Assay Development and Screening

Multi-Sensor Integrated Multi-Organ-on-Chips Platforms

Tuesday, February 6
12:00 PM - 12:30 PM
Location: 6C

We have developed a fully integrated multi-organ-on-a-chip platform consisting of both biomimetic human organoid models and auxiliary sensing units for continuous, in situ monitoring of organoid behaviors towards pharmaceutical compounds in an automated and uninterrupted manner. This platform was designed to be modular, consisting of a breadboard for microfluidic routing via built-in pneumatic valves, microbioreactors for hosting organoids, a physical sensing unit for measurement of the microenvironment parameters, one or multiple electrochemical sensing units for detection of soluble biomarkers secreted by the organoids, medium reservoir, and bubble traps. Individual modules were interconnected with Teflon tubes to allow for fluid flow. This multi-organ-on-chips platform was further hosted in a custom-designed benchtop incubator capable of maintaining the ambient temperature and when necessary, carbon dioxide control as well. The on-chip valving was achieved by pneumatic pressure applied through programmable Wago controller and Festo valves, using a set of MATLAB codes. These codes were written to also drive the electrochemical station, which was annexed to a multiplex detector, for automated electrochemical measurements at pre-determined time points. Physical sensing was achieved using a data acquisition (DAQ) card connected to a LabVIEW program, and was continuous during the entire course of experiments at desired data sampling rate. Miniature microscopes were directly fitted at the bottom of the microbioreactors to achieve in situ imaging. In addition, we successfully fabricated functional liver, liver cancer, and cardiac organoids within the microbioreactors. The liver and liver cancer organoids were fabricated through photopatternning of human primary hepatocytes and human HepG2 hepatoma cells in liver lobule-mimicking structures, while the cardiac organoids were produced by culturing human induced pluripotent stem cells-derived cardiomyocytes on photopatterned aligned grooves/ridges. Using the integrated approach, all the sensing was performed in situ in an uninterrupted and automated manner, allowing for long-term monitoring of drug-induced organoid toxicity in a human liver-and-heart-on-a-chip platform insulted by acetaminophen for 5 days and a human liver-cancer-and-heart-on-a-chip platform challenged with doxorubicin for 24 h, in both cases of which morphological changes of the organoids and alterations to their biomarker secretion were clearly observed. We believe that our novel platform will provide a new method for integrating existing biomimetic organoid models with a potential to achieve large-scale automation in the drug screening process.

Y. Shrike Zhang

Instructor of Medicine
Brigham and Women s Hospital, Harvard Medical School

Organs on chips, bioprinting, bioanalysis

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Multi-Sensor Integrated Multi-Organ-on-Chips Platforms



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