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 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.

[1]  Wei Feng,et al.  High-Contrast Visualization of Upconversion Luminescence in Mice Using Time-Gating Approach. , 2016, Analytical chemistry.

[2]  R. Nitschke,et al.  Quantum dots versus organic dyes as fluorescent labels , 2008, Nature Methods.

[3]  Juan Wang,et al.  Direct evidence of a surface quenching effect on size-dependent luminescence of upconversion nanoparticles. , 2010, Angewandte Chemie.

[4]  J. Luther,et al.  Absolute Photoluminescence Quantum Yields of IR-26 Dye, PbS, and PbSe Quantum Dots , 2010 .

[5]  Noah D Bronstein,et al.  Enhancing Quantum Yield via Local Symmetry Distortion in Lanthanide-Based Upconverting Nanoparticles , 2016 .

[6]  R. Tsien,et al.  Fluorescence-guided surgery with live molecular navigation — a new cutting edge , 2013, Nature Reviews Cancer.

[7]  Zhiyuan Hu,et al.  Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm , 2017, Nature Communications.

[8]  Dayong Jin,et al.  Controlling upconversion nanocrystals for emerging applications. , 2015, Nature nanotechnology.

[9]  Shuo Diao,et al.  Biological imaging using nanoparticles of small organic molecules with fluorescence emission at wavelengths longer than 1000 nm. , 2013, Angewandte Chemie.

[10]  Fan Zhang,et al.  Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging , 2018, Nature Nanotechnology.

[11]  John-Christopher Boyer,et al.  Absolute quantum yield measurements of colloidal NaYF4: Er3+, Yb3+ upconverting nanoparticles. , 2010, Nanoscale.

[12]  Shiping Yang,et al.  Core-Shell-Shell NaYbF4:Tm@CaF2@NaDyF4 Nanocomposites for Upconversion/T2-Weighted MRI/Computed Tomography Lymphatic Imaging. , 2016, ACS applied materials & interfaces.

[13]  M. C. Mancini,et al.  Bioimaging: second window for in vivo imaging. , 2009, Nature nanotechnology.

[14]  Jie Shen,et al.  Rare-Earth nanoparticles with enhanced upconversion emission and suppressed rare-Earth-ion leakage. , 2012, Chemistry.

[15]  P. Choyke,et al.  New strategies for fluorescent probe design in medical diagnostic imaging. , 2010, Chemical reviews.

[16]  Guanying Chen,et al.  Lifetime-Encoded Infrared-Emitting Nanoparticles for in Vivo Multiplexed Imaging. , 2018, ACS nano.

[17]  J. Paul Robinson,et al.  Tunable lifetime multiplexing using luminescent nanocrystals , 2013, Nature Photonics.

[18]  P. Prosposito,et al.  Fluorescence efficiency of four infrared polymethine dyes , 2003 .

[19]  B. Wall,et al.  Rare-earth-doped biological composites as in vivo shortwave infrared reporters , 2013, Nature Communications.

[20]  Deming Liu,et al.  Optimal Sensitizer Concentration in Single Upconversion Nanocrystals. , 2017, Nano letters.

[21]  A. Vahrmeijer,et al.  Image-guided cancer surgery using near-infrared fluorescence , 2013, Nature Reviews Clinical Oncology.

[22]  Ghada I. Koleilat,et al.  NIR-emitting colloidal quantum dots having 26% luminescence quantum yield in buffer solution. , 2007, Journal of the American Chemical Society.

[23]  A. Alivisatos.  Semiconductor Clusters, Nanocrystals, and Quantum Dots , 1996, Science.

[24]  F. Auzel.  Upconversion and anti-Stokes processes with f and d ions in solids. , 2004, Chemical reviews.

[25]  P. Prosposito,et al.  IR-Luminescent Molecules in Hybrid Materials , 2003 .

[26]  Kezhi Zheng,et al.  Advances in highly doped upconversion nanoparticles , 2018, Nature Communications.

[27]  Wei Feng,et al.  Upconversion luminescence imaging of cells and small animals , 2013, Nature Protocols.

[28]  D. Jaque,et al.  Overcoming Autofluorescence: Long‐Lifetime Infrared Nanoparticles for Time‐Gated In Vivo Imaging , 2016, Advanced materials.

[29]  P. Prosposito,et al.  Femtosecond dynamics of IR molecules in hybrid materials , 2001 .

[30]  J. Frangioni.  In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[31]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[32]  Zhuang Liu,et al.  Upconversion nanophosphors for small-animal imaging. , 2012, Chemical Society reviews.

[33]  J. Bünzli,et al.  Lanthanide NIR luminescence for telecommunications, bioanalyses and solar energy conversion , 2010 .

[34]  D. Boas,et al.  In vivo imaging and analysis of cerebrovascular hemodynamic responses and tissue oxygenation in the mouse brain , 2018, Nature Protocols.

[35]  J. W. Stouwdam,et al.  Near-infrared Emission of Redispersible Er3+, Nd3+, and Ho3+ Doped LaF3 Nanoparticles , 2002 .

[36]  J. Valenta,et al.  Photoluminescence quantum yield of PbS nanocrystals in colloidal suspensions , 2015 .