Gut-on-a-chip (Image: Harvard University) Model of finger-like villi (Image: John March at Cornell University, Ithaca, NY)

A MINIATURE, pulsating model of the human gut could help in the study of digestive disorders.


The human gut is a hectic place – muscles are continually contracting, cells are constantly being lost and grown, and the entire surface is teeming with bacteria. This complexity has made the gut tricky to study using cells grown in a Petri dish. A “gut-on-a-chip” could help with that, and also provide a realistic environment to test drugs for intestinal disease.

To make the device, Donald Ingber and his colleagues at Harvard University’s Wyss Institute in Boston fitted silicon layers together to form three parallel channels and spread a membrane seeded with human intestinal cells across the middle channel.

To recreate peristalsis – the pulsing movements that push food along the gut – the team set up a vacuum in the two outer channels. By changing the pressure in these channels, they were able to stretch the membrane of cells in the middle one, replicating the pulsations.

The group also attempted to mimic the collection of human gut bacteria. Culturing gut bacteria in dishes is difficult as even “friendly” species kill the intestinal cells they are grown on for energy. To get around this, the team set up a supply of nutrient-rich fluid, which provided the bacteria with all the energy they needed (Lab on a Chip, DOI: 10.1039/c2lc40074j).

In Petri dishes, cells coated with bacteria normally survive for 50 hours. “What’s really cool is that they’ve extended this to 150 hours,” says John March at Cornell University in Ithaca, New York. Keeping the bugs alive for longer will allow researchers to mimic diseases that are influenced by bacterial communities.

March is working on another way to model the intestine by mimicking the finger-like structures that make up the gut lining. The group made miniature collagen scaffolds in the shape of these villi then seeded them with intestinal cells (Biotechnology and Bioengineering, DOI: 10.1002/bit.24518). March says their 3D model absorbed drugs “much more like the mammalian gut” than cells in a dish.

Ingber’s team hope their device will provide a new way of studying gut disorders. “There are currently no good therapies to treat disorders like Crohn’s disease, and one reason is that there are no good animal models that predict human response,” says Geraldine Hamilton, who also worked on the project. The team hope the chip will model how drugs interact with and get absorbed by the body.

March says it would be interesting to combine his and Ingber’s devices to see if they produce a better simulation of the gut.