Device Could Crack Case on Pulmonary Diseases

R&D DIGEST

A lung-on-a-chip that re-creates respiratory crackles might help doctors understand whether the crackling is a contributor to lung damage or just a symptom of a disease. Lung crackles, which can be heard inside a patient's chest using a stethoscope, are associated with a number of pulmonary diseases including asthma, pneumonia, and congestive heart failure.

Researchers at the University of Michigan (Ann Arbor) developed the device to find out how small fluid plugs form in the lungs. When thick liquid plugs clog the airway, crackling is the sound heard as a person breathes. It's difficult to study these crackles in humans and animals, and it's not possible [to replicate them] in typical cell culture systems such as culture dishes, says Shuichi Takayama, associate professor in the university's department of biomedical engineering.

The chip is currently being used to study the potential causes of lung diseases. Although the chip could eventually be used to test therapeutics, Takayama points out that that would be a complex process. “The lung-on-a-chip by itself would be a relatively specialized assay system in the current stage, because it's relatively complicated,” he says.

The plastic wafer is about the size of a large postage stamp. The chip is made of two rubber sheets with its two grooved sides attached together and a sheet of polyester in between the sides. The airway channel, which is 200 μm, is lined with airway cells. It is located adjacent to a blood vessel channel that supplies the cells with liquid nutrients.

In a microchannel lined with human airway cells, the biomedical engineers re-created crackles that are produced by liquid plugs when they rupture. “We created a small airway on a chip where we could readily see the cells and control the liquid plugs that form and rupture, and then systematically re-created the different physiological conditions to see how cells would respond,” says Takayama.

The researchers used the chip to observe how breathing occurs in fetuses, healthy children, and adults. They recreated the liquid flow over airway cells and saw no damage to the cells. “But when we have liquid plugs with little surfactant moving through the little airways, like what happens in many diseases, we see a lot of cellular-level injuries,” says Takayama. These injuries are caused by fluid mechanical stresses that are exerted on the cell. The chip could also measure the damage that the lung crackles cause on surrounding cells.

In addition to observing crackles and their relation to lung diseases, the researchers could make the chip smoke to see how bad a smoking habit is for the microfluidic lung. “This is the only microfluidic chip that ‘breathes' and that one can ‘listen' to,” Takayama adds.

In the future, Takayama would like to integrate biochemical analysis capabilities into the device. He stresses that although the chip has potential in drug testing or other therapeutics, he doesn't foresee its use in a high-throughput-screening type of system.

“In the long term, we do think about things like incorporating other micro­engineered body parts together to make animals on a chip or minihuman types of things, but that's kind of far off.”

The researchers' work on the lung-on-a-chip was published in a November edition of the Proceedings of the National Academy of Sciences.

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