Petal-like Gap-Enhanced Raman Tags with Controllable Structures for High-Speed Raman Imaging

Surface-enhanced Raman scattering (SERS) is widely used for in vitro and in vivo bioimaging applications. However, reproducible and controllable fabrication of SERS tags with high density of electromagnetic hot-spots is still challenging. We report an improved strategy for the synthesis of core/shell Raman tags with high density of hot-spots and high immobilization of reporter molecules. The strategy is based on simultaneous growth and functionalization of an Au shell around Au nanospheres coated with 4-nitrobenzenethiol (NBT). The amount of added 4-NBT is key factor to control the structure SERS response of the resulting particles. Specifically, we demonstrate the formation of gap-enhanced Raman tags (GERTs) with a smooth solid shell (sGERTs), petal-like GERTs (pGERTs), and mesoporous Au particles (mGERTs) filled with Raman molecules. In contrast to NBT molecules, similar thiols such as 1,4-benzenedithiol (BDT) and 2-naphtalenethiol (NT) do not support the formation of pGERTs and mGERTs. To explain this finding, we proposed a growth mechanism based on the unique chemical structure of NBT. The SERS response of optimized pGERTs is 50 times higher than that from usual sGERTs, which makes pGERTs suitable for single-particle spectroscopy. We demonstrate successful application of pGERTs for high-speed cell imaging using 10 ms accumulation time per pixel and a total imaging time of about 1 min. Because of the high SERS response and unique porous structure, these nanoparticles have great potential for bioimaging and other applications.