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Scanning probe microscopy

Nature Reviews Methods Primers volume 1, Article number: 36 (2021) Cite this article

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Abstract

Scanning probe microscopy (SPM), a key invention in nanoscience, has by now been extended to a wide spectrum of basic and applied fields. Its application to basic science led to a paradigm shift in the understanding and perception of matter at its nanoscopic and even atomic levels. SPM uses a sharp tip to physically raster-scan samples and locally collect information from the surface. Various signals can be directly detected by SPM in real space with atomic or nanoscale resolution, which provides insights into the structural, electronic, vibrational, optical, magnetic, (bio)chemical and mechanical properties. This Primer introduces the key aspects and general features of SPM and SPM set-up and variations, with particular focus on scanning tunnelling microscopy and atomic force microscopy. We outline how to conduct SPM experiments, as well as data analysis of SPM imaging, spectroscopy and manipulation. Recent applications of SPM to physics, chemistry, materials science and biology are then highlighted, with representative examples. We outline issues with reproducibility, and standards on open data are discussed. This Primer also raises awareness of the ongoing challenges and possible ways to overcome these difficulties, followed by an outlook of future possible directions.

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Fig. 1: Basic set-up for scanning probe microscopy.
Fig. 2: Scanning tunnelling microscopy set-up.
Fig. 3: Basics of atomic force microscopy.
Fig. 4: Schematics of scanning probe spectroscopy and manipulations.
Fig. 5: Typical results of scanning probe microscopy experiments.
Fig. 6: Applications of scanning probe microscopy in physics.
Fig. 7: Applications of scanning probe microscopy in chemistry.
Fig. 8: Applications of scanning probe microscopy in materials science.
Fig. 9: High-resolution atomic force microscopy imaging of biological systems.

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References

  1. Binnig, G., Rohrer, H., Gerber, C. & Weibel, E. Surface studies by scanning tunneling microscopy. Phys. Rev. Lett. 49, 57–61 (1982). This work reports the first atomically resolved image of conductive surfaces with STM.

    Article  ADS  Google Scholar 

  2. Binnig, G., Quate, C. F. & Gerber, C. Atomic force microscope. Phys. Rev. Lett. 56, 930–933 (1986). This work develops AFM for probing non-conductive surfaces.

    Article  ADS  Google Scholar 

  3. Quate, C. F. Vacuum tunneling — a new technique for microscopy. Phys. Today 39, 26–33 (1986).

    Article  Google Scholar 

  4. Lortscher, E., Widmer, D. & Gotsmann, B. Next-generation nanotechnology laboratories with simultaneous reduction of all relevant disturbances. Nanoscale 5, 10542–10549 (2013).

    Article  ADS  Google Scholar 

  5. Besocke, K. An easily operable scanning tunneling microscope. Surf. Sci. 181, 145–153 (1987).

    Article  ADS  Google Scholar 

  6. Pan, S. H., Hudson, E. W. & Davis, J. C. He-3 refrigerator based very low temperature scanning tunneling microscope. Rev. Sci. Instrum. 70, 1459–1463 (1999).

    Article  ADS  Google Scholar 

  7. Gerber, C., Binnig, G., Fuchs, H., Marti, O. & Rohrer, H. Scanning tunneling microscope combined with a scanning electron-microscope. Rev. Sci. Instrum. 57, 221–224 (1986).

    Article  ADS  Google Scholar 

  8. Oliva, A. I., Romero, A., Pena, J. L., Anguiano, E. & Aguilar, M. Electrochemical preparation of tungsten tips for a scanning tunneling microscope. Rev. Sci. Instrum. 67, 1917–1921 (1996).

    Article  ADS  Google Scholar 

  9. Zhang, R. et al. Chemical mapping of a single molecule by plasmon-enhanced Raman scattering. Nature 498, 82–86 (2013).

    Article  ADS  Google Scholar 

  10. Crommie, M. F., Lutz, C. P. & Eigler, D. M. Confinement of electrons to quantum corrals on a metal-surface. Science 262, 218–220 (1993). This article demonstrates the ability of manipulating atoms and constructing artificial quantum structures.

    Article  ADS  Google Scholar 

  11. Eigler, D. M. & Schweizer, E. K. Positioning single atoms with a scanning tunneling microscope. Nature 344, 524–526 (1990).

    Article  ADS  Google Scholar 

  12. Stroscio, J. A. & Eigler, D. M. Atomic and molecular manipulation with the scanning tunneling microscope. Science 254, 1319–1326 (1991).

    Article  ADS  Google Scholar 

  13. Assig, M. et al. A 10 mK scanning tunneling microscope operating in ultra high vacuum and high magnetic fields. Rev. Sci. Instrum. 84, 033903 (2013).

    Article  ADS  Google Scholar 

  14. Meng, W. et al. 30 T scanning tunnelling microscope in a hybrid magnet with essentially non-metallic design. Ultramicroscopy 212, 112975 (2020).

    Article  Google Scholar 

  15. Patera, L. L. et al. Real-time imaging of adatom-promoted graphene growth on nickel. Science 359, 1243–1246 (2018).

    Article  ADS  Google Scholar 

  16. Eren, B. et al. Activation of Cu(111) surface by decomposition into nanoclusters driven by CO adsorption. Science 351, 475–478 (2016).

    Article  ADS  Google Scholar 

  17. Pfisterer, J. H. K., Liang, Y. C., Schneider, O. & Bandarenka, A. S. Direct instrumental identification of catalytically active surface sites. Nature 549, 74–77 (2017).

    Article  ADS  Google Scholar 

  18. Meyer, G. & Amer, N. M. Novel optical approach to atomic force microscopy. Appl. Phys. Lett. 53, 1045–1047 (1988).

    Article  ADS  Google Scholar 

  19. Drake, B. et al. Imaging crystals, polymers, and processes in water with the atomic force microscope. Science 243, 1586–1589 (1989).

    Article  ADS  Google Scholar 

  20. Martin, Y., Williams, C. C. & Wickramasinghe, H. K. Atomic force microscope force mapping and profiling on a sub 100-Å scale. J. Appl. Phys. 61, 4723–4729 (1987).

    Article  ADS  Google Scholar 

  21. Hansma, P. K. et al. Tapping mode atomic-force microscopy in liquids. Appl. Phys. Lett. 64, 1738–1740 (1994).

    Article  ADS  Google Scholar 

  22. Schwenk, J. et al. Achieving μeV tunneling resolution in an in-operando scanning tunneling microscopy, atomic force microscopy, and magnetotransport system for quantum materials research. Rev. Sci. Instrum. 91, 071101 (2020).

    Article  ADS  Google Scholar 

  23. Herruzo, E. T., Perrino, A. P. & Garcia, R. Fast nanomechanical spectroscopy of soft matter. Nat. Commun. 5, 3126 (2014).

    Article  ADS  Google Scholar 

  24. Dufrene, Y. F. et al. Imaging modes of atomic force microscopy for application in molecular and cell biology. Nat. Nanotechnol. 12, 295–307 (2017).

    Article  ADS  Google Scholar 

  25. Ando, T., Uchihashi, T. & Kodera, N. High-speed AFM and applications to biomolecular systems. Annu. Rev. Biophys. 42, 393–414 (2013).

    Article  Google Scholar 

  26. Ohnesorge, F. & Binnig, G. True atomic-resolution by atomic force microscopy through repulsive and attractive forces. Science 260, 1451–1456 (1993).

    Article  ADS  Google Scholar 

  27. Giessibl, F. J. Atomic-resolution of the silicon (111)-(7 × 7) surface by atomic-force microscopy. Science 267, 68–71 (1995).

    Article  ADS  Google Scholar 

  28. Giessibl, F. J. The qPlus sensor, a powerful core for the atomic force microscope. Rev. Sci. Instrum. 90, 011101 (2019).

    Article  ADS  Google Scholar 

  29. Bull, M. S., Sullan, R. M. A., Li, H. B. & Perkins, T. T. Improved single molecule force spectroscopy using micromachined cantilevers. ACS Nano. 8, 4984–4995 (2014).

    Article  Google Scholar 

  30. Florin, E. L., Moy, V. T. & Gaub, H. E. Adhesion forces between individual ligand–receptor pairs. Science 264, 415–417 (1994).

    Article  ADS  Google Scholar 

  31. Muller, D. J. & Dufrene, Y. F. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. Nat. Nanotechnol. 3, 261–269 (2008).

    Article  ADS  Google Scholar 

  32. Huber, F., Lang, H. P., Backmann, N., Rimoldi, D. & Gerber, C. Direct detection of a BRAF mutation in total RNA from melanoma cells using cantilever arrays. Nat. Nanotechnol. 8, 125–129 (2013).

    Article  ADS  Google Scholar 

  33. Dufrene, Y. F., Martinez-Martin, D., Medalsy, I., Alsteens, D. & Muller, D. J. Multiparametric imaging of biological systems by force-distance curve-based AFM. Nat. Methods 10, 847–854 (2013).

    Article  Google Scholar 

  34. Krieg, M. et al. Atomic force microscopy-based mechanobiology. Nat. Rev. Phys. 1, 41–57 (2019).

    Article  Google Scholar 

  35. Gunther, P., Fischer, U. & Dransfeld, K. Scanning near-field acoustic microscopy. Appl. Phys. B 48, 89–92 (1989).

    Article  ADS  Google Scholar 

  36. Giessibl, F. J. High-speed force sensor for force microscopy and profilometry utilizing a quartz tuning fork. Appl. Phys. Lett. 73, 3956–3958 (1998). This work pioneers qPlus-based AFM, which was demonstrated to surpass the spatial resolution of STM.

