In vivo physiological processes are, in many ways, the least accessible to direct investigation in mice, humans and other mammals, despite significant advances in in vivo imaging. While biological complexity increases with physiological relevance in model organisms, this unfortunately leads to increased experimental difficulty.
Unsurprisingly, the use of model organisms such as mice and Drosophila physiologically exceeds engineered tissue approaches 6, 7. These systems cover a spectrum of physiological relevance, with 2D cell cultures the least relevant, followed in increasing order by 3D cell cultures, organoids and OoCs. The OoC is a relatively recent addition to the toolbox of model biological systems available to life science researchers to probe aspects of human pathophysiology and disease.
Working on the microscale lends a unique opportunity to attain a higher level of control over the microenvironment that ensures tissue life support, as well as a means to directly observe cell and tissue behaviour. This is achieved by containing them inside vessels conditioned to sustain a reasonable semblance of the in vivo environment, from a biochemical and physical point of view. OoCs comprise advanced in vitro technology that enables experimentation with biological cells and tissues outside the body. Although they are much simpler than native tissues and organs, scientists have discovered that these systems can often serve as effective mimics of human physiology and disease. The organ is a more relatable term that refers to the miniature tissues grown and residing in the microfluidic chips, which can recapitulate one or more tissue-specific functions. The chip takes the form of a microfluidic device containing networks of hair-fine microchannels for guiding and manipulating minute volumes (picolitres up to millilitres) of solution 3, 4, 5. The organ-on-a-chip (OoC) is an intriguing scientific and technological development in which biology is coupled with microtechnology 1, 2 to mimic key aspects of human physiology. Alongside this is a discussion of current and future applications of OoC technology, to inform design and operational decisions during the implementation of OoC systems. The Primer covers guiding principles and considerations to design, fabricate and operate an OoC, as well as subsequent assaying techniques to extract biological information from OoC devices. This Primer is intended to give an introduction to the aspects of OoC that need to be considered when developing an application-specific OoC. There are as many examples of OoCs as there are applications, making it difficult for new researchers to understand what makes one OoC more suited to an application than another. Combining advances in tissue engineering and microfabrication, OoCs have gained interest as a next-generation experimental platform to investigate human pathophysiology and the effect of therapeutics in the body. To better mimic human physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions.
Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips.
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