Human-On-Chips
In 2010, when a team from the Wyss Institute at Harvard University published the first paper describing the idea of a biomimetic microsystem that had the ability recreate the critical functions of the human lung, the idea was purely scientific. 4 years later, in 2014, some scientists from the Wyss created a company called Emulate, which is now working with larger corporations, such as Johnson and Johnson, to use organs-on-chips as a substitute for live animals for pre-clinical trials testing. This year, the idea won the title of “Design of the Year” by London’s Design Museum.
Just as it sounds, organ-on-chip is a microchip that is embedded with microfluidic tubes lined with the human cells that correspond to the particular function that the chip is mimicking (ex. lung cell lines for a lung-on-chip, etc.) Air, nutrients, blood, and even infection-causing bacteria can be pumped through these hollow tubes in order to physically model such a system in the human body.
The chips are similar the chips in your computer; instead of moving electrons through silicon as is happening as you read this, these push tiny amounts of chemicals from cell cultures from various parts of the human body. The ultimate goal of such an organ-on-chip would be to encapsulate the complexity of interactions between species in a real body in a realistic way in order to decrease our dependence on using animals as test subjects, but also decrease the enourmous time and revenue it currently takes to develop drugs.
Currently, researchers at the Wyss and at Emulate are seeking to create ten different human organ-on-chips (including complex organs such as lung, heart, kidney, liver, gut, bone marrow, pancreas, and more). The possibilities with such a solution to the end of personalized medicine are limitless — imagine if parts of your real cells were able to be cultured into a “human-on-chip” device and you could see how you would react (in terms of safety and efficacy) to a certain drug, therapy, or chemical. Furthermore, it could be an amazing analysis tool for the health of your cells.
Why Organ-On-Chips?
Tissue culture of human cell lines (known as 2D cell cultures) has existed for almost a century. While the use of these types of cultures is extremely useful for biomedical research, and especially the development of preliminary data, they don’t necessarily exhibit the exact behavior that the cells inhibit in vivo (meaning, in a living body). Think of cells as people. If we lived alone in the world, we would live completely differently than if we live in a community, where tasks that need to be done can be distributed among the different individuals. Similarly, when cells “live” in a community, that is, in organs, they function differently than when they are made in cell cultures. To mimic this difference in function, a 3D cell culture is necessary. These were discovered around 50 years ago, and rely on things such as hydrogels, composed of varying materials and polymers, that make cells polarize and interact with each other in a way slightly more similar to what happens in real life. Such methods also have limitations, for example, it’s difficult to get tissue-tissue interactions, analyze behavior over long periods of time, or quantify dynamic behaviors, such as transport or absorption of materials. These cells also don’t get exposed to mechanical forces that real cells come into contact with all the time (such as shear force, tension, stress, and more.)
To mimic tissues more exactly, the cells need to be placed in conditions that are more comparable to the ones they experience inside the body. The goal of such a device isn’t to build an entire organ, but to find minimal functions that can be precisely recapitulated at either tissue or organ level. The designs range from simple ones, such as a single microfluidic chamber which has one kind of cultured cell which exhibits behaviors of some epithelial cells, to more complex ones, such as multiple microchannels with porous membrane connections, to mimic things like the blood-brain barrier. The idea is to capture physiologically relevant things such as physical forces, circulating immune cells, that react to toxins and drugs and other environmental perturbations. In doing so, much more complex interaction data can be garnered than traditional cell culture methods.
Organs-on-chips present an incredible opportunity to replace the 3-dimensional structure of a real organ into a small microfluidic device. It allows scientists to have amazing insight into the dynamics of various elements that organs interact with, and brings us one step closer to truly understanding what is taking place in our bodies in a temporal scale.
Most importantly, these devices encompass one of the most basic principles of design: they are efficient. According to Don Ingber, the founding director of the Wyss,
Design in its greatest simplicity is minimizing any system down to its elements so as to have the greatest impact.
With the nature of biology changing and becoming more and more interdisciplinary, good research requires good design, and organs on chips are a testament to this.
