Microfluidic devices microenvironment

Abstract Microfluidic devices offer a realistic environment for cell cultures as it is related to scales found in biological systems. The aim is to create more in vivo like systems, in comparison to 2D plate cultures. Creating 3D cell culture constructs increase the cell s functionality. By controlling the microenvironment (e.g., cell matrix, flow rate, temperature) cell functionality can be increased even more. As microfluidic devices allow for precise control of the microenvironment, they are a paramount tool to study stem cells and their differentiation caused by external factors. We will give an overview of the use of microfluidic devices for some biological problems, and especially as a cell culture platforms. We focus on 3D cell cultures and stem cells and their microenvironment. 

In this chapter, we will discuss the advantages for microfluidic devices as cell culture platforms. Then we will introduce 3D cell cultures as a way to overcome the limitations of the standard 2D cell culture methods, especially in microfluidic devices. Furthermore, we will show how to control the microenvironment inside the devices and how it affects cell cultures. Finally, apphcations in stem cell differentiation highlight the need of culture techniques and control inside the microfluidic devices. 

Our third microfluidic device described in this chapter is a miniature tumor microenvironment system in which a cluster of tumor cells (i.e., a spheroid), fibroblasts, and endothelial cells are cocultured in a system that mimics the tumor microenvironment (Fig. 6) (Hockemeyer et al., 2014). This device provides an ideal tool to study these cell—ceU interactions in a simulated tumor microenvironment. 

The most common tumor-on-a-chip platforms are the cancer marker detecting devices. Usually, the microfluidics devices with specially design channel structures can collect circulating tumor cells [49, 77-79]. Nanoparticle screening platforms to create a microenvironment that mimics tumor tissues and nearby vessels were also used [28] in drug screening and delivery systems. A tumor-on-a-chip... 

Zervantonakis, I.K., Kothapalh, C.R., Chung, S., Sudo, R., Kamm, R.D. Microfluidic devices for studying heterotypic cell-cell interactions and tissue specimen cultures under controlled microenvironments. Biomicrofluidics 5, 13406 (2011). doi 10.1063/ 1.3553237... 

The development of a cellular microenvironment in a microfluidic chip starts with device fabrication. The most commonly used material for fabrication is polydimethylsiloxane (PDMS). One of the most important components to develop such platforms is the extracellular matrix (ECM), which is the 3D cellular microenvironment. Different approaches have been followed to pattern the ECM inside the microfluidic device, which will significantly affect the arrangement of cells on the chip. Following this, the target cells are seeded and cultured. Such cell culture techniques would be common for drug screening as well as the fundamental research. But for CTCs detection, usually the antibodies will be immobilized on the chip before introducing the cells. 

Microfluidics provides the bioengineering and life science communities with an unprecedented opportunity to engineer tissues at the cellular and molecular level by creating microenvironments with extremely high spatial and temporal resolution. Microfluidic devices for tissue engineering are still in their infancy. Application of techniques and exploitation of phenomenon that occur at these size scales have been used to create conqrlex cellular architectures and deliver spatial cues and soluble signals, but to... 

The soluble microenvironment is typically controlled via micromanipulations of fluid motion and composition in a discipline known as microfluidics. A microfluidic device is essentially comprised of the same main components of the above-described bioreactors, and adhere to the same basic requirements ... 

Breast-on-a-chip and splenon-on-a-chip systems have also utilized microfluidic technology. However, their capacities are limited. The breast-on-a-chip devices only mimic the distribution of anatomical vessels of a breast rather than the whole microenvironment containing glandular, fatty, and vascular tissues. The device can be integrated with other tumor-on-a-chip devices to further mimic tumor development in the breast. The splenon-on-a-chip system just simulates the blood filtering function of in vivo splenon using a microfluidic two-phase flow structure. Those chips still lack of accuracy to mimic tissue and cellular level. 

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