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.

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.

This project is the second in the series of EC-financed parts of the Graphene Flagship. The Graphene Flagship is a 10 year research and innovation endeavour with a total project cost of 1,000,000,000 euros, funded jointly by the European Commission and member states and associated countries. The first part of the Flagship was a 30-month Collaborative Project, Coordination and Support Action (CP-CSA) under the 7th framework program (2013-2016), while this and the following parts are implemented as Core Projects under the Horizon 2020 framework. The mission of the Graphene Flagship is to take graphene and related layered materials from a state of raw potential to a point where they can revolutionise multiple industries. This will bring a new dimension to future technology – a faster, thinner, stronger, flexible, and broadband revolution. Our program will put Europe firmly at the heart of the process, with a manifold return on the EU investment, both in terms of technological innovation and economic growth. To realise this vision, we have brought together a larger European consortium with about 150 partners in 23 countries. The partners represent academia, research institutes and industries, which work closely together in 15 technical work packages and five supporting work packages covering the entire value chain from materials to components and systems. As time progresses, the centre of gravity of the Flagship moves towards applications, which is reflected in the increasing importance of the higher - system - levels of the value chain. In this first core project the main focus is on components and initial system level tasks. The first core project is divided into 4 divisions, which in turn comprise 3 to 5 work packages on related topics. A fifth, external division acts as a link to the parts of the Flagship that are funded by the member states and associated countries, or by other funding sources. This creates a collaborative framework for the entire Flagship.

This proposal describes the third stage of the EC-funded part of the Graphene Flagship. It builds upon the results achieved in the ramp-up phase (2013 - 2016) and the first core project (2016 - 2018), and covers the period April 2018 - March 2020. The progress of the flagship follows the general plans set out in the Framework Partnership Agreement, and the second core project represents an additional step towards higher technology and manufacturing readiness levels. The Flagship is built upon the concept of value chains, one of which is along the axis of materials-components-systems; the ramp-up phase placed substantial resources on the development of materials production technologies, the first core project moved to emphasise components, and the second core project will move further towards integrating components in larger systems. This evolution is manifested, e.g., in the introduction of six market-motivated spearhead projects during the Core 2 project.

The launch of a novel drug to the market is preceded by clinical testing and validation both on animal in vitro and in vivo models. Animal models used in drug development have known methodological drawbacks leading to the failure of drugs. Further, animal tests are associated with ethical issues. Moreover, a strong bias in in-human testing still overlooks major population groups e.g. children, women, different ethical groups. It is estimated that 197,000 deaths per year in the EU are caused by Adverse Drug Reactions (ADRs) and the total cost to society of ADRs is €79 billion. The emerging Organ-on-Chip (OOC) field, an alternative to animal test, brings great potential for safe testing and validation: An OOC-systems consists of a 3D-microstructured channel network embedded on a small plastic device that simulates the mechanics and physiological response of an entire organ or organs. Project UNLOOC will develop, optimize, and validate a multitude of ECS-based tools to build OOC-models to replace animal and in-human testing. UNLOOC aims to combine three important characteristics for routine use of OOC models, i.e platforms that combine ECS-based technologies with established biological material, capitalize on AI, parallelized test set-ups allowing efficient high-throughput demands, and standardized procedures enabling reliable results. UNLOOC will develop ECS-based hardware and software tools and validate them in five Use Cases (UCs) performed in 10 European countries. The applications developed and validated will be used by academia and pharma industry to drive drug development, create cosmetics without animal test, personalized medicine and gain new insights into disease. Given the large OOC market, these solutions have great economic value, on average it would result in cost reduction of up to $169M and $706M per new drug reaching the market and will put Europe at the forefront of this booming research field (see impact section for details).