The organ on a chip is a microfluidic culture device that recapitulates the complicated structures and functions associated with the living human organs. The microdevices are composed of a clear flexible polymer that is almost the size of a USB memory stick and comprises hollow microfluidic channels lined up with living human organ cells and human blood vessel cells. These living, three-dimensional cross-sections of the human organs tend to provide a transparent window into their inner workings and the effects that the drugs can have on them, without involving any humans or animals.
The organ on a chip has been designed in order to recreate the natural physiology and mechanical forces that are experienced by the cells within the human body in an accurate manner. The chips are made to be lined up with living human cells and their tiny fluidic channels help in reproducing both blood and/or airflow just as within the human body. Their flexibility will in turn allow the chips for recreating breathing motions or undergoing muscular contractions. Every organ on chip comprising the lung, liver, intestine, or brain is about the size of an AA battery. The transparency of the organ on chips will allow the researchers in order to view the organ’s functionality, behavior, and response at both the cellular as well as molecular level.
Organ on a Chip Device
Need for Organ on a Chip Device
Drug development process is extremely tedious and has several demerits associated with it. It is both slow and expensive and it can take up to about 10 years with an average cost of USD 3 billion to bring a brand new compound from the lab bench to the market. A major reason for this inefficiency arises from the traditional reliance on testing the drugs in animals before they can be tested on humans. Moreover, the animal models do not tend to entirely reflect human physiology, suggesting that drugs that appear to be safe and effective in animals carry the risk to turn out harmful and ineffective in the case of humans. This mismatch in biology leads to several useless or toxic drugs, while they advance at a great expense through various clinical trials. On the other hand, the potentially effective compounds might actually never make it to the market. Therefore, the organ on chip model is a great alternative to human biology and diseases in vitro, in order to accelerate the development of new drugs and personalized medicine.
Different Organ on Chip Technology
Liver Organ on a Chip
The hepatic system is considered to be the major site of drug/toxin metabolism. The liver comprises of a series of complex hepatic lobules which confer the multicellular functional communication. The maintenance of the physiology of hepatocytes for an extended period of time is quite challenging. Kane et al. had designed the first liver-based system that comprised the microfluidic pores in which the 3T3-J2 fibroblasts and the rat liver cells were cultured together in order to mimic an airway interface. The rat hepatocytes that were supposed to be cultured in the chip are capable of continuously and stably synthesizing albumin and undergoing metabolism.
Organ on a Chip-Lung
The gas exchange in the lungs can be regulated by the alveoli which can also be challenging to reproduce in vitro. Microfluidics is capable of establishing extracorporeal lung models as lung pathologies via accurate fluid flow, as well as sustained gaseous exchange. The current studies have also focused on regulating the airway mechanical pressure, the blood-blood barrier (BBB), and the effects of the shear forces on the pathophysiological processes.
Kidney Organ on a Chip
The kidneys are mainly responsible for maintaining the osmotic pressure drug excretion. The kidney toxicity will lead to an irreversible loss of renal infiltration thereby highlighting the need for drug screening systems. Both filtration and reabsorption tend to take place in the nephrons that comprise the glomerulus, renal capsules, and the renal tubule. Microfluidics also help in simulating the fluid environment that helps in supporting the tubular cell growth and helps in providing the porous membrane support for maintaining the cellular polarity. The major disadvantage associated with conventional cell culture systems is that the cell differentiation into the functional cells tends to require extended culture times and external signal detection systems.
Organ on a Chip-Heart
The emergence of microfluidics has given rise to in vitro bionic studies related to cardiac tissues. The myocardium can be considered to be a major component of the heart. The beating associated with the cardiomyocytes can be used in order to directly assess the drug effects and is directly related to the pumping of the heart. Also, in the year 2012, Grosberg et al. used PDMS for producing an elastic film along with a surface texture and implantable neonatal rat CMs on the membrane in order to form a muscular membrane.
Intestine Organ on a Chip
The oral form of drugs has to transverse the smaller intestine in order to enter the bloodstream. Villi are considered to be the key component in absorption and their morphology can be expected to be maintained on the chip. Imura et al. had also developed the chips for simulating the intestinal system, comprising of the glass slide permeable membrane and PDMS sheet containing the channels.
