Uniform silver-containing metal nanostructures with well-defined nanogaps hold great promise for ultrasensitive surface-enhanced Raman scattering (SERS) analyses. Nevertheless, the direct synthesis of such nanostructures with strong and stable SERS signals remains extremely challenging. Here, we report a DNA-mediated approach for the direct synthesis of gold-silver nano-mushrooms with interior nanogaps. The SERS intensities of these nano-mushrooms were critically dependent on the area of the nanogap between the gold head and the silver cap. We found that the formation of nanogaps was finely tunable by controlling the surface density of 6-carboxy-X-rhodamine (ROX) labeled single-stranded DNA (ssDNA) on the gold nanoparticles. We obtained nano-mushrooms in high yield with a high SERS signal enhancement factor of ~1.0 × 10⁹, much higher than that for Au-Ag nanostructures without nanogaps. Measurements for single nanomushrooms show that these structures have both sensitive and reproducible SERS signals.

A novel nano- and micro-integrated protein chip (NMIPC) that can detect proteins with ultrahigh sensitivity has been fabricated. A microfluidic network (μFN) was used to construct the protein chips, which allowed facile patterning of proteins and subsequent biomolecular recognition. Aqueous phase-synthesized, water-soluble fluorescent CdTe/CdS core-shell quantum dots (aqQDs), having high quantum yield and high photostability, were used as the signaling probe. Importantly, it was found that aqQDs were compatible with microfluidic format assays, which afforded highly sensitive protein chips for cancer biomarker assays.