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“The almighty graphene”, a podcast by Elisabet Prats

Elisabet Prats Alfonso, a researcher in the team coordinating NANBIOSIS U8 Micro– Nano Technology Unit explains in a podcast her most recent research based on the functionalization of chemical and biochemical sensor platforms as well as the characterization of materials such as graphene for both neuronal recording and biomarker detection. Her work is part of the Graphene Flagship project in which she collaborates with relevant European groups.

Eli Prat as a researcher Ph.D. in Chemistry and also dedicated to dissemination is a great exemple for the NANBIOSIS aim to encourage STEAM scientific vocations especially among girls.

In addition, she is the author, together with Helena González and Oriol Marimón, of the book “Elementum and the great robbery of Nurú” (La Esfera de los Libros, 2020), a scientific novel aimed at children .

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The suitability of flexible graphene depth neuralprobes for in vivo electrophysiology research

  • A study published in “Nature Nanotechnology” shows that flexible brain probes made of graphene micro-transistors can be used to record pathological brain signals associated with epilepsy with excellent fidelity and high spatial resolution.
  • This research was led by the Catalan Institute of Nanoscience and Nanotechnology (ICN2), the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC) and the University College London Queen Square Institute of Neurology (UK).

Barcelona, Wednesday 22 December 2021. The ability to record and map the full range of brain signals using electrophysiological probes will greatly advance our understanding of brain diseases and aid the clinical management of patients with diverse neurological disorders. However, current technologies are limited in their ability to accurately obtain with high spatial fidelity ultraslow brain signals. In a paper published today in Nature Nanotechnology, an international team of researchers report a flexible neural probe made of graphene-based field-effect transistors capable of recording the full spectrum of brain signals, including infraslow; and demonstrate the ability of these devices to detect with high fidelity electrographic signatures of the epileptic brain.

Epilepsy is the most common serious brain disorder worldwide, with up to 30% of people unable to control their seizures using traditional anti-epileptic drugs. For drug-refractory patients, epilepsy surgery may be a viable option. Surgical removal of the area of the brain where the seizures first start can result in seizure freedom; however, the success of surgery relies on accurately identifying the seizure onset zone (SOZ).  Epileptic signals span over a wide range of frequencies –much larger than the band monitored in conventional EEG.  Electrographic biomarkers of a SOZ include very fast oscillations as well as infraslow activity and direct-current (DC) shifts. The latter, in particular, can provide very relevant information associated with seizure onset but are seldom used due to the poor performance of current probes to record these types of slow brain signals. Application of this technology will allow researchers to investigate the role infraslow oscillations play in promoting susceptibility windows for the transition to seizure, as well as improving detection of clinically relevant electrophysiological biomarkers associated with epilepsy.

The graphene depth neural probe (gDNP) developed by the authors of this research consists of a millimetre-long linear array of micro-transistors imbedded in a micrometre-thin polymeric flexible substrate. The flexible gDNP devices were chronically implanted in small animal models of seizures and epilepsy. The implanted devices provided outstanding spatial resolution and very rich wide bandwidth recording of epileptic brain signals over weeks. In addition, extensive chronic biocompatibility tests confirmed no significant tissue damage and neuro-inflammation, attributed to the biocompatibility of the used materials, including graphene, and the flexible nature of the gDNP device.

Future clinical translation of this technology offers the possibility to identify and confine much more precisely the zones of the brain responsible for seizure onset before surgery, leading to less extensive resections and better outcomes. Ultimately, this technology can also be applied to improve our understanding of other neurological diseases associated with ultraslow brain signals, such as traumatic brain injury, stroke and migraine.

This study was led by ICREA Prof. Jose A Garrido, head of the ICN2 Advanced Electronic Materials and Devices Group, Dr Anton Guimerà-Brunet, from the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC) & CIBER-BBN, and Dr Rob Wykes, from the University College London Queen Square Institute of Neurology (UK) & the Nanomedicine Lab of the University of Manchester (UK). First author of the paper is Dr Andrea Bonaccini Calia, a former member of Prof. Garrido’s group. This study was conducted in the frame of the EU project Graphene Flagship. It benefited from multidisciplinary collaborations and received valuable contributions from researchers at the Nanomedicine Lab of the University of Manchester (UK), the Universitat Autònoma de Barcelona (Spain), the CIBER-BBN with the participation of its ICTS NANBIOSIS and g.tec medical engineering GmbH (Austria).

