Nearly two decades ago, a groundbreaking discovery in the field of biomedical research emerged, known as organ-on-a-chip technology, which quickly captivated the interest of scientists across the globe. Led by a bioengineer Donald E. Ingber at Harvard University, this innovative approach aimed to recreate the complex structure and functions of human organs within laboratory settings. By using specialized techniques, researchers successfully developed miniature models of organs, opening up new possibilities for studying human physiology in the lab.
The National Institutes of Health's Tissue Chip for Drug Screening program began in 2010 as a five-year partnership among NIH, the Defense Advanced Research Projects Agency (DARPA) and the U.S. Food and Drug Administration (FDA). Since 2012, the program has been led and managed by the National Center for Advancing Translational Sciences (NCATS). This collaborative initiative brought together experts from various fields, including biology, engineering, and materials science, to accelerate the development of organ-on-a-chip models for drug discovery and toxicity testing. Through these joint efforts, scientists achieved significant milestones in replicating organ-level functions and understanding how different organs interact on these tiny systems.
In 2012 researchers from Harvard University's Wyss Institute unveiled an innovative "human-on-a-chip" platform. By combining multiple organ-on-a-chip models, such as the lung, heart, liver, and blood-brain barrier, this groundbreaking system provided a comprehensive representation of human organ systems. By mimicking organ interactions, this platform offered a more accurate environment for drug testing and disease modeling, laying the foundation for future biomedical research.
Nowadays, the field continues to evolve. Researchers are now embarking on a transition from organ-on-a-chip to an even more ambitious concept known as patient-on-a-chip. This innovative leap aims to replicate the complexity of an individual patient's physiology within a single integrated system. By incorporating patient-specific cells, genetic information, and utilizing artificial intelligence (AI) algorithms, scientists hope to create personalized models capable of predicting an individual's response to specific treatments or therapies.
Let us delve into the evolution of organ-on-a-chip technology, exploring key contributors to this field, and the emergence of patient-on-a-chip models.
What is organ-on-a-chip technology?
Imagine a technology that can recreate the complex environment of our organs on a tiny chip. That's exactly what organ-on-a-chip (OOC) technology does. It's a cutting-edge approach that mimics the structure and function of human organs in a laboratory setting. By synthesizing organ-like units on a chip, OOC technology can simulate the behavior and physiology of tissues and organs, bringing us closer to understanding how our bodies work. This exciting innovation has the potential to revolutionize drug development and screening, offering a more accurate and reliable alternative to traditional methods. With organ chips, we can overcome the limitations of 2D cell cultures and animal trials, which often fall short in accurately predicting human responses. By providing a more realistic environment for cells to grow and interact, organ chips can significantly reduce the failure rate in late-stage human trials, making drug development faster, more cost-effective, and ultimately delivering more effective treatments. The success of organ chips is made possible by advancements in 3D bioprinting, fluidic chips, and 3D cell culture techniques, with the latter allowing cells to thrive under conditions that closely resemble the human body.
What are the leading organ-on-a-chip companies?
Since its inception, numerous organ-on-a-chip companies have emerged in this field, pushing the boundaries of innovation and making significant contributions to advancing our understanding of human biology.
One such organ-on-a-chip company is Emulate, based in the US, has developed an automated bio-emulation platform that creates a micro-engineered living environment for studying neuronal and vascular endothelial cells. By combining micro-engineering techniques with living human cells, Emulate's platform offers a new way to comprehend the effects of diseases, medicines, chemicals, and foods on human health.
Another prominent company in the organ-on-a-chip landscape is a Swiss company InSphero. InSphero provides 3D-cell-based assay solutions and scaffold-free 3D organ-on-a-chip technology for in vitro testing. Their technology allows for the early detection of pharmaceutical and toxic risks, reducing the need for animal testing in the pharmaceutical and biotechnology industries.
Elveflow, led by CEO Guilhem Velvé Casquillas, is situated in Paris and specializes in fluid control tools for microsystems. Their offerings provide research labs and clinical diagnostic centers with precise control over microfluidic systems, enabling them to conduct experiments with a high level of accuracy.
Netherlands-based Mimetas focuses on creating organ-on-a-chip products for compound testing, screening, and basic research. Their technology allows clinicians to test compounds on miniaturized organ models using 3D cell culture with continuous perfusion, offering a high-throughput approach.
MesoBiotech provides integrative solutions for research, teaching, and large-scale applications. Their sophisticated stem cell technologies involve creating artificial basement membranes consisting of gelatin nanofibers and functional proteins. These culture patches can be merged with microfluidic devices to produce organ-on-a-chip and microphysiological systems, which are essential for disease modeling, toxicity testing, drug screening, and regenerative medicine research.
