| Single-walled carbon nanotubes (SWNTs) are a new class of nanomaterials, which have been intensely investigated due to their distinct electronic, mechanical, optical and chemical properties. Interfacing this inorganic material with biological systems, however, is a relatively unexplored area with exciting potential applications in high-throughput proteomic studies, disease diagnosis and nanobiotechnology. This graduate thesis focuses on the development of novel biosensors and bioassays to address these challenges by taking advantage of the unique properties offered by SWNTs.; Utilizing the inherent semiconducting characteristics of nanotubes, electronic biosensors based on SWNT field-effect transistors capable of highly specific, label-free and real-time detection were developed. By judiciously controlling the device-solution interface via noncovalent chemical functionalization, sensitive and selective detection of protein binding as well as DNA hybridization was achieved. Additionally, mechanistic studies were carried out to investigate the origin of the observed signals. Extensive characterization revealed that electronic effects occurring at the metal-nanotube interfaces, rather than along the length of the nanotubes, were the major contributors to the overall sensing signal.; The high surface area of a carbon nanotube film was employed to increase the number of binding sites and thus the loading of surface-immobilized receptors. Surfactant coating of the surface of the film imparts biocompatibility as well as provides anchoring of specific antigens; and the capture of targeted antibodies was detected using quartz crystal microbalance. The utility of this system was demonstrated by highly accurate diagnoses of the autoimmune disease rheumatoid arthritis (RA) based on autoantibody levels from patient sera. Moreover, the developed carbon nanotube-based assay exhibits greater sensitivity and predictive values than both the clinical standard technique of Enzyme-linked Immunosorbent Assay (ELISA) and the next generation diagnostic platform of microarray.; Lastly, the innate spectroscopic Raman signatures of carbon nanotubes were exploited in devising novel biological labels from aqueous-soluble SWNTs. Nanotube-tagged antibodies were shown to outperform their traditional fluorescent counterparts in detection sensitivity by ∼3 orders of magnitude, with stable signals that did not suffer from photobleaching. Their usage was also compatible with protocols for many existing fluorescence-based assays, making them highly attractive as ultrasensitive alternative labels. |
