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Advances and challenges for fluorescence nanothermometry

Abstract

Fluorescent nanothermometers can probe changes in local temperature in living cells and in vivo and reveal fundamental insights into biological properties. This field has attracted global efforts in developing both temperature-responsive materials and detection procedures to achieve sub-degree temperature resolution in biosystems. Recent generations of nanothermometers show superior performance to earlier ones and also offer multifunctionality, enabling state-of-the-art functional imaging with improved spatial, temporal and temperature resolutions for monitoring the metabolism of intracellular organelles and internal organs. Although progress in this field has been rapid, it has not been without controversy, as recent studies have shown possible biased sensing during fluorescence-based detection. Here, we introduce the design principles and advances in fluorescence nanothermometry, highlight application achievements, discuss scenarios that may lead to biased sensing, analyze the challenges ahead in terms of both fundamental issues and practical implementations, and point to new directions for improving this interdisciplinary field.

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Fig. 1: Typical temperature-sensing strategies and working mechanisms of different nanothermometers.
Fig. 2: Examples of intracellular and in vivo temperature sensing with fluorescent nanothermometers.
Fig. 3: Factors that often induce artifacts and biased temperature readouts.
Fig. 4: New designs of temperature-responsive materials.
Fig. 5: Examples of new modalities for accurate sensing.
Fig. 6: Temperature monitoring and imaging of mitochondria in live cells.
Fig. 7: High temperature resolution, reliability and volumetric thermometry are needed for in vivo applications.

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References

  1. Jaque, D. & Vetrone, F. Luminescence nanothermometry. Nanoscale 4, 4301–4326 (2012).

    CAS  PubMed  Google Scholar 

  2. Brites, C. D. S. et al. Instantaneous ballistic velocity of suspended Brownian nanocrystals measured by upconversion nanothermometry. Nat. Nanotechnol. 11, 851–856 (2016).

    CAS  PubMed  Google Scholar 

  3. Geitenbeek, R. G. et al. In situ luminescence thermometry to locally measure temperature gradients during catalytic reactions. ACS Catal. 8, 2397–2401 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Mi, C., Zhou, J., Wang, F., Lin, G. & Jin, D. Ultrasensitive ratiometric nanothermometer with large dynamic range and photostability. Chem. Mater. 31, 9480–9487 (2019). This paper presents a ratiometric nanothermometer that exploits the phonon-assisted thermal enhancement of the emission of UCNPs, achieving the highest reported thermal sensitivity for lanthanide-based thermometers: 9.6% K−1 at 300 K.

    CAS  Google Scholar 

  5. Kucsko, G. et al. Nanometre-scale thermometry in a living cell. Nature 500, 54–58 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Kiyonaka, S. et al. Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells. Nat. Methods 10, 1232–1238 (2013).

    CAS  PubMed  Google Scholar 

  7. Hattori, K. et al. ASK1 signalling regulates brown and beige adipocyte function. Nat. Commun. 7, 11158 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Okabe, K. et al. Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy. Nat. Commun. 3, 705 (2012). This work demonstrates the use of fluorescence lifetime imaging microscopy to measure the heterogeneous temperature distribution within cells at diffraction-limited spatial resolutions.

    PubMed  Google Scholar 

  9. Xu, M. et al. Ratiometric nanothermometer in vivo based on triplet sensitized upconversion. Nat. Commun. 9, 2698 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. Zhu, X. et al. Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature. Nat. Commun. 7, 10437 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhu, X. et al. Upconversion nanocomposite for programming combination cancer therapy by precise control of microscopic temperature. Nat. Commun. 9, 2176 (2018). This paper presents a multifunctional nanocomposite—combining UCNPs, photothermal agents and anticancer drugs—for hyperthermia therapy and thermally activated drug delivery with in situ temperature control in mice.

    PubMed  PubMed Central  Google Scholar 

  12. Zhou, H., Sharma, M., Berezin, O., Zuckerman, D. & Berezin, M. Y. Nanothermometry: from microscopy to thermal treatments. ChemPhysChem 17, 27–36 (2016).

