Development of closely-coupled nanostructures for advanced sensing and imaging

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The proposed research program aims to develop closely-coupled nanoparticle assemblies as optical sensors for the unmet needs in biomedical research, healthcare and security. Sensing based on single plasmonic nanostructure is shown to be invaluable for elucidating biomolecular interactions in the microenvironment; however demonstrations have thus far been limited to proof-of-concept studies because of the inaccessibility of the customized research-grade instrumentation setups. The proposed work aims to overcome this drawback by designing bioprogrammable bottom-up self-assembled nanoparticle clusters. These plasmonic assemblies exhibit enhanced light scattering to enable the extrapolation of the optical response of thousands of sensors in parallel from darkfield microscopy images. The objectives are to develop and evaluate the sensing platform for bioanalysis down to the single-cell level, and to establish the capability of spatial mapping of molecular distribution and chemical gradient in the microenvironment. Specifically, the proposed research aims to develop new biomolecular linkers, novel multifunctional nanoparticles and large-area multiplexed sensing patch to reach the goals. In the first research area, we will design new biomolecular linkers based on nucleic acids and their hybrid conjugates with peptides for imparting responsivity of the plasmonic assemblies to biomarkers such as microRNA and proteins. The detection of biomolecules from single cells will be pursued to verify the applicability of the technology in analyzing the cellular distribution of biomarkers. In the second research area, we will develop a new class of nanoparticle assemblies comprising orthogonal optical properties of fluorescence and localized surface plasmon resonance. In combination with the newly developed biomolecular linkers, the multifunctional assemblies will be integrated into a robust large-area flexible sensing patch to enable multiplexed detection for field or point-of-care applications. The proposed sensing platform contrasts existing single-cell analytical technologies and molecular imaging techniques which require large instrumentations, centralized laboratory and sample preparation that is laborious and costly. By developing portable, economical and user-friendly sensing platform for analyses that otherwise could only be carried out in research settings, our work will help bridge the gap of fundamental research and practical applications.