    Article  ADS  Google Scholar 

  37. Repp, J., Meyer, G., Stojkovic, S. M., Gourdon, A. & Joachim, C. Molecules on insulating films: scanning-tunneling microscopy imaging of individual molecular orbitals. Phys. Rev. Lett. 94, 026803 (2005).

    Article  ADS  Google Scholar 

  38. Heinrich, A. J., Gupta, J. A., Lutz, C. P. & Eigler, D. M. Single-atom spin-flip spectroscopy. Science 306, 466–469 (2004).

    Article  ADS  Google Scholar 

  39. You, S., Lu, J. T., Guo, J. & Jiang, Y. Recent advances in inelastic electron tunneling spectroscopy. Adv. Phys. X 2, 907–936 (2017).

    Google Scholar 

  40. Butt, H. J., Cappella, B. & Kappl, M. Force measurements with the atomic force microscope: technique, interpretation and applications. Surf. Sci. Rep. 59, 1–152 (2005).

    Article  ADS  Google Scholar 

  41. Bartels, L., Meyer, G. & Rieder, K. H. Basic steps of lateral manipulation of single atoms and diatomic clusters with a scanning tunneling microscope tip. Phys. Rev. Lett. 79, 697–700 (1997).

    Article  ADS  Google Scholar 

  42. Lee, H. J. & Ho, W. Single-bond formation and characterization with a scanning tunneling microscope. Science 286, 1719–1722 (1999).

    Article  Google Scholar 

  43. Ho, W. Single-molecule chemistry. J. Chem. Phys. 117, 11033–11061 (2002).

    Article  ADS  Google Scholar 

  44. Jiang, Y., Huan, Q., Fabris, L., Bazan, G. C. & Ho, W. Submolecular control, spectroscopy and imaging of bond-selective chemistry in single functionalized molecules. Nat. Chem. 5, 36–41 (2013).

    Article  Google Scholar 

  45. Ternes, M., Lutz, C. P., Hirjibehedin, C. F., Giessibl, F. J. & Heinrich, A. J. The force needed to move an atom on a surface. Science 319, 1066–1069 (2008).

    Article  ADS  Google Scholar 

  46. Hopkins, L. C., Griffith, J. E., Harriott, L. R. & Vasile, M. J. Polycrystalline tungsten and iridium probe tip preparation with a Ga+ focused ion-beam. J. Vac. Sci. Technol. B 13, 335–337 (1995).

    Article  Google Scholar 

  47. Chen, C. J. Microscopic view of scanning tunneling microscopy. J. Vac. Sci. Technol. A 9, 44–50 (1991).

    Article  ADS  Google Scholar 

  48. Stockle, R. M., Suh, Y. D., Deckert, V. & Zenobi, R. Nanoscale chemical analysis by tip-enhanced Raman spectroscopy. Chem. Phys. Lett. 318, 131–136 (2000).

    Article  ADS  Google Scholar 

  49. Kurouski, D., Mattei, M. & Van Duyne, R. P. Probing redox reactions at the nanoscale with electrochemical tip-enhanced Raman spectroscopy. Nano. Lett. 15, 7956–7962 (2015).

    Article  ADS  Google Scholar 

  50. Bartels, L. et al. Dynamics of electron-induced manipulation of individual CO molecules on Cu(111). Phys. Rev. Lett. 80, 2004–2007 (1998).

    Article  ADS  Google Scholar 

  51. Kichin, G., Weiss, C., Wagner, C., Tautz, F. S. & Temirov, R. Single molecule and single atom sensors for atomic resolution imaging of chemically complex surfaces. J. Am. Chem. Soc. 133, 16847–16851 (2011).

    Article  Google Scholar 

  52. Gross, L. et al. High-resolution molecular orbital imaging using a p-wave STM tip. Phys. Rev. Lett. 107, 086101 (2011).

    Article  ADS  Google Scholar 

  53. Gross, L. et al. Bond-order discrimination by atomic force microscopy. Science 337, 1326–1329 (2012).

    Article  ADS  Google Scholar 

  54. Peng, J. B. et al. Weakly perturbative imaging of interfacial water with submolecular resolution by atomic force microscopy. Nat. Commun. 9, 122 (2018). This article develops hydrogen-sensitive AFM for probing water molecules with submolecular resolution.

    Article  ADS  Google Scholar 

  55. Monig, H. et al. Submolecular imaging by noncontact atomic force microscopy with an oxygen atom rigidly connected to a metallic probe. ACS Nano. 10, 1201–1209 (2016).

    Article  Google Scholar 

  56. Guo, J. et al. Real-space imaging of interfacial water with submolecular resolution. Nat. Mater. 13, 184–189 (2014).

    Article  ADS  Google Scholar 

  57. Hapala, P. et al. Mechanism of high-resolution STM/AFM imaging with functionalized tips. Phys. Rev. B 90, 085421 (2014).

    Article  ADS  Google Scholar 

  58. Muller, D. J., Fotiadis, D., Scheuring, S., Muller, S. A. & Engel, A. Electrostatically balanced subnanometer imaging of biological specimens by atomic force microscope. Biophys. J. 76, 1101–1111 (1999).

    Article  Google Scholar 

  59. Uchihashi, T., Kodera, N. & Ando, T. Guide to video recording of structure dynamics and dynamic processes of proteins by high-speed atomic force microscopy. Nat. Protoc. 7, 1193–1206 (2012).

    Article  Google Scholar 

  60. Wilson, N. R. & Macpherson, J. V. Carbon nanotube tips for atomic force microscopy. Nat. Nanotechnol. 4, 483–491 (2009).

    Article  ADS  Google Scholar 

  61. Besenbacher, F., Jensen, F., Laegsgaard, E., Mortensen, K. & Stensgaard, I. Visualization of the dynamics in surface reconstructions. J. Vac. Sci. Technol. B 9, 874–878 (1991).

    Article  Google Scholar 

  62. Loth, S., Etzkorn, M., Lutz, C. P., Eigler, D. M. & Heinrich, A. J. Measurement of fast electron spin relaxation times with atomic resolution. Science 329, 1628–1630 (2010).

    Article  ADS  Google Scholar 

  63. Terada, Y., Yoshida, S., Takeuchi, O. & Shigekawa, H. Real-space imaging of transient carrier dynamics by nanoscale pump-probe microscopy. Nat. Photonics 4, 869–874 (2010). This work pushes the temporal resolution of STM to an ultra-fast scale by laser-combined STM.

    Article  ADS  Google Scholar 

  64. Yoshida, S. et al. Probing ultrafast spin dynamics with optical pump-probe scanning tunnelling microscopy. Nat. Nanotechnol. 9, 588–593 (2014).

    Article  ADS  Google Scholar 

  65. Cocker, T. L. et al. An ultrafast terahertz scanning tunnelling microscope. Nat. Photonics 7, 620–625 (2013).

    Article  ADS  Google Scholar 

  66. Cocker, T. L., Peller, D., Yu, P., Repp, J. & Huber, R. Tracking the ultrafast motion of a single molecule by femtosecond orbital imaging. Nature 539, 263–267 (2016).

    Article  ADS  Google Scholar 

  67. Martin, Y. & Wickramasinghe, H. K. Magnetic imaging by force microscopy with 1000-Å resolution. Appl. Phys. Lett. 50, 1455–1457 (1987).

    Article  ADS  Google Scholar 

  68. Hartmann, U. Magnetic force microscopy. Annu. Rev. Mater. Sci. 29, 53–87 (1999).

    Article  ADS  Google Scholar 

  69. Kaiser, U., Schwarz, A. & Wiesendanger, R. Magnetic exchange force microscopy with atomic resolution. Nature 446, 522–525 (2007).

    Article  ADS  Google Scholar 

  70. Wiesendanger, R., Guntherodt, H. J., Guntherodt, G., Gambino, R. J. & Ruf, R. Observation of vacuum tunneling of spin-polarized electrons with the scanning tunneling microscope. Phys. Rev. Lett. 65, 247–250 (1990). This work develops the first spin-polarized STM, allowing the probing of magnetic properties of surfaces at atomic scale.

    Article  ADS  Google Scholar 

  71. Wiesendanger, R. Spin mapping at the nanoscale and atomic scale. Rev. Mod. Phys. 81, 1495–1550 (2009).

    Article  ADS  Google Scholar 

  72. Vu, L. N., Wistrom, M. S. & Vanharlingen, D. J. Imaging of magnetic vortices in superconducting networks and clusters by scanning squid microscopy. Appl. Phys. Lett. 63, 1693–1695 (1993).

    Article  ADS  Google Scholar 

  73. Vasyukov, D. et al. A scanning superconducting quantum interference device with single electron spin sensitivity. Nat. Nanotechnol. 8, 639–644 (2013).

    Article  ADS  Google Scholar 

  74. Chang, A. M. et al. Scanning Hall probe microscopy. Appl. Phys. Lett. 61, 1974–1976 (1992).

    Article  ADS  Google Scholar 

  75. Baumann, S. et al. Electron paramagnetic resonance of individual atoms on a surface. Science 350, 417–420 (2015). This article develops the first ESR-STM for measuring ESR and quantum coherence with atomic precision.

