In the past two years, a concept of “Organ-on-a-Chip” technology has gained substantial momentum in the bioengineering world. The main objective of this technology is to introduce a low-cost platform to animal and clinical studies for drug screening and toxicology applications. Currently, the drug development process on average takes up to 14 years to move from discovery phase to the clinic and costs up to $2 billion. To evaluate candidates for certain drugs, they are first tested on 2D platforms such as petri dishes, then in small animals and then in series of human clinical trials. Even then, large amount of drugs that work during animal testing fail to properly work in humans. This is because the animals used to test these drugs are not always the best indicators of the human anatomy. Also, the small sample of human patients used in the clinical trials fail to predict its true efficacy. Bioengineers have taken up the challenge to bridge the gap between in-vitro experiments performed in the lab and the human clinical trials.
Organ-on-a-chip technology is exactly as it reads. It is a replication of a specific organ interface on a microchip. It provides a platform that mimics the human organ and can be used to test developing drugs without having to invade a living body. The goal is to replace the 2D in-vitro assays and substantially improve the outcome of animal and clinical studies by enhancing the predictive power of in-vitro computational models. The overall objective is not to make replacement organs for transplant, but to “replicate just enough of organ’s functions to make the chips useful in testing chemical substances for therapeutic and toxic effects” says Donald Ingber, M.D., Ph.D., the founding director of Wyss Institute for Biologically Inspired Engineering at Harvard University.
Organ-on-a-chip technology is not a brand new concept. It has been around for number of years. In 2010, Dongeun Huh and his team from Wyss Institute introduced a microsystem called “lung-on-a-chip” that closely mimic the critical functional alveolar-capillary interface of the human lung. This microdevice contains number of small hollow channels consist of a porous and flexible membrane. This membrane is coated with extracellular matrix to create the alveolar-capillary barrier. Both sides of the membrane are lined with living lung cells and endothelial cells. The two micro-channels, created by the separation of the membrane, allows for air flow as well as blood flow to deliver the appropriate nutrients to the living cells. The microarchitecture also contains side channels, connected to vacuum, which allows the entire alveolar-capillary interface to stretch and relax. This generates peristalsis-like motion similar to ones found in human lungs during normal respiratory cycle. To validate the accuracy of this device, Huh introduced real life injuries to the cells by applying appropriate conditions of pulmonary infection and pulmonary edema. The chip performed quite well under these conditions and provided promising results. The overview on his validation experiments are discussed in this video.
In 2013, Huh published a robust step-by-step protocol to reproduce the breathing lung-on-a-chip. His protocol also brought a flexibility of adapting this in-vivo like technology for other human organ chips. So far, similar methods have been used to integrate the tissue-tissue interfaces in other human organs such as intestine, kidney, liver, brain, heart, skeletal muscle, eye and breast. Furthermore, bioengineers have started connecting these organ specific chips in series of network to investigate a comprehensive effect of the compound. In human body, after injecting a compound, it circulates in the blood stream and goes through several organs such as liver, kidney, and intestines before reaching its intended healing site. To accurately predict the response of a certain medicine or a chemical, it would be ideal to see its effect in a chain of multiple organs. After testing reactivity of the drug on a single organ-on-chip, next step would be to see its effect in the organ network chip. This would include network of multiple tissue-tissue interaction chips connected in a single circuit by blood vessels. Eventually the process can be build up to an entire human network chip. As Ali Khademhosseini, Ph.D., professor at Harvard-MIT’s division of Health Sciences and Technology says, “The perception of chips being just cute little things is changing, and there is now more of the view that they can make a significant impact.”
Due to a high demand of creating robust preclinical screening models, this technology has a promising future. But, having worked in the biopharmaceutical industry, it is quite clear to me that it is one thing to have a novel idea be published in a paper and completely another to have it be implemented for commercial use. A Boston startup, launched in July 2014, called Emulate Inc. hopes to create a new industry standard, to predict human responses to chemicals with greater reliability than animal models. They aim to automate and commercialize the organ-on-a-chip platform to expedite the drug development process. Recently, Emulate has even been nominated for the Design of the Year 2015 award by the Design Museum in London. This innovative platform has been creating quite the buzz in american healthcare sector by getting attention from NIH to venture capitalists. However, the biggest hurdle for it will be to create a new norm in the presence of strict protocols put together by the biopharmaceutical industry.
A term “disruptive innovation” come to my mind as I discuss this. Organ-on-a-chip will truly revolutionize the field of toxicology and the pharmaceutical drug development process. Not just by providing an incredible platform that will enhance the predictive power of in-vitro experiments but also by advancing the field of personalized medicine. Imagine having medicine that is unique to each patients developed by using their own cells lined on their individualized Organ-on-a-chip. The enormous impact of this technology will eventually shakeup the existing adamant rules of biopharmaceutical industry by merging economical, ethical and scientific concerns.