Ultrabright gap-enhanced Raman tags for high-speed bioimaging

Abstract

Surface-enhanced Raman spectroscopy (SERS) is advantageous over fluorescence for bioimaging due to ultra-narrow linewidth of the fingerprint spectrum and weak photo-bleaching effect. However, the existing SERS imaging speed lags far behind practical needs, mainly limited by Raman signals of SERS nanoprobes. In this work, we report ultrabright gap-enhanced Raman tags (GERTs) with strong electromagnetic hot spots from interior sub-nanometer gaps and external petal-like shell structures, larger immobilization surface area, and Raman cross section of reporter molecules. These GERTs reach a Raman enhancement factor beyond 5 × 109 and a detection sensitivity down to a single-nanoparticle level. We use a 370 μW laser to realize high-resolution cell imaging within 6 s and high-contrast (a signal-to-background ratio of 80) wide-area (3.2 × 2.8 cm2) sentinel lymph node imaging within 52 s. These nanoprobes offer a potential solution to overcome the current bottleneck in the field of SERS-based bioimaging.