Gap-enhanced resonance Raman tags for live-cell imaging
Surface-enhanced Raman scattering (SERS) nanotags are widely used in biomedical field including live-cell imaging due to the high specificity from their fingerprint spectrum and the multiplexing capability from the ultra-narrow linewidth. However, long-term live-cell Raman imaging is limited due to the photodamage from a relatively long exposure time and a high laser power, which are needed for acquiring detectable Raman signals. In this work, we attempt to resolve this issue by developing ultrabright gap-enhanced resonance Raman tags (GERRTs), consisting of the petal-like gold core and silver shell with near-infrared resonant reporters of IR-780 embedded in between, for long-term and high-speed live-cell imaging. GERRTs exhibit the ultrahigh Raman intensity down to a single-nanoparticle level in the aqueous solution and solid state upon 785 nm excitation, allowing for high-resolution time-lapse live-cell Raman imaging with an exposure time of 1 ms per pixel and a laser power of 50 μW. Under this measurement condition, we can possibly capture dynamic cellular processes with a high temporal resolution, and track living cells for long periods of time owing to the reduced photodamage to cells. These nanotags open new opportunities for ultrasensitive, low-phototoxic, and long-term live-cell imaging.