Innovative Device Mimics the Human Lung, on a Microchip

Developed by researchers at Harvard University (Harvard, Boston, MA, USA), Harvard Medical School (Boston, MA, USA), and Children's Hospital Boston (MA, USA), the novel lung-on-a-chip microdevice takes a new approach to tissue engineering by placing two layers of living tissues--the lining of the lung's air sacs and the blood vessels that surround them--across a porous, flexible boundary. Air is delivered to the lung lining cells, a rich culture medium flows in the capillary channel to mimic blood, and cyclic mechanical stretching of the structure mimics breathing.

To determine how well the device replicates the natural responses of living lungs to stimuli, the researchers tested its reaction to inhaled living E. coli bacteria. They introduced the bacteria into the air channel on the lung side of the device and at the same time streamed white blood cells (WBCs) through the channel on the blood vessel side. The lung cells detected the bacteria and, through the porous membrane, activated the blood vessel cells, which in turn triggered an immune response that ultimately caused the WBCs to move to the air chamber and destroy the bacteria. The investigators, however, have not yet demonstrated the system's capability to mimic gas exchange between the air sac and bloodstream.

Created using a microfabrication strategy that utilizes clear rubbery materials, the device--which is about the size of a standard rubber eraser--is translucent, providing a window into the inner-workings of the human lung without having to invade a living body. As such, it has the potential to be a valuable tool for testing the effects of environmental toxins, absorption of aerosolized therapeutics, and the safety and efficacy of new drugs. The study describing the new device was published in the June 25, 2010, issue of Science.

"We really can't understand how biology works unless we put it in the physical context of real living cells, tissues, and organs,” said senior author Donald Ingber, M.D., Ph.D., founding director of Harvard's Wyss Institute for Biologically Inspired Engineering. "The ability of the lung-on-a-chip device to predict absorption of airborne nanoparticles and mimic the inflammatory response triggered by microbial pathogens provides proof-of-principle for the concept that organs-on-chips could replace many animal studies in the future.”

"The ability to recreate realistically both the mechanical and biological sides of the in vivo coin is an exciting innovation,” commented Rustem Ismagilov, Ph.D., a professor of chemistry at the University of Chicago (IL, USA), who specializes in biochemical microfluidic systems. "The potential to use human cells while recapitulating the complex mechanical features and chemical microenvironments of an organ could provide a truly revolutionary paradigm shift in drug discovery.”

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Harvard Medical School
Children's Hospital Boston
University of Chicago