Cell Culture on a Chip

Cell culture on a chip On-chip cell culture... 

On-Chip Cell Culture Cell Culture on a Chip... 

A number of devices have been made based on this microvalve system. One of the first devices built was a cell sorter on a chip. By manipulating nanoliters of fluid, different strains of fluorescently activated E. coli were introduced, sorted according to their fluorescent properties, recovered from the chip, and cultured. 

Zhang C, Zhao Z, Abdul Rahim NA. van Noort D, Yu H. 2009. Towards a human-on-chip Culturing multiple cell types on a chip with compartmentalized microenvironments. Lab Chip. 9(22) 3185. 

Our laboratory has fabricated several generations of micro cell culture analog (pCCA) devices, also called animal-on-a-chip or body-on-a-chip . In... 

Li N, Tourovskaia A, Folch A. Biology on a chip Microfabrication for studying the behavior of cultured cells. Crit Rev Biomed Eng 2003 31 423-88. 

Tourovskaia A, Figueroa-Masot X, Folch A. Differentiation-on-a-chip A microfluidic platform for long-term cell culture studies. Lab Chip 2005 5 14-9. 

More recently, perifusion systems have been introduced, allowing a constant flow of medium over a cell culture [16]. This also allows the development of the so-called lab-on-a-chip approaches, in which the flow of medium can be directed serially over different cell cultures, allowing the study of, e.g., the formation of an active metabolite in one cell culture (hepatocytes) and the subsequent measurement of a selective effect in a cell culture that is located... 

I. Meyvantsson, J.W. Warrick, S. Hayes, A. Skoien and D.J. Beebe, Automated cell culture in high density tubeless microfluidic device arrays. Lab on a Chip, 8(5), 717-724 (2008). 

Goto et al. demonstrated the integration of a bioassay system that illustrated all processes required for a bioassay, that is, cell culture, chemical stimulation of cells, chemical and enzymatic reactions, and detection, on a chip using CFCP (Figure 35.10). By using the temperature control device, spatial temperature control of the system was possible, with areas on the chip maintained at different temperatures. Nitric oxide released from macrophage-like cells stimulated by lipopolysac-charide was successfully monitored by this system. The total assay time was reduced from 24 to 4 h, and the detection limit for nitric oxide was improved from 1 x 10 m to 7 x 10 M compared with the conventional batch methods. Moreover, the system could monitor a time course of the release, which is difficult to measure by conventional methods. 

Fig. 5 Liver-on-a-chip platform. (A) A microfluidic liver on a chip consisting of a liver cell chamber in the center surrounded by a nutrient flow chamber to mimic the structure of the liver (Adapted from [29]). (B) Microengineered perfusion of the hepatic culture (Adapted from [58]). (C) 3D microfluidic liver on a chip consists of two different chambers connected with a tube (Adapted from [57]).

Fig. 7 An example of tumor-on-a-chip devices (Adapted from [28]). (A) In vivo breast tumor microenvironment was formed by vascular endothelial cells, lymphatic endothelial cells and tumor cells. (B) Schematic of the tumor-microenvironment-on-chip. (C) Image of fabricated prototype and schematic of the perfusion setup of the tumor-on-a-chip device. (D) Tumor tissue equivalent (lx 107 cells/ml and 6 mg-collagen/ml) was created on the tumor-on-a-chip device and cultured for 3 days. At Day 0, tumor cells, indicated by arrows, loosely aggregated within the collagen matrix. The cells prohferated and hound tightly at Day 3. Scale bar is 300 pm.

In the beginning, microfluidic devices were used to generate 3D tumor spheroids with a controllable density and diameter [80, 81]. Microfluidic devices have also been used to sort out different cancer cells [80] and balance the cell density of multi-inflow [82], To investigate the interaction between normal cells and tumor cells, several 3D platforms have been developed to co-culture normal cells and tumor cells [48], Although 3D platforms cannot be considered as organ-on-a-chip devices, they enable further investigate in vitro tumor cell behavior. 

In addition to major organs, such as a heart, lung, and liver, kidney- [30], splenon-[85, 86] and breast- [87] on-a-chip devices have been developed. Fig. 9 shows the schematics of these three devices. Kidney-on-a-chip devices include a porous membrane where kidney cells and epithelial are cultured in each side. This membrane, which is similar to the one used in the lung-on-a-chip device, consists of the central channel and two sub-channels—an apical luminal channel and a basal interstitial space. Compared to the traditional microfluidic system, the exposure of the epithelial cell layer to the certain shear stress generated by inflow mimics the in vivo kidney tubules, resulting in promotion of epithelial cell polarization and primary cilia formation. This platform is useful for the study of kidney toxicity during drug development. 

In 2D cell culture on chip, cell adhesion has been extensively studied on patterned surfaces for it is critical to cellular functions. Micropattems have been used to study the cellular interactions with various materials such as metals, polymers, self-assembled monolayers, extracellular matrix proteins, cell adhesion peptides, and other bioactive molecules. The physical and chemical properties of a substrate affect the attachment and growth of cells on it, and many studies have demonstrated that different topographical features of a surface affect cell attachment. Glass, sflicon, and polydimethylsiloxane (PDMS) are widely used as substrate materials of ceU culture microchips. 

Flow Cytometer Lab-on-a-Chip Devices, Fig. 8 Flow cytometer Lab-on-a-Chip (a) setup and SEM image of the second-generation micro cell sorter chip with integrated holding/culturing chamber (a sheathing buffer inlet,... 

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