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

The optically transparent biological window in the near-infrared (NIR) spectral range allows deep-tissue excitation and the detection of fluorescence signals(1,2). 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 (tau) scheme in which about 5,000 ytterbium signal transducers are condensed within an optically inert and biocompatible CaF2 shell (2.3nm), which forms a 14.5nm tau-dot. Because of the long-lived and spectrally narrowly defined excited state of pure ytterbium ions, the NIR tau-dot can convert the NIR pulsed excitation into long-decaying luminescence with an efficiency approaching 100%. Within a safe injection dosage of 13 mu gg(-1), an excitation power density of 1.1mW cm(-2) was sufficient to image organs with a signal-to-noise ratio of >9. The high brightness of tau-dots further allows long-term in vivo passive targeting and dynamic tracking in a tumour-bearing mouse model.