AxoSim, with CEO Lowry Curley leading the way in the US, has developed a neurological drug discovery platform. Their platform focuses on preclinical pharmaceutical development and therapeutic development, simulating the in vivo nervous system in an in vitro setting. This provides an alternative to costly and ineffective animal testing and 2D models.
TARA Biosystems has developed a biotech platform that utilizes predictive cardiac tissue models to transform cardiac medication discovery. By using stem cells to create heart cells, TARA Biosystems enables the measurement of changes in human cardiac function without the need for human testing, accelerating the development of medicines. In April 2022, TARA Biosystems was aquired by Valo Health, to be incorporated into the latter's end-to-end AI in drug discovery platform Opal.
These are just a few examples of the key players in the organ-on-a-chip field. From Emulate's bio-emulation platform to InSphero's 3D organ-on-a-chip technology and Elveflow's fluid control tools, each company brings unique contributions to advancing the understanding of human biology. As the field continues to grow, these key players, along with others like Mimetas, MesoBiotech, AxoSim, TARA Biosystems, and many more, are driving innovation and paving the way for exciting possibilities in personalized medicine and drug discovery.
From organ-on-a-chip to patient-on-a-chip technology
Multi-organ tissue chip system
Image credit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307665/
The high cost of drug development and safety testing is partly due to the limitations of current pre-clinical models. These models often fail to accurately represent how drugs behave in the human body, leading to potential side effects and unexpected outcomes. To address this, scientists are seeking alternatives to traditional cell cultures and animal testing. One promising approach is the use of organoids, which are 3D models formed by self-assembling stem cells into mini-organs. While organoids offer a more realistic representation of human biology, they still have limitations. They lack the dynamic nature of real organs and fail to simulate the interactions between different organs in the body.
Enter the organ-on-a-chip technology, also known as organ chips. These chips are microfluidic devices that aim to replicate the functions of human organs in vitro. Unlike static organoid cultures, organ chips allow for the flow of fluids, mimicking the dynamic exchange of nutrients and signals that occur in living tissues. By integrating multiple mature tissues on a chip and enabling communication through fluid perfusion, scientists hope to create a more comprehensive "body on a chip" model that closely resembles human physiology.
In a recent study published in Nature Biomedical Engineering, researchers made significant progress towards this goal. They developed a multi-organ chip system that integrated mature heart, liver, bone, and skin tissues, allowing them to interact and communicate as they would in the human body. The tissues were cultured within their unique microenvironments, separated by an endothelial layer, and connected to a recirculating bloodstream. This setup enabled the tissues to communicate and maintain their phenotypes, providing a more realistic model for studying drug metabolism and toxicity.
While the multi-organ chip system is a remarkable achievement, there are still challenges to overcome. The current system includes only a limited number of tissues, limiting its ability to capture the complexity of the whole human physiology. Future research will focus on developing internal circulation systems to provide fluid flow for the engineered multi-organs. However, this groundbreaking advance brings us closer to the ultimate goal of creating patient-specific models for drug testing and personalized medicine. The potential of these organ chips is immense and holds promise for improving drug development and patient care in the future.
Transforming Drug Development with Patient-on-a-Chip Technology and Artificial Intelligence
An Israeli-based biotech company Quris has taken patient-on-a-chip drug testing to the next level by incorporating artificial intelligence (AI). Quris uses AI algorithms trained on vast amounts of data from the patient-on-a-chip systems to predict the safety and effectiveness of drugs. This could potentially streamline the drug development process and lead to safer and more efficient treatments. However, the widespread adoption of this technology by drug companies remains to be seen.
Organ chips go beyond just growing human tissues. They actively mimic the environment of the human body, with air and blood flowing through tiny channels. Some chips can even expand and contract tissues to simulate movements like breathing or digestion. By connecting different organ chips and allowing fluid transfer between them, researchers can create a microphysiological system that closely resembles the complex interactions between organs in the human body.
While challenges have existed in obtaining living human cells for the chips and designing more compact systems, recent advances have made these hurdles easier to overcome. Quris' systems, for example, are smaller and can fit up to a hundred "patients" on a single chip. By generating substantial data and training their AI algorithms, Quris aims to make predictions about drug safety. This integration of AI into organ chip systems has the potential to revolutionize drug development and improve success rates.
Despite the incredible potential of organ chips, the transition away from traditional animal testing methods has been gradual. Pharmaceutical companies are cautious about adopting new technologies due to the significant costs and risks involved. However, as more data becomes available to directly compare animal testing with patient-on-a-chip testing, companies may become more confident in making the switch. While animal testing may still be necessary for certain research questions, patient-on-a-chip technology offers a promising alternative, providing valuable insights into human cells and tissues.
As these microscopic systems generate more data on how drugs impact our bodies, artificial intelligence will play a crucial role in transforming that data into meaningful insights. The combination of organ chips and AI has the potential to revolutionize drug development, improve success rates, and ultimately benefit patients worldwide.
Topics: Emerging Technologies