Prussian Blue as a Highly Sensitive and Background-Free Resonant Raman Reporter

We report a surprising discovery that Prussian blue (PB) can be employed as a highly sensitive and background-free resonant Raman reporter. Conventional Raman reporters show multiple spectral bands in the fingerprint region, which are generally overlapped with those from dominant endogenous biomolecules, and are thus difficult to be separated. Herein, we found that PB only possesses a strong and sharp single-band in the cellular Raman-silent region, where no Raman signals from biological species were observed. Therefore, the Raman spectra from PB and endogenous biomolecules are completely resolved without resorting to complicated spectral unmixing. Moreover, PB holds a strong UV–vis absorption band between 500 and 900 nm, which is resonant with the incident detection lasers, providing extremely high sensitivity. Through assembly of PB onto plasmonic cores, a new surface-enhanced resonance Raman scattering (SERRS) probe was achieved with a high signal-to-background ratio (SBR). We demonstrated the performance of the PB-based SERRS tags for high-sensitivity immunoassay and cancer cell imaging.