H2020Individual fellowship2021–2023

PORTable STaNDOuTs · Perfused Organs-on-a-Chip integrated with TEER measurement technique: A novel approach towards studying non-targeted drug induced organ toxicity

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration: 2021-04-14 → 2023-04-13
EU contribution: €184,708
Participants: 1
Scheme: MSCA-IF

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Results in brief

Perfused Organs-on-a-Chip integrated with TEER measurement technique: A novel approach towards studying non-targeted drug induced organ toxicity

The growing global concern over the outbreak of new diseases and disease conditions makes it pertinent to synthesise new drug molecules to protect the society from any undesirable health conditions. The process of drug development is time–consuming, taking about 10 to 15 years and cost-ineffective, involving more than a billion Euros. To consider a newly synthesised drug molecule safe for human administration, the drug must undergo two stages, namely, preclinical and clinical trials in the drug developmental process. During the preclinical stages, the efficacy, toxicity and pharmacokinetics-pharmacodynamics (PK-PD) based data of the drugs are collected. It has been found that about one out of ten drugs tested fail in the clinical trials owing to inefficient and unsuitable models available for the preclinical trial stage of the drug development process. In the light of this, the EU-funded MSCA-IF project, ‘PORTable STaNDOuTs’, was aimed to develop a novel sensor-based electronic device that can be integrated on Organs-on-a-chip microfluidic platform to measure trans-endo(epi)thelial electrical resistance (TEER) measurements to replace the conventional time-consuming and cost-ineffective preclinical procedures in the drug development process. TEER measurement is rapid and non-invasive, and helps in assessing the integrity of the tissue layer barrier of different organs necessary for homeostasis in the human body. The developed novel device demonstrated the promising capability to measure TEER/impedance of the tissue layer of any organ system grown on a microfluidic platform. Thus, the developed device capable of supporting growth and monitoring of the 3D biological constructs within the microfluidic platform can be appropriately termed a microphysiological system (MPS).

Data: CORDIS, © European Union

Project objective

PORTable STaNDOuTs aims to develop a multiple Organs-on-a-Chip (MOOC) microfluidic device integrated with electrodes for carrying out Transepithelial electrical resistance (TEER) measurements. The key motivation for adopting such an approach is to develop a rapid, versatile and cost-effective prototype with ability for real-time monitoring to replace the conventional long and cost-ineffective preclinical procedures involved in the drug development process. On administration of an oral pharmaceutical drug, major organs that are involved in the absorption and metabolism of drug are intestine and liver. The drug is then distributed to different target organs such as brain, heart, lung, etc. Finally, the drug metabolites are eliminated from the human system with the help of kidney. Additionally, it has also been found that certain drug metabolites produced by the liver cause non-target drug induced organ toxicity. TEER measurement is a rapid and non-invasive technique for the real-time detection of pathophysiology. TEER indicates the integrity of the cell membrane barrier of different organs that is necessary for maintaining homeostasis within the human body. In view of this, we intend to fabricate a physiologically-mimicking perfused intestine-liver-kidney microfluidic chip with provision for carrying out in-chip TEER measurements. The device will be designed to consist of three compartments for organs namely, intestine, liver and kidney, independently equipped with electrodes for measuring TEER values to detect the integrity of cell membrane barriers in each organ compartment. The developed device will be then subsequently validated for its ability to study drug-induced nephrotoxity. Furthermore, the device will also be made versatile to incorporate other organs of interest to study non-target organ toxicity. Thus, the developed MOOC microfluidic device will surely boost the drug development process that will successively improve the health security of the society.

Original text from CORDIS.

Participants

CHERRY BIOTECH · MONTREUILCoordinatorFrance

PORTable STaNDOuTs · Perfused Organs-on-a-Chip integrated with TEER measurement technique: A novel approach towards studying non-targeted drug induced organ toxicity

Results in brief

Perfused Organs-on-a-Chip integrated with TEER measurement technique: A novel approach towards studying non-targeted drug induced organ toxicity

Project objective

Participants

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