DR. D.Y. PATIL BIOTECHNOLOGY AND BIOINFORMATICS INSTITUTE
At present, the way we discover new drugs is far too time-consuming and costly, leaving more diseases untreated. This is because the present tools and technologies available for us to predict whether the drug efficacy or safety, more often than not give inaccurate predictions. They fail to predict how the drug will behave once it is in humans. The primary tools available to us are – Cell Cultures and Animal Testing.
The disadvantage of cell cultures is that the cells don’t behave in vitro (outside) as they do in vivo (inside). And while animal models tell us a lot about how a drug may act in a complex organism, they are not as accurate for humans, due to different physiology, anatomy, and genetic differences, to name a few.
So, what are organs-on-a-chip?
They are a micro-scale system that mimic the human body environment. They can especially be used for diseases that are specific to humans with no known animal models like some autoimmune diseases, e.g., Systemic Lupus Erythematosus. They use techniques from the computer chip manufacturing industry to make these structures at a scale relevant to both the cells and their environment. It involves the use of microfluidics along with living cells to mimic the natural physiological and mechanical environment in the body.
Structure of a chip
- The chip has three fluidic channels – In the center, it has a porous, flexible membrane.
- On this membrane, we can add human cells on the top, e.g. – from our lungs, and in the bottom, there are capillary cells (the cells present in our blood vessels).
- There are two channels, one above and one below, the membrane. There is air flowing through the top channel – called the air channel, and blood through the bottom one – called the blood channel.
- On the side, there are vacuum channels that provide the mechanical forces to stretch and contract the membrane – mimicking how we breathe.
- This ensures that the cells experience the same environment outside (in vitro) as they do inside the body (in vivo).
Figure 1. An organ-on-a-chip with a porous membrane in the middle on which cells are cultured, an air channel on the top, and a blood channel on the bottom. Mechanical stress is applied to the side to stretch and contract the membrane.
Image Credit -Wyss Institute at Harvard University.
- Most of the materials used to produce organ-on-a-chip device ought to be optically clear for viewing and imaging functions, though whether they are stiff or flexible depends on the utilization of the device.
- The materials must have the correct chemistry and reactivity to not affect the system. Glass and silicone are used as materials for microfluidic devices.
- A commonly used soft, synthetic polymer is polydimethylsiloxane (PDMS). It is optically clear, easy to stretch and fabricate, and has high oxygen porosity.
- The systems that are mechanically stable will use thermoplastics like polystyrene. They are stiff materials with stable surface chemistries. Different synthetic polymers utilized in creating these systems are Poly(methyl methacrylate) (PMMA) and polycarbonate.
- Natural materials, like collagen in the form of hydrogels, have additionally been accustomed to assist cell organization. Scientists are also trying to design software apps that can collect data and give precise control of the microenvironment in the chip.
Now some of the challenges that are encountered while fabricating these chips are-
- Defining the context of use – These chips are reverse engineered, i.e. only the key components that are required for functionality are used. This makes it difficult to use these chips to study certain disorders such as psychiatric disorders. If we take the example of the brain, the chips never completely recapitulate a fully functional organ.
- Cell scaffolds– Deciding the material used on which the cells can be grown is a huge challenge as it has to be compatible with external modifications and should be biocompatible.
- Universal Medium – Different tissues require different nutrients for their growth. Thus, formulating a universal medium for all types of tissues, which could also be used to link multiple chips, is difficult.
Currently, these chips are being used as models for complex diseases such as cancer, to study how it affects different organs and various brain disorders such as Parkinson’s.
Future of organs-on-a-chip-
Now, a whole pipeline of different organ chips is currently being worked upon by various labs such as MIT, Wyss Institute, ARTORG Center for Biomedical Engineering Research, University of Bern, to name a few. The true power of this technology which was pioneered by the researchers at the Wyss Institute at Harvard, USA, however, really comes from the fact that they can be fluidically linked, just as in our body, different organ systems are linked via blood, researchers at the Wyss Institute are currently prototyping an instrument which can achieve the same as there is fluid flowing across these cells, so we can interconnect multiple chips together to form what can be called as a virtual human on a chip. The goal is to recreate sufficient functionality so that we can make better predictions of what’s going to happen inside humans.
Figure 2: Predicted future of organs-on-a-chip Image Credit -Wyss Institute at Harvard University
They could also change the way we do clinical trials in the future. Right now, the average participants in clinical trials are usually adults. There aren’t many clinical trials in which children take part and the only safety data we have on a drug for children is the one that we obtain from adults. They may not respond in the same way as adults. There are other things like genetic differences in a population that may lead to people with these differences having adverse drug reactions as compared to someone else who may not react at all. This can be prevented by taking stem cells from a particular person, thus creating a personalized chip that can pave the way for personalized medicine.
In conclusion, there is a lot that we don’t know yet about the human body and its mechanisms but hopefully, this technology will bring us a step closer to understanding our body and to a healthier future.