Surface-Enhanced Raman Scattering Active Plasmonic Nanoparticles with Ultrasmall Interior Nanogap for Multiplex Quantitative Detection and Cancer Cell Imaging

Abstract

Due to its large enhancement effect, nanostructure-based surface-enhanced Raman scattering (SERS) technology had been widely applied for bioanalysis and cell imaging. However, most SERS nanostructures suffer from poor signal reproducibility, which hinders the application of SERS nanostructures in quantitative detection. We report an etching-assisted approach to synthesize SERS-active plasmonic nanoparticles with 1 nm interior nanogap for multiplex quantitative detection and cancer cell imaging. Raman dyes and methoxy poly(ethylene glycol) thiol (mPEG-SH) were attached to gold nanoparticles (AuNPs) to prepare gold cores. Next, Ag atoms were deposited on gold cores in the presence of Pluronic F127 to form a Ag shell. HAuCl4 was used to etch the Ag shell and form an interior nanogap in Au@AgAuNPs, leading to increased Raman intensity of dyes. SERS intensity distribution of Au@AgAuNPs was found to be more uniform than that of aggregated AuNPs. Finally, Au@AgAuNPs were used for multiplex quantitative detection and cancer cell imaging. With the advantages of simple and rapid preparation of Au@AgAuNPs with highly uniform, stable, and reproducible Raman intensity, the method reported here will widen the applications of SERS-active nanoparticles in diagnostics and imaging.

Sub‐5 nm Metal Nanogaps: Physical Properties, Fabrication Methods, and Device Applications

“…In recent years, core–shell nanoparticles with interior nanogaps have attracted increasing attention due to their unique chemical and physical properties, as the gap size can be easily tuned by controlling the thickness of the spacer between metal core and shell, consequently controlling the extent of the coupling and induced near‐field enhancement between the core and shell. As exhibited in Figure c–f, dielectric layers, DNA, small organic molecules, and polymers have been employed as spacers to form interior nanogaps. Although dielectric spacers are easily coated on metal cores, their thickness is normally on the scale of tens of nanometers .…”

Intracellular and Cellular Detection by SERS‐Active Plasmonic Nanostructures

“…Yang et al. developed a plasmonic sensor with a 1 nm interior nanogap for multiplexed quantitative detection and bioimaging of cancer cells . The NNPs were prepared through silver deposition on AuNP cores modified with Raman dyes and PEG in the presence of Pluronic F127.…”

“…[83] The infiltrative tumor margins and microscopics atellite metastases were specifically identified and eliminated, thus leading to completet umor surgery.Y ang et al developed ap lasmonic sensorw ith a1nm interior nanogap for multiplexedq uantitative detection andb ioimaging of cancer cells. [84] The NNPs were prepared through silver deposition on AuNP cores modifiedw ith Ramand yes and PEG in the presence of Pluronic F127. Further silver shell etchingw ith HAuCl 4 was conducted to enhance the Raman signals.…”

Visual Quantitative Detection of Circulating Tumor Cells with Single‐Cell Sensitivity Using a Portable Microfluidic Device

“…The spread of the primary tumor to remote sites is the major cause of cancer complications and the usual reason for cancer‐related deaths . Early cancer detection is crucial for enhanced prognosis and ease of cancer management.…”