Perfusion based microfluidic cell culture chip

In virtue of the characteristic small dimensions and the applied low flow rates, the flow is laminar in perfusion based microfluidic cell culture chips. Consequently, convection only exists in the direction of the applied flow (x-direction), whereas in the directions perpendicular to the flow (y- and z-direction) only diffusion contributes to mass transfer. This is schematically illustrated in Fig. 2b, depicting a pronounced flow in x-direction. Due to short distances, mass transfer by diffusion is sufficiently effective in providing nutrients and removing metabolic waste during continuous perfusion, eliminating formation of concentration gradients, and hence accumulation of metabolic waste. Furthermore, the small dimensions of microfluidic cell... 

The primary goal in using perfusion based microfluidic cell culture chips is to achieve a high degree of control over the microenvironment that the cultured cells are exposed to, i.e. to create a microenvironment that resembles the one cells are exposed to in vivo. In order to illustrate the difference between traditional culture vessels and perfusion based microfluidic cell culture chips, an effective culture volume (ECV) has been proposed as a descriptive concept [4]. ECV is a combined function of the characteristic mode of mass transfer (convection or diffusion), the magnitude of the mass transfer in all directions (x, y, z) in space (Fig. 2) as well as the extent of protein adsorption to the surfaces in a system. In vivo systems, e.g. tissue as part of an organ, are characterized by a fluid volume that is comparable to the volume of the cells in the tissues as well as by diffusive mass transfer. Based on these features the ECV of in vivo systems is small. 

To facilitate a semi-quantitative comparison of mass transfer in traditional in vitro culture vessels and perfusion based microfluidic cell culture chips, the Peclet number (Eq. 1) has been used [4] ... 

When designing perfusion based microfluidic cell culture chips, the primary areas of concern are the type of flow profile a system generates and an appropriate approach for fluid delivery into the system that facilitates the planned cell based experiments. Upon making a structural design that meets the set requirements, the subsequent step comprises the choice of material and method of fabrication suitable for the chosen material. 

Implementation of fluidic functions inside a plate reader is however not a straightforward task. For short-term detection, the chip depicted in Fig. lOf [16] in the Chapter Perfusion Based Cell Culture Chips of this book could be amenable for use with a plate reader since its function does not require any external pump. However, for long- term real-time monitoring, this system is not suitable due to the need for a CO2 incubator. An alternative approach could be based on a multichannel pump, suitable for integration with a polymeric microfluidic cell culture chip independent of a CO2 incubator. The pump shown in Fig. 10b [17] in the Chapter Perfusion Based Cell Culture Chips of this book could function as the basis for such an approach. 

Goral, V.N., Hsieh, Y.-C., Petzold, O.N., Clark, J.S., Yuen, P.K., Paris, R.A. Perfusion-based microfluidic device for three-dimensional dynamic primary human hepatocyte cell culture in the absence of biological or synthetic matrices or coagulants. Lab. Chip. 10, 3380-3386 (2010). doi 10.1039/c01c00135j... 

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