Did you know that it is now possible to study human organs inside micro-chips? Organ-on-a-chip or lab-on-a-chip is a cell culture chip that stimulates activities and physiological responses of human tissue(s) or organ(s). Try to picture a cell culture chip as a platform housing miniaturized cell culture chambers. The chambers are micro-sized channels (microchannels) where cells of various types can be loaded and cultured. The microchannels are connected to the medium/media (providing nutrients to the cells) and outlets (removing cellular waste). Different sizes and designs of a cell culture chip are adopted by researchers based on their experimental objectives.
“Imagine the day when injection needles are micro-sized—pain-free injection is guaranteed (Hooray, kids!)”
Organ-on-a-chip technology is based on micro-electro-mechanical systems (MEMS), which are used to create devices made up of components in the size of micrometers. As the name implies, MEMS devices are microscopic devices with mechanical parts and/or electrical components. With MEMS technology, sensors and devices can be made smaller without compromising their functionalities.
Applications of MEMS span from sensors and displays, such as those we use in cars and video games, to devices critical to health sciences. A good example is the MEMS accelerometers used in game controllers for the Nintendo Wii. Bio-MEMS have applications in medical and health related technologies, as found in miniaturized diagnostic tools, such as blood-analysis chips developed by an international team of researchers that can be used to process whole blood samples for disease diagnosis. Or, imagine the day when injection needles are micro-sized—pain-free injection is guaranteed (Hooray, kids!).
So, how exactly are MEMS devices and cell culture chips fabricated to reconstruct miniature physiological environments? Different materials such as silicon, metals, ceramics and polymers are used in fabricating these devices. Manufacturing involves a series of processes based on semiconductor device fabrication. First, the desired layout of a device is drawn in CAD (computer-aided design) software, creating a 2D pattern (the mask). The mask is then used to turn the 2D drawing into 3D cell culture chambers, by depositing a thin layer of light-sensitive material on a substrate (silicon) and then selectively removing it to produce a desirable 3D cell culture platform (microchannels and microchambers) for experimental needs. To recapitulate in vitro (outside human bodies) physiological processes, researchers design and fabricate the cell culture platform, which are loaded with different types of cells (lung, kidney, intestine, etc.) in the experiments.
“Fully integrated human liver-heart-on-chips have been recreated, and there are more to come.”
So far, organs that have been explored in vitro include the kidney, intestines, heart, bone, retina, vessels…and more! The blood-brain-barrier (BBB), the semi-permeable membrane that separates systemic circulation from the central nervous system, has also been studied using the on-chip device. In one study, researchers mimicked the BBB by culturing rat brain endothelial cells inside a microchannel. The BBB model was used to study neuroinflammation by looking at how the model responded to the inflammatory substance TNF-α. The same model can potentially be used in screening drugs for neurological diseases. Researchers have also utilized the microfabrication technology to build in vitro models of the human retina-on-a-chip and blinking eye-on-a-chip in order to study eye diseases. The blood-retina barrier (BRB), a restrictive barrier that regulates ions, proteins, and water into and out of the retina, has been studied by using the retina-on-a-chip. The BRB is of particular importance as the breakdown leads to debilitating eye diseases, including diabetic retinopathy and age-related macular degeneration. Researchers have also used these models to study retinal cellular interactions and the remodeling of vasculature.
In addition to physiological responses, inflammatory processes and unregulated angiogenesis (formation of blood vessels) have also been recapitulated inside the microdevices, as they are associated with pathological processes and tumor formation. In addition to building an organ-on-a-chip with a single tissue of interest, researchers are now building integrated multi-organ-on-chips systems, connecting multiple organs to create a more physiologically relevant microphysiological system. Fully integrated human liver-heart-on-chips have been recreated, and there are more to come.
Do not underestimate the on-chip models – they are more than just reconstructing organs in vitro. Although it is still in the experimental stage, chips have been used to test how the tissues respond to certain diseases or the efficiency and effect of drugs. It is therefore possible to build in vitro disease models, opening more doors in pharmacological research. Applying advanced engineering technology to medical fields to investigate clinically relevant problems is really cool, isn’t it?
Yang, S. (2011, March 16). New blood analysis chip could lead to disease diagnosis in minutes. Retrieved from http://news.berkeley.edu/2011/03/16/standalone-lab-on-a-chip/
Cho, H., Seo, J. H., Wong, K. H. K., Terasaki, Y., Park, J., Bong, K., . . . Irimia, D. (2015). Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology. Scientific Reports, 5, 15222. doi: 10.1038/srep15222
Zhang, Y. S., Aleman, J., Shin, S. R., Kilic, T., Kim, D., Mousavi Shaegh, S. A., . . . Khademhosseini, A. (2017). Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci U S A, 114(12), E2293-E2302. doi: 10.1073/pnas.1612906114