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Fewer steps in the lab, one more leap for organs-on-chips

New protocol for manufacturing Organs-on-Chips enables labs worldwide to study human biology in vitro

By Lindsay Brownell

Fewer steps in the lab, one more leap for organs-on-chips
Organ Chips, like this Kidney Chip, consist of clear upper and lower components through which run parallel channels (red and blue) separated by a semipermeable membrane. The upper component’s channel is seeded with the cells of a given organ type, while the lower component’s channel is seeded with endothelial cells to mimic blood vessels. Credit: Wyss Institute at Harvard University

(BOSTON) — Organs-on-Chips (Organ Chips) allow scientists an unprecedented ability to study the physiology of human organs in a lifelike environment in vitro, and have been shown to faithfully mimic organ activities and disease states in vivo. These qualities make Organ Chips a valuable tool for developing drugs and studying biological mechanisms without subjecting animals or humans to potentially dangerous substances. However, the large numbers of Organ Chips needed for biological studies can be difficult to manufacture in labs that lack specialized equipment like clean rooms and soft lithography tools, limiting their widespread use in research.

Now, a new protocol published by the Wyss Institute for Biologically Inspired Engineering at Harvard University in the Journal of Visual Experiments (JoVE) combines multi-scale patterning of Organ Chip parts into a single step, saving time, improving reproducibility and traceability, and reducing the likelihood of contamination. The approach allows for more rapid prototyping of new designs while reducing manual labor, and represents an important step in scaling up Organ Chip manufacturing for academic and research applications.

“We hope this new protocol will enable researchers in labs around the world to create Organ Chips more easily and quickly, helping to drive future advances in drug discovery and development as well as personalized medicine,” said first author Richard Novak, Ph.D., a Senior Staff Engineer at the Wyss Institute.

Fewer steps in the lab, one more leap for organs-on-chips
Custom 3D-printed molds for the top and bottom Organ Chip components (A and B) allow the easy fabrication of multiple top and bottom components at once (C and D) to scale up Organ Chip production for research. Credit: Wyss Institute at Harvard University

Each Organ Chip consists of three components made of a clear silicone rubber polymer: a top channel, a bottom channel attached to a microscope slide, and a porous membrane between the two channels. When the components are assembled, each channel is seeded with either organ cells or blood vessel cells, and the membrane allows the exchange of molecules between the two, as happens with human organs in vivo.

While some parts of the protocol are difficult to automate, it enables fabrication of dozens of chips per week by a single researcher with greater accuracy and less hands-on time than previous protocols.

“Organ Chips provide a way for researchers to gain insight into human biology at the cell, tissue, and organ levels without the need for harming humans or animals. We hope that this new protocol will allow more labs to enter this field and explore entirely new research paths using this technology,” said corresponding author and Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Additional authors of the paper include Elizabeth Calamari, Carlos Ng, Susan Clauson, and Sasan Firoozinezhad of the Wyss Institute, and former Wyss Institute members Meredyth Didier, Youngjae Choe, Bret Nestor, Jefferson Puerta, and Rachel Fleming.

This research was supported by DARPA, FDA, NIH, and the Bill and Melinda Gates Foundation.

This video from the Journal for Visual Experiments shows the process of a new protocol for manufacturing Organ Chips using 3D-printed molds and fewer, simpler steps, enabling labs around the world to make and use Organ Chips for their own research. Credit: Journal of Visual Experiments
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