On-Chip Cell Culture

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. 

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

Cell Culture (2D and 3D) on Chip Cell Patterning on Chip... 

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

Matsubara, Y., Murakami, Y., Kobayashi, M., Morita, Y., and Tamiya, E. (2004). Application of on-chip cell cultures for the detection of allergic response. Biosens. Bioelectron. 19, 741-747. 

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. 

Cultures of primary cardiac myocytes (chick embryo) were formed on fibronectin patterned acrylic surfaces [198]. A microtextured PDMS chip with 20-urn-wide pegs was used to promote cell culture. After coating the PDMS chip with a thin layer of laminin, neonatal rat cardiac myocytes were cultured on it. The cultured cells are typically 50 p.m in length and 10-15 p.m in diameter. The PDMS chip was cast on a mold with parylene structures patterned on a Si wafer. Using the same mold, a poly(lactic/glycolic acid) (PLGA) chip could also be made for culture of rat cardiac fibroblasts [900]. 

In this chapter we introduce various techniques for fabricating miniature cell culture devices and cell-based biosensors, provide examples of human and animal cells immobilized on the chip devices, and explain different approaches to pattern multiple types of cells on one device. The application of nano and micro techniques in precise control over the cellular microenvironment is discussed. Selective cell-based biosensors are described later in the chapter. Finally, we conclude that these novel cell culture systems, coupled with predictions from in silico mathematical modeling, can potentially improve predictions of human clinical responses and enable better understanding of toxicological mechanisms. 

Capability for surface modification that allow cell attachment (for on-chip mono layer cell culture of adherent cells)... 

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... 

There are many other endothelial, epithelial, fibroblast cell lines, and primary cells that have been used for on-chip cultures. Some examples are as follows ... 

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. 

Torisawa YS, Shiku H, Yasukawa T, Nishizawa M, Matsue T. Multi-channel 3-D cell culture device integrated on a silicon chip for anticancer drug sensitivity test. Biomaterials 2005 26 2165-72. 

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... 

More sophisticated in vitro systems exist, such as human on chip microsystems, in which various cell types are cultivated in different miniaturized chambers linked by a microfluidic network in which a cell culture medium is circulated to mimic blood flow through organs [5, 6]. However, even in that case, we need extrapolation modelling to scale up the data obtained to the target animal species (typically humans). A purely experimental approach would also be quite expensive if PK were to be predicted for various dosing schedules and levels. We will see in the following section how PBPK computational models can help. 

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