    Article  ADS  Google Scholar 

  76. Willke, P. et al. Hyperfine interaction of individual atoms on a surface. Science 362, 336–339 (2018).

    Article  ADS  Google Scholar 

  77. Yang, K. et al. Coherent spin manipulation of individual atoms on a surface. Science 366, 509–512 (2019).

    Article  ADS  Google Scholar 

  78. Rugar, D., Budakian, R., Mamin, H. J. & Chui, B. W. Single spin detection by magnetic resonance force microscopy. Nature 430, 329–332 (2004).

    Article  ADS  Google Scholar 

  79. Balasubramanian, G. et al. Nanoscale imaging magnetometry with diamond spins under ambient conditions. Nature 455, 648–651 (2008).

    Article  ADS  Google Scholar 

  80. Matey, J. R. & Blanc, J. Scanning capacitance microscopy. J. Appl. Phys. 57, 1437–1444 (1985).

    Article  ADS  Google Scholar 

  81. Yoo, M. J. et al. Scanning single-electron transistor microscopy: imaging individual charges. Science 276, 579–582 (1997).

    Article  Google Scholar 

  82. Nonnenmacher, M., Oboyle, M. P. & Wickramasinghe, H. K. Kelvin probe force microscopy. Appl. Phys. Lett. 58, 2921–2923 (1991).

    Article  ADS  Google Scholar 

  83. Guthner, P. & Dransfeld, K. Local poling of ferroelectric polymers by scanning force microscopy. Appl. Phys. Lett. 61, 1137–1139 (1992).

    Article  ADS  Google Scholar 

  84. Gruverman, A., Alexe, M. & Meier, D. Piezoresponse force microscopy and nanoferroic phenomena. Nat. Commun. 10, 1661 (2019).

    Article  ADS  Google Scholar 

  85. Rabe, J. P. & Buchholz, S. Commensurability and mobility in two-dimensional molecular patterns on graphite. Science 253, 424–427 (1991).

    Article  ADS  Google Scholar 

  86. Askadskaya, L. & Rabe, J. P. Anisotropic molecular-dynamics in the vicinity of order–disorder transitions in organic monolayers. Phys. Rev. Lett. 69, 1395–1398 (1992).

    Article  ADS  Google Scholar 

  87. Ciesielski, A. et al. Dynamic covalent chemistry of bisimines at the solid/liquid interface monitored by scanning tunnelling microscopy. Nat. Chem. 6, 1017–1023 (2014).

    Article  Google Scholar 

  88. Itaya, K. & Tomita, E. Scanning tunneling microscope for electrochemistry—a new concept for the insitu scanning tunneling microscope in electrolyte-solutions. Surf. Sci. 201, L507–L512 (1988).

    Article  ADS  Google Scholar 

  89. Fukuma, T., Kobayashi, K., Matsushige, K. & Yamada, H. True molecular resolution in liquid by frequency-modulation atomic force microscopy. Appl. Phys. Lett. 86, 193108 (2005).

    Article  ADS  Google Scholar 

  90. Fukuma, T., Ueda, Y., Yoshioka, S. & Asakawa, H. Atomic-scale distribution of water molecules at the mica–water interface visualized by three-dimensional scanning force microscopy. Phys. Rev. Lett. 104, 016101 (2010).

    Article  ADS  Google Scholar 

  91. Korchev, Y. E., Bashford, C. L., Milovanovic, M., Vodyanoy, I. & Lab, M. J. Scanning ion conductance microscopy of living cells. Biophys. J. 73, 653–658 (1997).

    Article  Google Scholar 

  92. Korchev, Y. E., Negulyaev, Y. A., Edwards, C. R. W., Vodyanoy, I. & Lab, M. J. Functional localization of single active ion channels can the surface of a living cell. Nat. Cell Biol. 2, 616–619 (2000).

    Article  Google Scholar 

  93. Mangold, S., Harneit, K., Rohwerder, T., Claus, G. & Sand, W. Novel combination of atomic force microscopy and epifluorescence microscopy for visualization of leaching bacteria on pyrite. Appl. Environ. Microb. 74, 410–415 (2008).

    Article  Google Scholar 

  94. Guillaume-Gentil, O. et al. Force-controlled manipulation of single cells: from AFM to FluidFM. Trends. Biotechnol. 32, 381–388 (2014).

    Article  Google Scholar 

  95. Muralt, P. & Pohl, D. W. Scanning tunneling potentiometry. Appl. Phys. Lett. 48, 514–516 (1986).

    Article  ADS  Google Scholar 

  96. Eriksson, M. A. et al. Cryogenic scanning probe characterization of semiconductor nanostructures. Appl. Phys. Lett. 69, 671–673 (1996).

    Article  ADS  Google Scholar 

  97. Topinka, M. A. et al. Imaging coherent electron flow from a quantum point contact. Science 289, 2323–2326 (2000).

    Article  ADS  Google Scholar 

  98. Shiraki, I., Tanabe, F., Hobara, R., Nagao, T. & Hasegawa, S. Independently driven four-tip probes for conductivity measurements in ultrahigh vacuum. Surf. Sci. 493, 633–643 (2001).

    Article  ADS  Google Scholar 

  99. Baringhaus, J. et al. Exceptional ballistic transport in epitaxial graphene nanoribbons. Nature 506, 349–354 (2014).

    Article  ADS  Google Scholar 

  100. Lewis, A., Isaacson, M., Harootunian, A. & Muray, A. Development of a 500-Å spatial-resolution light-microscope. 1. Light is efficiently transmitted through λ/16 diameter apertures. Ultramicroscopy 13, 227–231 (1984).

    Article  Google Scholar 

  101. Inouye, Y. & Kawata, S. Near-field scanning optical microscope with a metallic probe tip. Opt. Lett. 19, 159–161 (1994).

    Article  ADS  Google Scholar 

  102. Zenhausern, F., Martin, Y. & Wickramasinghe, H. K. Scanning interferometric apertureless microscopy — optical imaging at 10 Angstrom resolution. Science 269, 1083–1085 (1995).

    Article  ADS  Google Scholar 

  103. Zhang, Y. et al. Visualizing coherent intermolecular dipole–dipole coupling in real space. Nature 531, 623–627 (2016).

    Article  ADS  Google Scholar 

  104. Wei, T., Xiang, X. D., WallaceFreedman, W. G. & Schultz, P. G. Scanning tip microwave near-field microscope. Appl. Phys. Lett. 68, 3506–3508 (1996).

    Article  ADS  Google Scholar 

  105. Lai, K., Ji, M. B., Leindecker, N., Kelly, M. A. & Shen, Z. X. Atomic-force-microscope-compatible near-field scanning microwave microscope with separated excitation and sensing probes. Rev. Sci. Instrum. 78, 063702 (2007).

    Article  ADS  Google Scholar 

  106. Nowak, D. et al. Nanoscale chemical imaging by photoinduced force microscopy. Sci. Adv. 2, e1501571 (2016).

    Article  ADS  Google Scholar 

  107. Ni, T. et al. Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity. Sci. Adv. 6, eaax8286 (2020).

    Article  ADS  Google Scholar 

  108. Gross, L., Mohn, F., Moll, N., Liljeroth, P. & Meyer, G. The chemical structure of a molecule resolved by atomic force microscopy. Science 325, 1110–1114 (2009).

    Article  ADS  Google Scholar 

  109. Guo, J. et al. Nuclear quantum effects of hydrogen bonds probed by tip-enhanced inelastic electron tunneling. Science 352, 321–325 (2016).

    Article  ADS  Google Scholar 

  110. Necas, D. & Klapetek, P. Gwyddion: an open-source software for SPM data analysis. Cent. Eur. J. Phys. 10, 181–188 (2012).

    Google Scholar 

  111. Horcas, I. et al. WSxM: a software for scanning probe microscopy and a tool for nanotechnology. Rev. Sci. Instrum. 78, 013705 (2007).

    Article  ADS  Google Scholar 

  112. Rigato, A., Rico, F., Eghiaian, F., Piel, M. & Scheuring, S. Atomic force microscopy mechanical mapping of micropatterned cells shows adhesion geometry-dependent mechanical response on local and global scales. ACS Nano. 9, 5846–5856 (2015).

    Article  Google Scholar 

  113. Smolyakov, G., Formosa-Dague, C., Severac, C., Duval, R. E. & Dague, E. High speed indentation measures by FV, QI and QNM introduce a new understanding of bionanomechanical experiments. Micron 85, 8–14 (2016).

    Article  Google Scholar 

  114. Kuhlbrandt, W. The resolution revolution. Science 343, 1443–1444 (2014).

    Article  ADS  Google Scholar 

  115. Tang, G. et al. EMAN2: an extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38–46 (2007).

    Article  Google Scholar 

  116. vanHeel, M., Harauz, G., Orlova, E. V., Schmidt, R. & Schatz, M. A new generation of the IMAGIC image processing system. J. Struct. Biol. 116, 17–24 (1996).

    Article  Google Scholar 

  117. Shaikh, T. R. et al. SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs. Nat. Protoc. 3, 1941–1974 (2008).

    Article  Google Scholar 

  118. Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).

    Article  Google Scholar 

  119. Ruan, Y. et al. Structural titration of receptor ion channel GLIC gating by HS-AFM. P Natl. Acad. Sci. 115, 10333–10338 (2018).

    Article  Google Scholar 

  120. Fechner, P. et al. Structural information, resolution, and noise in high-resolution atomic force microscopy topographs. Biophys. J. 96, 3822–3831 (2009).

    Article  ADS  Google Scholar 

  121. Muller, D. J., Fotiadis, D. & Engel, A. Mapping flexible protein domains at subnanometer resolution with the atomic force microscope. FEBS Lett. 430, 105–111 (1998).

