Single upconversion nanoparticle imaging at sub-10 W cm

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising single-molecule probes given their non-blinking, photobleach-resistant luminescence upon infrared excitation. However, the weak luminescence of sub-50 nm UCNPs limits their single-particle detection to above 10 kWcm(−2) that is impractical for live cell imaging. Here, we systematically characterize single-particle luminescence for UCNPs with various formulations over a 10(6) variation in incident power, down to 8 Wcm(−2). A core-shell-shell (CSS) structure (NaYF(4)@NaYb(1-x)F(4):Er(x)@NaYF(4)) is shown to be significantly brighter than the commonly used NaY(0.78)F(4):Yb(0.2)Er(0.02). At 8 Wcm(−2), the 8% Er(3+) CSS particles exhibit a 150-fold enhancement given their high sensitizer Yb(3+) content and the presence of an inert shell to prevent energy migration to defects. Moreover, we reveal power-dependent luminescence enhancement from the inert shell, which explains the discrepancy in enhancement factors reported by ensemble and previous single-particle measurements. These brighter probes open the possibility of cellular and single-molecule tracking at low irradiance.