NANBIOSIS U8. Micro – Nano Technology Unit has been used for the deposit of thin layers (Polyimide) for the manufacture of flexible devices (U8-S05) and for the growth and transfer of graphene (U8-S02) in flexible device disks.

Related animation

Reference article:

Andrea Bonaccini Calia, Eduard Masvidal-Codina, Trevor M. Smith, Nathan Schäfer, Daman Rathore, Elisa Rodríguez-Lucas, Xavi Illa, Jose M. De la Cruz, Elena Del Corro, Elisabet Prats-Alfonso, Damià Viana, Jessica Bousquet, Clement Hébert, Javier Martínez-Aguilar, Justin R. Sperling, Matthew Drummond, Arnab Halder, Abbie Dodd, Katharine Barr, Sinead Savage, Jordina Fornell, Jordi Sort, Christoph Guger, Rosa Villa, Kostas Kostarelos, Rob Wykes, Anton Guimerà-Brunet, and Jose A. Garrido, Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes. Nature Nanotechnology, 2021. DOI: https://dx.doi.org/10.1038/s41565-021-01041-9

For more information:

Institut Català de Nanociència i Nanotecnologia (ICN2)
Marketing and Communication Department
Àlex Argemí, Head of Marketing and Communication
alex.argemi@icn2.cat; +34 635 861 543


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Graphene sensors read low-frequency neural waves associated with distinct brain states

Xavier Illa, Anton Guimrea y Eduard Masvidal, researchers of the CIBER-BBN group GAB Lab at IMB-CNM led by Rosa Villa, are coauthors of a study recently published in “Nature Communication”, in which it is demonstrated that graphene-based active sensor arrays are a mature technology for large-scale application in wide frequency band neural sensing interfaces. NANBIOSIS U8 Micro– Nano Technology Unit has been used in the development of the research.

This research has been carruied out within the framework of the European Project “Graphene Flagship. The scientists have developed a sensor based on CVD graphene that detects brain signals in a wide frequency band, from extremely low frequencies to high frequency oscillations. The sensor is biocompatible and could be used to measure and predict brain states. Furthermore, the graphene sensors could be used in chronic implants due to their high stability in the brain.

Further information: News by the Graphene Flagship website.

Article of reference:

Garcia-Cortadella R, Schwesig G, Jeschke C, Illa X, Gray AL, Savage S, Stamatidou E, Schiessl I, Masvidal-Codina E, Kostarelos K, Guimerà-Brunet A, Sirota A, Garrido JA. Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity.  Nat Commun 12, 211 (2021). https://doi.org/10.1038/s41467-020-20546-w

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Hybridization of men and machines, with Rosa Villa

Prof. Rosa Villa, Scientific Director of NANBIOSIS U8 Micro– Nano Technology Unit, and group leader of the research group of biomedical applications of ICNM–CSIC and CIBER-BBN, has participated in the program of National Radio of Spain “The Open Future: Biobots” led by Tato Puerto.

Following the recent presentation by a team of American scientists of the design of “reprogrammable organisms”, halfway between a robot and a living being, that is, an extraordinary living machine made from frog cells, the program of National Radio of Spain called “Open Future” has dedicated a session to explain what are “Biobots” and to generate debate and reflexion with experts like Prof, Rosa Villa.

Asked about the current outlook and futute of the “Hybridization of men and machines“, Rosa Villa has explained that in the area of ​​micro and nanotechnology, (where her group works), the hybridization takes place to make neural interfaces, to interrelate with the human brain registering many more signals from the brain and being able to offer patients greater mobility for artificial prosthetics or even other human enhancement activities. The main problem for this at a technological level is that a series of biological and material processes have to be carried out while these processes need to be easilly integrated by the human body. The functioning of the brain is still very unknown, the brain is a very closed box, very well protected and inaccessible but the amount of signals that are registered is spectacular. The latest technologies and materials, such as graphene, make it possible to build sensors with smaller electrodes that allow many signal points to be recorded in the brain at the same time, with a signal quality that was not possible to reach until now which allows scientists to know a series of high and low frequency signals that give very useful information from the brain, not only to know how it works, but also to predict diseases such as epilepsy or Alzheimer’s.

The program can be listen here, in Spanish

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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:

The hidden brain activity
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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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