Cell Culture And Differentiation On Patterned Substrate And In Microfluidic Devices

Microfluidics and patterning technologies are now widely used for cell biology studies. Of particular interest is to use these new technologies to control more precisely the stem cell culture and differentiation. In this work, both embryonic and mesenchymal stem cells are used to evaluate the feasibility of such an application. First, "degas induced patterning" and soft UV nanoimprint lithography methods are introduced, taking into account the specificity of the cell patterning requirements. While the "degas induced patterning" allows to define easily both physical and chemical patterns, the soft UV nanoimprint lithography provides a much higher resolution with an improved pattern stability. Also single cell pattern arrays could be obtained in microfluidic devices and then cultured for a long term observation. Second, a general microfluidic device configuration, which is composed of a micro-well array with micro-channel connections, has been studied to evaluate the performance of embryonic stem cell culture and differentiation on different substrates. The results show that even though the culture of stem cells can be done with different substrates, the differentiation is more critically depending on the cell-material adhesion. Third, multi-chamber and multi-compartment microfluidic devices are also designed for culture and differentiation of mesenchymal stem cells. By adapting the existing protocols, both adipogenic and neural differentiation are realized. Then a cellular network patterning has been tested with both mesenchymal stem cells and mouse embryonic stem cells, in order to achieve a derived neuronal network formation. Finally, multi-electrode arrays have been fabricated for on chip signal transduction studies.