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.

PHOENIX aims to revolutionise biomedical research by developing the next generation human-based Organs-on-chips (OoC). OoC is a promising technology potentially able to outperform conventional preclinical models in providing patho-physiologically relevant setting for investigating human diseases, thus tackling the limited translational value of animal testing. OoC wide adoption is currently hampered by poor maturation of cellular models and shortage of non-destructive readout methods. PHOENIX will take current OoC platforms to the next level, overcoming such limitations by integration of core technologies already validated by the Consortium, namely Electric Recording (3dMEA), Force Sensing (3dFORCE) and Mechanical Stimulation (3dMECH). Two platforms will be developed: i) μHeart, to model functional cardiac tissues, and ii) μNMC to model neuro-muscular circuits. PHOENIX ecosystem will be completed by satellite products and qualified against specific contexts of use in clinically and industrially relevant environments. PHOENIX potential will be showcased with two genetic pathologies as demonstrators: LMNA-cardiomyopathies and Freidreich’s Ataxia, conditions in which electrical instability and mechanical impairment play important roles. For each platform, two versions will be released (Base and Pro), addressing the need of identified customer segments (research labs and Pharma/Biotech). In line with the 3Rs, PHOENIX platforms represent the ideal clinically relevant tools to test drugs and gene therapies, leading to faster/safer development processes, reducing the need for animal testing. Robust dissemination, exploitation and communication activities will address both key stakeholders (OoC players, end-users, end-beneficiaries and regulatory bodies) and society at large, fostering acceptance, adoption, economic viability and regulatory compliance. PHOENIX will last 4 years with a Consortium comprising 9 partners (Academic, SMEs and LEs) from 4 EU Countries.