Multi Organ on a Chip
An array of physiological pathways also requires continued media circulation and inter-tissue interactions. The single organ chips tend to fail to describe the full complexity, functional changes, as well as integrity of the organ function. The “multi organ on a chip”, also known as the “human organ on a chip” helps in constructing the multiple organs thereby attracting obvious attention. The multi organ on a chip culture cells of different organs and tissues simultaneously are connected by channel (such as the bionic blood vessel) in order to achieve the multi-organ integration, thereby permitting the examination of interactions for establishing a system.
Factors bolstering the growth of Organ on a Chip Market
- The increasing focus on the development of animal model substitutes and disease modeling has led to an increase in the demand for organ on chips, leading to a rise in the organ on a chip market growth. For instance, on May 03, 2021, the Wyss Institute-led collaboration that was spanning four labs had used the Institute’s organ on chip technology for identifying the antimalarial drug amodiaquine as a potent inhibitor for infection with the SARS-CoV-2, the virus causing COVID-19.
- The increase in research initiatives for the development of advanced bioartificial organs has also impacted the growth of the organ on a chip market. For instance, on April 01, 2020, MIT researchers developed the “Organ on a chip” in order to aid the process of drug development.
- The increasing demand for drug screening in the healthcare sector is another factor fostering the organ on a chip market growth. There is a very high demand for animal testing alternatives in the drug screening arena. It is majorly because the organ on chip technology plays an important role in the development of drugs and vaccines that are under clinical trials.
- The rising demand for organ on a chip for lung-based organ culture and kidney-related applications are also among the major factors behind the growth of the organ on a chip market. The research community and the biopharmaceutical industry have mobilized with unprecedented speed against the COVID-19 pandemic. Therefore, the organ on a chip can be assumed to be one of the most promising and go-to-technology during the development of vaccines and drugs which have been under clinical studies for the treatment of infection. For instance, in the year March 2020, as part of the World Health Organization’s (WHO) Research and Development Blueprint response to the COVID-19 outbreak, the emulated lung chip can be used for providing the preclinical insights into the efficacy of hydroxychloroquine for COVID-19.
Top players in the Organ on a Chip Market
The organ on a chip market is emerging due to certain factors and as a result, many companies are exploring the domain.
Some of the leading companies that are currently dominating the organ on a chip market are:
AxoSim – Los Angeles, United States
AxoSim is a contract research organization that helps in empowering advancements in human neuroscience through their drug discovery platforms, comprising the NerveSim product powered by Nerve-on-a-Chip and the BrainSim. This organ on chip company helps the pharmaceutical companies in the development of drugs faster by mimicking the in vivo nervous system in an in vitro setting. The AxoSim’s platforms are revolutionizing the way in which the biopharmaceutical companies help in the development of neurological drugs. AxoSim helps in delivering human data faster and easier. It reduces clinical failure, thereby enabling the companies to offer effective drugs quickly and at an easier cost. The company was founded for addressing unsustainably higher clinical failure rates that cost the pharmaceutical companies billions of dollars and patients waiting for new medicines as well as therapies related to neurological diseases. The NerveSim and the BrainSim are the key products in AxoSim’s product portfolio.
Emulate-Massachussets, United States
Emulate Inc. is a privately held organ on chip company that helps in the creation of in vitro models for understanding how diseases, medicines, chemicals, and foods tend to affect human health. The lab-ready Human Emulation System had comprised of three basic components: Zoë® Culture Module, Organ-Chips, and analytical software applications. The platforms provide a window into the inner workings of human biology and diseases-thereby offering the researchers a new technology designed for the prediction of human response with greater precision and detail than the conventional cell culture or animal-based experimental testing. The Brain Chips, Colon Intestine-Chip, Duodenum Intestine-Chip, Kidney-Chips, Liver-Chips, and Lung-Chips are the key products in Emulate’s product portfolio.
CN Bio Innovations – Cambridge, United Kingdom
CN Bio is a leading bioengineering organ on chip company that specializes in both the single and multi-organ microphysiological systems as well as innovative lab technologies. The company’s aim is to provide systems that generate clinically translatable data that can help in enhancing the development of medicines in the future. The company’s organ on a chip, also known as the PhysioMimix allows the modeling of human biology in the lab. As a micro physiological system, it can be used for culturing the healthy and diseased tissue models and studying the multi-organ interactions, and investigation of the ADME and toxicity.
