Tracking the Dynamics of Human Metabolism using Spectroscopy-Integrated Liver-on-Chip Microdevices

Project Information

OCLD

Grant agreement ID: 681870

DOI

10.3030/681870

Project closed

EC signature date 7 July 2016

Start date 1 October 2016

End date 30 September 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 118 175,00

EU contribution

€ 2 118 175,00

Coordinated by

THE HEBREW UNIVERSITY OF JERUSALEM
Israel

Periodic Reporting for period 4 - OCLD (Tracking the Dynamics of Human Metabolism using Spectroscopy-Integrated Liver-on-Chip Microdevices)

Reporting period: 2021-04-01 to 2021-09-30

Summary of the context and overall objectives of the project

The natural cycle of day and night on our planet introduces inherent cycles to our local environment. These cyclical differences in light, temperature and food availability produce hormonal oscillations in higher organisms that allow us to better prepare for morning activity as well as prolonged fasting during the night. Disruption of these circadian rhythms leads to metabolic syndrome, obesity and type-2 diabetes. These metabolic diseases are pronounced in nightshift workers and are exacerbated by widespread light pollution. While current work on circadian rhythms focuses on animal models, differences in metabolism, physiology and genetics make it difficult to translate these findings to clinical results. In this project we sought to develop a three-dimensional models of human organs that maintain natural metabolic rhythms in a micro fluidic environment that mimic human physiology.

Our model successfully captured metabolic oscillations in a 3D model of the human liver, as well as the onset of circadian rhythms in a 3D model of a developing embryo. This proprietary technology was patented at the Hebrew University of Jerusalem and licensed to Tissue Dynamics, a groundbreaking Organ-on-Chip company developing the first physiological bioanalyzer. The last 18 months of the project included major breakthroughs identifying novel metabolic mechanisms of drug induced kidney and cardiac injury as well as identified virus-induced lipotoxicity as a cause of lung damage in COVID-19.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We integrated in line metabolic sensors in our liver on chip microdevice, enabling a real time analysis of metabolic fluxes. This work was published with L’Oreal (Paris, France) on the cover of Lab Chip, 2019. We developed an automated flow control unit together with Fluigent (Paris,France) capable of oscillating hormones and temperature in organ on chip microdevices. This technology was submitted as a patent application and licensed to Tissue Dynamics Ltd.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We have published several high impact papers and submitted a patent application. Several other projects on kidney and heart on a chip are ongoing.

Human micro-liver showing metabolic zonation on chip