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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 >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.

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The data that support the plots within this paper and other findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

This project was primarily supported by the National Key R&D Program of China (2017YFA0205100), the National Natural Science Foundation of China (21527801, 21722101, 61729501 and 51720105015), the Strategic Seeding Fund of the UTS Institute for Biomedical Materials and Devices (IBMD) and the Australian Research Council (ARC) Future Fellowship Scheme (to D.J., FT 130100517). The authors thank X. Chen, D. Tu and W. You for their help with lifetime measurements.

Author information

W.F., D.J. and F.L. conceived the project and supervised the research. Y.Gu synthesized the nanoparticles and was primarily responsible for conducting the experiments. Z.G., F.W. and D.J. designed and modified the optical spectroscopy and imaging instruments. Y.Gu, D.J., J.Z., W.F. and F.L. analysed the results, prepared the figures and wrote the manuscript. All authors participated in discussions and editing of the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Wei Feng or Dayong Jin or Fuyou Li.

Supplementary information

  1. Supplementary Information

    This file contains more information about the work, Supplementary Figures 1–37 and Supplementary Tables 1–4.

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Fig. 1: Schematic illustration of the high brightness of time-domain optical transducers provided by luminescent τ-dot nanocrystals.
Fig. 2: Morphology characterization and luminescence intensity measurements of time-domain τ-dots, upconversion and downshifting nanocrystals.
Fig. 3: Comparison of the luminescence imaging performances of as-prepared NIR τ-dots, typical upconversion nanoparticles used in the NIR I region and downshifting nanoparticles used in the NIR II region that were injected in mice through the tail vein.
Fig. 4: Multiplexed time-resolved bioimaging of lifetime-tunable NaYbF4@CaF2 τ-dot nanocrystals.
Fig. 5: Comparison of performances in passive tumour-targeting experiments of α-NaYbF4@CaF2 NIR τ-dots in time-gated detection mode and c.w. mode and β-NaYbF4,2%Er,2%Ce@NaYF4 downshifting nanoparticles emitting around 1,550 nm.