Nano-mechanical Fabrication of Nano-scale Surface Patterns for Cell Patterning

採用納米機械製造技術實現基於表面納米結構的細胞排列方法研究

Student thesis: Doctoral Thesis

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Award date17 Jan 2020

Abstract

In the natural environment, individual cells with a specific morphology, delicate construction, and unique functions exist in living organisms; indeed, billions of these cells gather in an orderly fashion to create well-organized and multi-functional entities, such as human organs. The principles that drive the emergence of all kinds of cellular patterns, along with their underlying biological orders, are fascinating; thus, the cues that regulate cell behavior during various vital movements have been the focus of research activities worldwide. Surface nanotopographical cue is of great importance because it is everywhere in the extracellular matrix, where the survival of cells relies on. Considering that the investigation on cells at micro- and nano-scale is still unattainable in vivo, cell patterning in vitro can serve as a powerful tool to explore the numerous interactions between cells and their surrounding microenvironments. Along with the rapid development of micro- and nano-manufacturing techniques, which have reached the fabrication precision comparable to cells, and the advances in biological sciences, which revealed novel physical and biochemical phenomena, several techniques for the arrangement of cells are emerging. Prior patterning methodologies are mainly classified into two categories, namely, active and passive. The active approaches utilize various external forces to manipulate cells for achieving patterns, while passive methods modify the substrate surfaces chemically or mechanically for implementing the geometry control of cells on micro- and nano-patterns.

In this thesis, two advanced micro-patterning techniques for localizing and assembling cells, namely lift-off cell lithography and gelatin methacrylate based 3D bio-printing, are studied to produce custom cellular patterns with clean backgrounds and cell-driven actuators, respectively. Moreover, the use of nano-grooved surfaces borrowed from optical discs is investigated to induce myoblast proliferation and growth, and myotube differentiation and alignment. Due to the limitation of the feature size on discs, a nano-fabrication method based on nano-mechanical indentation is explored to potentially develop a technology that could generate size-controllable nano-scale surface patterns and mimic the natural nanotopography of the extracellular matrix. In brief, a conical probe installed on a nanoindenter is applied to create nanocavities, and the key relationships between structural dimensions and operating parameters are examined. Finally, other related applications of the nano-structures fabricated by this developed technology are discussed.