Design and optimised production of an integrated nanopillar platform

There has been a recent trend in the study of cell response to nanotopographical cues and substrate mechanical properties, represented best by the interaction between a cell and an array of sub-millimetre scale polymeric pillars. This has led to an increased understanding of the driving forces behind cell behaviours like differentiation, proliferation and migration, and has been greatly facilitated by replication techniques that reduce the time and cost of device fabrication. Low throughput and the lack of a standardised format can make integration into widely used biological investigative techniques difficult. This thesis aims to overcome these issues by combining high throughput replication by injection moulding with a format familiar to most biologists; the well-plate. Firstly, the fabrication process of large area, high aspect ratio nanopillar arrays is optimised to improve production yield. A quality analysis process for setting part tolerances is developed to define batch production. The various mechanisms that contribute to high quality replication accuracy are identified and linked to mechanical and thermal stresses. This is used as a predictive tool for intelligent device design for three pillar devices. These devices are integrated into in-house fabricated 24-well plates using ultrasonic welding, and the yield of successful devices is measured. As a cell moves across a pillar it bends it, thus in order to fully understand the mechanics at play the model used for pillar bending must be accurate. To this end, an investigation was carried out to determine the limitations of using the Euler-Bernoulli spring constant to define pillar deflection under a load. Hard limits are set on the aspect ratio of a pillar, as well as the overall side-wall angle and how these two couple. Lastly, a new amendment to the Euler- Bernoulli equation is derived to account for non-linear pillar sidewalls. As replication accuracy is dominant in determining pillar bending mechanics and part tolerances, a fabrication process is designed to create pillars that promote replication accuracy using an inductively coupled plasma to control individual pillar dimensions. This results in high speed etching, nanometre scale resolution and control of pillar profile angle within 0.5°. Presented here is a process allowing for the smooth transition from design of individual high aspect ratio nanostructures to fully fabricated arrays. These arrays have been used in a subsequent biology experiment to great success, with one array accurately representing the stiffness bone microenvironment and each individual array stimulating a unique cell response. By using an integrated nanopillar array like this, the design process can be steered towards positive hits in larger scale experiments, allowing for fast processing of results and rapid design changes