Automated canceR-on-A-CHip orgaN-specific metastatIc spreaD

Informations projet

ARACHNID

N° de convention de subvention: 101158013

DOI

10.3030/101158013

Projet clôturé

Date de signature de la CE 27 Juin 2024

Date de début 1 Juillet 2024

Date de fin 31 Decembre 2025

Financé au titre de

• European Research Council (ERC)

Coût total

Aucune donnée

Contribution de l’UE

€ 150 000,00

Coordonné par

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

Periodic Reporting for period 1 - ARACHNID (Automated canceR-on-A-CHip orgaN-specific metastatIc spreaD)

Période du rapport: 2024-07-01 au 2025-12-31

Résumé du contexte et des objectifs généraux du projet

Cancer remains one of the leading causes of death worldwide and continues to pose major challenges for biomedical research and drug development. Despite decades of progress, most experimental cancer therapies fail during development, largely because existing preclinical models cannot accurately reproduce complex biological processes such as tumor growth and metastasis. Conventional laboratory models rely either on simplified cell cultures that poorly reflect physiological environments or on animal models that are costly, ethically sensitive, and not always predictive of human responses.
Microfluidic “organ-on-chip” (OoC) technologies have emerged as promising tools to recreate aspects of human physiology in controlled laboratory systems. These platforms allow cells to be cultured in miniaturized environments where physical and biochemical conditions can be precisely regulated. However, many existing systems remain limited in flexibility and scalability and cannot easily reproduce dynamic multi-tissue interactions such as those occurring during metastatic dissemination.
The ARACHNID project addresses this challenge by developing an automated microfluidic platform designed to model key aspects of tumor progression and metastatic dissemination in vitro. The system integrates multiple cell culture chambers connected through programmable microfluidic channels regulated by microvalves, enabling controlled communication between cellular compartments and dynamic modulation of the microenvironment.
The objective of this PoC project was to transform the initial research prototype into a robust and reproducible platform capable of supporting biological experiments relevant to cancer research and drug testing. By improving the ability to model tumor behavior in vitro, ARACHNID aims to contribute to more predictive preclinical testing of anticancer therapies and support the development of alternative methods that may reduce reliance on animal experimentation.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

During this PoC project, the ARACHNID platform was further developed and validated as a microfluidic system capable of modeling tumor-microenvironment (TME) interactions relevant to metastatic processes and drug testing. Activities focused on engineering optimization, system automation, fluidic characterization, and biological validation using relevant cellular models.
The device architecture was refined through several design iterations to ensure reliable operation and reproducible experimental conditions. Attention was devoted to the geometry of the main and secondary culture chambers and the connecting microfluidic channels, enabling controlled communication between compartments.
A key technical achievement was the development of an automated control system enabling programmable regulation of microvalves within the device. The control software was fully redesigned and implemented in Python, replacing the earlier MATLAB-based prototype. This transition removed reliance on proprietary software and enabled release of the control framework as an open-source tool, improving accessibility and reproducibility.
Mechanical testing defined safe pressure ranges for microvalve actuation and confirmed device stability under cyclic operation. Fluidic characterization demonstrated predictable relationships between applied pressure and flow behavior, confirming reliable microfluidic control.
Biological validation experiments confirmed compatibility of the platform with multiple cancer-related cell models. Several cell lines, including neuroblastoma cells and cell types representing metastatic target environments, were successfully cultured in the device.
Preliminary drug testing experiments were conducted in collaboration with the biotechnology company Biogenera S.p.A. Tumor cells cultured in the system were exposed to candidate therapeutic compounds, including BGA002, a MYCN-targeted drug under development for neuroblastoma. Fluorescence-based viability assays demonstrated the ability of the platform to detect differential drug responses across cell lines, supporting its potential use in preclinical drug screening.
A major outcome of the project was the protection of the core technology through intellectual property. The automated microfluidic platform and associated methods are protected by Italian industrial invention patent n. 102024000020743. In coordination with the University of Padova Technology Transfer Office, international protection has also been pursued through a PCT application (PCT/IB2025/059295, filed 17 09 2025) extending protection beyond the national level.
Overall, the PoC successfully advanced ARACHNID from a research prototype toward a robust experimental system capable of supporting controlled studies of TME interactions

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

ARACHNID advances the state of the art in tumor-on-chip technologies by enabling selective and time-resolved control of communication between tumor and metastatic target environments through automated microvalve regulation. Most existing microfluidic cancer models rely on static or continuously perfused systems that cannot dynamically control signaling interactions between compartments. ARACHNID instead allows programmable modulation of inter-compartment communication, providing a flexible framework for studying TME interactions.
Experimental results demonstrate that the platform can operate reliably under controlled pressure conditions while maintaining viable cultures across multiple tumor and stromal cell lines. Biological experiments confirmed compatibility with relevant cell models and demonstrated the ability to detect differential responses to therapeutic compounds. Drug testing experiments performed with Biogenera further demonstrated the platform’s capacity to capture cell-line-specific treatment responses.
The project also achieved significant progress in intellectual property protection and technological readiness. The ARACHNID platform is protected by Italian patent n. 102024000020743, and international protection has been pursued through PCT application PCT/IB2025/059295. These steps strengthen the technology’s commercial positioning and support future development.
Further uptake of the platform will require expanded biological validation across additional tumor models, benchmarking against other OoC systems, and improvements in manufacturability and scalability. Engagement with industrial stakeholders and regulatory initiatives supporting New Approach Methodologies (NAMs) will also facilitate adoption in preclinical research.
Building on the results of this PoC, a follow-up proposal has been submitted to the EIC Advanced Innovation Challenges (EIC-AIC) programme to further validate the technology through structured benchmarking and application-driven testing. The proposed project involves industrial stakeholders including Biogenera S.p.A. and Champions Oncology, a CRO specializing in translational oncology models.
Overall, the ARACHNID PoC project demonstrated the technical feasibility, biological applicability, and initial commercial potential of the platform, establishing a foundation for further validation and industrial deployment.

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