The first entirely 3D-printed organ-on-a-chip with integrated sensing has been built by researchers from Harvard University. The 3D-printed heart-on-a-chip can be customized to a patient’s disease or heart structure to help scientists collect reliable data for short-term and long-term studies.

The first entirely 3D-printed organ-on-a-chip with integrated sensing has been built by researchers from Harvard University. The 3D-printed heart-on-a-chip can be customized to a patient’s disease or heart structure to help scientists collect reliable data for short-term and long-term studies.

And because organs-on-chips mimic the structure and function of native tissue, the Wyss Institute says they have emerged as a promising alternative to traditional animal testing, adding that “animal models often do not accurately mimic human pathophysiology.”

To create the heart on a chip, Harvard and Wyss Institute researchers developed six printable inks with integrated sensors. They then printed the inks onto a chip.

“This new programmable approach to building organs-on-chips not only allows us to easily change and customize the design of the system by integrating sensing but also drastically simplifies data acquisition,” said Johan Ulrik Lind, Ph.D., first author of the paper and postdoctoral fellow at SEAS and the Wyss Institute.

“Our microfabrication approach opens new avenues for in vitro tissue engineering, toxicology and drug screening research,” said Kit Parker, Ph.D., senior coauthor of the study, who is a Wyss Core Faculty member and Tarr Family Professor of Bioengineering and Applied Physics at SEAS.

Previously, the Wyss Institute has developed organ chips that mimic the structure and functions of the heart, muscle, tongue, lung, intestine, kidney and bone marrow. But the design process is quite expensive, apparently, as the devices “are built in clean rooms using a complex, multi-step lithographic process and collecting data requires microscopy or high-speed cameras.”

“Our approach was to address these two challenges simultaneously via digital manufacturing,” says Travis Busbee, coauthor of the paper and graduate student at Wyss and SEAS. “By developing new printable inks for multi-material 3D printing, we were able to automate the fabrication process while increasing the complexity of the devices.”

The researchers developed six different inks that integrated soft strain sensors within the micro-architecture of the tissue. In a single, continuous procedure, the team 3D printed those materials into a cardiac micro-physiological device – a heart on a chip – with integrated sensors.

“We are pushing the boundaries of three-dimensional printing by developing and integrating multiple functional materials within printed devices,” says Jennifer Lewis, Sc.D., who is a Wyss Core Faculty member and the Hansj org Wyss Professor of Biologically Inspired Engineering at SEAS, and senior coauthor of the study. “This study is a powerful demonstration of how our platform can be used to create fully functional, instrumented chips for drug screening and disease modeling.”

The heart-on-a-chip is made entirely using multi-material 3D printing in a single automated procedure, integrating six custom printing inks at micrometer resolution. (Credit: Lewis Lab)

The chip contains multiple wells, each with separate tissues and integrated sensors, allowing researchers to study many engineered cardiac tissues at once. To demonstrate the efficacy of the device, the team performed drug studies and longer-term studies of gradual changes in the contractile stress of engineered cardiac tissues, which can occur over the course of several weeks.

“Researchers are often left working in the dark when it comes to gradual changes that occur during cardiac tissue development and maturation because there has been a lack of easy, non-invasive ways to measure the tissue functional performance,” says Lind. “These integrated sensors allow researchers to continuously collect data while tissues mature and improve their contractility. Similarly, they will enable studies of gradual effects of chronic exposure to toxins.”

“Translating micro-physiological devices into truly valuable platforms for studying human health and disease requires that we address both data acquisition and manufacturing of our devices,” says Parker. “This work offers new potential solutions to both of these central challenges.”