Microfluidic flow. Microfluidics is defined as the science and technology of fluid manipulation in small channels with at least one-dimension less than 1mm. Microfluidic cell culture platforms can better mimic the dynamics of cellular environments in vivo compared to standard static cell culture formats. In these devices, cells are cultured in microscopic xxxxxxxx, while the xxxxxxxx are refreshed with cell medium by perfusion. Continuous flow is advantageous for tissues because supply of nutrients is more constant and helps removal of waste accumulation of harmful products. Fluid flow in microfluidic channels is laminar, which can be used to sustain microfluidic gradients for a long time (Takayama et al. 2001). Moreover, more relevant cellular microenvironments are created by exposing cells to physiological levels of fluid shear stress and other mechanical forces, such as cyclic strain and compression (Xxxxxx and Xxxxxx 2014). The introduction of microfluidic channels in bioreactors offers the ability to construct miniaturized, complex devices with multiple compartments and allows for automation of cell culture processes (Nisisako and Torii 2008). Other advantages are reduced sample/reagent consumption and the potential for high throughput analysis. Most platforms use passive gravity-based flow, but also active pumping has been implemented because the former requires a large volume of cell medium and dilution of important soluble factors is an undesired consequence. Further, external tubing and pumps add to the complexity of the use of the system. Challenges related to microfluidic cell culture are development of procedures for proper cell seeding, avoiding bubble formation and evaporation, small culture volume, perfusion rate and shear stress. There are various ways to load cells into microfluidic channels, for instance syringe injection or gravity-based flow. The typically high number of cells can lead to clogging or fast nutrient depletion and waste accumulation. Air bubbles can be detrimental to cells as their bursting can rupture the cell membrane. They can also block microchannels and thus impede fluid flow. Microfluidic flow is used in OoC’s to replenish culture medium to the cells, remove waste, add drugs or other molecules of interest, or add shear stress to the cells under investigation. Therefore, it is a crucial parameter to consider in increasing reproducibility of OoC systems and to enable true comparison between systems. Further, microfluidic flow allows au...