    Article  Google Scholar 

  122. Gari, R. R. S. et al. Direct visualization of the E. coli Sec translocase engaging precursor proteins in lipid bilayers. Sci. Adv. 5, eaav9404 (2019).

    Article  ADS  Google Scholar 

  123. Scheuring, S., Rigaud, J. L. & Sturgis, J. N. Variable LH2 stoichiometry and core clustering in native membranes of Rhodospirillum photometricum. EMBO J. 23, 4127–4133 (2004).

    Article  Google Scholar 

  124. Murugesapillai, D. et al. Accurate nanoscale flexibility measurement of DNA and DNA–protein complexes by atomic force microscopy in liquid. Nanoscale 9, 11327–11337 (2017).

    Article  Google Scholar 

  125. Binnig, G., Rohrer, H., Gerber, C. & Weibel, E. 7 × 7 reconstruction on Si(111) resolved in real space. Phys. Rev. Lett. 50, 120–123 (1983).

    Article  ADS  Google Scholar 

  126. Teichmann, K. et al. Controlled charge switching on a single donor with a scanning tunneling microscope. Phys. Rev. Lett. 101, 076103 (2008).

    Article  ADS  Google Scholar 

  127. Zheng, H., Weismann, A. & Berndt, R. Manipulation of subsurface donors in ZnO. Phys. Rev. Lett. 110, 226101 (2013).

    Article  ADS  Google Scholar 

  128. Usman, M. et al. Spatial metrology of dopants in silicon with exact lattice site precision. Nat. Nanotechnol. 11, 763–768 (2016).

    Article  ADS  Google Scholar 

  129. Kloth, P., Kaiser, K. & Wenderoth, M. Controlling the screening process of a nanoscaled space charge region by minority carriers. Nat. Commun. 7, 10108 (2016).

    Article  ADS  Google Scholar 

  130. Guo, C. Y. et al. Probing nonequilibrium dynamics of photoexcited polarons on a metal-oxide surface with atomic precision. Phys. Rev. Lett. 124, 206801 (2020).

    Article  ADS  Google Scholar 

  131. Schofield, S. R. et al. Atomically precise placement of single dopants in Si. Phys. Rev. Lett. 91, 136104 (2003).

    Article  ADS  Google Scholar 

  132. He, Y. et al. A two-qubit gate between phosphorus donor electrons in silicon. Nature 571, 371–375 (2019).

    Article  ADS  Google Scholar 

  133. Heinrich, A. J., Lutz, C. P., Gupta, J. A. & Eigler, D. M. Molecule cascades. Science 298, 1381–1387 (2002).

    Article  ADS  Google Scholar 

  134. Khajetoorians, A. A., Wegner, D., Otte, A. F. & Swart, I. Creating designer quantum states of matter atom-by-atom. Nat. Rev. Phys. 1, 703–715 (2019).

    Article  Google Scholar 

  135. Romming, N. et al. Writing and deleting single magnetic skyrmions. Science 341, 636–639 (2013).

    Article  ADS  Google Scholar 

  136. Ternes, M., Heinrich, A. J. & Schneider, W. D. Spectroscopic manifestations of the Kondo effect on single adatoms. J. Phys.-Condens. Mat. 21, 053001 (2009).

    Article  ADS  Google Scholar 

  137. Heinrich, B. W., Braun, L., Pascual, J. I. & Franke, K. J. Protection of excited spin states by a superconducting energy gap. Nat. Phys. 9, 765–768 (2013).

    Article  Google Scholar 

  138. Nadj-Perge, S. et al. Observation of Majorana fermions in ferromagnetic atomic chains on a superconductor. Science 346, 602–607 (2014).

    Article  ADS  Google Scholar 

  139. Choi, D. J. et al. Colloquium: atomic spin chains on surfaces. Rev. Mod. Phys. 91, 041001 (2019).

    Article  ADS  Google Scholar 

  140. Hla, S. W., Bartels, L., Meyer, G. & Rieder, K. H. Inducing all steps of a chemical reaction with the scanning tunneling microscope tip: towards single molecule engineering. Phys. Rev. Lett. 85, 2777–2780 (2000).

    Article  ADS  Google Scholar 

  141. Meng, X. Z. et al. Direct visualization of concerted proton tunnelling in a water nanocluster. Nat. Phys. 11, 235–239 (2015).

    Article  Google Scholar 

  142. Stipe, B. C., Rezaei, M. A. & Ho, W. Single-molecule vibrational spectroscopy and microscopy. Science 280, 1732–1735 (1998). This article develops IETS, enabling detection of single-molecule vibrations for chemical identification.

    Article  ADS  Google Scholar 

  143. Stipe, B. C., Rezaei, H. A. & Ho, W. Localization of inelastic tunneling and the determination of atomic-scale structure with chemical specificity. Phys. Rev. Lett. 82, 1724–1727 (1999).

    Article  ADS  Google Scholar 

  144. Kim, Y., Motobayashi, K., Frederiksen, T., Ueba, H. & Kawai, M. Action spectroscopy for single-molecule reactions—experiments and theory. Prog. Surf. Sci. 90, 85–143 (2015).

    Article  ADS  Google Scholar 

  145. Lauhon, L. J. & Ho, W. Single molecule thermal rotation and diffusion: acetylene on Cu(001). J. Chem. Phys. 111, 5633–5636 (1999).

    Article  ADS  Google Scholar 

  146. Pascual, J. I., Lorente, N., Song, Z., Conrad, H. & Rust, H. P. Selectivity in vibrationally mediated single-molecule chemistry. Nature 423, 525–528 (2003).

    Article  ADS  Google Scholar 

  147. Hahn, J. R. & Ho, W. Oxidation of a single carbon monoxide molecule manipulated and induced with a scanning tunneling microscope. Phys. Rev. Lett. 87, 166102 (2001).

    Article  ADS  Google Scholar 

  148. Kyriakou, G. et al. Isolated metal atom geometries as a strategy for selective heterogeneous hydrogenations. Science 335, 1209–1212 (2012).

    Article  ADS  Google Scholar 

  149. Bikondoa, O. et al. Direct visualization of defect-mediated dissociation of water on TiO2(110). Nat. Mater. 5, 189–192 (2006).

    Article  ADS  Google Scholar 

  150. Setvin, M. et al. Reaction of O2 with subsurface oxygen vacancies on TiO2 anatase (101). Science 341, 988–991 (2013).

    Article  ADS  Google Scholar 

  151. Li, S. W., Chen, S. Y., Li, J., Wu, R. Q. & Ho, W. Joint space–time coherent vibration driven conformational transitions in a single molecule. Phys. Rev. Lett. 119, 176002 (2017).

    Article  ADS  Google Scholar 

  152. de Oteyza, D. G. et al. Direct imaging of covalent bond structure in single-molecule chemical reactions. Science 340, 1434–1437 (2013).

    Article  ADS  Google Scholar 

  153. Gross, L. et al. Measuring the charge state of an adatom with noncontact atomic force microscopy. Science 324, 1428–1431 (2009).

    Article  ADS  Google Scholar 

  154. Fatayer, S. et al. Molecular structure elucidation with charge-state control. Science 365, 142–145 (2019).

    Article  ADS  Google Scholar 

  155. Sugimoto, Y. et al. Chemical identification of individual surface atoms by atomic force microscopy. Nature 446, 64–67 (2007).

    Article  ADS  Google Scholar 

  156. Xu, J. Y. et al. Determining structural and chemical heterogeneities of surface species at the single-bond limit. Science 371, 818–822 (2021).

    Article  ADS  Google Scholar 

  157. Su, Y. Z., Fu, Y. C., Yan, J. W., Chen, Z. B. & Mao, B. W. Double layer of Au(100)/ionic liquid interface and its stability in imidazolium-based ionic liquids. Angew. Chem. Int. Edit. 48, 5148–5151 (2009).

    Article  Google Scholar 

  158. Ye, S., Ishibashi, C. & Uosaki, K. Anisotropic dissolution of an Au(111) electrode in perchloric acid solution containing chloride anion investigated by in situ STM–the important role of adsorbed chloride anion. Langmuir 15, 807–812 (1999).

    Article  Google Scholar 

  159. Wu, Z. L. & Yau, S. L. Examination of underpotential deposition of copper on Pt(111) electrodes in hydrochloric acid solutions with in situ scanning tunneling microscopy. Langmuir 17, 4627–4633 (2001).

    Article  Google Scholar 

  160. Yoshimoto, S., Higa, N. & Itaya, K. Two-dimensional supramolecular organization of copper octaethylporphyrin and cobalt phthalocyanine on Au(111): molecular assembly control at an electrochemical interface. J. Am. Chem. Soc. 126, 8540–8545 (2004).

    Article  Google Scholar 

  161. Fukuma, T., Kimura, M., Kobayashi, K., Matsushige, K. & Yamada, H. Development of low noise cantilever deflection sensor for multienvironment frequency-modulation atomic force microscopy. Rev. Sci. Instrum. 76, 053704 (2005).

    Article  ADS  Google Scholar 

  162. Ichii, T., Fujimura, M., Negami, M., Murase, K. & Sugimura, H. Frequency modulation atomic force microscopy in ionic liquid using quartz tuning fork sensors. Jpn. J. Appl. Phys. 51, 08KB08 (2012).

    Article  Google Scholar 

  163. Purckhauer, K. et al. Imaging in biologically-relevant environments with AFM using stiff qPlus sensors. Sci. Rep. 8, 9330 (2018).

