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).

Compared to the pace of innovation in electronic consumer products, the pace of innovation for medical devices is lagging behind. It is the overarching objective of Moore4Medical to accelerate innovation in electronic medical devices. Moore4Medical emerging medical applications that offer significant new opportunities for the ECS industry including: active implantable devices (bioelectronic medicines), organ-on-chip, drug adherence monitoring, smart ultrasound, radiation free interventions and continuous monitoring. The new technologies will help fighting the increasing cost of healthcare by: reducing the need for hospitalization, helping the development of personalized therapies, and realizing intelligent point-of-care diagnostic tools. Moore4Medical will bring together 68 specialists from 12 countries who will develop open technology platforms for these emerging fields to help them bridge “the Valley of Death” in shorter time and at lower cost. Open technology platforms used by multiple users for multiple applications with the prospect of medium to high volume markets are an attractive proposition for the European ECS industry. The combination of typical MedTech applications with an ECS style platform approach will enhance the competitiveness for the emerging medical domains addressed in Moore4Medical. With value and IP moving from the technology level towards applications and solutions, defragmentation and open technology platforms will be key in acquiring and maintaining a premier position for Europe in the forefront of affordable healthcare

Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting 300 million people with a lifetime prevalence of 15%. Approximately one third of all MDD patients fail to respond to currently established treatments based on medication and psychotherapy, thus falling into the category of Treatment-Resistant Depression (TRD) patients. Electroconvulsive therapy (ECT), repetitive Transcranial Magnetic Stimulation (tRMS), Vagus nerve stimulation, deep brain stimulation (DBS) and transcranial focused ultrasound (tFUS) still show poor spatial resolution (ECT, tRMS, tFUS) or low network coverage (VNS, DBS), with average remission rates in clinical trials still lower than 30 %. Apart from the existing stimulation hurdles, reliable biomarkers for depression are needed as a diagnostic tool, and, in the case of NT, to determine the stimulation efficacy and allow for personalized treatment. The UPSIDE project proposes a minimally invasive, high spatial resolution and multi-brain region stimulation and recording system to largely exceed the capabilities of existing NT for depression. Our objective is to research and validate in vivo an hybrid neurotechnology consisting of an epidural focused ultrasound (eFUS) stimulator employing three-dimensional beamforming, and a high-density epidural EEG recording system. Epidural deployment of these devices will be enabled by novel methods for massive integration and miniaturization of high-performing piezoelectric ultrasound materials and high-fidelity organic bioelectronic materials with high energy-efficient complementary metal-oxide semiconductor (CMOS) technology in a biocompatible manner. The UPSIDE project will result in a demonstrator which will allow, for the first time, network stimulation and simultaneous biomarker readout in behavioral experiments with animal models featuring depression-like symptoms. This technological breakthrough will pave the way towards a personalized treatment for TRD.