Application of Soft Lithography and Micro-Fabrication on Neurobiology

Abstract

Soft lithography should be regarded as a complement to common lithography, providing a low-expertise route toward micro/nanofabrication and playing an important role in microfluidics (YN Xia & Whitesides, 1998). The resolution ranges from 5 to 100 nanometer (Pilnam Kim, et al. 2008). Patterns generated by the soft lithography are transfered repeatedly to the soft flexible materials, and then are printed on the medium substrates. In this field, micro contact printing (μCP) is the most widely used technique, especially in bioscience research. Combined with microfluidic patterns technology, several kinds of the extracellular matrix proteins like polymers can be printed to make cells grow according to the designed patterns (Tai Hyun Park, et al. 2003). The cell growth, differentiation in vitro can be regulated in the respect of spatial structure of extracellular matrix(Y. Nam, et al. 2004). So the morphology of neural cells and the influence of spatial structure can be investigated on the micron or even nano-scale level substrates. The closed loop of neural cells can be constructed in order to simulate the complex neural network in vivo. Finally, communication with the specific environment in vitro will be achieved by multi-electrode arrays (MEA). Our previous work used μCP technique can build more solid patterns. By comparing three different extracellular matrixes, PEI can obtain much better results, which adhering more neural cells to form reliable design. However, it is not perfect for the specific neural network construction and the patterned neural cell culture on MEA. In subsequent research, we improved the parameters of the template and achieved a big progress on microfluidic patterning technique to microfabricate patterns. Patterns of biomaterials were constructed with the help of the advanced soft lithography to do the primary cell culture, such as dopaminergic neurons in the substantial nigra and GABAergic neurons in the striatum. Finally, the biocompatibility of MEA was validated initially by primary striatal neuronal culture. Meanwhile, new strategy of structural microfabrication on MEA surface was further explored.