Useful and promising as they are, organ on a chip devices demand careful attention when being designed. They are to mimic the natural habitat of the cells and the researcher must be aware of the privileges and restrictions of the technology to maximize this similarity. In designing an organ on a chip three main features must be carefully considered: The cell source, flow dynamics, and the architecture of the chips.
Similar to regular cell cultures in Petri dishes or flasks, a common source for cells used in an organ on a chip is immortalized cell lines. Although these cell lines are simple to use and grow, they do not fully mimic the functionality of the desired organ due to the genetic modifications. Another method is to use primary cells directly isolated from the body. However, it is known that these cells might change their gene expression levels a few days after isolation from the main organ. Therefore, researchers have started employing induced pluripotent stem cells (iPSCs) to overcome the aforementioned issues. Fibroblasts can be easily isolated from the donor’s skin and be converted to adult stem cells using standard protocols. Adult stem cells can proliferate and differentiate into the desired cell lineage. Chemical and mechanical cues are developed that guide the iPSCs to differentiate into a specific cell type. Exploiting iPSCs is advantageous in that they carry the same genetic code as the donor. Therefore, a mini-organ of choice can be made using to highly mimic the actual physiological condition as the patient.
Along with providing a biologically relevant microenvironment for cell culture, microfluidics technology offers superior control over the flow dynamics. Many cell types in the body are associated with certain mechanical force (compression and tension), or shear forces and their normal behavior is contingent upon the presence of these dynamic mechanical or flow conditions. For example, endothelial cells are highly responsive to mechanical actuation. In order for the microsystem to mimic the actual environment, flow conditions including oxygen and nutrients rate, the blood flow rate, and shear stress (in the case of shear-sensitive cells) should be taken into account. A major mechanical force that cells experience in organ on a chip devices is the shear force. The fluid flow over the cells causes friction that in turn results in cells experiencing a shear force on their surface. The shear force in microchannels is dependent on the fluid velocity and channel dimensions and needs to be carefully optimized to mimic the conditions that cells experience in vivo. Fluid flow velocity could be adjusted by changing the height of the channel or the input flow rate in the syringe pump if a syringe pump is used. This way, the perfusion could be also controlled to ensure the proper delivery of the nutrient and drug compounds to the cell and efficient waste removal.
Compression and tension can be adjusted by adding vacuum channels on the sides of the cell reservoir. By cyclic suction/blow in the vacuum channel, the cell reservoir experiences cyclic tensions and compression. This can be very helpful in the lung on a chip or intestine on a chip where the cells need to undergo compression and tension to resemble the in vivo conditions.
Organ on a chips, as opposed to conventional methods for cell culturing, allow a variety of structures to be exploited to better mimic the natural environment of the cells. Depending on the cell type used in the OOC, the proper structure can be developed. Some common structures include but are not limited to:
-2D compartments: These structures are the simplest type of organ on a chips. They consist of the main chamber where the cells reside and one or multiple side channels that are responsible for nutrient
and drug perfusion. The side channels can be separated from the main chamber by a microarray. The side channels work as blood veins and the microarray as the barrier that allows drugs smaller than a certain size to pass.
-3D porous membrane: Here, the device includes three layers of microfluidic channels. It is a suitable platform for cases where the interaction of two layers of cells is of interest. Normally, in the bottom channel, a specific type of cell is cultured and is in contact through a middle porous membrane with the top channel where another cell type is cultured. The membrane in between is porous and allows cross-talk between the cells.
A side-channel can be added to these chips in more sophisticated systems. The side channels if connected to vacuum can stretch and deform the middle cell culture chambers. Periodic vacuuming of these side channels induces a periodic motion on the cells. This configuration is suitable for organ on a chips where a periodic motion is conceivable in the natural habitat of the cells such as lung on a chips and heart on a chips.
Organ on a chips are versatile and are not limited to these types. Creative minds of researchers are improving the organ on a chips on a daily basis. To name a few, chips for mimicking lung airways while smoking, chips with cardiac muscle and skeletal muscle contraction, and liver chips capable of blood purification are among these innovations.
There are questions that should be addressed before moving the organ on a chips to the mainstream applications. Learn more about these aspects of organ on a chips.