Live-Cell Pyrophosphate Imaging by in Situ Hot-Spot Generation

Controlling the electromagnetic hot- spotgeneration is essential for surface-enhanced Raman scattering (SERS) assays. Current hot- spot-based SERS assays have been extensively studied in solutions or on substrates. However, probing biospecies by controlling the hot- spotassembly in living systemshas not been demonstrated thus far. Herein, we report a background-free SERS probe for imaging pyrophosphate (PPi), a biochemically significant anion, in living cells. Intracellular PPi is able to induce the nanoparticle dimerization, thus creating an intense electromagnetic hot spotand dramatically enhancing the signal of the Raman reporters residing in the hot spot. More impressively, the reporter we used in this study provides a strong and sharp single peak in the cellular Raman-silent region (1800–2800 cm–1), thus eliminating the possible background interference. This strategy could be readily extended to detect other biomarkers by only replacing the recognition ligands.