    Article  ADS  Google Scholar 

  164. Rode, S., Oyabu, N., Kobayashi, K., Yamada, H. & Kuhnle, A. True atomic-resolution imaging of (101‾4) calcite in aqueous solution by frequency modulation atomic force microscopy. Langmuir 25, 2850–2853 (2009).

    Article  Google Scholar 

  165. Fukuma, T., Higgins, M. J. & Jarvis, S. P. Direct imaging of lipid-ion network formation under physiological conditions by frequency modulation atomic force microscopy. Phys. Rev. Lett. 98, 106101 (2007).

    Article  ADS  Google Scholar 

  166. Hiasa, T., Kimura, K. & Onishi, H. Hydration of hydrophilic thiolate monolayers visualized by atomic force microscopy. Phys. Chem. Chem. Phys. 14, 8419–8424 (2012).

    Article  Google Scholar 

  167. Martin-Jimenez, D., Chacon, E., Tarazona, P. & Garcia, R. Atomically resolved three-dimensional structures of electrolyte aqueous solutions near a solid surface. Nat. Commun. 7, 12164 (2016).

    Article  ADS  Google Scholar 

  168. Imada, H., Kimura, K. & Onishi, H. Water and 2-propanol structured on calcite (104) probed by frequency-modulation atomic force microscopy. Langmuir 29, 10744–10751 (2013).

    Article  Google Scholar 

  169. Zhong, J. H. et al. Probing the electronic and catalytic properties of a bimetallic surface with 3 nm resolution. Nat. Nanotechnol. 12, 132–136 (2017).

    Article  ADS  Google Scholar 

  170. Newkome, G. R. et al. Nanoassembly of a fractal polymer: a molecular “Sierpinski hexagonal gasket”. Science 312, 1782–1785 (2006).

    Article  ADS  MathSciNet  Google Scholar 

  171. Hussain, H. et al. Structure of a model TiO2 photocatalytic interface. Nat. Mater. 16, 461–466 (2017).

    Article  ADS  Google Scholar 

  172. Peng, J. et al. Surface coordination layer passivates oxidation of copper. Nature 586, 390–394 (2020).

    Article  ADS  Google Scholar 

  173. Balajka, J., Pavelec, J., Komora, M., Schmid, M. & Diebold, U. Apparatus for dosing liquid water in ultrahigh vacuum. Rev. Sci. Instrum. 89, 083906 (2018).

    Article  ADS  Google Scholar 

  174. Balajka, J. et al. High-affinity adsorption leads to molecularly ordered interfaces on TiO2 in air and solution. Science 361, 786–788 (2018).

    Article  ADS  Google Scholar 

  175. Peng, J. B. et al. The effect of hydration number on the interfacial transport of sodium ions. Nature 557, 701–705 (2018).

    Article  ADS  Google Scholar 

  176. Barth, J. V., Costantini, G. & Kern, K. Engineering atomic and molecular nanostructures at surfaces. Nature 437, 671–679 (2005).

    Article  ADS  Google Scholar 

  177. Manne, S. & Gaub, H. E. Molecular-organization of surfactants at solid–liquid interfaces. Science 270, 1480–1482 (1995).

    Article  ADS  Google Scholar 

  178. Holland, N. B., Qiu, Y. X., Ruegsegger, M. & Marchant, R. E. Biomimetic engineering of non-adhesive glycocalyx-like surfaces using oligosaccharide surfactant polymers. Nature 392, 799–801 (1998).

    Article  ADS  Google Scholar 

  179. Theobald, J. A., Oxtoby, N. S., Phillips, M. A., Champness, N. R. & Beton, P. H. Controlling molecular deposition and layer structure with supramolecular surface assemblies. Nature 424, 1029–1031 (2003).

    Article  ADS  Google Scholar 

  180. Zhong, D. Y. et al. Linear alkane polymerization on a gold surface. Science 334, 213–216 (2011).

    Article  ADS  Google Scholar 

  181. Foster, J. S. & Frommer, J. E. Imaging of liquid-crystals using a tunnelling microscope. Nature 333, 542–545 (1988).

    Article  ADS  Google Scholar 

  182. Ruffieux, P. et al. On-surface synthesis of graphene nanoribbons with zigzag edge topology. Nature 531, 489–492 (2016).

    Article  ADS  Google Scholar 

  183. Messina, P. et al. Direct observation of chiral metal-organic complexes assembled on a Cu(100) surface. J. Am. Chem. Soc. 124, 14000–14001 (2002).

    Article  Google Scholar 

  184. Ma, R. Z. et al. Atomic imaging of the edge structure and growth of a two-dimensional hexagonal ice. Nature 577, 60–63 (2020).

    Article  ADS  Google Scholar 

  185. Zhang, J. et al. Real-space identification of intermolecular bonding with atomic force microscopy. Science 342, 611–614 (2013).

    Article  ADS  Google Scholar 

  186. Shang, J. et al. Assembling molecular Sierpinski triangle fractals. Nat. Chem. 7, 389–393 (2015).

    Article  Google Scholar 

  187. Han, Z. M. et al. Imaging the halogen bond in self-assembled halogenbenzenes on silver. Science 358, 206–210 (2017).

    Article  ADS  Google Scholar 

  188. Okawa, Y. & Aono, M. Materials science — nanoscale control of chain polymerization. Nature 409, 683–684 (2001).

    Article  ADS  Google Scholar 

  189. Muller, W. T. et al. A strategy for the chemical synthesis of nanostructures. Science 268, 272–273 (1995).

    Article  ADS  Google Scholar 

  190. Cai, J. M. et al. Atomically precise bottom-up fabrication of graphene nanoribbons. Nature 466, 470–473 (2010).

    Article  ADS  Google Scholar 

  191. Chen, Y. C. et al. Molecular bandgap engineering of bottom-up synthesized graphene nanoribbon heterojunctions. Nat. Nanotechnol. 10, 156–160 (2015).

    Article  ADS  Google Scholar 

  192. Slota, M. et al. Magnetic edge states and coherent manipulation of graphene nanoribbons. Nature 561, 691–695 (2018).

    Article  ADS  Google Scholar 

  193. Groning, O. et al. Engineering of robust topological quantum phases in graphene nanoribbons. Nature 560, 209–213 (2018).

    Article  ADS  Google Scholar 

  194. Rizzo, D. J. et al. Topological band engineering of graphene nanoribbons. Nature 560, 204–208 (2018).

    Article  ADS  Google Scholar 

  195. Lee, J. et al. Interplay of electron-lattice interactions and superconductivity in Bi2Sr2CaCu2O8+δ. Nature 442, 546–550 (2006).

    Article  ADS  Google Scholar 

  196. Hess, H. F., Robinson, R. B., Dynes, R. C., Valles, J. M. Jr & Waszczak, J. V. Scanning-tunneling-microscope observation of the Abrikosov flux lattice and the density of states near and inside a fluxoid. Phys. Rev. Lett. 62, 214–216 (1989).

    Article  ADS  Google Scholar 

  197. Hoffman, J. E. et al. Imaging quasiparticle interference in Bi2Sr2CaCu2O8+δ. Science 297, 1148–1151 (2002).

    Article  ADS  Google Scholar 

  198. McElroy, K. et al. Relating atomic-scale electronic phenomena to wave-like quasiparticle states in superconducting Bi2Sr2CaCu2O8+δ. Nature 422, 592–596 (2003).

    Article  ADS  Google Scholar 

  199. Vershinin, M. et al. Local ordering in the pseudogap state of the high-Tc superconductor Bi2Sr2CaCu2O8+δ. Science 303, 1995–1998 (2004).

    Article  ADS  Google Scholar 

  200. Song, C. L. et al. Direct observation of nodes and twofold symmetry in FeSe superconductor. Science 332, 1410–1413 (2011).

    Article  ADS  Google Scholar 

  201. Neto, E. H. D. et al. Ubiquitous interplay between charge ordering and high-temperature superconductivity in cuprates. Science 343, 393–396 (2014).

    Article  ADS  Google Scholar 

  202. Cai, P. et al. Visualizing the evolution from the Mott insulator to a charge-ordered insulator in lightly doped cuprates. Nat. Phys. 12, 1047–1051 (2016).

    Article  Google Scholar 

  203. Li, W. et al. Phase separation and magnetic order in K-doped iron selenide superconductor. Nat. Phys. 8, 126–130 (2012).

    Article  Google Scholar 

  204. Parker, C. V. et al. Fluctuating stripes at the onset of the pseudogap in the high-Tc superconductor Bi2Sr2CaCu2O8+x. Nature 468, 677–680 (2010).

    Article  ADS  Google Scholar 

  205. Wise, W. D. et al. Charge-density-wave origin of cuprate checkerboard visualized by scanning tunnelling microscopy. Nat. Phys. 4, 696–699 (2008).

    Article  Google Scholar 

  206. Comin, R. et al. Charge order driven by Fermi-arc instability in Bi2Sr2–xLaxCuO6+δ. Science 343, 390–392 (2014).

    Article  ADS  Google Scholar 

  207. Hamidian, M. H. et al. Detection of a Cooper-pair density wave in Bi2Sr2CaCu2O8+x. Nature 532, 343–347 (2016).

    Article  ADS  Google Scholar 

  208. Zhang, T. et al. Experimental demonstration of topological surface states protected by time-reversal symmetry. Phys. Rev. Lett. 103, 266803 (2009).

