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

Abstract

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 4nitrobenzenethiol (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.

Tumor Phantom with Incorporated SERS Tags: Detectability in a Turbid Medium

“…The intensity of the strongest Raman line was about 16,000 counts (30 mW, 10 s) which was in line with our previous study [26]. We chose the p-GERTs as the SERS tag because they have the strongest SERS response and photostability compared with such tags as Au Nanorods, Ag nanocubes, Au nanostars and gap-enhanced Raman tags with a solid shell [26].…”

“…In agreement with previously reported data [28], the SERS spectrum had characteristic Raman bands dominated by the strongest mode of ν (NO 2 ) at 1331 cm −1 and several minor modes at 723, 854, 1083, 1575, 359 cm −1 . The intensity of the strongest Raman line was about 16,000 counts (30 mW, 10 s) which was in line with our previous study [26]. We chose the p-GERTs as the SERS tag because they have the strongest SERS response and photostability compared with such tags as Au Nanorods, Ag nanocubes, Au nanostars and gap-enhanced Raman tags with a solid shell [26].…”

“…Petal-like gap-enhanced Raman (p-GERTs) tags were obtained by using a template based two-step protocol according to a previous paper [26]. Briefly, at the first stage 20-nm spherical Au cores were prepared according [27].…”

Improving SERS bioimaging of subcutaneous phantom in vivo with optical clearing

“…Petal‐like gap‐enhanced Raman (p‐GERTs) tags [38, 39] were chosen as SERS tags in our study. Nanoparticles were obtained using previously described method [37, 38].…”

“…Nanoparticles were obtained using previously described method [37, 38]. Briefly, 20‐nm spherical Au cores were prepared according [39] and concentrated to a particle number concentration of 1.8 × 10 12 mL −1 . Then 300 μL of NBT (2 mM) was added to Au cores (10 mL) and incubated at room temperature for 20 minutes.…”