    CAS  PubMed  Google Scholar 

  13. Suzuki, M. & Plakhotnik, T. The challenge of intracellular temperature. Biophys. Rev. 12, 593–600 (2020).

    PubMed  PubMed Central  Google Scholar 

  14. Zhou, J. et al. Activation of the surface dark-layer to enhance upconversion in a thermal field. Nat. Photonics 12, 154–158 (2018).

    CAS  Google Scholar 

  15. Zhou, J., Chizhik, A. I., Chu, S. & Jin, D. Single-particle spectroscopy for functional nanomaterials. Nature 579, 41–50 (2020).

    CAS  PubMed  Google Scholar 

  16. Quintanilla, M. & Liz-Marzán, L. M. Guiding rules for selecting a nanothermometer. Nano Today 19, 126–145 (2018).

    CAS  Google Scholar 

  17. Chrétien, D. et al. Mitochondria are physiologically maintained at close to 50 °C. PLoS Biol. 16, e2003992 (2018). This paper reports on the large temperature differential between mitochondria of fully functional cells and their environment using MitoThermo Yellow as a temperature sensor.

    PubMed  PubMed Central  Google Scholar 

  18. Li, Q. et al. Surface-modified silicon nanoparticles with ultrabright photoluminescence and single-exponential decay for nanoscale fluorescence lifetime imaging of temperature. J. Am. Chem. Soc. 135, 14924–14927 (2013).

    CAS  PubMed  Google Scholar 

  19. Kalytchuk, S. et al. Carbon dot nanothermometry: Intracellular photoluminescence lifetime thermal sensing. ACS Nano 11, 1432–1442 (2017).

    CAS  PubMed  Google Scholar 

  20. Varshni, Y. P. Temperature dependence of the energy gap in semiconductors. Physica 34, 149–154 (1967).

    CAS  Google Scholar 

  21. Maestro, L. M. et al. CdSe quantum dots for two-photon fluorescence thermal imaging. Nano Lett. 10, 5109–5115 (2010).

    CAS  PubMed  Google Scholar 

  22. Maestro, L. M. et al. CdTe quantum dots as nanothermometers: towards highly sensitive thermal imaging. Small 7, 1774–1778 (2011).

    CAS  PubMed  Google Scholar 

  23. Vetrone, F. et al. Temperature sensing using fluorescent nanothermometers. ACS Nano 4, 3254–3258 (2010).

    CAS  PubMed  Google Scholar 

  24. Balabhadra, S. et al. Boosting the sensitivity of Nd3+-based luminescent nanothermometers. Nanoscale 7, 17261–17267 (2015).

    CAS  PubMed  Google Scholar 

  25. Senapati, S. & Nanda, K. K. Red emitting Eu:ZnO nanorods for highly sensitive fluorescence intensity ratio based optical thermometry. J. Mater. Chem. C. Mater. Opt. Electron. Devices 5, 1074–1082 (2017).

    CAS  Google Scholar 

  26. Donner, J. S., Thompson, S. A., Kreuzer, M. P., Baffou, G. & Quidant, R. Mapping intracellular temperature using green fluorescent protein. Nano Lett. 12, 2107–2111 (2012).

    CAS  PubMed  Google Scholar 

  27. Zondervan, R., Kulzer, F., van der Meer, H., Disselhorst, J. A. J. M. & Orrit, M. Laser-driven microsecond temperature cycles analyzed by fluorescence polarization microscopy. Biophys. J. 90, 2958–2969 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Neumann, P. et al. High-precision nanoscale temperature sensing using single defects in diamond. Nano Lett. 13, 2738–2742 (2013).

    CAS  PubMed  Google Scholar 

  29. Tsai, P.-C. et al. Measuring nanoscale thermostability of cell membranes with single gold-diamond nanohybrids. Angew. Chem. Int. Ed. Engl. 56, 3025–3030 (2017).

    CAS  PubMed  Google Scholar 

  30. Plakhotnik, T., Doherty, M. W., Cole, J. H., Chapman, R. & Manson, N. B. All-optical thermometry and thermal properties of the optically detected spin resonances of the NV center in nanodiamond. Nano Lett. 14, 4989–4996 (2014).