    Article  ADS  Google Scholar 

  209. Cheng, P. et al. Landau quantization of topological surface states in Bi2Se3. Phys. Rev. Lett. 105, 076801 (2010).

    Article  ADS  Google Scholar 

  210. Jiang, Y. P. et al. Landau quantization and the thickness limit of topological insulator thin films of Sb2Te3. Phys. Rev. Lett. 108, 016401 (2012).

    Article  ADS  Google Scholar 

  211. Beidenkopf, H. et al. Spatial fluctuations of helical Dirac fermions on the surface of topological insulators. Nat. Phys. 7, 939–943 (2011).

    Article  Google Scholar 

  212. Okada, Y. et al. Direct observation of broken time-reversal symmetry on the surface of a magnetically doped topological insulator. Phys. Rev. Lett. 106, 206805 (2011).

    Article  ADS  Google Scholar 

  213. Hor, Y. S. et al. Superconductivity in CuxBi2Se3 and its implications for pairing in the undoped topological insulator. Phys. Rev. Lett. 104, 057001 (2010).

    Article  ADS  Google Scholar 

  214. Okada, Y. et al. Observation of Dirac node formation and mass acquisition in a topological crystalline insulator. Science 341, 1496–1499 (2013).

    Article  ADS  Google Scholar 

  215. Inoue, H. et al. Quasiparticle interference of the Fermi arcs and surface-bulk connectivity of a Weyl semimetal. Science 351, 1184–1187 (2016).

    Article  ADS  Google Scholar 

  216. Zhu, S. Y. et al. Nearly quantized conductance plateau of vortex zero mode in an iron-based superconductor. Science 367, 189–192 (2020).

    Article  ADS  Google Scholar 

  217. Sun, H. H. et al. Majorana zero mode detected with spin selective Andreev reflection in the vortex of a topological superconductor. Phys. Rev. Lett. 116, 257003 (2016).

    Article  ADS  Google Scholar 

  218. Gomes, K. K., Mar, W., Ko, W., Guinea, F. & Manoharan, H. C. Designer Dirac fermions and topological phases in molecular graphene. Nature 483, 306–310 (2012).

    Article  ADS  Google Scholar 

  219. Slot, M. R. et al. Experimental realization and characterization of an electronic Lieb lattice. Nat. Phys. 13, 672–676 (2017).

    Article  Google Scholar 

  220. Drost, R., Ojanen, T., Harju, A. & Liljeroth, P. Topological states in engineered atomic lattices. Nat. Phys. 13, 668–671 (2017).

    Article  Google Scholar 

  221. Zhang, Y. B. et al. Giant phonon-induced conductance in scanning tunnelling spectroscopy of gate-tunable graphene. Nat. Phys. 4, 627–630 (2008).

    Article  Google Scholar 

  222. Feng, B. J. et al. Experimental realization of two-dimensional boron sheets. Nat. Chem. 8, 564–569 (2016).

    Article  Google Scholar 

  223. Brihuega, I. et al. Quasiparticle chirality in epitaxial graphene probed at the nanometer scale. Phys. Rev. Lett. 101, 206802 (2008).

    Article  ADS  Google Scholar 

  224. Rutter, G. M. et al. Scattering and interference in epitaxial graphene. Science 317, 219–222 (2007).

    Article  ADS  Google Scholar 

  225. Chiu, M. H. et al. Determination of band alignment in the single-layer MoS2/WSe2 heterojunction. Nat. Commun. 6, 7666 (2015).

    Article  ADS  Google Scholar 

  226. Zhang, C. D. et al. Visualizing band offsets and edge states in bilayer–monolayer transition metal dichalcogenides lateral heterojunction. Nat. Commun. 7, 10349 (2016).

    Article  ADS  Google Scholar 

  227. Zhu, J. Q. et al. Argon plasma induced phase transition in monolayer MoS2. J. Am. Chem. Soc. 139, 10216–10219 (2017).

    Article  Google Scholar 

  228. Wang, Z. C. et al. Local engineering of topological phase in monolayer MoS2. Sci. Bull. 64, 1750–1756 (2019).

    Article  Google Scholar 

  229. Uri, A. et al. Mapping the twist-angle disorder and Landau levels in magic-angle graphene. Nature 581, 47–52 (2020).

    Article  ADS  Google Scholar 

  230. Wong, D. L. et al. Cascade of electronic transitions in magic-angle twisted bilayer graphene. Nature 582, 198–202 (2020).

    Article  ADS  Google Scholar 

  231. Zondiner, U. et al. Cascade of phase transitions and Dirac revivals in magic-angle graphene. Nature 582, 203–208 (2020).

    Article  ADS  Google Scholar 

  232. Brar, V. W. et al. Gate-controlled ionization and screening of cobalt adatoms on a graphene surface. Nat. Phys. 7, 43–47 (2011).

    Article  Google Scholar 

  233. Lee, J. et al. Imaging electrostatically confined Dirac fermions in graphene quantum dots. Nat. Phys. 12, 1032–1036 (2016).

    Article  Google Scholar 

  234. Low, T. et al. Polaritons in layered two-dimensional materials. Nat. Mater. 16, 182–194 (2017).

    Article  ADS  Google Scholar 

  235. Chen, J. N. et al. Optical nano-imaging of gate-tunable graphene plasmons. Nature 487, 77–81 (2012).

    Article  ADS  Google Scholar 

  236. Chen, W. O. et al. Direct observation of van der Waals stacking-dependent interlayer magnetism. Science 366, 983–987 (2019).

    Article  ADS  Google Scholar 

  237. Liu, F. C. et al. Room-temperature ferroelectricity in CuInP2S6 ultrathin flakes. Nat. Commun. 7, 12357 (2016).

    Article  ADS  Google Scholar 

  238. Ohmann, R. et al. Real-space imaging of the atomic structure of organic–inorganic perovskite. J. Am. Chem. Soc. 137, 16049–16054 (2015).

    Article  Google Scholar 

  239. Leng, K. et al. Molecularly thin two-dimensional hybrid perovskites with tunable optoelectronic properties due to reversible surface relaxation. Nat. Mater. 17, 908–914 (2018).

    Article  ADS  Google Scholar 

  240. Hieulle, J. et al. Imaging of the atomic structure of all-inorganic halide perovskites. J. Phys. Chem. Lett. 11, 818–823 (2020).

    Article  Google Scholar 

  241. Liu, T. C. et al. In situ quantification of interphasial chemistry in Li-ion battery. Nat. Nanotechnol. 14, 50–56 (2019).

    Article  ADS  Google Scholar 

  242. Verde, M. G. et al. Elucidating the phase transformation of Li4Ti5O12 lithiation at the nanoscale. ACS Nano. 10, 4312–4321 (2016).

    Article  Google Scholar 

  243. Eerenstein, W., Mathur, N. D. & Scott, J. F. Multiferroic and magnetoelectric materials. Nature 442, 759–765 (2006).

    Article  ADS  Google Scholar 

  244. Garcia, V. et al. Giant tunnel electroresistance for non-destructive readout of ferroelectric states. Nature 460, 81–84 (2009).

    Article  ADS  Google Scholar 

  245. Seidel, J. et al. Conduction at domain walls in oxide multiferroics. Nat. Mater. 8, 229–234 (2009).

    Article  ADS  Google Scholar 

  246. Zhao, T. et al. Electrical control of antiferromagnetic domains in multiferroic BiFeO3 films at room temperature. Nat. Mater. 5, 823–829 (2006).

    Article  ADS  Google Scholar 

  247. Lu, H. et al. Mechanical writing of ferroelectric polarization. Science 336, 59–61 (2012).

    Article  ADS  Google Scholar 

  248. Jesse, S. et al. Direct imaging of the spatial and energy distribution of nucleation centres in ferroelectric materials. Nat. Mater. 7, 209–215 (2008).

    Article  ADS  Google Scholar 

  249. Gruverman, A., Wu, D. & Scott, J. F. Piezoresponse force microscopy studies of switching behavior of ferroelectric capacitors on a 100-ns time scale. Phys. Rev. Lett. 100, 097601 (2008).

    Article  ADS  Google Scholar 

  250. Geng, Y. N., Lee, N., Choi, Y. J., Cheong, S. W. & Wu, W. D. Collective magnetism at multiferroic vortex domain walls. Nano Lett. 12, 6055–6059 (2012).

    Article  ADS  Google Scholar 

  251. Gross, I. et al. Real-space imaging of non-collinear antiferromagnetic order with a single-spin magnetometer. Nature 549, 252–256 (2017).

    Article  ADS  Google Scholar 

  252. Muller, D. J. & Engel, A. Voltage and pH-induced channel closure of porin OmpF visualized by atomic force microscopy. J. Mol. Biol. 285, 1347–1351 (1999).

    Article  Google Scholar 

  253. Mulvihill, E. et al. Mechanism of membrane pore formation by human gasdermin-D. EMBO J. 37, e98321 (2018).

    Article  Google Scholar 

  254. Leung, C. et al. Atomic force microscopy with nanoscale cantilevers resolves different structural conformations of the DNA double helix. Nano. Lett. 12, 3846–3850 (2012).

    Article  ADS  Google Scholar 

  255. Pasquina-Lemonche, L. et al. The architecture of the Gram-positive bacterial cell wall. Nature 582, 294–297 (2020). This AFM article brings exciting new insight into the architecture of bacterial cell walls.

    Article  ADS  Google Scholar 

  256. Engel, A. & Muller, D. J. Observing single biomolecules at work with the atomic force microscope. Nat. Struct. Biol. 7, 715–718 (2000).

