Pre- and post-marketing data on drug side effects show that neurotoxicity and cardiotoxicity are frequently missed or underestimated during pre-clinical testing. Neuro- and cardiotoxicity caused by pollutants including pesticides and industrial chemicals are equally difficult to assess. This results in suffering of individuals and in a considerable burden to society. One of the main reasons is that currently available testing approaches have several shortcomings, including sensitivity, human-relevance and suitability for non-invasive long-term recording. This project will develop a revolutionary and fully non-invasive technology to record in-vitro electrical signals from human neuronal and cardiac cells. High spatial resolution, combined with parallel recording of electrical signal coordination and propagation among thousands of neurons or cardiomyocytes, will allow the assessment and quantification of subtle disturbances by toxicants from the drug, pesticides and industrial chemicals sectors. The full non-invasiveness will enable, for the first time, the long-term functional in-vitro monitoring of biologically relevant cellular models, paving the way toward the reliable assessment of chronic toxicities. The novel biosensing technique (VICE) will emerge from the efforts of nanotechnology developers in close collaboration with toxicologists and specialists in surface functionalization and electrophysiological data acquisition. With its joint expertise, the consortium will continuously refine the VICE biosensor with innovative functionalities while thoroughly testing it in toxicology and pharmacologicy experiments. This will not only lead to a revolutionary approach to monitor functions of heart and brain cells, but also ensure the direct applicability to relevant questions in safety sciences and pharmacology. Ultimately, the project will elicit the future development of a whole new class of biosensors based on the groundbreaking concept of VICE.

There is a need for a paradigm shift in the treatment of drug-resistant epilepsy. Several routes have been explored to modulate or silence dysfunctional neural circuits, through genetic, electrical, magnetic or optical means. All have serious limitations due to the unphysiological mechanisms used to regulate neuronal activity. In IN-FET, we address this issue by manipulating the elementary building blocks of cell excitability: ions. IN-FET tackles the visionary idea of altering neuronal firing and synaptic transmission by direct ionic actuation at the microscopic scale, while monitoring cell responses by arrays of nanoscale transistors. We will develop and test, in vitro, the use of active polymers to trap or release electrochemically specific ions in the extracellular milieu surrounding neurons. These will be integrated with ion sensors and ultra-sensitive nanowire arrays, offering closed-loop regulation of cellular electrical activity. We will deliver for the first time a device that can physiologically modulate the neuronal membrane potential, the synaptic release probability, and glutamatergic NMDA receptors activation by altering potassium, calcium, and magnesium ionic concentrations in a controlled and spatially-confined manner. High-resolution simultaneous probing of cell activity will be performed by Si-nanowire vertical transistors, penetrating the membranes and detecting the cell electrical activity at unprecedented spatial and temporal resolutions. In conclusion, IN-FET's multidisciplinary consortium brings together state-of-the-art electrochemistry, 3-d nanofabrication, nanoelectronics, and numerical simulations, and combines neuronal biophysics to device modeling. IN-FET will thus establish the proof-of-principle for a breakthrough biocompatible neuromodulation technology, with a clear impact for future brain implants for epilepsy treatment, advancing neuroscience, biomedical microsystems engineering, and nano-neurotechnology.

The goal of BrainCom is to develop a new generation of neuroprosthetic devices for large-scale and high density recording and stimulation of the human cortex, suitable to explore and repair high-level cognitive functions. Since one of the most invalidating neurospychological conditions is arguably the impossibility to communicate with others, BrainCom primarily focuses on the restoration of speech and communication in aphasic patients suffering from upper spinal cord, brainstem or brain damage. To target broadly distributed neural systems as the language network, BrainCom proposes to use novel electronic technologies based on nanomaterials to design ultra-flexible cortical and intracortical implants adapted to large-scale high-density recording and stimulation. The main challenge of the project is to achieve flexible contact of broad cortical areas for stimulation and neural activity decoding with unprecedented spatial and temporal resolution. Critically, the development of such novel neuroprosthetic devices will permit significant advances to the basic understanding of the dynamics and neural information processing in cortical speech networks and the development of speech rehabilitation solutions using innovative brain-computer interfaces. Beyond this application, BrainCom innovations will enable the study and repair of other high-level cognitive functions such as learning and memory as well as other clinical applications such as epilepsy monitoring using closed-loop paradigms. BrainCom will be carried out by a consortium assembled to foster the emergence of a new community in Europe acting towards the development of neural speech prostheses. Thanks to its high interdisciplinarity involving technology, engineering, biology, clinical sciences, and ethics, BrainCom will contribute advances to all levels of the value chain: from technology and engineering to basic and language neuroscience, and from preclinical research in animals to clinical studies in humans.

This proposal describes the third core project of the Graphene Flagship. It forms the fourth phase of the FET flagship and is characterized by a continued transition towards higher technology readiness levels, without jeopardizing our strong commitment to fundamental research. Compared to the second core project, this phase includes a substantial increase in the market-motivated technological spearhead projects, which account for about 30% of the overall budget. The broader fundamental and applied research themes are pursued by 15 work packages and supported by four work packages on innovation, industrialization, dissemination and management. The consortium that is involved in this project includes over 150 academic and industrial partners in over 20 European countries.

The 2D Experimental Pilot Line (2D-EPL) project will establish a European ecosystem for prototype production of Graphene and Related Materials (GRM) based electronics, photonics and sensors. The project will cover the whole value chain including tool manufacturers, chemical and material providers and pilot lines to offer prototyping services to companies, research centers and academics. The 2D-EPL targets to the adoption of GRM integration by commercial semiconductor foundries and integrated device manufacturers through technology transfer and licensing. The project is built on two pillars. In Pillar 1, the 2D-EPL will offer prototyping services for 150 and 200 mm wafers, based on the current state of the art graphene device manufacturing and integration techniques. This will ensure external users and customers are served by the 2D-EPL early in the project and guarantees the inclusion of their input in the development of the final processes by providing the specifications on required device layouts, materials and device performances. In Pillar 2, the consortium will develop a fully automated process flow on 200 and 300 mm wafers, including the growth and vacuum transfer of single crystalline graphene and TMDCs. The knowledge gained in Pillar 2 will be transferred to Pillar 1 to continuously improve the baseline process provided by the 2D-EPL. To ensure sustainability of the 2D-EPL service after the project duration, integration with EUROPRACTICE consortium will be prepared. It provides for the European actors a platform to develop smart integrated systems, from advanced prototype design to small volume production. In addition, for the efficiency of the industrial exploitation, an Industrial Advisory Board consisting mainly of leading European semiconductor manufacturers and foundries will closely track and advise the progress of the 2D-EPL. This approach will enable European players to take the lead in this emerging field of technology.