In the early 2000s, the concept of organ-on-a-chip technology, also known as microphysiological systems, emerged as a way to replicate the structure and function of human organs in a laboratory setting. Donald E. Ingber, a bioengineer at Harvard University, was a key early player in this field, developing the first organ-on-a-chip models using microfabrication techniques. The National Institutes of Health (NIH) established the Tissue Chip for Drug Screening program in 2012, which stimulated the development of organ-on-a-chip technology. This program brought together researchers from various disciplines, such as biology, engineering, and materials science, to create organ-on-a-chip models for drug discovery and toxicity testing. In 2012, researchers at Harvard University’s Wyss Institute for Biologically Inspired Engineering created a “human-on-a-chip” platform that integrated multiple organ-on-a-chip models, including the lung, heart, liver, and blood-brain barrier. This system was able to simulate how different organs in the human body work together. This gave a more accurate picture of how the human body works.
In 2017, the FDA announced a collaboration with the Wyss Institute to evaluate organ-on-a-chip technology for drug development and toxicity testing. This was a notable milestone when the FDA acknowledged organ-on-a-chip technology as a legitimate tool for drug development. Many companies, including MIMETAS, InSphero, and TARA Biosystems, have emerged in recent years to develop and commercialize organ-on-a-chip technology. These firms have created a variety of organ-on-a-chip models for a variety of applications, including drug development, disease research, and toxicity testing. Overall, organ-on-a-chip technology has progressed from simple 2D cell culture systems to more complex 3D systems capable of replicating the structure and function of multiple human organs. Even though the technology is still in its early stages, it has the potential to revolutionize drug development and disease research by creating more accurate and reliable models of how the human body works.
Convergence of Technologies
Tissue engineering and microfabrication have converged to aid in the development of organ-on-a-chip technology. Early 2D monocultures have given way to more sophisticated 3D co-culture systems. By manipulating the cellular microenvironment and geometrical arrangement, researchers can now achieve cell polarization, direct cell-cell interaction, and the propagation of chemical and electrical signaling.
In addition, the handling of primary cell sources and the integration of these cells into artificial structures to promote organ-like functions have improved. The use of induced pluripotent stem cells (iPSCs) promises personalization of organ-chips for patient-specific clinical trials and research on disease phenotypes and drug responses.
Microsystems technology, adapted from the integrated circuit industry, has also played a major role in the success of organ-on-a-chip tech. By transferring lithographic patterns, researchers can now fabricate nanoscale and microscale structures, resulting in a change in the way in vitro bioreactors and cell biological systems are conceived, run, and monitored.
Organ function in vitro can now be studied using organ-specific chips. Designed to mimic the organ’s cellular and extracellular features in response to biochemical and physical cues, these chips maintain and simulate organ function.
Organ-on-chip systems are very important because they allow for multi-parametric readouts of organ function.
Artificial intelligence (AI). can play a significant role in organ-on-a-chip systems by analyzing large amounts of data generated by these systems and providing insights that would be difficult to obtain through manual methods. AI techniques such as machine learning, deep learning, and computer vision can be used to analyze images of cells and tissues on the chips, predict cellular behavior, and identify patterns and trends in the data.
One application of AI in organ-chip systems is in the development and optimization of the microfabrication techniques used to create the chips. AI algorithms can be used to design and optimize the microscale structures on the chips, such as the size and shape of the channels and the distribution of cells.
AI can also be used to monitor and control the conditions on the chips, such as temperature, pH, and nutrient levels. This can help to ensure that the cells on the chips are kept in the optimal environment for growth and function. AI methods are essential for processing complex multimodal data obtainable from organ-on-a-chip systems.
Let’s have a look at the 17 most innovative companies engineering organ-on-a-chip systems and related technologies in the United States, European countries, and Israel.
1) Bi/ond
The company is based in the Netherlands and develops custom organ-on-a-chip solutions for in vitro testing, including their key products, inCHIPit and comPLATE. For instance, inCHIPit has an open well for tissues, a porous membrane, and a bottom compartment for oxygen and nutrient-delivering microchannels. This enables the longitudinal evaluation of organoid tissue cultures using microscope-compatible instruments.
2) InSephero
Based in Switzerland, this company offers 3D-cell-based assay solutions as well as scaffold-free 3D organ-on-a-chip technology for in vitro testing that yields biologically relevant insights. The technology developed by InSphero aids in the early detection of pharmaceuticals and toxic risks, allowing the pharmaceutical and biotechnology industries to reduce the use of animals in testing.