    Article  Google Scholar 

  257. Matzke, R., Jacobson, K. & Radmacher, M. Direct, high-resolution measurement of furrow stiffening during division of adherent cells. Nat. Cell Biol. 3, 607–610 (2001).

    Article  Google Scholar 

  258. Cisneros, D. A., Hung, C., Franz, C. A. & Muller, D. J. Observing growth steps of collagen self-assembly by time-lapse high-resolution atomic force microscopy. J. Struct. Biol. 154, 232–245 (2006).

    Article  Google Scholar 

  259. Viani, M. B. et al. Probing protein–protein interactions in real time. Nat. Struct. Biol. 7, 644–647 (2000).

    Article  Google Scholar 

  260. Muller, D. J. & Engel, A. Conformations, flexibility, and interactions observed on individual membrane proteins by atomic force microscopy. Methods Cell Biol. 68, 257–299 (2002).

    Article  Google Scholar 

  261. Mari, S. A. et al. Gating of the MlotiK1 potassium channel involves large rearrangements of the cyclic nucleotide-binding domains. Proc. Natl Acad. Sci. USA 108, 20802–20807 (2011).

    Article  ADS  Google Scholar 

  262. Koster, D. A., Croquette, V., Dekker, C., Shuman, S. & Dekker, N. H. Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB. Nature 434, 671–674 (2005).

    Article  ADS  Google Scholar 

  263. Kodera, N., Yamamoto, D., Ishikawa, R. & Ando, T. Video imaging of walking myosin V by high-speed atomic force microscopy. Nature 468, 72–76 (2010). This article on high-speed AFM demonstrates direct imaging of a single motor protein at work.

    Article  ADS  Google Scholar 

  264. Eskandarian, H. A. et al. Division site selection linked to inherited cell surface wave troughs in mycobacteria. Nat. Microbiol. 2, 17094 (2017).

    Article  Google Scholar 

  265. Shibata, M., Yamashita, H., Uchihashi, T., Kandori, H. & Ando, T. High-speed atomic force microscopy shows dynamic molecular processes in photoactivated bacteriorhodopsin. Nat. Nanotechnol. 5, 208–212 (2010).

    Article  ADS  Google Scholar 

  266. Preiner, J. et al. IgGs are made for walking on bacterial and viral surfaces. Nat. Commun. 5, 4394 (2014).

    Article  ADS  Google Scholar 

  267. Uchihashi, T., Iino, R., Ando, T. & Noji, H. High-speed atomic force microscopy reveals rotary catalysis of rotorless F1-ATPase. Science 333, 755–758 (2011).

    Article  ADS  Google Scholar 

  268. Chiaruttini, N. et al. Relaxation of loaded ESCRT-III spiral springs drives membrane deformation. Cell 163, 866–879 (2015).

    Article  Google Scholar 

  269. Sakiyama, Y., Mazur, A., Kapinos, L. E. & Lim, R. Y. H. Spatiotemporal dynamics of the nuclear pore complex transport barrier resolved by high-speed atomic force microscopy. Nat. Nanotechnol. 11, 719–723 (2016).

    Article  ADS  Google Scholar 

  270. Ruan, Y. et al. Direct visualization of glutamate transporter elevator mechanism by high-speed AFM. Proc. Natl Acad. Sci. USA 114, 1584–1588 (2017).

    Article  Google Scholar 

  271. Shibata, M. et al. Real-space and real-time dynamics of CRISPR–Cas9 visualized by high-speed atomic force microscopy. Nat. Commun. 8, 1430 (2017).

    Article  ADS  Google Scholar 

  272. Heath, G. R. & Scheuring, S. High-speed AFM height spectroscopy reveals μs-dynamics of unlabeled biomolecules. Nat. Commun. 9, 4983 (2018).

    Article  ADS  Google Scholar 

  273. Muller, D. J., Buldt, G. & Engel, A. Force-induced conformational change of bacteriorhodopsin. J. Mol. Biol. 249, 239–243 (1995).

    Article  Google Scholar 

  274. Lin, Y. C. et al. Force-induced conformational changes in PIEZO1. Nature 573, 230–234 (2019).

    Article  ADS  Google Scholar 

  275. Hansma, H. G. et al. Reproducible imaging and dissection of plasmid DNA under liquid with the atomic force microscope. Science 256, 1180–1184 (1992).

    Article  ADS  Google Scholar 

  276. Hoh, J. H., Lal, R., John, S. A., Revel, J. P. & Arnsdorf, M. F. Atomic force microscopy and dissection of gap-junctions. Science 253, 1405–1408 (1991).

    Article  ADS  Google Scholar 

  277. Alsteens, D. et al. Atomic force microscopy-based characterization and design of biointerfaces. Nat. Rev. Mater. 2, 17008 (2017).

    Article  ADS  Google Scholar 

  278. Viani, M. B. et al. Fast imaging and fast force spectroscopy of single biopolymers with a new atomic force microscope designed for small cantilevers. Rev. Sci. Instrum. 70, 4300–4303 (1999).

    Article  ADS  Google Scholar 

  279. Miyagi, A. & Scheuring, S. Automated force controller for amplitude modulation atomic force microscopy. Rev. Sci. Instrum. 87, 053705 (2016).

    Article  Google Scholar 

  280. Janshoff, A., Neitzert, M., Oberdorfer, Y. & Fuchs, H. Force spectroscopy of molecular systems — single molecule spectroscopy of polymers and biomolecules. Angew. Chem. Int. Edit. 39, 3213–3237 (2000).

    Google Scholar 

  281. Muller, D. J., Helenius, J., Alsteens, D. & Dufrene, Y. F. Force probing surfaces of living cells to molecular resolution. Nat. Chem. Biol. 5, 383–390 (2009).

    Article  Google Scholar 

  282. Schillers, H. et al. Standardized nanomechanical atomic force microscopy procedure (SNAP) for measuring soft and biological samples. Sci. Rep. 7, 5117 (2017).

    Article  ADS  Google Scholar 

  283. Lomakin, A. J. et al. The nucleus acts as a ruler tailoring cell responses to spatial constraints. Science 370, 310–322 (2020).

    Article  Google Scholar 

  284. Stewart, M. P. et al. Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. Nature 469, 226–230 (2011). This article unravels the biological mechanism of how mammalian cells round up to enter mitosis and divide.

    Article  ADS  Google Scholar 

  285. Ramanathan, S. P. et al. Cdk1-dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement. Nat. Cell Biol. 17, 148–159 (2015).

    Article  Google Scholar 

  286. Medalsy, I. D. & Muller, D. J. Nanomechanical properties of proteins and membranes depend on loading rate and electrostatic interactions. ACS Nano. 7, 2642–2650 (2013).

    Article  Google Scholar 

  287. Rigato, A., Miyagi, A., Scheuring, S. & Rico, F. High-frequency microrheology reveals cytoskeleton dynamics in living cells. Nat. Phys. 13, 771–775 (2017).

    Article  Google Scholar 

  288. Moy, V. T., Florin, E. L. & Gaub, H. E. Intermolecular forces and energies between ligands and receptors. Science 266, 257–259 (1994).

    Article  ADS  Google Scholar 

  289. Milles, L. F., Schulten, K., Gaub, H. E. & Bernardi, R. C. Molecular mechanism of extreme mechanostability in a pathogen adhesin. Science 359, 1527–1532 (2018).

    Article  ADS  Google Scholar 

  290. Evans, E. A. & Calderwood, D. A. Forces and bond dynamics in cell adhesion. Science 316, 1148–1153 (2007).

    Article  ADS  Google Scholar 

  291. Friddle, R. W., Noy, A. & De Yoreo, J. J. Interpreting the widespread nonlinear force spectra of intermolecular bonds. Proc. Natl Acad. Sci. USA 109, 13573–13578 (2012).

    Article  ADS  Google Scholar 

  292. Benoit, M., Gabriel, D., Gerisch, G. & Gaub, H. E. Discrete interactions in cell adhesion measured by single-molecule force spectroscopy. Nat. Cell Biol. 2, 313–317 (2000).

    Article  Google Scholar 

  293. Helenius, J., Heisenberg, C. P., Gaub, H. E. & Muller, D. J. Single-cell force spectroscopy. J. Cell Sci. 121, 1785–1791 (2008).

    Article  Google Scholar 

  294. Alsteens, D. et al. Nanomechanical mapping of first binding steps of a virus to animal cells. Nat. Nanotechnol. 12, 177–183 (2017).

    Article  ADS  Google Scholar 

  295. Lang, H. P. & Gerber, C. Microcantilever sensors. Top. Curr. Chem. 285, 1–27 (2008).

    Article  Google Scholar 

  296. McKendry, R. et al. Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array. Proc. Natl Acad. Sci. USA 99, 9783–9788 (2002). This pioneering microcantilever-based work directly detects the binding of complementary strands of DNA.

    Article  ADS  Google Scholar 

  297. Burg, T. P. et al. Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature 446, 1066–1069 (2007).

    Article  ADS  Google Scholar 

  298. Martinez-Martin, D. et al. Inertial picobalance reveals fast mass fluctuations in mammalian cells. Nature 550, 500–505 (2017).

    Article  ADS  Google Scholar 

  299. Sader, J. E., Chon, J. W. M. & Mulvaney, P. Calibration of rectangular atomic force microscope cantilevers. Rev. Sci. Instrum. 70, 3967–3969 (1999).