    CAS  PubMed  Google Scholar 

  31. Choi, S., Agafonov, V. N., Davydov, V. A. & Plakhotnik, T. Ultrasensitive all-optical thermometry using nanodiamonds with a high concentration of silicon-vacancy centers and multiparametric data analysis. ACS Photonics 6, 1387–1392 (2019).

    CAS  Google Scholar 

  32. Fan, J.-W. et al. Germanium-vacancy color center in diamond as a temperature sensor. ACS Photonics 5, 765–770 (2018).

    CAS  Google Scholar 

  33. Alkahtani, M. et al. Tin-vacancy in diamonds for luminescent thermometry. Appl. Phys. Lett. 112, 241902 (2018).

    Google Scholar 

  34. Huang, H., Delikanli, S., Zeng, H., Ferkey, D. M. & Pralle, A. Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nat. Nanotechnol. 5, 602–606 (2010).

    CAS  PubMed  Google Scholar 

  35. Nakano, M. et al. Genetically encoded ratiometric fluorescent thermometer with wide range and rapid response. PLoS One 12, e0172344 (2017).

    PubMed  PubMed Central  Google Scholar 

  36. Savchuk, O. A., Silvestre, O. F., Adão, R. M. R. & Nieder, J. B. GFP fluorescence peak fraction analysis based nanothermometer for the assessment of exothermal mitochondria activity in live cells. Sci. Rep. 9, 7535 (2019).

    PubMed  PubMed Central  Google Scholar 

  37. Kriszt, R. et al. Optical visualisation of thermogenesis in stimulated single-cell brown adipocytes. Sci. Rep. 7, 1383 (2017).

    PubMed  PubMed Central  Google Scholar 

  38. Xie, T.-R., Liu, C.-F. & Kang, J.-S. Dye-based mito-thermometry and its application in thermogenesis of brown adipocytes. Biophys. Rep. 3, 85–91 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Jenkins, J., Borisov, S. M., Papkovsky, D. B. & Dmitriev, R. I. Sulforhodamine nanothermometer for multiparametric fluorescence lifetime imaging microscopy. Anal. Chem. 88, 10566–10572 (2016).

    CAS  PubMed  Google Scholar 

  40. Arai, S., Lee, S. C., Zhai, D., Suzuki, M. & Chang, Y. T. A molecular fluorescent probe for targeted visualization of temperature at the endoplasmic reticulum. Sci. Rep. 4, 6701 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Gota, C., Okabe, K., Funatsu, T., Harada, Y. & Uchiyama, S. Hydrophilic fluorescent nanogel thermometer for intracellular thermometry. J. Am. Chem. Soc. 131, 2766–2767 (2009).

    CAS  PubMed  Google Scholar 

  42. Tsuji, T., Yoshida, S., Yoshida, A. & Uchiyama, S. Cationic fluorescent polymeric thermometers with the ability to enter yeast and mammalian cells for practical intracellular temperature measurements. Anal. Chem. 85, 9815–9823 (2013).

    CAS  PubMed  Google Scholar 

  43. Tsuji, T., Ikado, K., Koizumi, H., Uchiyama, S. & Kajimoto, K. Difference in intracellular temperature rise between matured and precursor brown adipocytes in response to uncoupler and β-adrenergic agonist stimuli. Sci. Rep. 7, 12889 (2017).

    PubMed  PubMed Central  Google Scholar 

  44. Kimura, H. et al. The thermogenic actions of natriuretic peptide in brown adipocytes: the direct measurement of the intracellular temperature using a fluorescent thermoprobe. Sci. Rep. 7, 12978 (2017).

    PubMed  PubMed Central  Google Scholar 

  45. Oyama, K. et al. Walking nanothermometers: spatiotemporal temperature measurement of transported acidic organelles in single living cells. Lab Chip 12, 1591–1593 (2012).

    CAS  PubMed  Google Scholar 

  46. Takei, Y. et al. A nanoparticle-based ratiometric and self-calibrated fluorescent thermometer for single living cells. ACS Nano 8, 198–206 (2014).

    CAS  PubMed  Google Scholar 

  47. Yang, J.-M., Yang, H. & Lin, L. Quantum dot nano thermometers reveal heterogeneous local thermogenesis in living cells. ACS Nano 5, 5067–5071 (2011).

