Nanomaterials for biological imaging and biomedical diagnostic applications [electronic resource]
Keywords: Chemistry

This thesis describes the use of inorganic nanomaterials for spectroscopic applications in biomedical imaging in vitro and ex vivo as well as in diagnostic sensor applications. Nanomaterials exhibit unique electronic, optical, magnetic, and chemical properties due to their small size and low dimensionality compared with their bulk counterparts. Exploitation of these phenomena has been the subject of much research in the past few decades, since Feynman famously informed us that there is "Plenty of Room at the Bottom." Components of relatively large chemical systems, quantum physical systems, and biomolecules converge in the nanometer size range, the so-called "nano-bio interface." Control of objects on this length scale affords a wealth of potential applications in biomedicine. However, inorganic nanomaterials and biological systems are not without their incompatibilities. Chemical modification and surface engineering are necessary to successfully employ nanomaterials in biological applications. To exploit the inherent optical properties of single-walled carbon nanotubes (SWNTs) in sensitive and multiplexed medical imaging and diagnostic applications, they must be rendered biocompatible by non-covalent modification. Indeed, it is shown that a suspension of SWNTs via functional amphiphiles affords a supramolecular complex that may be interfaced with biological systems. Resonance Raman scattering molecular imaging of cancer in vitro is demonstrated. The simple chemical structure and high Raman scattering cross section of SWNTs is exploited to prepare a library of SWNT labels for Raman-based immunostaining of ex vivo cancer tissue. Furthermore, the benefits and pitfalls of Raman scattering compared with traditional fluorescence methodologies are discussed. In addition to the optical properties of SWNTs, gold (and silver) nanoparticles possess unique localized surface plasmon resonances in the visible and near-infrared. Coupling of electromagnetic radiation to these plasmon modes effectively increases the local field strength within several nanometers from the nanoparticle surface, enhancing proximal optical phenomena, producing the surface-enhanced Raman scattering (SERS) effect, as well as plasmon-enhanced fluorescence. In order to prepare plasmonic films for SERS and fluorescence-enhancing applications, novel chemical and physical approaches will be presented. Biocompatible SWNTs conjugated to target-specific biomolecules are employed as Raman scattering labels in a SERS-based immunoassay. The combination of the SERS effect with the large Raman scattering intensity of SWNTs affords a protein assay capable of fM detection in microarray format. In addition to SERS, fluorescence-enhancement owing to chemically prepared plasmonic gold films was also realized. The enhancement of both the local electric field and NIR fluorescence emission rate via the coupling of scattering nanoparticle plasmon modes can lead to NIR fluorescence enhancement (NIR-FE) under appropriate conditions. Here, those conditions are optimized to yield the NIR-FE effect in the context of microarray immunoassays. The rapid and simple methodology developed affords high sensitivity detection of cancer and autoimmune disease biomarkers, offering a broad dynamic range applicable to a wide variety of assays. Comparisons are drawn between the SERS and NIR-FE methodologies, along with a discussion of their merits and future research directions.