Biosensing with Engineered Nanostructures

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9821049HalasA new approach to biosensing utilizing nanoparticles with specifically engineered electromagnetic resonances is proposed. Two specific goals are targeted: (I) the fabrication and demonstration of an all optical in vivo glucose sensor, and (2) The development of a streamlined, all optical bioassay for the detection of plasma proteins in whole blood. Metal Nanoshells, composite nanoparticles consisting of a dielectric core and an ultrathin gold shell, possess a strong plasmon excitation whose resonant frequency is controlled by the particle core diameter and shell thickness. By varying the nanoparticle's core/shell ratio, this resonance may be positioned at any wavelength across much of the visible and near infrared regions of the spectrum. When the nanoshell plasmon is resonant with a Raman excitation laser, enormous surface enhanced Raman scattering (SERS) enhancements have been observed from molecules adsorbed to the individual nanoshells. These enhancements occur without contributions from nanoparticle aggregation, as is typical with solid metal nanoparticle SERS enhancements. This effect provides a highly sensitive, high information content all-optical probe of molecular species in the local vicinity of individual nanoparticles suspended in a solution or other media. In addition, the plasmon resonance may be placed in a spectral "water window" of high infrared transmissivity in biological fluids and tissue, facilitating simple in vitro and in vivo sensing designs. Protein-conjugated nanoshell species, synthesized using the many well-established protocols of immunogold, will be utilized as specific functional agents in the development of new optically-based biosensing applications. Both sensor projects consist of bioconjugate-nanoshell attachment and activity studies, a series of nanoshell SERS-enhanced Raman spectroscopic studies for the biochemical species and reactions of interest, and characterization of the Raman-based monitors versus standard calibration methods. In the case of the glucose sensor development these investigations will be followed by incorporation of the bioconjugate-nanoshell species into hydrogel media and in viva in the final stage. This project provides an exciting, goal oriented interdisciplinary series of studies that combines expertise in nanoparticle synthesis, immunochemistry, Raman and infrared spectroscopy, and quantitative and statistical analysis. The work described in this proposal is consistent with the demonstrated expertise of the two Principal Investigators. This project will stimulate and unite graduate students in the disciplines of electrical engineering, applied physics, bioengineering and biochemistry toward goals of major technical and societal impact.***