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Amplified stimulated emission in upconversion nanoparticles for super-resolution nanoscopy

Abstract

Lanthanide-doped glasses and crystals are attractive for laser applications because the metastable energy levels of the trivalent lanthanide ions facilitate the establishment of population inversion and amplified stimulated emission at relatively low pump power1,2,3. At the nanometre scale, lanthanide-doped upconversion nanoparticles (UCNPs) can now be made with precisely controlled phase, dimension and doping level4,5. When excited in the near-infrared, these UCNPs emit stable, bright visible luminescence at a variety of selectable wavelengths6,7,8,9, with single-nanoparticle sensitivity10,11,12,13, which makes them suitable for advanced luminescence microscopy applications. Here we show that UCNPs doped with high concentrations of thulium ions (Tm3+), excited at a wavelength of 980 nanometres, can readily establish a population inversion on their intermediate metastable 3H4 level: the reduced inter-emitter distance at high Tm3+ doping concentration leads to intense cross-relaxation, inducing a photon-avalanche-like effect that rapidly populates the metastable 3H4 level, resulting in population inversion relative to the 3H6 ground level within a single nanoparticle. As a result, illumination by a laser at 808 nanometres, matching the upconversion band of the 3H4 → 3H6 transition, can trigger amplified stimulated emission to discharge the 3H4 intermediate level, so that the upconversion pathway to generate blue luminescence can be optically inhibited. We harness these properties to realize low-power super-resolution stimulated emission depletion (STED) microscopy and achieve nanometre-scale optical resolution (nanoscopy), imaging single UCNPs; the resolution is 28 nanometres, that is, 1/36th of the wavelength. These engineered nanocrystals offer saturation intensity two orders of magnitude lower than those of fluorescent probes currently employed in stimulated emission depletion microscopy, suggesting a new way of alleviating the square-root law that typically limits the resolution that can be practically achieved by such techniques.

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Figure 1: Probing upconversion luminescence using dual-laser illumination.
Figure 2: Competition between absorption and stimulated emission.
Figure 3: The photon-avalanche-like process underlying enhanced population inversion.
Figure 4: Optical switching efficiency with respect to Tm doping concentration.
Figure 5: Super-resolution imaging of the highly-doped UCNPs.

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Acknowledgements

This project was primarily supported by the Australian Research Council (ARC) Future Fellowship Scheme (D.J., FT 130100517), the ARC Centre of Excellence for Nanoscale BioPhotonics (CE140100003), the Natural Science Foundation of China (61428501, 31327901, 61475010), and the National Instrumentation Project of China (2013YQ03065102). Y. Lu acknowledges support from a Macquarie University Research Fellowship.

Author information

Authors and Affiliations

Authors

Contributions

D.J. and P.X. conceived the project. D.J., P.X. and J.A.P. supervised the research. Y. Liu, X.Y., F.W., X.Z. and Z.Z. conducted the optical experiments. S.W., J. Zhao, D.L., J. Zhou, and C.M. synthesized the upconversion nanoparticles. Y. Lu carried out the modelling. Y. Lu, Y. Liu, X.Y., X.Z., X.V., P.X. and D.J. analysed the results, prepared the figures and wrote the manuscript. All authors participated in discussion and editing of the manuscript.

Corresponding authors

Correspondence to Yiqing Lu, Peng Xi or Dayong Jin.

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The authors declare no competing financial interests.

Additional information

Reviewer Information Nature thanks Y. D. Suh and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Extended data figures and tables

Extended Data Figure 1 Optical layout of the dual-laser confocal/super-resolution microscope for probing NaYF4:Yb,Tm nanocrystals.

SMF, single-mode fibre; PMF, polarization-maintaining fibre; MMF, multi-mode fibre; DC1 and DC2, dichroic filters; L1, L2 and L3, collimation/collection lenses; HWP, half-wave plate; QWP, quarter-wave plate; VPP, vortex phase plate; SPAD, single-photon avalanche diode; M, mirror.

Extended Data Figure 2 Upconversion emission spectra of 8% (left) and 1% (right) Tm-doped UCNPs.

The 980 nm and 808 nm laser powers measured at the objective back aperture were 1 and 10 mW, respectively.

Extended Data Figure 3 Transient responses of 650 nm upconversion emission under synchronous 980 nm and 808 nm pulses.

Left, 8% Tm-doped UCNPs; right, 1% Tm-doped UCNPs. The 980 nm laser power was fixed at 1 mW, while the 808 nm laser power was varied from 0 to 40 mW (both measured at the objective back aperture).

Extended Data Figure 4 Modelling of the photon-avalanche-like process in upconversion materials.

a, Simplified three-level energy diagram of an upconversion system containing sensitizers and emitters. b, Block diagram illustrating photon avalanche as a feedback process, with its type (positive or negative) determined by the sign of (k – bW3). c, Numerical simulation of the emitter populations based on the rate parameters reported previously14. Comparison between non-resonant ground-level pumping (top) and resonant ground-level pumping (bottom) shows that the threshold occurs only if non-resonant ground-level pumping is employed. See Methods for details.

Extended Data Figure 5 Simulation of the Yb–Tm upconversion system.

a, Energy level diagram used for rate equation modelling. b, Rate parameters simulated for the 8% Tm-doped UCNPs. c, Comparison between the simulation and the experimental results for the 8% Tm-doped UCNPs under dual-laser excitation with different pulse sequences (left and right). d, Numerical simulation of the emitter populations under 980 nm pumping only, using the obtained c1 value (left), and by artificially setting c1 = 1 to reveal the threshold (right). Details of rate equation modelling are given in Methods.

Extended Data Figure 6 TEM images of the NaYF4:Yb,Tm nanocrystals.

The Yb doping concentration was fixed at 20 mol%, and aj, the Tm doping concentrations are respectively 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 and 8 mol%. All nanocrystals have average sizes around 40 nm. Scale bar, 100 nm.

Extended Data Figure 7 Simulation of the optical switching at 455 nm for 8% Tm-doped UCNPs.

a, The 455 nm depletion ratio as a function of the 808 nm probing rate, which is simulated using the rate parameters listed in Extended Data Fig. 5b. The curve fits well to 1/(1 + I/IS) except for the high power range. b, Emitter populations as a function of time, again simulated using the rate parameters listed in Extended Data Fig. 5b. The 980 nm pumping is turned on at time = 0 s, while the 808 nm probing is turned on at time = 0.5 ms. Note the overlap between n1 (3H6 ground level) and n3 (3H4 intermediate level) once the 808 nm probing is turned on.

Extended Data Figure 8 Time-series upconversion-STED images recorded for the same sample area under continuous laser excitation and scanning.

The sample slide contains 40-nm UCNPs with 8% Tm and 20% Yb. The 455 nm upconversion emission photon count is colour coded. The 980 and 808 nm laser powers at the objective back aperture were 1 and 30 mW, respectively. The scan step is 20 nm and the pixel dwell time is 4 ms. Scale bar, 500 nm.

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Liu, Y., Lu, Y., Yang, X. et al. Amplified stimulated emission in upconversion nanoparticles for super-resolution nanoscopy. Nature 543, 229–233 (2017). https://doi.org/10.1038/nature21366

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