What is organ-on-chip?

Organ-on-chip technology can bridge the gap between simple 2D-cell-culture and very complex animal experiments. This innovative approach models human tissue and reproduces physiological processes of the human body in vitro on a biochip.  Organ-on-chip thereby reduces the number animals that need to be used in research and development and provides a much more relevant in vitro model than standard 2D-cell-culture applications. Organ-on-chip therefore has the enormous potential to shape the future of drug development and biomedical research.

What is organ-on-chip – a definition

Organ-chip,

organ-on-chip

or

even organ-on-a-chip.

Different names but it all stands for the same.

Organ-on-chip is defined by the European organ-on-chip society (EUROoCS) as:

If that was a bit hard to digest, we think that Japhettes explanation in the video below is quite on point.

How does organ-on-chip technology work?

Now that we have defined what OoC is, we are going to look into the biological and technical details on how it works.

Organ-on-chip models join the essential cellular components of an organ with the biomechanical forces of the human body by combining tissue culture with microfluidics.

Cells that make up the organ tissue in an OoC model are cultured on a biochip with parallel channels. Typically, they contain one upper and one lower channel (such as our BC002) divided by a porous membrane. The different channels allow to cultivate organ-specific tissue compartments such as an endothelial and epithelial layer. The porous membrane that separates these layers allows for small molecules to pass through, supporting proper nutrition, cell-cell communication and physiological responses. Furthermore, coating of the membrane with an extracellular matrix aids cellular attachment.

During culture, biochips are connected to peristaltic pumps allowing for fluid flow. This perfusion simulates biomechanical forces from the human body such as blood flow in a vasculature, peristalsis in the gut or breathing of the lung. This feature in turn not only allows for a more physiological growth of the tissues than in 2D cultures but also allows for immune invasion and vascular drug application.

Organ-on-chip models divide into two major groups – single-organ systems and multi-organ systems. Multi-organ models interconnected two or more single-organ models to reproduce the interactions and metabolic pathways that occur in vivo. This is particularly interesting to simulate metastasis in cancer models or the metabolization of drugs that are taken up by the lung or intestine and then further processed by the liver.

Although OoC technology is more comprehensive than 2D culture, the read-outs can be achieved with similar methods. Dynamic42 biochips have the format of a microscopy slide, allowing for imaging of the organ model. Samples of supernatants can be taken at any time during or after a treatment. Additionally, with the DynamicOrgan System also end-point analysis of the tissue is possible as the tissue can be extracted from the biochip.

What is organ-on-chip used for?

OoC technology can benefit a wide range of scientific fields and industries. The method helps companies in biotech, as well as in the chemical, pharmaceutical and food industries, in the pre-clinical evaluation of newly developed substances intended for use in humans. This covers a broad spectrum from small molecules and chemicals to nanomaterials and biologicals such as antibodies.

OoC will be particularly interesting for the future of preclinical drug development where developing compounds are targeting one specific molecule. For example, antibodies targeting a tumor or other diseased cell. Those targets will rarely be conserved in animals. Therefore, organ models offer a new and more precise way to screen in a human system for function of these drugs and therapies. This is probably also one of the reasons why the FDA picked monoclonal antibodies for their first pilot program on animal free development of new drugs.

In addition, organ-on-chip technology is well suited to uncover fundamental scientific research questions. Academic scientists have the opportunity to incorporate organ models into their research to investigate molecular mechanisms under biologically human-relevant conditions such as multicellular interaction, perfusion, pathogen-host interaction, and biomechanical stimulation.

If you would like to learn more about what has been done with OoC models, take a look at this blog.

Can organ-on-chip replace animal testing?

OoC models make it possible to conduct biomedical research without animal testing or reduce the number of animals used in preclinical drug development. This not only makes results more accurate but also reduces ethical and legal concerns as well as cost.

Research related to the release of new drugs can benefit from OoC as well. Drugs can be tested for side effects quickly, easily and accurately. In the development of new drugs, OoCs helps determine the exact mode of action and precisely define the field of application. Particularly useful is OoC in assessing the toxicity if a new compound. If the drug proves to be toxic to the organ model (such as a liver-on-chip) there is no need to test them in animals, avoiding unnecessary animal experimentation in accordance with the 3R principle – reduce, replace, refine.

Taken together, organ-on-chip technology will reduce the numbers of animals used, but won’t replace animals just yet. To learn more on this subject, take a look at this recently published opinion piece by our CEO Dr Martin Raasch.

Conclusion

OoC technology is a sustainable alternative to streamline research, make drug development more efficient and cost-effective, and permanently reduce animal testing and side effects to humans.

At Dynamic42 we help bridge the gap between 2D and animals and make complex modelling also available for cell culture. If you would like to learn more about our DynamicOrgan System or Contract Research Services, please do not hesitate to contact us. Our experts will be happy to advise you on the possible applications of our organ models in your research questions.

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