Doctor of Philosophy (PhD)


Department of Chemistry

Document Type



Atomic force microscopy (AFM) is an analytical technique in which a tipped probe is gently scanned across the surface in a raster pattern to generate digital images of a sample at the nanoscale. The AFM instrument has three general operational modes, which are contact, non-contact and tapping-mode, that can be used to examine materials at the atomic level. Single-molecular details of biological molecules and other soft organic materials can be captured with minimal denaturation in either ambient or liquid environments when using tapping-mode AFM. In tapping-mode, the probe is driven to oscillate vertically while the tip is scanned across the sample, touching the surface intermittently for a nanosecond before retraction. In this dissertation, a brief history of AFM studies is outlined for applications in life sciences. The sample preparation techniques, operational modes, and potential biological applications will be described. A summary of AFM studies of the structure, assembly, protein-cell interactions, and mechanical properties of proteins of the extracellular matrix (ECM) is presented. Nanoscale surface characterization studies of soft metal organic polyhedra compounds deposited on mica were conducted using AFM to provide information on the structure and size of the compounds. Investigations of DNA-protein interaction were conducted using AFM to provide detailed information of the biomolecular complexes. Nanoscale topography and phase images were captured in ambient conditions using tapping-mode to reveal details of the morphology of DNA and protein samples that were prepared on freshly cleaved muscovite mica. Nanopatterning studies with DNA and with selected organosilanes were conducted using methods of colloidal lithography, which is a nanopatterning technique in which a surface mask of colloidal particles is used to produce regular geometric nanostructures on a 1×1 cm2 substrates. High-resolution AFM images captured in tapping-mode revealed nanostructures on the surface after the particle mask was rinsed away. Cursor profiles from AFM images were used to evaluate the depth and width of the nanostructures. Colloidal nanolithography provides a tool to control where biomolecules bind to the surface, which provides molecular-level insight for surface studies of biomolecular reactions. Potential applications for nanolithography include designs for surface biosensors or other electronic devices.



Committee Chair

Jayne C. Garno