TissUse GmbH – Berlin, Germany
TissUse is a vibrant growth company that had developed the “Multi-Organ-Chip” platform that helps in providing unparalleled preclinical insights at the systemic level using human tissues. The enabling organ on chip technology platform comprises a miniaturized construct that can closely simulate the activities of several human organs in their true physiological construct. The TissueUse’s Multi-Organ Chips tend to provide a new approach for prediction, for example, the toxicity, ADME, profiles, and efficacy in vitro, thereby reducing and replacing animal laboratory animal testing and streamlining the human clinical trials.
InSphero – Schlieren, Switzerland
InSphero is made for perfecting the 3D cell organ on chip technology in order to get more physiologically relevant in-vitro insights. The company aims to predict the human responses to therapies that will improve the lives of patients around the world. InSphero assay-ready spheroid microtissues have been engineered and certified for use in critical drug development applications, validated to ensure uniform size, robust functionality, and give reproducible results. This organ on chip company develops the 3D InSight™ Microtissues using the most advanced 3D cell culture technologies that are available for producing highly predictive, fully QC’d organotypic in vitro models ready to use in pharma drug discovery, efficacy, and safety. The microtissues form the foundation of 3D InSight™ platforms in both drug discovery and safety that we all tend to rely on our research collaborations as well as services. Many of our liver and islet models are also available as assay-ready microtissues, shipped live and ready to use to labs throughout Europe and North America.
Recent Highlights in the Organ on a Chip Market
- On October 12, 2021, Koppes was awarded a USD 1.96 million early-stage investigator grant from NIH.
- On September 07, 2021, a Boston’s biotech startup, Emulate that was working on the “Organ on a Chip” system raised approximately USD 82 million.
- On March 10, 2021, the organ on a chip project received a huge grant in order to make the leap from the lab.
- On March 02, 2021, CN Bio had awarded Innovate UK grant for developing the single and multi-organ models for COVID-19 research.
- On September 29, 2020, NIH awarded USD 35.5 million for using the tiny, bioengineered organ models for improving the development and design of the clinical trial.
- On April 01, 2020, MIT Researchers developed the “Organ on a chip” model that can aid in the drug development process.
The development of an organ on a chip has attracted worldwide attention, thereby making greater scientific advancements in the organ on a chip market. Various numbers of organ on a chip device have been designed and prepared so far by several key organ on chip companies. Numerous human organs have been studied thoroughly for the construction of the organ on a chip device. The ultimate goal of an organ on a chip device is that it involves the integration of numerous organs onto a single chip and thereby building a complicated multi organ on a chip model, achieving a “human-on-a-chip”.
Furthermore, organ on a chip devices has seen widespread use in biomedical science and technology, including experimental regenerative medicine and precision healthcare. The fundamental advantages of organ on a chip technology are the ability to create a customized human model with functional responses at the organ or tissue level, avoiding the need for animal models, vastly improving novel drug discovery processes for personal healthcare, and providing new opportunities in the organ on a chip market. The study of internal irradiation for humans is an emerging organ on a chip application that presents problems because of the lack of a defined model for risk calculation of internal irradiation.
Despite the organ on a chip device which is being constructed rapidly, the humans-on-a-chip theory remains quite distant. The PDMS material or the polydimethylsiloxane material is relatively thicker than the in vivo morphology, however, it is the most widely used material for development. A decrease in the absorbance of small hydrophobic molecules will also affect solvent safety and efficacy. Therefore, it is necessary for the identification of suitable alternative materials.
The other major problem that can be observed at present is that the manufacturing organ on a chip cost and the experimental implementation is expensive and time-consuming, which is not at all conducive to the widespread use and development of the organ chips, therefore the components should be of lower cost and should be easier to dispose of. More expensive components should be considered to be reusable. Also, in terms of the integrated system components, the media volume and the connector size should be reduced for general usage. The collection of the samples on the chip might also interfere with the operations, thereby resulting in changes in the concentration of various metabolites. Thus, more suitable types of sensors are required for such purposes. Also, universal cell culture mediums that seemed to be suitable for different types of organs are also required. Most critically, as the number of organs on the chip tends to increase, the functionality tends to become more complex and the generated data carries non-translatable risks.