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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - OCLD (Tracking the Dynamics of Human Metabolism using Spectroscopy-Integrated Liver-on-Chip Microdevices)

Teaser

Summary

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 model of the human liver that maintains natural physiological rhythms through the oscillations of day and night hormones, mimicking 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. Our technology presents a unique opportunity for the study of time-of-day dependent drug toxicity and efficacy, as well as a critical tool for the design of new pharmaceutical interventions for metabolic diseases such as obesity and type-2 diabetes.

Work performed

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 Lâ€™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.