The integration of biosensors into the clinic can transform the ability to monitor personal and public health. High sensitivity and specificity have been realized leveraging nanostructured sensors and surface enhanced Raman spectroscopy (SERS), which can be further integrated by fluorescence to push the boundaries of sensitivity, selectivity, and multiplexing. However, to ensure accurate and reliable applicability, the nanostructured probes need to be designed, synthesized, and characterized very rigorously. In my talk, I will report on our development of intracellular probes for the detection of viral pathogens, providing tips and guidelines to reduce opsonization, increase stability, reduce cytotoxicity, and improve performance.
Gold nanostars are well-known as effective substrates for applications in which near field enhancements are sought, owing to their uniquely sharp protruding spikes. In particular, we have shown how they can be employed to build sensing platforms for the direct identification of small molecule analytes via surface enhanced Raman spectroscopy (SERS) achieving femtomolar limits of detection. We have also demonstrated how they can be conjugated to peptides for the identification of cancerous cells, and to aptamers for targeting and recognition of prostate cancer cells, with reduced cytotoxicity compared to other colloidal counterparts. Herein, we will show how gold nanostars can be uniquely employed for the identification of influenza virus mutations at the single cell levels and how silica coating layers can be selectively employed to increase stability and biocompatibility and tune the electric field enhancement. However, what is also well known about these nanoparticles is that they are severely impacted by synthetic protocols with low batch-to-batch reproducibility and substantial sample polydispersity, which limit their applicability and scale up. We have addressed this issue by developing a novel bottom-up seed-mediated protocol that produces nanostars with tunable spike lengths and intense localized surface plasmon resonance (LSPR) bands that fall well into the IR region of the spectrum. The unique plasmonic properties of these nanostars, which are also characterized by multiple, well-separated higher harmonics of the fundamental LSPR mode, promise to render them quite advantageous for biomedical applications.
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