Living, Breathing Lung-on-a-Chip
Donald E. Ingber, M.D., Ph.D.,
Wyss Institute for Biologically Inspired Engineering
NIEHS Grant R01ES016665
NIEHS-supported researchers have developed a device that mimics a living and breathing human lung on a microchip roughly the size of a quarter. This device was developed in response to the Nanoscience and Nanotechnology in Biology and Medicine Program. The research team is located at the Wyss Institute for Biologically Inspired Engineering at Harvard University.
The device has the potential to be a valuable research tool for testing the effects of environmental agents, and the absorption, safety and efficacy of drug candidates. The device may help accelerate and reduce the expense of drug development by reducing the reliance on current models, in which testing of a single substance can cost more than $2 million.
The lung-on-a-chip device uses a new approach to tissue engineering which places tissue from the lining of the alveoli and the blood vessels that surround them across a porous membrane. Air flows across the lung cells while culture medium, mimicking blood, is pumped through the capillaries. Mechanical stretching of the device mimics the expansion and contraction of the lungs during breathing.
The researchers tested the device by introducing E. coli bacteria on the lung cell side of the device while allowing white blood cells to flow through the capillaries. The lung cells detected the bacteria, and through the porous membrane, activated the blood vessel cells, which caused an immune response resulting in the white blood cells movement to the air chamber where they killed the bacteria. They conducted additional tests with nanoparticles found in commercial products and air and water pollutants. The results show that the nanoparticles passed through the lung tissue and into the capillary system. Mechanical stretching greatly enhanced the nanoparticle absorption. The investigators are following up these studies with others to test the gas exchange capacity of the device. The team is also working to build other model systems to mimic the intestinal system, bone marrow, and cancer models.
Citation: Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science. 2010 Jun 25;328(5986):1662-8.
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