    CAS  PubMed  Google Scholar 

  48. Tanimoto, R. et al. Detection of temperature difference in neuronal cells. Sci. Rep. 6, 22071 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Jin, D. et al. Nanoparticles for super-resolution microscopy and single-molecule tracking. Nat. Methods 15, 415–423 (2018).

    CAS  PubMed  Google Scholar 

  50. Simpson, D. A. et al. Non-neurotoxic nanodiamond probes for intraneuronal temperature mapping. ACS Nano 11, 12077–12086 (2017).

    CAS  PubMed  Google Scholar 

  51. Baffou, G., Rigneault, H., Marguet, D. & Jullien, L. A critique of methods for temperature imaging in single cells. Nat. Methods 11, 899–901 (2014).

    CAS  PubMed  Google Scholar 

  52. Uchiyama, S., Gota, C., Tsuji, T. & Inada, N. Intracellular temperature measurements with fluorescent polymeric thermometers. Chem. Commun. (Camb.) 53, 10976–10992 (2017).

    CAS  Google Scholar 

  53. Okabe, K., Sakaguchi, R., Shi, B. & Kiyonaka, S. Intracellular thermometry with fluorescent sensors for thermal biology. Pflug. Arch. 470, 717–731 (2018).

    CAS  Google Scholar 

  54. Kiyonaka, S. et al. Validating subcellular thermal changes revealed by fluorescent thermosensors. Nat. Methods 12, 801–802 (2015).

    CAS  PubMed  Google Scholar 

  55. Bastos, A. R. N. et al. Thermal properties of lipid bilayers determined using upconversion nanothermometry. Adv. Funct. Mater. 29, 1905474 (2019).

    CAS  Google Scholar 

  56. Suzuki, M., Zeeb, V., Arai, S., Oyama, K. & Ishiwata, S. The 105 gap issue between calculation and measurement in single-cell thermometry. Nat. Methods 12, 802–803 (2015).

    CAS  PubMed  Google Scholar 

  57. Baffou, G., Rigneault, H., Marguet, D. & Jullien, L. Reply to: “Validating subcellular thermal changes revealed by fluorescent thermosensors” and “The 105 gap issue between calculation and measurement in single-cell thermometry”. Nat. Methods 12, 803 (2015).

    CAS  PubMed  Google Scholar 

  58. Wang, C. et al. Determining intracellular temperature at single-cell level by a novel thermocouple method. Cell Res. 21, 1517–1519 (2011).

    PubMed  PubMed Central  Google Scholar 

  59. Rajagopal, M. C. et al. Transient heat release during induced mitochondrial proton uncoupling. Commun. Biol. 2, 279 (2019).

    PubMed  PubMed Central  Google Scholar 

  60. Inomata, N., Toda, M., Sato, M., Ishijima, A. & Ono, T. Pico calorimeter for detection of heat produced in an individual brown fat cell. Appl. Phys. Lett. 100, 154104 (2012).

    Google Scholar 

  61. Inomata, N., Inaoka, R., Okabe, K., Funatsu, T. & Ono, T. Short-term temperature change detections and frequency signals in single cultured cells using a microfabricated thermistor. Sens. Biosensing Res. 27, 100309 (2020).

    Google Scholar 

  62. Hu, S. et al. Quantifying surface temperature of thermoplasmonic nanostructures. J. Am. Chem. Soc. 140, 13680–13686 (2018).

    CAS  PubMed  Google Scholar 

  63. Sugimura, T., Kajimoto, S. & Nakabayashi, T. Label-free imaging of intracellular temperature by using the O−H stretching Raman band of water. Angew. Chem. Int. Ed. Engl. 59, 7755–7760 (2020).

    CAS  PubMed  Google Scholar 

  64. Yuexuan, Y. & Daocheng, W. Research shortcomings of fluorescent nanothermometers in biological and medical fields. Nanomed. (Lond.) 15, 735–738 (2020).

    Google Scholar 

  65. Shen, Y. et al. Ag2S nanoheaters with multiparameter sensing for reliable thermal feedback during in vivo tumor therapy. Adv. Funct. Mater. (in the press).

