Continuous-wave near-infrared stimulated-emission depletion microscopy using downshifting lanthanide nanoparticles
Source abstract
Abstract
Stimulated-emission depletion (STED) microscopy has profoundly extended our horizons to the subcellular level1-3. However, it remains challenging to perform hours-long, autofluorescence-free super-resolution imaging in near-infrared (NIR) optical windows under facile continuous-wave laser depletion at low power4,5. Here we report downshifting lanthanide nanoparticles that enable background-suppressed STED imaging in all-NIR spectral bands (λexcitation = 808 nm, λdepletion = 1,064 nm and λemission = 850-900 nm), with a lateral resolution of below 20 nm and zero photobleaching. With a quasi-four-level configuration and long-lived (τ > 100 μs) metastable states, these nanoparticles support near-unity (98.8%) luminescence suppression under 19 kW cm-2 saturation intensity. The all-NIR regime enables high-contrast deep-tissue (~50 μm) imaging with approximately 70 nm spatial resolution. These lanthanide nanoprobes promise to expand the application realm of STED microscopy and pave the way towards high-resolution time-lapse investigations of cellular processes at superior spatial and temporal dimensions.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Advanced Fluorescence Microscopy Techniques · Photoreceptor and optogenetics research · bioluminescence and chemiluminescence research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (37)
Show source-provided references
1. Hell, S. W. Far-field optical nanoscopy. Science 316, 1153–1158 (2007).10.1126/science.1137395 ↗
2. Hell, S. W. & Wichmann, J. Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt. Lett. 19, 780–782 (1994).10.1364/OL.19.000780 ↗
3. Vicidomini, G. et al. Sharper low-power STED nanoscopy by time gating. Nat. Methods 8, 571–573 (2011).10.1038/nmeth.1624 ↗
4. Klar, T. A., Jakobs, S., Dyba, M., Egner, A. & Hell, S. W. Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc. Natl Acad. Sci. USA 97, 8206–8210 (2000).10.1073/pnas.97.15.8206 ↗
5. Willig, K. I., Harke, B., Medda, R. & Hell, S. W. STED microscopy with continuous wave beams. Nat. Methods 4, 915–918 (2007).10.1038/nmeth1108 ↗
6. Chen, B.-C. et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346, 1257998 (2014).10.1126/science.1257998 ↗
7. Bates, M., Huang, B., Dempsey, G. T. & Zhuang, X. Multicolor super-resolution imaging with photo-switchable fluorescent probes. Science 317, 1749–1753 (2007).10.1126/science.1146598 ↗
8. Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642–1645 (2006).10.1126/science.1127344 ↗
9. Fölling, J. et al. Fluorescence nanoscopy by ground-state depletion and single-molecule return. Nat. Methods 5, 943–945 (2008).10.1038/nmeth.1257 ↗
10. Gwosch, K. C. et al. MINFLUX nanoscopy delivers 3D multicolor nanometer resolution in cells. Nat. Methods 17, 217–224 (2020).10.1038/s41592-019-0688-0 ↗
11. Klar, T. A. & Hell, S. W. Subdiffraction resolution in far-field fluorescence microscopy. Opt. Lett. 24, 954–956 (1999).10.1364/OL.24.000954 ↗
12. Eggeling, C. et al. Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457, 1159–1162 (2008).10.1038/nature07596 ↗
13. Vicidomini, G., Bianchini, P. & Diaspro, A. STED super-resolved microscopy. Nat. Methods 15, 173–182 (2018).10.1038/nmeth.4593 ↗
14. Hoebe, R. et al. Controlled light-exposure microscopy reduces photobleaching and phototoxicity in fluorescence live-cell imaging. Nat. Biotechnol. 25, 249–253 (2007).10.1038/nbt1278 ↗
15. An, Z. et al. Stabilizing triplet excited states for ultralong organic phosphorescence. Nat. Mater. 14, 685–690 (2015).10.1038/nmat4259 ↗
16. Bünzli, J.-C. G., Chauvin, A.-S., Kim, H. K., Deiters, E. & Eliseeva, S. V. Lanthanide luminescence efficiency in eight-and nine-coordinate complexes: role of the radiative lifetime. Coord. Chem. Rev. 254, 2623–2633 (2010).10.1016/j.ccr.2010.04.002 ↗
17. Malta, O. Mechanisms of non-radiative energy transfer involving lanthanide ions revisited. J. Non Cryst. Solids 354, 4770–4776 (2008).10.1016/j.jnoncrysol.2008.04.023 ↗
18. O’Brien, J. J. & O’Brien, J. F. The Laporte selection rule in electronic absorption spectroscopy. J. Coll. Sci. Teach. 29, 138–140 (1999).
