Chip seen to aid toxin tests by mimicking human lung

This “lung-on-a-chip” microdevice was created by Harvard University scientists for drug and toxin testing.
This “lung-on-a-chip” microdevice was created by Harvard University scientists for drug and toxin testing.

— A coin-sized device created by Harvard University researchers mimics the workings of a human lung on a computer chip. They’re hoping it will provide a way to test drugs and assess the impact of environmental pollutants.

The see-through lung-on a-chip contains two chambers separated by a flexible, porous membrane lined with human lung cells on one side and cells from capillary blood vessels on the other. It acts like the air sacs that make up human lungs, rhythmically stretching and expanding to duplicate the effects of breathing.

The faux lung may save drug companies time and money by enabling them to gauge the effects of inhaled medications, said Donald Ingber, the founding director of Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston and lead designer of the device. Ingber’s work was published Thursday in the journal Science.

“It’s a technological tour de force,” said Norman Edelman, chief medical officer of the American Lung Association and a pulmonologist at Stony Brook University Medical Center in Stony Brook, N.Y. “To be able to simulate all those biological functionson a chip is wonderful.”

The technology will need to be compared to conventional methods of testing medications in laboratory mice to show it can accurately measure drug effects, Edelman said in a telephone interview.

In a separate study also published in Science, researchers at Yale University took apart and rebuilt the lung of a rat. They stripped away all the living cells and tissue from the rat lung and used the remaining structure as a scaffold, loading new cells on it to create an engineered laboratory lung. The lung was implanted in a living rat and functioned for close to an hour, exchanging carbon dioxide and oxygen as normal lungs do.

“This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans,” Laura Niklason, a biomedical engineering professor and lead author of the study, said in a statement.

Harvard’s Ingber has spent 30 years working in the field of tissue engineering, the effort to synthesize tissues and organs in the laboratory. His current project got started three years ago when his co-author Dongeun Huh and colleagues at the University of Michigan developed a forerunner to the current device that simulated the small airways of the lungs.

“They flowed little fluid droplets to mimic mucus on the lungs, and it made a crackling noise that was precisely what I learned to listen for when I was a medical student and put a stethoscope on a patient,” he said.

Ingber and his team improved on this idea by creating a device that also incorporated the mechanical stresses of expanding and contracting lungs and the effects that one group of cells has on another when they are connected and interacting, Ingber said.

“People have worked for years on improving cell-culture systems for use in drug discovery and have gone from cells to groups of cells,” he said. “Organs are the next step up.”

Ingber and his colleagues tested the system by trickling fresh white blood cells on the capillary side of the membrane and then putting E. coli bacteria on the airway side. When they added the bacteria, the blood cells abruptly stuck to the membrane and migrated across it to engulf the bacteria and kill them, just as would occur with a lung infection in a person.

Tiny nanoparticles that act like pollutants in the air also were sent into the airway channel and the team could watch as they were absorbed into the lining of the tissue and across the membrane.

Ingber plans to make use of new technology to put stem cells made from a patient’s own skin onto the chip to simulate his or her diseased tissue - a personalized lung surrogate.

The institute also is developing synthetic hearts, kidneys and even tumors that may eventually be linked together to gauge the effect of new therapies on interactive organ systems, Ingber said.

Business, Pages 19 on 06/28/2010

Upcoming Events