Project Actions

A modular methodology to revolutionize human-based disease modelling

Action 1

PHOENIX Platforms Development

Building µHeart and µNMC from MVP prototypes to PDMS-free Base/+ and high-throughput Pro versions.

At a Glance
Timeline
M1 – M36
Action Leader
MICRONIT
Core Technology
3dMECH, 3dMEA, 3dFORCE

Action 1 focuses on the engineering and biological development of the two core PHOENIX platforms: µHeart (cardiac) and µNMC (neuromuscular circuitry). The goal is to move from initial Minimum Viable Products (MVP) based on established technologies to advanced, industrially-relevant versions. These include the Base/+ versions, which utilize PDMS-free materials to avoid drug absorption, and the Pro versions, optimized for high-throughput screening. Each platform integrates mechanical stimulation, electrical recording, and force sensing to recapitulate human physiology with unprecedented precision.

Key Outputs

  • Validated µHeart and µNMC MVP prototypes.
  • PDMS-free, automation-compatible Base/+ platforms.
  • High-throughput Pro platforms for industrial screening.

Work Packages

  • WP1: Development of MVP versions (Lead: POLIMI, M1–12)
  • WP2: Development of Base/+ versions (Lead: TU Delft, M2–36)
  • WP3: Development of Pro versions (Lead: MICRONIT, M7–36)
Action 2

PHOENIX satellite products

Controllers, readout systems, and commercial-use gene-edited iPSC lines powering the PHOENIX ecosystem.

At a Glance
Timeline
M2 – M36
Action Leader
NMI
Enables
Base/+ manual & Pro automated workflows

This action develops the modular hardware and biological resources required to operate the PHOENIX platforms effectively. It includes the uBox-4 (the mechanical stimulation controller), high-precision Flow Controllers for automated fluid management, and advanced Read-out systems for real-time data acquisition. Additionally, Action 2 delivers a library of gene-edited iPSC lines (healthy and diseased) to ensure biological standardization across the consortium and for future commercial users.

Key Outputs

  • Integrated Flow Controller and uBox-4 systems.
  • Advanced electrophysiological and force read-out hardware.
  • Library of standardized gene-edited cell lines.

Work Packages

  • WP4: Development of entry-level satellite products (Lead: MCS, M2–18)
  • WP5: Development of upgraded satellite products (Lead: NMI, M2–36)
Action 3

PHOENIX demonstrators

Clinically relevant disease models on PHOENIX platforms: LMNA-cardiomyopathies and Friedreich's Ataxia.

At a Glance
Timeline
M2 – M48
Action Leader
CNR
Clinical Leads
ICH (Humanitas), CNR

Action 3 provides the clinical proof-of-concept for the PHOENIX ecosystem. We implement two major genetic disease models: LMNA-cardiomyopathies (LMNA-CMP), characterized by electrical and mechanical dysfunction, and Friedreich's Ataxia (FRDA), focusing on neuromuscular circuit impairment. By comparing results from our platforms with clinical patient data, we demonstrate the predictive power of human-based in vitro models over traditional animal testing.

Key Outputs

  • Functional LMNA-CMP cardiac model on µHeart.
  • Pathological FRDA neuromuscular model on µNMC.
  • Comparison reports between in vitro data and clinical patient cohorts.

Work Packages

  • WP6: Setup of healthy cardiac and NMC models (Lead: CNR, M2–18)
  • WP7: Implementation of pathological demonstrators within μHeart and μNMC MVP (Lead: ICH, M14–24)
  • WP8: Unravelling mechanisms of pathologies related to main disease phenotypes (Lead: ICH, M25–36)
  • WP9: Unravelling mechanisms of pathologies related to secondary disease phenotypes (Lead: CNR, M37–48)
Action 4

Testing of PHOENIX platforms

End-user driven testing, SOPs, and qualification in industrial and regulatory contexts.

At a Glance
Timeline
M13 – M48
Action Leader
BIOMIMX
Focus
Stability, Reproducibility, QC

This action ensures that PHOENIX platforms are ready for the market and regulatory acceptance. Through extensive alpha-testing and cross-site validation, we establish Standard Operating Procedures (SOPs) for every component of the ecosystem. The focus is on verifying the stability and reproducibility of the readouts when used by different operators, ensuring that the platforms provide reliable data for drug screening and toxicity evaluation.

Key Outputs

  • Comprehensive SOPs for platform operation and data analysis.
  • Qualification reports for the Base/+ and Pro versions.
  • Cross-site validation data demonstrating inter-laboratory reproducibility.

Work Packages

  • WP10: Establishment of the initial setups (Lead: BIOINTAXIS, M13–18)
  • WP11: Alpha-testing of the Base/+ versions (Lead: BIOMIMX, M19–36)
  • WP12: Qualification of the Pro versions (Lead: NMI, M31–48)
Action 5

DCES, Impact & Management POLIMI META

Ensuring responsible innovation, dissemination, business exploitation, and ethical compliance.

At a Glance
Timeline
M1 – M48
Action Leader
POLIMI
Includes
POLIMI-META (SSH), Ethics, Exploitation

Action 5 coordinates the strategic impact and governance of PHOENIX. It manages Dissemination, Communication, Exploitation and Societal Engagement to maximize visibility among scientific and industrial communities and foster technology transfer. Crucially, this action includes Ethics Requirements and Social Sciences and Humanities (SSH) research led by POLIMI-META, investigating the ethical and socio-economic barriers to the adoption of non-animal models in medical research.

Key Outputs

  • Strategic Dissemination and Communication Plan.
  • Exploitation Strategy and Intellectual Property (IP) management.
  • Ethical compliance reports and SSH impact analysis on the 3Rs transition.

Work Packages

  • WP13-15: Project management (Lead: POLIMI, M1–48)
  • WP16-18: Dissemination, Communication, Exploitation and Societal engagement (Lead: POLIMI, M1–48)
  • WP19: Ethics Requirements (Lead: POLIMI, M1–48)
Action 6

Safety Evaluation (PHOENIX-SE) Hop-On

Scaling-up through low-cost screen-printed electronics for high-throughput cardiac safety screening.

At a Glance
Timeline
M13 – M48
Action Leader
TECSR
Focus
Scalability & Regional Impact (Widening)

Introduced through the Hop-On facility, Action 6 addresses the industrial need for scalable and cost-effective safety screening. We develop µSafeHeart, a specialized version of the cardiac platform utilizing low-cost screen-printed electrodes. This allows for massive scaling of cardiac safety and toxicology tests, making human-based in vitro screening accessible to a wider range of pharmaceutical players and CROs. This action also strengthens the project's impact in the Widening region by establishing advanced manufacturing and testing capabilities in Serbia.

Key Outputs

  • Design and fabrication of low-cost screen-printed electrodes.
  • Validated µSafeHeart platform for routine toxicology screening.
  • Impact report on the adoption of PHOENIX technologies in Southeast Europe.

Work Packages

  • WP20: μSafeHeart Platform for Cardiac Safety Screening I (Lead: TECSR)
  • WP21: μSafeHeart Platform for Cardiac Safety Screening II (Lead: TECSR)