Periodic Reporting for period 1 - UNLOOC (Unlocking data content of Organ-On-Chips)
Periodo di rendicontazione: 2024-05-01 al 2025-04-30
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).
Key impacts of UNLOOC technology are: i) More efficient drug development, ii) Improved drug safety, iii) Reduced reliance on animal testing, iv) Personalised medicine, v) New insights into disease mechanisms, vi) New release procedures for drugs and chemicals, vii) New tools to release chemicals. Towards these goals all technical WPs and UCs have delivered significant impact: WP2 covered the roadmaps for all technologies involved, sensors as well as components and modules (D2.1 – D2.4) the requirements for all UCs (D2.4 – 2.10) the validation plan (D2.10) and requirements for the multi-level data analysis (D2.11) serving as foundation for all technical work and impact generated. WP3 developed a multitude of hardware from sensor, microfluidic devices, instrument modules, optical elements, electronics or biological and chemical components. Instrument modules and microfluidics together with subcomponents are summarized in D3.1. WP3 hardware development and its evaluation resulted already in three PEER reviewed publications. WP 4 focussing at software and AI compiled the roadmap guiding the development for this WP and its interactions (D4.8) as well as the data management definition report (D4.2). The system level development in WP5 just started and the main work will be carried out in year 2 and 3, same is valid for WP6. WP7 covers data security, data management and ethics and is interlinked with the work in the technical WPs. Main scientific impact that should be highlighted are the realization of a 4-donor-plate in UC1, lipidomics, RAMAN spectroscopy and lattice light sheet results on the analytical end in UC1. UC2a achieved the release of the first integrated SOMP-design (singel-organ multiwell plate) and provided minimized versions to the partners to start with the integration of epithelium- and cancer-cells. UC2b (MOMP – Multi-organ multi-well plate) can report a a scaled-down format for flexible integration and sensor testing that might serve as development platform for further projects. Special highlight is the development of a membrane not only having defined pore sized, but also a defined position and these membranes can be stacked together forming various multilayer pore-size arrays. UC3 (skin-on-chip) highlights the microfluidic modules for the various sensors in this UC ranging from electrochemical-, TEER to optical sensors and the development of special electronic features. Two of the three PEER reviewed papers resulted from UC3. UC4 (Blood-brain-barrier) provided the third scientific publication and has to report a variety of prototyped organ-on-chip modules, sensor developments, an incubator prototype as well as on application data and data analysis. UC5 (lung-on-chip) scientific impact includes a prototyped perfusion lid, the proof-of-concept for bio-impedance measurements, implementation of donor collection (two hospitals agreed to provide 40 donors), and finally UC5 provided data for the analytical engine and served as first test case giving guidance to the other UCs.
Highlights in this area for year 1:
1. Several of UNLOOC-project members gathered together and were granted an R&D project working on aspects of standardization of organ-on-chip systems: MFMET II
2. Internationalisation: A multitude of exhibitions, conferences, oral and poster presentation on international level demonstrated the outcome of UNLOOC
3. Technical highlights beyond the state of the art are: First diversity panel in UC1, first integrated UC2a design, new porous membrane realization technology in UC2b, microfluidic modules and a multitude of new sensors in UC3, novel incubator and chip modules in UC4 or the incubation lid in UC5.
1. Several of UNLOOC-project members gathered together and were granted an R&D project working on aspects of standardization of organ-on-chip systems: MFMET II
2. Internationalisation: A multitude of exhibitions, conferences, oral and poster presentation on international level demonstrated the outcome of UNLOOC
3. Technical highlights beyond the state of the art are: First diversity panel in UC1, first integrated UC2a design, new porous membrane realization technology in UC2b, microfluidic modules and a multitude of new sensors in UC3, novel incubator and chip modules in UC4 or the incubation lid in UC5.