When developing a new drug, researchers identify drug targets based on what is known about the biology of the disease and then engineer compounds that affect those targets. Preclinical testing in animals can offer information about a drug’s safety and effectiveness prior to human clinical trials, but those tests may not reveal potential side effects. Drugs that prove effective in animals often fail in human trials.

To overcome these testing challenges, MIT researchers pursued a technology that they call a “physiome on a chip,” which they believe could offer a way to model potential drug effects more accurately and rapidly. Before this project was launched, no one had succeeded in connecting more than a few different tissue types on a platform. Most researchers working on this kind of chip were using closed microfluidic systems, which allow fluid to flow in and out but do not offer an easy way to manipulate what is happening inside the chip.

The MIT team decided to create an open system, which essentially removes the lid and makes it easier to MIT engineers designed a microfluidic platform that connects engineered tissue from up to 10 organs, allowing them to replicate human-organ interactions. Source: Felice FrankelMIT engineers designed a microfluidic platform that connects engineered tissue from up to 10 organs, allowing them to replicate human-organ interactions. Source: Felice Frankelmanipulate the device and remove samples for analysis. The new platform, adapted from technology they previously developed and commercialized through U.K.-based CN BioInnovations, also incorporates several onboard 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 designed, linking up to 10 organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin and skeletal muscle. Each “organ” consists of clusters of 1 million to 2 million cells. While these tissues don’t replicate the entire organ, they perform many of its important functions. Most of the tissues originate from patient samples rather than from cell lines developed for lab use. These “primary cells” are more difficult to work with but offer a more representative model of organ function.

The system was used to deliver a drug to the gastrointestinal tissue, mimicking oral ingestion of a drug and allowing observation as the drug was transported to other tissues and metabolized. The researchers could measure where the drugs went, the effects of the drugs on different tissues, and how the drugs were broken down.

The most immediate applications for this physiome-on-a-chip technology involve modeling two to four organs. A model system for Parkinson’s disease that includes brain, liver, and gastrointestinal tissue is now under development for use in investigating investigate the hypothesis that bacteria found in the gut can influence the development of Parkinson’s disease.

The research is published in the journal Scientific Reports.

To contact the author of this article, email shimmelstein@globalspec.com