Lung, liver, skin or brain on a chip the size of an AA battery
Organ-on-a-chip (OOC) technology is an exciting concept combining 3D tissues with a microfluidics system, simulating the natural physiological and mechanical forces that cells experience in the body. In essence, the devices are coated with living cells and can be used in drug development, disease modelling or personalised medicine among many others.
So what’s the point?
All new medicines have to guarantee they will not cause any adverse effects on the person taking it, hence the extensive and complicated R&D process involved. Bringing a new drug to the market is a long, complicated, and expensive process that can take more than 10 years and many research animals before being tested in humans. Even with that incredible investment of time and resources, drugs can often fail due to differences in human and animal pathophysiologies that aren’t discovered until human trials.
To make the process of modelling human disease and developing new pharmaceuticals faster, safer, and on many counts cheaper, an alternative way of testing is required. We have seen the power of precision or personalised medicine – what if we could extract a bit of patients’ lung, intestine, kidney, skin or bone marrow and test the effects of a drug before it is administered to the patient?
How does it work?
All OOCs work under the same principle – small chips designed to simulate physiological and mechanical forces that cells experience in the human body. Scientists at Harvard’s Wyss Institute are at the forefront of this technology, creating clear flexible polymers containing hollow microfluidic channels lined with human organ-specific cells. The organs work by mimicking the physical microenvironments of living organs such as breathing motions in lungs and peristalsis-like deformations in the intestine by applying external mechanical and physiological stimuli (ie blood and/or air flow). Because the chips are see-through it is essentially possible to see inside an organism without disrupting it.
While putting each organ on a chip individually is extremely useful, linking and connecting multiple chips would allow scientists to better understand drug-drug interactions and predict human pharmacokinetic and pharmacodynamics responses to drugs. And that is exactly what the researchers at Wyss did.
To mimic the internal connections between organs, multiple chips were linked using an automated instrument allowing for fluid transfer between the common vascular channels. Thus, mimicking the whole-body physiology, controlling fluid flow and cell viability all with the real-time observation in mind. By connecting multiple organs together researchers gained the ability to analyse complex interconnected biochemical and physiological responses across up to ten different organs. Effectively creating a tiny Frankenstein’s monster.
Pharma and Beyond
The pharmaceutical industry is constantly evolving. There is a need for more human targeted preclinical modes that would allow for greater understanding of human diseases and drug mode of action, in turn increasing the success rate for drug candidates. Common cell-based assays lack the complexity and robustness required to fully characterise the response achieved in a microenvironment. On the other hand, animal models are complex and allow for a more in depth analysis with the downside of no direct and easy translation to humans. OOCs allow for growth through a simple incorporation of more tissues with proper function and no external aid.
Organs on a chip have successfully been applied in multiple studies, some of them include:
- Lungs (effects of pollution on lung cells)
- Liver (hepatotoxicity)
- Heart (heart diseases, cardiotoxicity)
- Brain (blood-brain barrier)
- Intestines (gastrointestinal disorders)
With the constantly growing success of OOC, researchers started creating tumours on a chip, allowing for new types of studies focusing on cancer cell interactions both physically and chemically and in turn the survival and proliferation of malignant cells.
It might be possible that in the near future your doctor can take a sample of your lung to devise the best course of treatment. Who knows, maybe that piece of your gut will help cure IBS! What if we had a complete human model where we could test what effect a drug has on every single organ in the human body and follow its metabolites through its entire life cycle? The possibilities are endless.