Development of three dimensional cellular culture microsystems based on isotropic microfabrication

Abstract

The recent advancement of microfluidics has demonstrated its superior performance in fields of genomic, proteomic and cellular analysis. In particular, the fine controllability of microfluidics in the microenvironments enables us to investigate cellular responses and physiology, which cannot be approached by conventional methods. In this thesis, novel isotropic shaped microstructures were developed to be used for in vivo like cellular alignment for tissue engineering and single cell array such as single cell capture, cultivation and retrieval to replace the tedious and time-consuming agar plate based colony selection process.

Vascular vessels play an important role in maintaining the homeostasis of the circulatory system, and they are involved in a number of vascular diseases such as atherosclerosis and thrombosis. Microfluidic-based biomimetic devices have demonstrated more reliable and high-throughput drug screening capability compared with the conventional static 2-D cell culture system. Research on the construction of an artificial microvascular system on a chip is one of the extensively focused areas. A study on the cardiovascular disease-related functions, and assessment of vascular toxicity in drug screening requires realistic in vitro vascular models. To this end, in chapter 2, a simple and efficient fabrication method for generating isotropic microfluidic channels with a circular-cross sectional geometry was developed by exploiting the reflow phenomenon to construct three dimensional endothelial cell layer. To form a three dimensional endothelial cell layer inside circular PDMS microchannels, we cultured primary human umbilical vein endothelial cells (HUVECs), and demonstrated successful cell adhesion, proliferation, and alignment along the channel. In chapter 3, the nanowrinkle as well as hierarchical nano/microwrinkle patterns on a PDMS substrate were developed by the strain responsive wrinkling method. The effect of the UV/O exposure time and the...