Previous such projects had not succeeded in connecting more than a few different tissue types on a platform. In addition, most used closed microfluidic systems that allowed fluid to flow in and out, but did not offer an easy way to manipulate what was happening inside the chip.
The MIT researchers chose to create an open system that was easier to manipulate and allowed for removal of samples for analysis, and that - unlike previous systems - incorporated several on-board pumps that can control the flow of liquid between the "organs," replicating the circulation of blood, immune cells, and proteins through the human body. The pumps also allow larger engineered tissues - for example tumors within an organ - to be evaluated.
Several versions of the chip were created, linking up to ten organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Each "organ" consists of clusters of one million to two million cells, which - while not replicating the entire organ - perform many of its important functions.
Most of these tissues came directly from patient samples rather than from cell lines developed for lab use. Such "primary cells," says Griffith, are more difficult to work with but offer a more representative model of organ function.
Using the system, the researchers showed that they could deliver a drug to the gastrointestinal tissue - mimicking oral ingestion of a drug - and then observe as the drug was transported to other tissues and metabolized. They could measure where the drugs went, the effects of the drugs on different tissues, and how the drugs were broken down.
In addition, they were able to model how drugs can cause unexpected stress on the liver by making the gastrointestinal tract "leaky," allowing bacteria to