3) AlveoliX
Another Swiss biotech in this field, which created in-vitro lung products for drug testing. The products of the company aid in simulating the biophysical properties of lungs, predicting the effects of respiratory drug candidates in humans, and reducing the number of candidates tested in clinical trials.
4) Mimetas
Mimetas is a Dutch company that develops organ-on-a-chip products for compound testing, screening, and basic research. Mimetas’ product enables clinicians to test compounds in high throughput on miniaturized organ models using 3D cell culture with continuous perfusion.
5) MesoBioTech
This French company offers integrative solutions for research, education, and large-scale applications. Their primary focus is on advanced stem cell technologies based on the fabrication of artificial basement membranes composed of a monolayer of gelatin nanofibers and functional proteins (culture patches). The patches could then be reversibly combined with microfluidic devices to create organs-on-a-chip and microphysiological systems, which are important for disease modeling, toxicity testing, drug screening, and regenerative medicine research.
6) Cherry Biotech
Another company out of France is focused on the development of a new generation of cell environment control suitable for organs-on-a-chip. They can culture and replicate any human organ in a physiological and pathological state using their patented microfluidic technique.
7) 4Dcell
This France-based biotech, has created an innovative 3D cell culture system that mimics in vivo conditions and, eventually, organ function through extensive regulation of the cell microenvironment. This system enables the acquisition of more physiologically relevant readouts.
8) TissUse
TissUse was founded in Germany and is focused on creating a one-of-a-kind “Multi-Organ-Chip” platform that uses human tissues to deliver exceptional preclinical knowledge on a systemic level. This multi-organ-on-chip contains four organs as well as a variety of organs-on-chip. It is currently developing a “human on a chip” with a dozen organs.
9) BEOnchip
This biotech company based in Spain creates innovative cell culture equipment to make the cells’ environment as bioimetic as possible. Their goal is to use this technology to improve drug testing, accelerate the development of new treatments, and reduce the cost of drug development.
10) Emulate
Boston-based Emulate created an automated bio-emulation platform for studying neuronal and vascular endothelial cells in a micro-engineered living environment. This platform is a new living system that combines micro-engineering with living human cells to better understand how diseases, medicines, chemicals, and foods affect human health.
11) Hurel
This US-based company specializes in advanced micro-liver tissue with a focus on microfluidic cell-based test systems. The company’s micro-liver tissue is metabolically active and can live in a cell culture for a long time. This lets clinicians recreate how drugs move through different tissues and organs.
12) AxoSim
This US-based biotech has created a platform for neurological drug discovery that focuses on preclinical pharmaceutical development. By simulating the in vivo nervous system in vitro, the platform offers an alternative to costly animal testing and ineffective 2D models.
13) Altis Biosystems
US-based Altis Biosystems is working on a stem cell platform for regenerating the human intestinal epithelium. RepliGut is a stem and differentiated cell organ-on-a-chip technology with a patent-pending biomimetic framework that allows the small intestine and colon to be customized based on geographic specificity from different donors.
14) TARA Biosystems
TARA created a biotech platform that leverages human biology and data to transform cardiac medication discovery. The platform generates heart cells from stem cells, allowing for the measurement of changes in human cardiac function without requiring human testing. This allows for the development of pharmaceuticals.
15) Nortis
This US-based biotech company has developed in-vitro technology to aid in the discovery of new medicin`es. By creating human tissues and organs in vitro on a disposable chip-like device, the company’s technology allows physicians to accelerate research.
16) BioIVT
The OrganDOT platform, developed by BioIVT in the United States, combines high-quality primary cultures with a stable air-liquid interface to recreate tissue architecture and functions. This technology has been used to create well-known models like pancreatic islets and lung airway epithelium.
17) Tissue Dynamics
Based in Israel, Tissue Dynamics is integrating advanced data science technologies into the organ-on-a-chip realm. This is an AI-driven bionic human organoid drug development company with human-related disease models and a sensor-illuminated drug discovery and development platform.
February 6, 2023
Andrii Buvailo, Ph.D.
Co-Founder, Director, BiopharmaTrend
Andrii Buvailo is a pharmaceutical industry analyst and writer, focusing on emerging companies (startups), technologies and trends in drug discovery, and R&D outsourcing. He received a master’s degree in Inorganic Chemistry and a PhD in Physical Chemistry from Kyiv National Taras Shevchenko University. His articles were published on Forbes.com, and market research reports were referenced by some of the leading life science organizations. He also participated in numerous scientific projects in Ukraine, Belgium, Germany, and the United States (DAAD, Horizon 2020, NATO, CRDF grants), and published in high-impact research journals.
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