Organ-On-A-Chip: A Cutting-Edge Drug Testing Device

 

What comes to your mind when you hear the term “organ-on-a-chip”? 

The current drug development procedures are very costly and time-consuming. According to estimates, each new drug takes ten years to develop and costs more than three billion dollars to bring to market. Furthermore, even though animal models used in laboratories for drug testing have significantly enhanced our knowledge and understanding of novel medicines development, there remains a significant gap between animal and human studies. As animal models do not accurately reflect human physiology, hence drug testing procedures also lack accuracy. Despite significant advances in computational and in vitro biology and toxicology over the last two decades, statistics show a failure rate of 80% in clinical trials, with 60% due to inefficiency and 30% due to toxicity. (Low et al., 2021) More predictive modeling and testing platforms for human responses are thus critical for accelerating the development of novel medication and personalized treatment.

An organ on a chip is pretty much similar to what it sounds. It is a sort of human organ recreation on a 3D multi-channel microfluidic culture chip that serves as an artificial organ by stimulating biological activities, biochemical functionalities and physiological responses similar to the actions of entire organs and organ systems (Moyer, 2011).

The Wyss Institute of Harvard University created this 3D organ device. The project's first product, lung-on-a-chip was no bigger than a thumb drive. Donald Ingber, the Founding Director of Wyss Institute said,

"We took a game-changing advance in microengineering made in our academic lab, and in just a handful of years, turned it into a technology that is now poised to have a major impact on society."

The main objective of these organ-on-a-chip systems is to mimic the physiological state of human organs. It organizes cells like the brain, kidney, and lung cells in different chambers of the microfluidic chip in a manner similar to that of the human body. A porous membrane is used as a substrate to define cell layers. These membranes serve as an interface for cellular communication between endothelial and epithelial cell layers. The cells are arranged in linked chambers, perfused with a recirculating tissue medium, to imitate a 3D microenvironment of functional tissue or organ.

Microfabrication and microfluidics are two core techniques influencing the development of organ chips.

The structure of each organ-on-a-chip model depends on a microfabrication that is well-suited to build microstructures allowing the control of cell shape. Whereas, microfluidics technology improves the in vitro mimicry of human organ function by emulating the physiological and mechanical environment that cells experience within the body (Wang & Duan, 2019).

By using microfluidic technology, researchers and pharmaceutical companies are now able to test drugs more efficiently in preclinical trials, contrary to conventionally used 2-dimensional cell cultures and animal models. The transparent material used to make Organ-on-a-Chip supports concurrent imaging and monitoring of the cells. Furthermore, fluid flow in microfluidic channels near the cells facilitates the delivery of nutrients, medicine, cytokines, and other elements to the cells while exposing them to the body's natural shear forces and fluid dynamics.

Benefits

The major benefit of these microphysiological chips is that by incorporating microsensors into the chip, scientists can control physiological properties such as fluidic share stress, biochemical conditions such as pH and oxygen supply, and optical parameters by altering the rate of flow or channel dimensions. (Bhatia and Ingber, 2014) These microsensors enable researchers to predict drug toxicity and treatment outcomes. Hence, organ-on-a-chip technology has the potential to improve drug discovery, pharmacodynamic studies, and preclinical drug testing, as well as patient-derived personal models. (Kalvelytė et al., 2017)

Moreover, these bioengineered chips provide information about disease physiopathology and human organ functionality. Also, allow a more precise prediction of the safety and efficacy of investigational drugs, circumventing the need for testing on live animals and humans.

During a press release Harvard’s researchers said,

“The microdevices have the potential ability to deliver transformative change to pharmaceutical development and human healthcare due to the accuracy at which they emulate human organ–level functions. They stand to significantly reduce the need for animal testing by providing a faster, less expensive, less controversial and accurate means to predict whether new drug compounds will be successful in human clinical trials.”

Future Perspective and Conclusion

Despite significant advances in the field of organ-on-a-chip, just like other developing technologies, obstacles remain in its path toward complete development. But, pharmaceutical companies have recognized the value of this technology as a novel in vitro model system for modeling diseases and screening drugs, and therefore are working for its development. (Sung, 2020) The National Center for Advancing Translational Sciences (NCATS), a part of the National Institutes of Health in the United States, is funding research on an 11-organ "human-body-on-a-chip" system. Experts predict that in the future, the focus will be on developing more complex multi-organ systems. Organ modules will interact with each other to mimic the biological processes of the human body. It will advance our knowledge of human diseases and drug development, allowing us to treat diseases more quickly, efficiently, and affordably. It will also reduce and may eliminate animal testing in laboratories. That would be a welcome change in the medical field.

 

 

References

·         Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P., & Tagle, D. A. (2021). Organs-on-chips: into the next decade. Nature Reviews Drug Discovery, 20(5), 345-361.

·         Moyer, M. W. (2011). Organs-on-a-Chip. Scientific American, 304(3), 19-19.

·         Wang, M., & Duan, B. (2019). Materials and Their Biomedical Applications. Encyclopedia of Biomedical Engineering, 135–152. https://doi.org/10.1016/b978-0-12-801238-3.99860-x

·         Bhatia, S. N., & Ingber, D. E. (2014). Microfluidic organs-on-chips. Nature biotechnology, 32(8), 760-772.

·         Kalvelytė, A. V., Imbrasaitė, A., Krestnikova, N., & Stulpinas, A. (2017). Adult stem cells and anticancer therapy. In Advances in molecular toxicology (Vol. 11, pp. 123-202). Elsevier.

·         Sung, J. H. (2020). A body-on-a-chip (BOC) system for studying gut-liver interaction. Methods in Cell Biology, 158, 1-10.

Websites

·         Human Organs-on-Chips. (2021, September 8). Wyss Institute. https://wyss.harvard.edu/technology/human-organs-on-chips/

·         Stoakes, S. M. F. (2018, December 11). What is Organ-on-a-Chip (OOC)? News-Medical.Net.https://www.news-medical.net/life-sciences/What-is-Organ-on-a-Chip-(OOC).aspx

·         Organ-on-a-Chip: microfluidic technology that can revolutionize the pharmaceutical industry. (2021, August 17). UFluidix. https://www.ufluidix.com/microfluidics-applications/organ-on-a-chip/

·         A promising futuristic device is already starting to change medicine. (2015, August 3). Business Insider. https://www.businessinsider.com/what-is-an-organ-on-a-chip-2015-7?international=true&r=US&IR=T

 

By: Hadia Islam