  66. Donner, J. S. et al. Imaging of plasmonic heating in a living organism. ACS Nano 7, 8666–8672 (2013).

    CAS  PubMed  Google Scholar 

  67. Deepankumar, K. et al. Temperature sensing using red fluorescent protein. Biotechnol. Bioprocess Eng. ; BBE 20, 67–72 (2015).

    CAS  PubMed  Google Scholar 

  68. Arai, S. et al. Micro-thermography in millimeter-scale animals by using orally-dosed fluorescent nanoparticle thermosensors. Analyst 140, 7534–7539 (2015).

    CAS  PubMed  Google Scholar 

  69. Ferdinandus et al. Facilely fabricated luminescent nanoparticle thermosensor for real-time microthermography in living animals. ACS Sens. 1, 1222–1227 (2016).

    CAS  Google Scholar 

  70. Carrasco, E. et al. Intratumoral thermal reading during photo-thermal therapy by multifunctional fluorescent nanoparticles. Adv. Funct. Mater. 25, 615–626 (2015).

    CAS  Google Scholar 

  71. Jaque, D. et al. Nanoparticles for photothermal therapies. Nanoscale 6, 9494–9530 (2014).

    CAS  PubMed  Google Scholar 

  72. Gustafson, T. P., Cao, Q., Wang, S. T. & Berezin, M. Y. Design of irreversible optical nanothermometers for thermal ablations. Chem. Commun. (Camb.) 49, 680–682 (2013).

    CAS  Google Scholar 

  73. Ximendes, E. C. et al. Unveiling in vivo subcutaneous thermal dynamics by infrared luminescent nanothermometers. Nano Lett. 16, 1695–1703 (2016).

    CAS  PubMed  Google Scholar 

  74. Ximendes, E. C. et al. In vivo subcutaneous thermal video recording by supersensitive infrared nanothermometers. Adv. Funct. Mater. 27, 1702249 (2017).

    Google Scholar 

  75. Ximendes, E. C. et al. In vivo ischemia detection by luminescent nanothermometers. Adv. Healthc. Mater. 6, 1601195 (2017).

    Google Scholar 

  76. Santos, H. D. A. et al. In vivo early tumor detection and diagnosis by infrared luminescence transient nanothermometry. Adv. Funct. Mater. 28, 1803924 (2018).

    Google Scholar 

  77. del Rosal, B. et al. In vivo contactless brain nanothermometry. Adv. Funct. Mater. 28, 1806088 (2018).

    Google Scholar 

  78. Liu, P. Y. et al. Cell refractive index for cell biology and disease diagnosis: past, present and future. Lab Chip 16, 634–644 (2016).

    CAS  PubMed  Google Scholar 

  79. Senden, T., Rabouw, F. T. & Meijerink, A. Photonic effects on the radiative decay rate and luminescence quantum yield of doped nanocrystals. ACS Nano 9, 1801–1808 (2015).

    CAS  PubMed  Google Scholar 

  80. Shen, Y., Lifante, J., Fernández, N., Jaque, D. & Ximendes, E. In vivo spectral distortions of infrared luminescent nanothermometers compromise their reliability. ACS Nano 14, 4122–4133 (2020). This work shows the impact of tissue absorption and scattering in the spectral features of nanothermometers, indicating how those can lead to erroneous temperature readouts.

    CAS  PubMed  Google Scholar 

  81. Akers, W. J. et al. Noninvasive photoacoustic and fluorescence sentinel lymph node identification using dye-loaded perfluorocarbon nanoparticles. ACS Nano 5, 173–182 (2011).

    CAS  PubMed  Google Scholar 

  82. Rodríguez-Sevilla, P. et al. Thermal scanning at the cellular level by an optically trapped upconverting fluorescent particle. Adv. Mater. 28, 2421–2426 (2016).

    PubMed  Google Scholar 

  83. Chan, M. S. et al. Stepwise ligand-induced self-assembly for facile fabrication of nanodiamond-gold nanoparticle dimers via noncovalent biotin-streptavidin interactions. Nano Lett. 19, 2020–2026 (2019).

