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Human Organs-on-Chips

Microchips lined by living human cells that could revolutionize drug development, disease modeling and personalized medicine

Clinical studies take years to complete and testing a single compound can cost more than $2 billion. Meanwhile, innumerable animal lives are lost, and the process often fails to predict human responses because traditional animal models often do not accurately mimic human pathophysiology. For these reasons, there is a broad need for alternative ways to model human diseases in vitro in order to accelerate the development of new drugs and advance personalized medicine.

Wyss Institute researchers and a multidisciplinary team of collaborators have engineered microchips that recapitulate the microarchitecture and functions of living human organs, including the lung, intestine, kidney, skin, bone marrow and blood-brain barrier. These microchips, called ‘organs-on-chips’, offer a potential alternative to traditional animal testing. Each individual organ-on-chip is composed of a clear flexible polymer about the size of a computer memory stick that contains hollow microfluidic channels lined by living human cells interfaced with a human endothelial cell-lined artificial vasculature, and mechanical forces can be applied to mimic the physical microenvironment of living organs, including breathing motions in lung and peristalsis-like deformations in the intestine. Because the microdevices are translucent, they provide a window into the inner workings of human organs.

We took a game-changing advance in microengineering made in our academic lab, and in just a handful of years, turned it into a technology that is now poised to have a major impact on society.

Donald Ingber

With their ability to host and combine the different cell and tissue types making up human organs, organs-on-chips present an ideal microenvironment to mimic human-specific pathophysiologies and enable molecular and cellular scale analysis and identification of new therapeutic targets within an organ-level context in vitro. They even allow recreating therapeutically relevant interfaces like the blood-brain-barrier, which has been engineered from human stem cells with a novel differentiation method to investigate drug pharmacokinetics and facilitate discovery of new therapeutics. In another example, researchers are given the means to culture living microbiome for extended times in direct contact with living human intestinal cells to enable insights into how these microbes influence health and disease or the modeling of infections with clinically relevant viruses to identify viral strategies and vulnerabilities. They also open up new possibilities to investigate how environmental factors like cigarette smoke affect tissue health and physiology in individual patients as shown in a smoking machine that precisely mimics human smoking behavior and its impact on human lung airway functions.

This short video explains how the design of the chips allows them to emulate organ–level functions. Credit: Wyss Institute at Harvard University

To mimic the interconnectedness of organs within humans, Wyss researchers also have developed an automated instrument to link multiple organs-on-chips together by their common vascular channels. This instrument, designed to mimic whole-body physiology, controls fluid flow and cell viability while permitting real-time observation of the cultured tissues and the ability to analyze complex interconnected biochemical and physiological responses across ten different organs. This holistic “human body-on-a-chip” approach will be used to rapidly assess systemic responses to new drug candidates, providing higher-level information on their safety and efficacy.

A Wyss Institute-launched startup company, Emulate, Inc. has licensed the technology and is now further developing and commercializing the Institute’s organs-on-chip technology and automated instruments to improve industrial development and personalized medicine by bringing these important research tools to widespread academic institutions as well as biotechnology, pharmaceutical, cosmetics and chemical companies.

Current work at the Wyss Institute is now focused on developing specific human disease models and leveraging the organ-on-chip platform to identify new therapeutics and clinical biomarkers, facilitate vaccine development and develop novel organ-specific drug delivery systems. In addition, Wyss researchers are exploring the potential of the technology for personalized medicine by engineering human stem cells that differentiate into highly functional specialized cell types on-chips. Wyss researchers are also investigating the use of digital manufacturing to automate fabrication of organs on chips and increase complexity of the devices, as demonstrated by development of the first entirely 3D-printed organ on a chip – a heart on a chip – with integrated soft strain sensors.

The Wyss Institute is currently seeking partners in their research and development efforts towards development of novel technologies for organ-specific targeting and drug delivery as well as clinical biomarkers and potential therapeutics that have been discovered using the organ-on-chip platform.

See in this video how the human small airway-on-a-chip has been created, how it functions and can be used for drug and biomarker discovery. Credit: Wyss Institute at Harvard University

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