In this article we talk about an innovative biotechnology which has the potential to revolutionize many life sciences industries by reducing time, cost, ethical implications and scientific limitations of drug development and biomedical research.
Definition
Organ-on-chip (OoC), also referred to as organ-on-a-chip or organ-chip, is a microfluidic in vitro device that replicates human organ biology on a miniature biochip – mimicking key functions and responses – to deliver human-relevant data for preclinical drug testing and biomedical research. OoC 3D models not only offer more accurate and cost-effective data in comparison to animal and standard 2D cell-culture models, but also enhance scientific research capabilities and help minimize the impact on animals.
Watch the video below where Dr. Japhette Kembou-Ringert from Dynamic42 provides a simpler explanation of what organ-on-chip is.
How does organ-on-chip work?
Organ-on-chip models combine tissue culture, bioengineering and microfluidics by joining the essential human cell components with the biomechanical forces of the human body on a biochip.
To help illustrate the physical components and functionality of a typical organ-on-chip we showcase BC002 which is the most popular biochip by Dynamic42 (see Pic.1).
This biochip consists of one upper and one lower channel divided by a porous membrane (see Pic.2 on the right). The two separate channels allow for cultivation of different organ-specific tissue layers, like endothelial and epithelial layers for example. The membrane which separates the channels allows for cell-to-cell molecular interaction between these layers while supporting proper nutrition and physiological responses of the tissues during culture. The membrane is coated with an extracellular matrix which aids cellular attachment.
The design of these biochips is such that when connected to a peristaltic pump during perfusion cell culture, the imitation of biological processes at work within an organ becomes possible through recreation of the human body biomechanical forces like vascular blood flow, gut peristalsis or lung breathing, etc. This model feature helps reproduce a more natural tissue growth physiology especially in comparison to the 2D culture. In combination with the use of human cells, it also allows for the possibility of testing immune invasion, effects of certain mechanical stresses or exposure to therapeutic molecules and drugs.
Organ-on-chip models can represent single-organ or multi-organ systems. Multiple single-organ models can be combined to form multi-organ systems to help reproduce interactions and metabolic pathways that occur among different organs in vivo. Some examples of multi-organ organ-on-chip systems include cancer metastasis simulation or chain drug metabolization study which starts with a lung or intestine intake that is further processed by the liver (see Pic. 3 below).
All Dynamic42 biochips have the microscopy slide format and can be readout using the imagining of an organ model. Supernatant samples can be taken at any time during or after treatments. Furthermore, the DynamicOrgan System allows for tissue extraction from the biochip which makes the end-point tissue analysis possible.
Organ-on-chip applications
Organ-on-chip technology can be applied in a variety of scientific fields and life sciences industries which rely on the testing of small molecules, chemical substances, nanomaterials and biologicals. This is a developing technology that hasn’t taken over the biolab benches yet which means that we are still learning about its potential applications.
The growing scientific criticism in the last few decades highlights the fact that a significant proportion of experimental drugs fail during clinical trials because the existing animal-based models cannot accurately predict how they will behave in humans. Offering the capability of testing in actual human cells and tissues, organ-on-chip technology will be particularly beneficial in preclinical drug development studies where it will speed up and facilitate the adaptation of new therapies from the lab to humans.
More specifically, OoC will be interesting for preclinical drug developments where biological compounds aim at targeting one specific molecule while controlling and varying the experiment conditions. For example, an antibody targeting a tumor or other diseased cells which would be very challenging to do in animal models. This type of capability makes it possible to test a patient’s response to a therapy leading the way to a customized treatment approach based on their pathology and genetic characteristics. Furthermore, OoC provides opportunities for using measurement techniques that are inaccessible in vivo and multiplying the number of analyses on a single medium.
Furthermore, these biochips are well-suited for helping dig deeper into the fundamental research science of biomolecular mechanisms under the human-relevant conditions such as multicellular interaction, tissue culture perfusion, pathogen-host interaction and biomechanical stimulation.
Can organ-on-chip replace animal testing?
Organ-on-chip is a sustainable technology which helps reduce the number of animals used in biomedical research and preclinical drug development as well as lower the costs, ethical and legal concerns in relation to such research and development.
The new drugs R&D benefit from the organ-on-chip in a way that the side effects and toxicity of new compounds can be tested quicker and more effectively avoiding unnecessary animal experimentation in accordance with the 3R principle: reduce, replace, refine.
However while offering many new possibilities, organ-on-chip technology won’t completely replace animals just yet. To learn more on this subject, read this opinion piece by the CEO of Dynamic42, Dr. Martin Raasch.
Conclusion
Organ-on-chip is a sustainable and rapidly-developing technology, pioneered by companies like Dynamic42, which offers the potential of many positive clinical outcomes and disease insights for a variety of life sciences and biotech applications while cutting costs, improving efficiency and minimizing the impact on animals. We are excited to support Dynamic42 in bringing these human-relevant organ models to the United States and Canada. Contact us if you would like to learn more about how this technology can assist in your research goals.