    CAS  PubMed  Google Scholar 

  84. Piñol, R. et al. Joining time-resolved thermometry and magnetic-induced heating in a single nanoparticle unveils intriguing thermal properties. ACS Nano 9, 3134–3142 (2015).

    PubMed  Google Scholar 

  85. Suo, H., Zhao, X., Zhang, Z. & Guo, C. 808 nm light-triggered thermometer-heater upconverting platform based on Nd3+-sensitized yolk-shell GdOF@SiO2. ACS Appl. Mater. Interfaces 9, 43438–43448 (2017).

    CAS  PubMed  Google Scholar 

  86. Marciniak, L., Pilch, A., Arabasz, S., Jin, D. & Bednarkiewicz, A. Heterogeneously Nd3+ doped single nanoparticles for NIR-induced heat conversion, luminescence, and thermometry. Nanoscale 9, 8288–8297 (2017).

    CAS  PubMed  Google Scholar 

  87. Roder, P. B., Smith, B. E., Zhou, X., Crane, M. J. & Pauzauskie, P. J. Laser refrigeration of hydrothermal nanocrystals in physiological media. Proc. Natl Acad. Sci. USA 112, 15024–15029 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Rahman, A. T. M. A. & Barker, P. F. Laser refrigeration, alignment and rotation of levitated Yb3+:YLF nanocrystals. Nat. Photonics 11, 634–638 (2017).

    CAS  Google Scholar 

  89. Li, Z. et al. Simultaneous local heating/thermometry based on plasmonic magnetochromic nanoheaters. Small 14, e1800868 (2018).

    PubMed  Google Scholar 

  90. Rodríguez-Sevilla, P., Arita, Y., Liu, X., Jaque, D. & Dholakia, K. The temperature of an optically trapped, rotating microparticle. ACS Photonics 5, 3772–3778 (2018).

    Google Scholar 

  91. Qiu, X. et al. Ratiometric upconversion nanothermometry with dual emission at the same wavelength decoded via a time-resolved technique. Nat. Commun. 11, 4 (2020). This paper presents a QD-UCNP nanocomposite emitting in the near infrared for lifetime-based in vivo thermometry.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Lane, N. Hot mitochondria? PLoS Biol. 16, e2005113 (2018).

    PubMed  PubMed Central  Google Scholar 

  93. Arai, S. et al. Mitochondria-targeted fluorescent thermometer monitors intracellular temperature gradient. Chem. Commun. (Camb.) 51, 8044–8047 (2015).

    CAS  Google Scholar 

  94. Homma, M., Takei, Y., Murata, A., Inoue, T. & Takeoka, S. A ratiometric fluorescent molecular probe for visualization of mitochondrial temperature in living cells. Chem. Commun. (Camb.) 51, 6194–6197 (2015).

    CAS  Google Scholar 

  95. Zhang, X., Sun, Q., Huang, Z., Huang, L. & Xiao, Y. Immobilizable fluorescent probes for monitoring the mitochondria microenvironment: a next step from the classic. J. Mater. Chem. B Mater. Biol. Med. 7, 2749–2758 (2019).

    CAS  PubMed  Google Scholar 

  96. Huang, Z., Li, N., Zhang, X., Wang, C. & Xiao, Y. Fixable molecular thermometer for real-time visualization and quantification of mitochondrial temperature. Anal. Chem. 90, 13953–13959 (2018).

    CAS  PubMed  Google Scholar 

  97. Jakobs, S., Stephan, T., Ilgen, P. & Brüser, C. Light microscopy of mitochondria at the nanoscale. Annu. Rev. Biophys. 49, 289–308 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Huang, X. et al. Fast, long-term, super-resolution imaging with Hessian structured illumination microscopy. Nat. Biotechnol. 36, 451–459 (2018).

    CAS  PubMed  Google Scholar 

  99. Stephan, T., Roesch, A., Riedel, D. & Jakobs, S. Live-cell STED nanoscopy of mitochondrial cristae. Sci. Rep. 9, 12419 (2019).

