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Long-term Microphysiological Sample Imaging for Evaluation of Polypharmacy in Liver

DELIVERy is an EIC pathfinder project aimed to build a radically new technology for personalized health care, which provides, for the first time, the possibility to investigate polypharmacy on individual patients.  The technology is combining micro-physiological systems (MPS) and super-resolution microscopy to allow physicians, biomedical scientists, and researchers to determine the phenotype at the nanoscale of human liver models and biopsies.

Objectives

  • The DeLIVERy project aims to develop a modular high-end and integrated MPS platform for high-throughput multi-drug testing of human liver cells and liver biopsies capable of maintaining the phenotype and assessing human liver tissue for a minimum of 14 days.
  • To develop novel compact high-speed super-resolution and label-free optical technologies that transcend the 250nm optical diffraction barrier for the dynamic visualization of morphological biomarkers in living human tissue sections permitting live imaging in the near-infrared spectral range for high-speed volumetric assessment.
  • To develop innovative technologies/protocols capable of utilizing human liver tissues for long-term drug testing with constant monitoring, which will reduce animal testing.
  • To assess the effects of polypharmacy on novel human liver in vitro models.

Our role

Conception and development of a  multiparametric and  MPS platform allowing liver biopsies, 3D models and cells phenotype maintenance and integration with the imaging system.

Support on the MPS models and drug testing protocols development to the biological and medical partners.

Microphysiological System (MPS)

As part of WP1 of the DeLIVERy project, Cherry Biotech are working to develop the first multiparametric Microphysiological System (MPS) platform for the culture and treatment of patient-specific cells for use with the biological models developed within the project.

Develop a user-friendly, long-term environmental control platform for complex MPS models (such as liver biopsies, spheroids or vascularized liver endothelial 3D ensembles)

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Tightly control the biophysical parameters (shear stress, dissolved o2, pH, temperature)

 Integration with imaging modalities
To achieve this, modules are being developed to control:

  • pH
  • Dissolved oxygen concentration
  • Temperature
  • Microfluidic flow control
  • Shear stress
  • Pressure

To date, prototypes of the custom platform have been developed, characterised and provided to the project partners in the DeLIVERy project (in Bielefeld, Tromso and Brussels). A representation of this platform can be seen in figure 1.

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Fig 1. CubiX Live Imaging

Expected Results

  • Automated multiparametric MPS platform allowing for the first-time accurate control and monitoring of dissolved gases, pH, temperature and shear stress at the MPS models microenvironments.
  • Disruptive integrated imaging system to achieve real-time imaging with near-infrared and nanoscopic capabilities of liver models in the MPS system (Figure 1).
  • Animal testing model substitute for drugs and multiple drugs long-term effects on the liver
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Representation of the various work packages within the project
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Example of the effect of a research compound on liver fenestrations (LSEC nanosctructures used as morphological biomarkers). SIM images of LSEC with cell membrane stain, 40x40μm. Credit: Karolina Szafranska, University of Tromso.
Pierre Gaudriault, PhD Late founder and Scientific Chief Business Developer
Chloe Porcier Chief Human Resources
Jeremy Cramer, PhD Co-Founder & CEO
Outreach and Cherry Biotech Global Strategy Fit Responsible
Jean-Robin Peiteado Mechatronics Project Manager
Alberto Ortega Responsible for Production, Industrialization and After-sales Service Manager
Mathilde Cadoux, PhD Immunologist Project Manager
Dario Fassini, PhD Responsible for the biological facilities and development of biological models
Harry Dawson, PhD Scientific Project Manager
EIC-logo-collaborations

This project has been funded by The European Union, under the grant agreement n° 101046928.

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them.

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