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The concept of “organ-on-a-chip” as a microfluidic in vitro cell culture system, that emulates the physiology of the key functional units of an organ, was first established by Huh et al., in their publication of a “lung-on-a-chip”, in 2010. This field has then developed rapidly and organ-on-a-chip is becoming a popular technology for biological research, due to the high expectations of simulating key aspects of the human physiology environment and the potential to replace animal models [1].
Organs-on-a-chip are tiny devices, usually smaller than the palm of a hand, that employ microfluidics technology to create microchannels and chambers, at the micron-scale size, for cell culturing, in a microenvironment similar to that of the cell’s natural habitat. These microfluidic devices are sealed, and sterile, and made of an optically transparent material that allows visual real-time monitoring and analysis of the cells. The organ-on-a-chip devices are made of a biocompatible polymer material and are of a modular nature. The modularity of the chips allows multiple modules, such as sensors and actuators, to be connected to the main chip for the analysis or manipulation of the cells [2].
In more sophisticated systems, the organ-on-a-chip can include multiple layers of cells, to make a more comprehensive model, or to study cell interaction. Organ-on-a-chip related to different organs (liver, kidney, gut, lung, heart, or vessels) can connect to each other, for the simultaneous analysis of multiple organs. For example, a heart-on-a-chip can connect to a liver-on-a-chip, through their common vascular channels, for cardiotoxicity testing of a new drug. Therefore, the combination of the cell culturing microchambers, and the assisting microfluidic side channels, create near-human environments that are biologically relevant for cell growth, toxicity testing, and personalized medicine [3].
The ultimate goal of organs-on-chips is to integrate different cells of various organs in a single chip and to build more complicated multiple organs-on-a-chip models, even human models to ultimately realize “human-on-chip”, like the one illustrated in Figure 1. This type of system will provide a new platform for the research of the human circulatory system, drug pharmacokinetics and pharmacodynamics [3,4].
Figure 1 – Design concept of a human body chip. One of the most promising in vitro systems for replicating the systemic responses of the human body. Retrieved from [4].
Nonetheless, organs-on-chips technology is still in its infancy. There are still a large number of technical and industrial challenges to be solved. The first one is to develop new suitable materials for cell culture. The existing materials on chips are normally based on polycarbonate, which has been widely used for cell culture, because of its good permeability and biological compatibility. However, polycarbonate has demonstrated to adsorb hydrophobic small molecules, which could result in a reduction of effective concentration and activity of the drug and in experimental errors. So chemical modification should be done, or other substitute materials are needed [3].
The second development that needs to be done is the incorporation of reliable human cells. The research of the next generation organs-on-chips will focus on the use of primary cells and human induced pluripotent stem cells, which have important implications for the study of specific diseases, personalized medicine, and new drug development [3].
Finally, due to the small size and low cell capacity of the chip, it is also important to develop highly sensitive detection strategies and devices. Only when the biological markers and cellular processes are accurately detected in real time, without the cell viability losses, the potential of the organs-on-chips can be fully realized. Therefore, developing suitable electrochemical, optical and immunological detection methods on chip, such as using all kinds of sensors and designing more standardized chips for matching with traditional biological detection methods, will also become the research focus [3].
Nevertheless, it is believed that, with the development of technology, organs-on-chip will show extraordinary talents in life science, medical and pharmaceutical research, in the near future.
References:
[1] Q. Wu et al., “Organ-on-a-chip: Recent breakthroughs and future prospects,” Biomed. Eng. Online, vol. 19, no. 1, pp. 1–19, 2020.
[2] “Organ-on-a-Chip: microfluidic technology that can revolutionize the pharmaceutical industry”, uFluidix, 2021. [Online]. Available: https://www.ufluidix.com/microfluidics-applications/organ-on-a-chip/. [Accessed: 15- Jul- 2021].
[3] W. Sun et al., “Organs-on-chips and Its Applications,” Chinese J. Anal. Chem., vol. 44, no. 4, pp. 533–541, 2016.
[4] J. W. Yang et al., “Organ-on-a-Chip: Opportunities for Assessing the Toxicity of Particulate Matter,” Front. Bioeng. Biotechnol., vol. 8, no. May, pp. 1–13, 2020.
