ANR 24 ModerniT

Physiological Microsystems with on-chip and off-line characterization of nano-pollutants evolution in biofluids and impacts on endoThelium and hemostasis

12/2024 – 06/2028
Budget: 500 k€
WP1 part: 170 k€
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Objectives

The ANR PRC (collaborative project) ModerniT (for Physiological Microsystems with on-chip and off-line characterization of nano-pollutants evolution in biofluids and impacts on endoThelium and hemostasis) aims to study nano-pollutants (NaPos).
NaPos are widely present in our environment with a recognized impact on the health of the population. It has been shown that NPs are able to enter the blood vessels, increase risk of cardiovascular diseases, induce endothelial rupture and alter the human body ability to self-repair including hemostasis. However, the mechanisms between the exposure to NPs and the effects on the organism are still poorly understood. The objective of the ModerniT project is therefore to develop a lab-on-chip type platform to follow the evolution of NPs in the bloodstream and to evaluate their vascular toxicity.
To achieve this objective the project will be divided into three work packages (WP):

• WP1: A set of different NaPos used as reference will be first be fully characterized focused on basic physicochemical characteristics (sizes, charges, chemistry etc.) in order to select and get a library of the most representative NaPos. Then, these nanomaterials will be incubated in biofluids, in static conditions, with increasing complexity (from water to whole blood) in order to study their behaviors and the formation of protein coronas.
• WP2: NaPos will be injected into a microfluidic circuit reproducing the vascular network. They will be transported in channels with a simplified biofluid (PBS+proteins, plasma) controlled in flowrate, pH and temperature. Optical dynamic scattering sensor will be integrated in the microfluidic device to monitor in-situ and in real time the evolution of the hydrodynamic size of NaPos. Electrodes will also be integrated in the device to follow the modification of surfaces charges. After circulation, physicochemical characterizations of NaPos as well as protein coronas formation will be repeated to compare them to the reference values.
• WP3: Selected NaPos will be introduced into 3 different microdevices for the detailed evaluation of vascular toxicity. A first microfluidic device designed as an organ-on-a-chip will reproduce the interaction of NaPos in flow with human endothelial cells and 3D models of blood capillaries to evaluate the impact of NaPos on human vascular tissues. Then, the effects of the modified NPs on primary and global hemostasis phenomena will be evaluated.

ANR PRC is a grant funded by the Agence Nationale de la Recherche Scientifique dedicated for collaborative research.

Main results

Groups involved

Publications of the project