Unit, explained last June, 11 at the Residence of Researchers of Barcelona the great scientific challenges in finding tools that allow a good interaction between the nervous and the artificial system.

This talk is part of the series of conferences organized by the CNM with the theme “Why research in micro-electronics?” Dr. Manuel Lozano, Director of the CNM, introduced the talk explaining that with microelectronic technology scientists  can capture the signals that occur in the nerves and in the brain and presented Rosa Villa  as a doctor  with a PhD in cochlear implants (electronic medical devices that perform the work of damaged parts of the inner ear (cochlea) to provide sound signals to the brain). Dr. Villa now directs the group of biomedical applications of the CNM that currently uses nano technologies in their research. Her training in medicine and microelectronics has allowed her to tackle electronic-based projects with biomedical application. Her lines of research are focused, nowadays, on neural interfaces and on organ-on-chip technology, (a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of the entire organs and organ systems, the group of Dr. Villa works mainly the liver, very useful for the test of drug patho-toxicity).

In this talk, Rosa Villa explains her second line research of neural interfaces, the development of suitable interfaces between the biological systems and electronic devices and how they study the improvement of the necessary technologies to restore the motor skills or to know how the brain works applying microelectronic techniques.  These investigations run into the main problems of biocompatibility and conectivity and Rosa Villa shows us her letter to Santa Claus to solve them and how graphene is being of great help.

You can see the whole conference clicking here

The video includes a funny class by Eli Prats to produce graphene at home.

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Graphene transistors as eficient transducers for electrocorticography

Researchers of Micro-Nano Technologies Unit (U8) of NANBIOSIS, are co-authors of a new paper published in Advanced Functional Materials. Neuroelectronic interfaces bridge the central nervous system to the outside world and hold great potential for functional restoration in persons with paralysis, other forms of motor dysfunction, or limb loss. Neuroscientists and neurosurgeons are thus looking for technologies that could ideally record the whole brain with a high spatial and temporal resolution. Electrocorticography (ECoG), the practice of placing arrays of large-diameter electrodes (few millimeters) directly on the cortex is the current clinical solution to obtaining brain recordings with high temporal resolution.

Recent research from the CIBER-BBN and  IMB-CNM Biomedical Applications group (IP Rosa Villa)  coordinator of NANBIOSIS Unit 8, in collaboration with ICN2 (IP JA Garrido) , IDIBAPS  (IP MV Sanchez Vives) and INSERM (IP B Yvert) groups,  has focused on the development of graphene technology for electrocorticography. Specifically, flexible graphene transistor arrays have been fabricated and applied to the in vivo measurement of local field potentials.

Graphene is one of the most promising material candidates for neural interfacing thanks to its biocompatibility, low dimensionality and mechanical properties. Additionally, graphene exhibits extraordinary electrical properties such as high carrier mobility and chemical stability, features that only few materials can offer therefore helping to create a very intimate interface between the tissue and the transducing system.

However, previous in vivo studies using single layer CVD graphene have used an electrode configuration. Instead, here they propose the use of a transistor configuration. The main reason for this choice is certainly the local preamplification inherent to a transistor. As a consequence, less environmental noise is picked by the device.

Their work presents a complete description of the fabrication technology, the operation of graphene solution-gated field-effect transistors (SGFET) in saline solution and of the custom characterization electronic system. The devices are finally used in in vivo experiments in which the transconductance and noise are first characterized during slow-wave activity followed by the recording of visual and auditory evoked activity as well as of synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies.

Full details of the fabrication, characterization and in vivo performance of the flexible graphene transistor probes can be found in the paper below.

Hébert, C., et al., Flexible Graphene Solution‐Gated Field‐Effect Transistors: Efficient Transducers for Micro‐Electrocorticography. Advanced Functional Materials, 2017.

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Graphene will revolutionize the world

Elisabet Prats, researcer of the GBIO Group, coordinator of Unit 8 of NANBIOSIS, participated in the  #ImproCiencia dissemination event, held on November 16 in Madrid organized by CIBER. Elisabet presented the Neurographene project as a monologue and explained how they are using graphene for Measure the electrical activity of the brain.

Based on the latest microfabrication technologies, the devices consist of graphene microsensor matrices mounted on flexible polymer substrates that adapt to the surface morphology of the brain.

Each sensor detects tiny changes in the electrical activity around it. Thus, the electrical activity generated by the neurons is detected as a small change in the conductivity of the graphene sensor. These devices are already being used in the study of sleep and epilepsy in animal models. The graphene sensor implanted on the brain surface allows the simultaneous recording of electrical activity in different regions of the cortex.

Also, the technology of flexible graphene sensors can be used in other biomedical applications in which it is necessary to obtain relevant information from the cerebral cortex. “Graphene will revolutionize the world,” said Elisabet Prats.

Graphene will revolutionize the world
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Graphene Flagship for Biomedical Tecnologies – Kick off meeting April 11-14 Barcelona

On April, 11-12 took place in Barcelona the kick off meeting of the new Graphene Flagship Work Package devoted to Biomedical Technologies, one emerging application area for graphene and other 2D materials. The Kick-off event, was co-organised by Dr. Rosa Villa (CNM-IMB-CSIC, CIBER-BBN) Scientific Coordinator of Unit 8 of NANBIOSIS (in the center of the first row in the photo). More than 35 Scientifics from 14 research groups attended to the meeting

The Graphene Flagship, the EU’s biggest ever research initiative, involves the coordination research of over 150 partners from more than 20 European countries withing a timeframe of 10 years. This project is implemented as a total of 15 research Work Packages on specific science and technology topics. The new Work Package will focus on the development of implants based on graphene and 2D-materials with therapeutic functionalities for specific clinical outcomes in neurology, ophthalmology and surgery, between other disciplines that will be further developed in the next phases of the Graphene Flagship.

The launch meeting held on 11 and 12 April in the Convalescence House of the Autonomous University of Barcelona (UAB), was co-organized by the ICN2, the National Microelectronics Centre (CNM-IMB-CSIC, CIBER-BBN; researcher Dr. CSIC. Villa Rosa) and IDIBAPS. This meeting began with two lectures given by well known neuroscientists, Dr. Gerardo Conesa, chief of neurosurgery at the Hospital del Mar (Barcelona) and Dr. Xavier Navarro,  the Institute of Neurosciences at the UAB and belonging to CIBERNED.

Nanbiosis_U8_Graphene Flagship for Biomedical Tecnologies
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Elisabet Prats is a young scientist, researcher at Biomonitoring group of CIBER-BBN and  CNM, which coordinates Unit 8 of NANBIOSIS, and a science disseminator with comedian monologues at “Big Van”.

[Elisabet Prats in Informativos.net]

As a science disseminator, Elisabet has recently appeared in media and forums explaining the progress made by her research group in the European project Graphene Flagship. For example, a graphene sensor to detect brain electrical activity, successfully presented at Mobile World Congress. Elisabet clearly explains “We are able to measure the electrical signals of the brain with graphene, graphene due to its versatility, allows the reduction in size of the sensors, giving much more information to the doctor” and describes a future in which “we shall control mechanical arms with brains implants”.

Nanbiosis_U8 - Biomedical applications of graphene, Elisabet Prats in Informativos.net
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