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Human-on-a-Chip

07/25/2012
Sarah C.P. Williams

The Wyss Institute has received $37 million from DARPA to integrate multiple organ-on-chips into a single automated instrument that tests whole-body effects of drugs.


Want to know the effectiveness or potential dangers of a new drug? Today, that requires extensive animal testing and then a leap to human clinical trials—where results are often drastically different from what was seen in animal models. But one day, it may be as simple as feeding the drug into a machine that mimics human biology. Researchers at Harvard University’s Wyss Institute for Biologically Inspired Engineering have just received $37 million from the Defense Advanced Research Projects Agency (DARPA) to combine up to 10 organs-on-chips into a single powerhouse.

The human lung-on-a-chip is only one of the organs-on-chips that scientists have developed using human-cell-lined microfluidics chambers on clear polymers. Source: The Wyss Institute for Biologically Inspired Engineering at Harvard University





“The goal is to develop an automated instrument that would literally have plug-and-play cartridges where you can plug in different organs,” explained Donald Ingber, the founding director of the Wyss. “You could have a lung, heart, liver, kidney, skin, and gut.” Then, a drug could be added and the effect on each organ system measured.

In 2010, Ingber and colleagues announced the first organ-on-chip, a lung-on-a-chip device (1). It’s about the size of a thumb drive and consists of a hollow chamber lined by layers of human cells. Researchers can control the contents and flow on each side of the chamber—in the case of the lungs, air is on one side and a blood substitute on the other; they also can apply suction through side chambers in the flexible device to rhythmically stretch and relax the lung tissue layers to mimic physiological breathing motions. Then, since the chip is see-through, they can monitor changes to the cells in real time.

Following in the footsteps of the lung, this March, Ingber’s group developed a human gut-on-a-chip (2). With that device, they recreated peristalsis—the rhythmic contraction of gut muscles— as well as trickling flow through the lumen with microbial inhabitants like in a real intestine. Kit Parker at the Wyss Institute is recreating chip-sized versions of the heart, and together they are building other chips that mimic other muscles and organs. Each device can be used to study the physiological effects of a drug or—by altering the cells used—the changes caused by a disease. But Ingber’s ultimate goal is one physiologically integrated human body-on-a-chip.

“The whole idea is to model animal-level physiology, where drug effect is not just determined by what a drug does to a cell or even a single organ,” Ingber said.

In this theoretical apparatus, each chip is connected via vascular channels that mimic the connections of the body. Artificial pumps would allow researchers to control the flow of medium between the chips. An aerosol-based drug could be delivered to the lung chip, for example, but then cardiac toxicity, liver metabolism, and kidney clearance could be studied as the drug moved through the machine.

DARPA’s interest in funding the project is likely based on their need to speed up the drug development process in response to bioterror threats or disease outbreaks. “When they’ve dealt with different national threats, like influenza as well as biothreats, they realized it takes too long to develop drugs and they need to accelerate that process,” he said.

The DARPA-funded program also has been receiving input from the FDA and NIH on what steps need to be taken to integrate these new technologies to gain wide acceptance of this approach. The first step—once they develop the integrated machine—will be to test well-studied drugs to see if they can recreate physiological findings that are already known.

References

  1. Huh, D., B.D. Matthews, A. Mammoto, M. Montoya-Zavala, H.Y. Hsein, D.E. Ingber. Reconstituting Organ-Level Lung Funtions on a Chip. 2010. Science vol. 328 no. 5986: 1662-1668.
  2. Kim, H.J., D. Huh, G. Hamilton, D.E. Ingber. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. 2012. Lab on a Chip 12:2165-2174.

Keywords:  disease models