The unique advantages of microfluidic systems and their ability to control various effective parameters have revolutionized the human approach to cell biology, which will pave the way for the availability and widespread use of high-efficiency human organs-on-chips. Cell and its internal structures having the micrometric physical dimensions can adapt well to the microfluidic environment since it was tailored to well-suite to various aspects of live cells to mimic the related natural milieu. The study of cell biology in microfluidics is an interdisciplinary field in which the biochemical, physicochemical, and biomechanical aspects together with the physical scale of cells should be considered. The microfluidic systems are highly beneficial in cell biology as they can lead to rapid responses, prevent reagent wastage, easy automatization, and the ability to adjust according to the cellular microenvironment. Also, by switching from macro- (Petri dishes and well plates) to microscale much more precise control can be applied over various patterns, biomechanical, spatial, and temporal gradients. Taking advantage of this unique control over the influencing factors and microenvironment, the high throughput microfluidic chips can be achieved, the first step is to fully and accurately understand the mechanisms and factors affecting cell behavior in a microfluidic environment. In summary, it can be claimed that the vast majority of factors influencing cellular behavior in the microfluidic environment can be studied under the domain of the cellular microenvironment and its components. In this chapter, we try to introduce the critical factors which may affect the natural cell behavior and its function in the microfluidic chip environment and to perform a detailed study on the cellular microenvironment. The goal is to maintain cells viable without any considerable changes in their function and keep them alive as long as possible to monitor their interaction and behaviors toward any