    PubMed  PubMed Central  Google Scholar 

  100. Yang, X. et al. Mitochondrial dynamics quantitatively revealed by STED nanoscopy with an enhanced squaraine variant probe. Nat. Commun. 11, 3699 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Wang, C. et al. A photostable fluorescent marker for the superresolution live imaging of the dynamic structure of the mitochondrial cristae. Proc. Natl Acad. Sci. USA 116, 15817–15822 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Santos, H. D. A. et al. Ultrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging. Nat. Commun. 11, 2933 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhou, J., Huang, B., Yan, Z. & Bünzli, J. G. Emerging role of machine learning in light-matter interaction. Light Sci. Appl. 8, 84 (2019).

    PubMed  PubMed Central  Google Scholar 

  104. Liu, L. et al. Wideband fluorescence-based thermometry by neural network recognition: Photothermal application with 10 ns time resolution. J. Appl. Phys. 118, 184906 (2015).

    Google Scholar 

  105. Munro, T., Liu, L., Glorieux, C. & Ban, H. CdSe/ZnS quantum dot fluorescence spectra shape-based thermometry via neural network reconstruction. J. Appl. Phys. 119, 214903 (2016).

    Google Scholar 

  106. Xiao, Y., Wan, C., Shahsafi, A., Salman, J. & Kats, M. A. Depth thermography: noninvasive 3D temperature profiling using infrared thermal emission. ACS Photonics 7, 853–860 (2020).

    CAS  Google Scholar 

  107. Yang, X.-F., Chang, J. H. & Rothman, S. M. Intracerebral temperature alterations associated with focal seizures. Epilepsy Res. 52, 97–105 (2002).

    PubMed  Google Scholar 

  108. Hayashi, T., Fukuda, N., Uchiyama, S. & Inada, N. A cell-permeable fluorescent polymeric thermometer for intracellular temperature mapping in mammalian cell lines. PLoS One 10, e0117677 (2015).

    PubMed  PubMed Central  Google Scholar 

  109. Qiao, J. et al. Ratiometric fluorescent polymeric thermometer for thermogenesis investigation in living cells. Anal. Chem. 87, 10535–10541 (2015).

    CAS  PubMed  Google Scholar 

  110. Qiao, J. et al. Simultaneous monitoring of mitochondrial temperature and ATP fluctuation using fluorescent probes in living cells. Anal. Chem. 90, 12553–12558 (2018).

    CAS  PubMed  Google Scholar 

  111. del Rosal, B. et al. Infrared-emitting QDs for thermal therapy with real-time subcutaneous temperature feedback. Adv. Funct. Mater. 26, 6060–6068 (2016).

    Google Scholar 

  112. Kato, H. et al. ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue. Life Sci. Alliance 3, e201900576 (2020).

    PubMed  PubMed Central  Google Scholar 

  113. Hoshi, Y. et al. Ischemic brain injury leads to brain edema via hyperthermia-induced TRPV4 activation. J. Neurosci. 38, 5700–5709 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Rexius-Hall, M. L., Uchiyama, S., Eddington, D. & Rehman, J. Glycolysis is required for rapid adipocyte thermogenesis induced by cold stress. FASEB J. 31 (Suppl. 1), 886.14 (2017).

    Google Scholar 

  115. Choi, J. et al. Probing and manipulating embryogenesis via nanoscale thermometry and temperature control. Proc. Natl Acad. Sci. USA 117, 14636–14641 (2020).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors acknowledge financial support from the Australian Research Council (ARC) Discovery Early Career Researcher Award Scheme (J. Z., DE180100669; B. R., DE200100985), the Chancellor’s Postdoctoral Fellowship Scheme at the University of Technology Sydney (J. Z.) and RMIT University (B. R.), the Ministerio de Economı́a y Competitividad-MINECO (MAT2016-75362-C3-1-R), the Ministerio de Ciencia e Innovacion of Spain (PID2019-106211RB-I00) and the Comunidad de Madrid (B2017/BMD-3867 RENIM-CM) co-financed by European Structural and Investment Fund, the European Commission Horizon 2020 project NanoTBTech and the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research B, 17H03075).

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Zhou, J., del Rosal, B., Jaque, D. et al. Advances and challenges for fluorescence nanothermometry. Nat Methods 17, 967–980 (2020). https://doi.org/10.1038/s41592-020-0957-y

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