The interplay between viral infection, host response, development of (hyper)inflammation and cardiovascular injury in COVID-19 is currently poorly understood which makes it difficult to predict which patients remain with mild symptoms only and which patients rapidly develop multi organ failure. The solution offered by DIGIPREDICT is an Edge Artificial Intelligence (AI) based, high-tech personalized computational and physical Digital Twin vehicle representing patient-specific (patho)physiology, with embedded disease progression prediction capability, focusing on COVID-19 and beyond. DIGIPREDICT proposes the first of its kind Digital Twin, designed, developed and calibrated on i) patient measurements of various Digital Biomarkers and their interaction, ii) Organ-On-Chips (OoCs) as physical counterpart using patient blood for personalized screening and iii) integration of those physiological readouts using AI at Edge technologies. The final goal is to identify and validate patient-specific dynamic digital fingerprints of complex disease state and prediction of the progression as a basis for assistive tools for medical doctors and patients. Using and improving state-of-the-art OoCs and Digital Biomarkers (for physiology and biomarkers in interstitial fluid) we will measure detailed response to viral infection. By closely monitoring the response with wearable multi-modal Edge AI patches, we aim to predict in near real-time the progression of the disease, support early clinical decision and to propose patient-specific therapy using existing drugs. We will combine scientific and technical excellence in a highly multi- and inter-disciplinary project, bringing together medical, biological, electronical, computer, signal processing and social science communities around Europe to setup Digital Twin at Edge. We will enable an Edge-to-Cloud vision, significantly advancing current state of the art and setting up a new European community for researching and applying Digital Twins.

Brain pathologies are highly complex disorders. Despite recent progress, their prognosis is grim, defining a high societal challenge. Bridging life sciences, bio-nanotechnology, engineering and ICT, GLADIATOR promises a vanguard and comprehensive theranostic (therapeutic+diagnostic) solution for brain malignancies. Through a multi-faceted breakthrough, GLADIATOR will provide, for the first time, a working prototype of a complete, autonomous and clinically applicable, nanonetwork-based, Molecular Communications system based on the conceptual framework of Externally Controllable Molecular Communications (ECMC). Using Glioblastoma Multiforme tumours, the most detrimental brain pathologies, as a proof-of-concept case, GLADIATOR will implement a platform of cell-based and electronic components. Implantable autologous organoids of engineered neural stem cells (iNSCs) will release rationally designed exosomal bio-nanomachines, delivering reprogramming (therapeutic) miRNAs and building nanonetworks. Interfering with the underlying biological environment, the nanonetworks will define a revolutionary intervention. A hybrid bio-electronic interface, consisting of coupled external and implantable devices, will enable communication channels with host-derived fluorescent bio-nanomachines via micro-optoelectronic sensors. The cellular, sub-cellular and electronic components will be integrated into a wireless ECMC network. This system will autonomously monitor the spatiotemporal tumour evolution and recurrence and generate, on demand, appropriate reprogramming interventions, by radiofrequency stimulation of iNSC renewal. A paradigm shift in Oncology Research is anticipated via the supra-discipline of “bio-nanomachine diagnostics”. GLADIATOR establishes a radical long-term vision leading to a drastic change in cancer therapy, also ushering the emergence of the ECMC field and transforming the burgeoning industry of Internet of Nano-bio-things, with high socioeconomic impact.

There remain urgent and unmet needs for the treatment of neurological diseases. Epilepsy is a serious, chronic brain disease characterized by recurrent seizures. Closed-loop, implanted devices offer ways to reduce seizures in drug-resistant patients but their efficacy is poor and they interrupt seizures only after they begin. PRIME capitalizes on a breakthrough discovery that transfer RNA (tRNA) fragments, a novel class of noncoding RNA, increase in patients in advance of when a seizure occurs. We propose to engineer human cells to respond to tRNA fragment elevations as the trigger for pre-emptive release of glial-derived neurotrophic factor (GDNF), a seizure-suppressing and disease-modifying treatment. Artificial Intelligence (AI) algorithms will be used to integrate OR or AND logic gate functions in the switching process, depending on the quantity and type of tRNA fragments and timing of their release in a given epileptic network and a second, fail-safe calcium-dependent pathway will allow GDNF release in the event of a breakthrough seizure. This enables a precise level of personalization in the design of the bio-computing cells, which will be encapsulated into a membrane device within the microenvironment scaffold, enabling the engineered cells to co-exist with natural brain tissue. Validation of the bio-computing cells will be tested in both in vitro microfluidic organ-on-a-chip as well as in vivo tests for effects on spontaneous seizures in rodents with epilepsy. PRIME’s results will provide a transformational diagnostic-therapeutic treatment for epilepsy and other neurological diseases that feature disrupted neuronal network function.