Fluidics Solutions

Pioneering work in the United States to create organs-on-chips could revolutionize the future of drug development. Four years ago scientists observed how a white blood cell reacts when it senses an infection. They watched the leukocyte as it wriggled through capillary cells the cells that line blood vessels and then through the cells that line the lung, to then engulf an invading bacterium. But this was not happening inside a patient, it was happening on a microchip. “It mimics the human response, it’s amazing to watch,” says Geraldine Hamilton, senior staff scientist at the Wyss Institute for Biologically Inspired Engineering.

Researchers at the Wyss Institute, which is based at Harvard University in Boston, Massachusetts, are pioneering the development of a whole pipeline of human organs-on-chips, including the lung, gut, heart, liver, skin, bone marrow, pancreas, kidney, eye and even a system that mimics the blood-brain barrier. The idea is to recreate the smallest functional unit of any particular organ in a micro-environment that closely imitates the human body, explains Hamilton.

To the naked eye, these ‘organs’ look nothing like the human body. A clear, flexible polymer is used to form the rectangular chips, which are about the size of a memory stick. Tiny channels pass through the chips like miniature ribbons, lined with living human cells, which vary depending on the organ being modelled. Other elements of the chip can also be customised.

So, for example, to create a lung-on-chip, the channels are split horizontally down the middle with a porous membrane. On top of the membrane, human lung cells grow and below it grow capillary cells. Air is passed over the top of the lung tissue and blood cells flow underneath the layer of capillary cells — mimicking the interface between the alveoli, the pockets of lung into which air is inhaled, and the blood vessels that carry oxygen away, all within the same tiny channels.

The flexibility of the chips means the mechanical forces that cells experience inside the human body can also be recreated. In the case of the lung-on-chip, the motion of breathing is simulated by applying a vacuum to side channels on the left and right of the main channel, stretching and relaxing the lung tissue inside.

This is important. Hamilton explains that Donald Ingber, who leads the organ-on-chip work at Wyss, showed that mechanical forces are key drivers of how a cell functions.

“We are trying to create an environment where they can function like they would in the body,” says Hamilton. Organs-on-chips can be used to determine whether a particular protein is a suitable target for drug development, to identify drug toxicity or even to assess efficacy, says Hamilton.

The technology is still in its infancy, but there is a need for it; at the moment the techniques used to discover and develop drugs — animal models and human cell lines — are too often failing to predict what will happen in humans. Of the drugs that make it to phase I trials, only about 10% successfully reach the market.

Hamilton believes that organs-on-chips could revolutionize the pharmaceutical industry by making drug development faster and cheaper, and by producing more successful therapies. Different disease states can be modelled on the chips and, crucially, drugs can be added to the channels and their effects on the tissue examined.