| This dissertation describes many novel strategies to direct biological and chemical nanomaterial assemblies both in solution and on surfaces as well as their applications in biodiagnostics. The major topic in this dissertation is the development and application of the bio-bar-code amplification assay that relies on DNA-modified nanoparticles and magnetic particles. The gold particles in this novel assay are encoded with genetic markers in the form of oligonucleotides (the bio-bar codes), and both gold nanoparticles and magnetic microparticles are modified with antibodies as target recognition elements. When the particles encounter target molecules, they are assembled and can be easily and quickly separated from solution using a magnetic field. Then, de-hybridized bar-code DNA strands can be detected with a variety of DNA detection methods. For each target captured, hundreds to thousands of bar-code strands are released, thereby providing significant amplification. The number of bar codes can be significantly increased by increasing particle size. For prostate specific antigen (a biomarker for prostate cancer) tested in vitro , the assay proved to be up to a million times more sensitive (∼aM sensitivity) than conventional enzyme-linked immunosorbent assays (ELISAs) for the same target (∼pM sensitivity). The bio-bar-code amplification method was also used to detect biomarkers for Alzheimer's disease, anthrax, HIV and prion diseases, some of which cannot be detected with conventional technologies. Moreover, this assay is amenable to use in a portable and automated "lab-on-a-chip" device by utilizing microfluidics.; A direct-write dip-pen nanolithography method for patterning polyhistidine-tagged proteins on nickel oxide surfaces without applying an electric field was developed. Using this method, one can generate biologically active protein nanoarrays with feature sizes as small as ∼80 nm on nickel oxide surfaces. The protein molecules in this system diffuse from the Ni-coated tips to the Ni-coated substrate much like alkanethiols on gold.; Finally, this dissertation describes a computational simulation method for studying the interactions between inorganic macrocycles and single-walled carbon nanotubes and fullerenes. |
