On-chip surface-enhanced Raman spectroscopy using nanosphere-lithography patterned antennas on silicon nitride waveguides.

A hybrid integration of nanoplasmonic antennas with silicon nitride waveguides enables miniaturized chips for surface-enhanced Raman spectroscopy at visible and near-infrared wavelengths. This integration can result in high-throughput SERS assays on low sampling volumes. However, current fabrication methods are complex and rely on electron-beam lithography, thereby obstructing the full use of an integrated photonics platform. Here, we demonstrate the electron-beam-free fabrication of gold nanotriangles on deep-UV patterned silicon nitride waveguides using nanosphere lithography. The localized surface-plasmon resonance of these nanotriangles is optimized for Raman excitation at 785 nm, resulting in a SERS substrate enhancement factor of 2.5 × 105. Furthermore, the SERS signal excited and collected through the waveguide is as strong as the free-space excited and collected signal through a high NA objective.

Gold nanodome SERS platform for label-free detection of protease activity.

Surface-enhanced Raman scattering provides a promising technology for sensitive and selective detection of protease activity by monitoring peptide cleavage. Not only are peptides and plasmonic hotspots similarly sized, Raman fingerprints also hold large potential for spectral multiplexing. Here, we use a gold-nanodome platform for real-time detection of trypsin activity on a CALNNYGGGGVRGNF substrate peptide. First, we investigate the spectral changes upon cleavage through the SERS signal of liquid-chromatography separated products. Next, we show that similar patterns are detected upon digesting surface-bound peptides. We demonstrate that the relative intensity of the fingerprints from aromatic amino acids before and after the cleavage site provides a robust figure of merit for the turnover rate. The presented method offers a generic approach for measuring protease activity, which is illustrated by developing an analogous substrate for endoproteinase Glu-C.

Gold nanodome-patterned microchips for intracellular surface-enhanced Raman spectroscopy.

While top-down substrates for surface-enhanced Raman spectroscopy (SERS) offer outstanding control and reproducibility of the gold nanopatterns and their related localized surface plasmon resonance, intracellular SERS experiments heavily rely on gold nanoparticles. These nanoparticles often result in varying and uncontrollable enhancement factors. Here we demonstrate the use of top-down gold-nanostructured microchips for intracellular sensing. We develop a tunable and reproducible fabrication scheme for these microchips. Furthermore we observe the intracellular uptake of these structures, and find no immediate influence on cell viability. Finally, we perform a proof-of-concept intracellular SERS experiment by the label-free detection of extraneous molecules. By bringing top-down SERS substrates to the intracellular world, we set an important step towards time-dependent and quantitative intracellular SERS.

Silver Alginate Hydrogel Micro- and Nanocontainers for Theranostics: Synthesis, Encapsulation, Remote Release, and Detection.

We have designed multifunctional silver alginate hydrogel microcontainers referred to as loaded microcapsules with different sizes by assembling them via a template assisted approach using natural, highly porous calcium carbonate cores. Sodium alginate was immobilized into the pores of calcium carbonate particles of different sizes followed by cross-linking via addition of silver ions, which had a dual purpose: on one hand, the were used as a cross-linking agent, albeit in the monovalent form, while on the other hand they have led to formation of silver nanoparticles. Monovalent silver ions, an unusual cross-linking agent, improve the sensitivity to ultrasound, lead to homogeneous distribution of silver nanoparticles. Silver nanoparticles appeared on the shell of the alginate microcapsules in the twin-structure as determined by transmission electron microscopy. Remote release of a payload from alginate containers by ultrasound was found to strongly depend on the particle size. The possibility to use such particles as a platform for label-free molecule detection based on the surface enhanced Raman scattering was demonstrated. Cytotoxicity and cell uptake studies conducted in this work have revealed that microcontainers exhibit nonessential level of toxicity with an efficient uptake of cells. The above-described functionalities constitute building blocks of a theranostic system, where detection and remote release can be achieved with the same carrier.