A Living, Breathing Lung-on-a-Chip

Human cells can be grown outside the human body. In a petri dish, they may develop in ways that resemble the cells inside the body. But their function and activity are limited. For example, in a dish, lung cells are just lung cells. They don’t breathe.

Using new technology, however, researchers have put lung cells on a chip. The cells on a chip have suddenly become a lung-on-a-chip, active, moving, and breathing.

In a paper published in the in the November 7 issue of Science Translational Medicine, researchers report on their use of recently-developed organ-on-a-chip technology. They describe how they built and used "a biomimetic microdevice that reconstitutes organ-level lung functions to create a human disease model-on-a-chip."

Caption: Wyss Institute's human breathing lung-on-a-chip. Credit: Wyss Institute, Harvard University. Usage Restrictions: None.

Already the device has led to two discoveries directly applicable to the lung disease, edema, which is a major concern for some cancer patients. First, development of the disease is accelerated by the physical movement of the lungs. This is "something that clinicians and scientists never suspected before," according to Donald Ingber, senior author of the study.

Second, researchers identified one drug, currently under development, that might help prevent the problem. For Ingber, this is the main attraction of organ-on-a-chip technology. "This on-chip model of human pulmonary edema can be used to identify new potential therapeutic agents in vitro," Ingber says.

This could accelerate the speed of drug development and testing while reducing the cost. The main advantage is that an organ-on-a-chip gives researchers the opportunity to test a wide array of potential drug compounds. Tests can be run not just on nonhuman animals or on cultured human cells but on functioning or working small-scale models of human organs.

Beyond its value in pharmaceutical research, it is not clear where this research may lead, but it is one more way in which the boundary we once drew between the living and the nonliving is being erased, along with the line between the natural and the artifical.

The work was funded by the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), Defense Advanced Research Projects Agency (DARPA), and the Wyss Institute for Biologically Inspired Engineering at Harvard University. The paper is entitled "A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice" and appears in the November 7, 2012 issue of Science Translational Medicine.

Merging Humans and Robots--More Coffee, Please

With the help of a tiny chip implanted in the brain, human beings who cannot move their own limbs are able to move a robotic arm, in one case taking a drink of coffee on one’s own for the first time in fifteen years.

"The smile on her face was a remarkable thing to see. For all of us involved, we were encouraged that the research is making the kind of progress that we had all hoped," said the trial's lead investigator, Leigh Hochberg, M.D., Ph.D., in a press release issued by the National Institutes of Health, which provided some of the funding. Hochberg is an associate professor of engineering at Brown University and a critical care neurologist at Massachusetts General Hospital (MGH)/Harvard Medical School.

The field of brain-computer interface research is not new, but this is the first peer-reviewed report of people using brain signals to control a robotic arm, making it perform in three-dimensional space much as their natural arms once did. By imagining they were controlling their paralyzed limb, they were able to move the robotic arm. Brain activity is detected as electrical activity by the BrainGate chip, processed by an external computer, and fed into a robot that translates the signals into movement.

More research is underway, and in fact this clinical trial is recruiting more volunteers.

Caption: The BrainGate array, which is implanted on the motor cortex, comprises nearly 100 electrodes on a chip the size of a baby aspirin. Credit: www.braingate2.org Usage Restrictions: With Credit.

With future advances, researchers hope to be able to improve the quality of movement in prosthetic limbs or to restore in part the function of paralyzed limbs, perhaps by creating an electronic by-pass to normal nerves.

"This is another big jump forward to control the movements of a robotic arm in three-dimensional space. We're getting closer to restoring some level of everyday function to people with limb paralysis," said John Donoghue, Ph.D., who leads the development of BrainGate technology and is the director of the Institute for Brain Science at Brown University.

Beyond therapy, it is possible to imagine other uses as we humans and our machines co-evolve and increasingly converge, probably to do more than drink coffee.

This report is published in the May 17, 2012 issue of Nature.