High-sensitivity imaging of time-domain near-infrared light transducer

Abstract

The optically transparent biological window in the near-infrared (NIR) spectral range allows deep-tissue excitation and the detection of fluorescence signals1,2. Spectrum-domain discrimination of NIR contrast agents via an upconversion or downshifting scheme requires sufficient (anti-) Stokes shift to separate excitation and fluorescence emission. Here, we report a time-domain (τ) scheme in which about 5,000 ytterbium signal transducers are condensed within an optically inert and biocompatible CaF2 shell (2.3 nm), which forms a 14.5 nm τ-dot. Because of the long-lived and spectrally narrowly defined excited state of pure ytterbium ions, the NIR τ-dot can convert the NIR pulsed excitation into long-decaying luminescence with an efficiency approaching 100%. Within a safe injection dosage of 13 μg g−1, an excitation power density of 1.1 mW cm−2 was sufficient to image organs with a signal-to-noise ratio of >9. The high brightness of τ-dots further allows long-term in vivo passive targeting and dynamic tracking in a tumour-bearing mouse model. By time-shifting short-pulse excitation photon energy into prolonged luminescent emission in the time domain, both the number of light signal transducers in sub-15 nm nanoparticles and the near-infrared-in to near-infrared-out conversion efficiency can be maximized, advancing in vivo optical bioimaging.