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

• Published in: Nature photonics Vol. 13; no. 8; pp. 525 - 531
• Main Authors: Gu, Yuyang, Guo, Zhiyong, Yuan, Wei, Kong, Mengya, Liu, Yulai, Liu, Yongtao, Gao, Yilin, Feng, Wei, Wang, Fan, Zhou, Jiajia, Jin, Dayong, Li, Fuyou
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2019; Nature Publishing Group
• Subjects: 639/301/357/354; 639/624/1107/510; 639/624/1111/55; 639/925/930/2735; Applied and Technical Physics; Bearing (direction); Biocompatibility; Contrast agents; Contrast media; Dosage; Efficiency; Emission; Emissions; Energy; Excitation spectra; Fluorescence; I.R. radiation; Infrared imaging; Infrared windows; Letter; Lifetime; Medical imaging; Nanocrystals; Nanomaterials; Nanoparticles; Near infrared radiation; Optics; Organs; Photonics; Physics; Quantum dots; Quantum Physics; Short pulses; Signal to noise ratio; Time domain analysis; Transducers; Tumors; Upconversion; Windows (intervals); Ytterbium
• ISSN: 1749-4885; 1749-4893
• DOI: 10.1038/s41566-019-0437-z

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 (τ) scheme in which about 5,000 ytterbium signal transducers are condensed within an optically inert and biocompatible CaF 2 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.