19. Wisser, M. D. et al. Strain-induced modification of optical selection rules in lanthanide-based upconverting nanoparticles. Nano Lett. 15, 1891–1897 (2015).10.1021/nl504738k ↗
20. Jackson, S. D. Towards high-power mid-infrared emission from a fibre laser. Nat. Photonics 6, 423–431 (2012).10.1038/nphoton.2012.149 ↗
21. Fernandez-Bravo, A. et al. Continuous-wave upconverting nanoparticle microlasers. Nat. Nanotechnol. 13, 572–577 (2018).10.1038/s41565-018-0161-8 ↗
22. Chen, X. et al. Confining energy migration in upconversion nanoparticles towards deep ultraviolet lasing. Nat. Commun. 7, 10304 (2016).10.1038/ncomms10304 ↗
23. Lee, C. et al. Giant nonlinear optical responses from photon-avalanching nanoparticles. Nature 589, 230–235 (2021).10.1038/s41586-020-03092-9 ↗
24. Lando, M., Kagan, J., Linyekin, B. & Dobrusin, V. A solar-pumped Nd:YAG laser in the high collection efficiency regime. Opt. Commun. 222, 371–381 (2003).10.1016/S0030-4018(03)01601-8 ↗
25. Wang, F., Deng, R. & Liu, X. Preparation of core–shell NaGdF4 nanoparticles doped with luminescent lanthanide ions to be used as upconversion-based probes. Nat. Protoc. 9, 1634–1644 (2014).10.1038/nprot.2014.111 ↗
26. Liu, Y. et al. Amplified stimulated emission in upconversion nanoparticles for super-resolution nanoscopy. Nature 543, 229–233 (2017).10.1038/nature21366 ↗
27. Rittweger, E., Han, K. Y., Irvine, S. E., Eggeling, C. & Hell, S. W. STED microscopy reveals crystal colour centres with nanometric resolution. Nat. Photonics 3, 144–147 (2009).10.1038/nphoton.2009.2 ↗
28. Han, K. Y., Kim, S. K., Eggeling, C. & Hell, S. W. Metastable dark states enable ground state depletion microscopy of nitrogen vacancy centers in diamond with diffraction-unlimited resolution. Nano Lett. 10, 3199–3203 (2010).10.1021/nl102156m ↗
29. Hanne, J. et al. STED nanoscopy with fluorescent quantum dots. Nat. Commun. 6, 7127 (2015).10.1038/ncomms8127 ↗
30. Gao, P., Prunsche, B., Zhou, L., Nienhaus, K. & Nienhaus, G. U. Background suppression in fluorescence nanoscopy with stimulated emission double depletion. Nat. Photonics 11, 163–169 (2017).10.1038/nphoton.2016.279 ↗
31. Koechner, W. Solid-State Laser Engineering 38–101 (Springer, 2006).
32. White, J. O. Parameters for quantitative comparison of two-, three-, and four-level laser media, operating wavelengths, and temperatures. IEEE J. Quantum Electron. 45, 1213–1220 (2009).10.1109/JQE.2009.2020607 ↗
33. Rehor, I. & Cigler, P. Precise estimation of HPHT nanodiamond size distribution based on transmission electron microscopy image analysis. Diam. Relat. Mater. 46, 21–24 (2014).10.1016/j.diamond.2014.04.002 ↗
34. Han, K. Y. et al. Three-dimensional stimulated emission depletion microscopy of nitrogen-vacancy centers in diamond using continuous-wave light. Nano Lett. 9, 3323–3329 (2009).10.1021/nl901597v ↗
35. Gu, Y. et al. High-sensitivity imaging of time-domain near-infrared light transducer. Nat. Photonics 13, 525–531 (2019).10.1038/s41566-019-0437-z ↗
36. Chen, C. et al. Multi-photon near-infrared emission saturation nanoscopy using upconversion nanoparticles. Nat. Commun. 9, 3290 (2018).10.1038/s41467-018-05842-w ↗
37. Jin, D. et al. Nanoparticles for super-resolution microscopy and single-molecule tracking. Nat. Methods 15, 415–423 (2018).10.1038/s41592-018-0012-4 ↗