There is substantial interest in the development of new diagnostic tools for biomedical applications. With these tools biologists will be able to develop better ideas of how individual cells function at the system level. The interactions of individual cells with the substrate upon which they reside, how cells move, and how they reproduce on the substrate are especially interesting areas. Cell mobility also appears to be different in cancerous and non-cancerous cells. As a step towards a smart microscope slide, nano-lights can be used to optically probe individual cells. This thesis focuses on the development of inexpensive nanopatterning techniques to produce arrays of nano-holes where the dimensions are substantially less than the wavelength of the interrogating light. The use of these arrayed subwavelength apertures (typically ~200 nm in diameter) allows one to exploit surface plasmon resonance effects because the distances between array elements are less than the decay length of the propagating surface plasmon. The resonant nature of the surfaces plasmon which can be modified by the size and periodicity of the array allows extras degrees of freedom with which to design biomolecular sensors.
A principle challenge of this work was to develop an inexpensive method where patterned structures can be produced on several different lengths scales. Confluent monolayers of cells are grown on cover slips or microscope slides of centimeter areas. The 10-100 μm scale sensing areas are where individual cells can be seeded and observed. Nanoholes of 100-400 nanometer diameters with 200-600 nm periodicity form arrays of subwavelength apertures within the micron scale features. These patterns can be produced using electron beam lithography or focused ion beam milling, but these methods are expensive and time consuming. In this thesis, the alternative technique of natural or nanosphere lithography is investigated. By arranging polystyrene spheres on the substrate in a two dimensional crystal. This allows the formation of a physical mask that can used to form the array of nanoapertures.
A key feature of the work performed in the thesis is the development of techniques that combine the placement of the individual drop containing the nanospheres, and then dragging the drop in controlled manner. This allows the uniform deposition of the nanospheres into a crystalline structure by providing a balance between the forces of evaporation and surface tension. The periodicity of the array is determined by size of the spheres. The size of the holes can be tailored by reactive ion etching. Furthermore, by patterning the substrate on the 10-100 micron scale using photolithography it was found that within the defined areas that very good crystals without defects could be formed. This allowed meeting the goal of defining micron scale arrays, while obtaining nanoscale patterns within the defined areas. Focused ion beam milling was also used produce suitable subwavelength aperture arrays and their optical properties were investigated.