    Article  ADS  Google Scholar 

  300. Sader, J. E. et al. A virtual instrument to standardise the calibration of atomic force microscope cantilevers. Rev. Sci. Instrum. 87, 093711 (2016).

    Article  ADS  Google Scholar 

  301. Staudacher, T. et al. Nuclear magnetic resonance spectroscopy on a (5-nanometer)3 sample volume. Science 339, 561–563 (2013).

    Article  ADS  Google Scholar 

  302. Besenbacher, F., Laegsgaard, E. & Stensgaard, I. Fast-scanning STM studies. Mater. Today 8, 26–30 (2005).

    Article  Google Scholar 

  303. Garg, M. & Kern, K. Attosecond coherent manipulation of electrons in tunneling microscopy. Science 367, 411–415 (2020).

    Article  ADS  Google Scholar 

  304. Albrektsen, O., Arent, D. J., Meier, H. P. & Salemink, H. W. M. Tunneling microscopy and spectroscopy of molecular-beam epitaxy grown GaAs–AlGaAs interfaces. Appl. Phys. Lett. 57, 31–33 (1990).

    Article  ADS  Google Scholar 

  305. Kehr, S. C. et al. Near-field examination of perovskite-based superlenses and superlens-enhanced probe–object coupling. Nat. Commun. 2, 249 (2011).

    Article  ADS  Google Scholar 

  306. Gruber, A. et al. Scanning confocal optical microscopy and magnetic resonance on single defect centers. Science 276, 2012–2014 (1997).

    Article  Google Scholar 

  307. Taylor, J. M. et al. High-sensitivity diamond magnetometer with nanoscale resolution. Nat. Phys. 4, 810–816 (2008).

    Article  Google Scholar 

  308. Thiel, L. et al. Quantitative nanoscale vortex imaging using a cryogenic quantum magnetometer. Nat. Nanotechnol. 11, 677–681 (2016).

    Article  ADS  Google Scholar 

  309. Thiel, L. et al. Probing magnetism in 2D materials at the nanoscale with single-spin microscopy. Science 364, 973–976 (2019).

    Article  ADS  Google Scholar 

  310. Bian, K. et al. Nanoscale electric-field imaging based on a quantum sensor and its charge-state control under ambient condition. Nat. Commun. 12, 2457 (2021).

    Article  ADS  Google Scholar 

  311. Schouteden, K. et al. Probing the atomic structure of metallic nanoclusters with the tip of a scanning tunneling microscope. Nanoscale 6, 2170–2176 (2014).

    Article  ADS  Google Scholar 

  312. Umeda, K. et al. Atomic-resolution three-dimensional hydration structures on a heterogeneously charged surface. Nat. Commun. 8, 093706 (2017).

    Article  Google Scholar 

  313. Moreno, C., Stetsovych, O., Shimizu, T. K. & Custance, O. Imaging three-dimensional surface objects with submolecular resolution by atomic force microscopy. Nano. Lett. 15, 2257–2262 (2015).

    Article  ADS  Google Scholar 

  314. Iwata, K. et al. Chemical structure imaging of a single molecule by atomic force microscopy at room temperature. Nat. Commun. 6, 7766 (2015).

    Article  ADS  Google Scholar 

  315. Alldritt, B. et al. Automated structure discovery in atomic force microscopy. Sci. Adv. 6, eaay6913 (2020).

    Article  ADS  Google Scholar 

  316. Grinolds, M. S. et al. Subnanometre resolution in three-dimensional magnetic resonance imaging of individual dark spins. Nat. Nanotechnol. 9, 279–284 (2014).

    Article  ADS  Google Scholar 

  317. Gil-Santos, E. et al. Optomechanical detection of vibration modes of a single bacterium. Nat. Nanotechnol. 15, 469–474 (2020).

    Article  ADS  Google Scholar 

  318. Frenken, J. W. M., Hamers, R. J. & Demuth, J. E. Thermal roughening studied by scanning tunneling microscopy. J. Vac. Sci. Technol. A 8, 293–296 (1990).

    Article  ADS  Google Scholar 

  319. Rico, F., Gonzalez, L., Casuso, I., Puig-Vidal, M. & Scheuring, S. High-speed force spectroscopy unfolds titin at the velocity of molecular dynamics simulations. Science 342, 741–743 (2013).

    Article  ADS  Google Scholar 

  320. Yu, H., Siewny, M. G. W., Edwards, D. T., Sanders, A. W. & Perkins, T. T. Hidden dynamics in the unfolding of individual bacteriorhodopsin proteins. Science 355, 945–949 (2017).

    Article  ADS  Google Scholar 

  321. Oesterhelt, F. et al. Unfolding pathways of individual bacteriorhodopsins. Science 288, 143–146 (2000).

    Article  ADS  Google Scholar 

  322. Raab, A. et al. Antibody recognition imaging by force microscopy. Nat. Biotechnol. 17, 902–905 (1999).

    Article  Google Scholar 

  323. Ebner, A., Wildling, L. & Gruber, H. J. Functionalization of AFM tips and supports for molecular recognition force spectroscopy and recognition imaging. Methods Mol. Biol. 1886, 117–151 (2019).

    Article  Google Scholar 

  324. Hinterdorfer, P., Baumgartner, W., Gruber, H. J., Schilcher, K. & Schindler, H. Detection and localization of individual antibody–antigen recognition events by atomic force microscopy. Proc. Natl Acad. Sci. USA 93, 3477–3481 (1996).

    Article  ADS  Google Scholar 

  325. Schoeler, C. et al. Ultrastable cellulosome–adhesion complex tightens under load. Nat. Commun. 5, 5635 (2014).

    Article  ADS  Google Scholar 

  326. Alsteens, D., Trabelsi, H., Soumillion, P. & Dufrene, Y. F. Multiparametric atomic force microscopy imaging of single bacteriophages extruding from living bacteria. Nat. Commun. 4, 2926 (2013).

    Article  ADS  Google Scholar 

  327. Alsteens, D., Garcia, M. C., Lipke, P. N. & Dufrene, Y. F. Force-induced formation and propagation of adhesion nanodomains in living fungal cells. Proc. Natl Acad. Sci. USA 107, 20744–20749 (2010).

    Article  ADS  Google Scholar 

  328. Alsteens, D. et al. Imaging G protein-coupled receptors while quantifying their ligand-binding free-energy landscape. Nat. Methods 12, 845–851 (2015).

    Article  Google Scholar 

  329. Pfreundschuh, M. et al. Identifying and quantifying two ligand-binding sites while imaging native human membrane receptors by AFM. Nat. Commun. 6, 8857 (2015).

    Article  ADS  Google Scholar 

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Acknowledgements

K.B. and Y.J. acknowledge support from the National Key R&D Program (Grant Nos 2016YFA0300901 and 2017YFA0205003), the National Natural Science Foundation of China (Grant Nos 11888101, 11634001 and 21725302), the Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDB28000000) and Beijing Municipal Science & Technology Commission (Grant No. Z181100004218006). C.G. acknowledges support from Swiss Nanoscience Institute (SNI), University of Basel. A.J.H. acknowledges support from the Institute for Basic Science (IBS) (Grant No. R027-D1). D.J.M. acknowledges support from the Swiss National Science Foundation (NCCR Molecular Systems Engineering) and the ETH Zurich (Grant ETH-20 17-2). S.S acknowledges the support from a National Institutes of Health (NIH) Director’s Pioneer Award (DP1AT010874 from the National Center for Complementary and Integrative Health (NCCIH)) and a NIH Research Project Grant (RO1NS110790 from the National Institute of Neurological Disorders and Stroke (NINDS)).

Author information

Authors and Affiliations

  1. International Center for Quantum Materials, School of Physics, Peking University, Beijing, P. R. China

    Ke Bian & Ying Jiang

  2. Swiss Nanoscience Institute (SNI), Institute of Physics, University of Basel, Basel, Switzerland

    Christoph Gerber

  3. Center for Quantum Nanoscience, Institute for Basic Science (IBS), Seoul, Republic of Korea

    Andreas J. Heinrich

  4. Department of Physics, Ewha Womans University, Seoul, Republic of Korea

    Andreas J. Heinrich

  5. Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Basel, Switzerland

    Daniel J. Müller

  6. Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA

    Simon Scheuring

  7. Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA

    Simon Scheuring

  8. Collaborative Innovation Center of Quantum Matter, Beijing, P. R. China

    Ying Jiang

  9. Interdisciplinary Institute of Light-Element Quantum Materials and Research Center for Light-Element Advanced Materials, Peking University, Beijing, P. R. China

    Ying Jiang

  10. CAS Center for Excellence in Topological Quantum Computation, University of Chinese Academy of Sciences, Beijing, P. R. China

    Ying Jiang

Authors
  1. Ke Bian
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  2. Christoph Gerber
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  3. Andreas J. Heinrich
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  4. Daniel J. Müller
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  5. Simon Scheuring
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Contributions

All authors read and edited the full article. Introduction (K.B. and Y.J.); Experimentation (K.B., C.G., A.J.H., D.J.M. and Y.J.); Results (S.S.); Application (K.B., C.G., A.J.H., D.J.M. and Y.J.); Reproducibility and data deposition (S.S.); Limitations and optimizations (Y.J.); Outlook (C.G., D.J.M. and Y.J.); Overview of the Primer (K.B. and Y.J.). With the exception of Y.J., all authors are listed alphabetically.

Corresponding author

Correspondence to Ying Jiang.

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The authors declare no competing interests.

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Nature Reviews Methods Primers thanks Y. Kim, C. Mueller-Renno, J. Xu, C. Ziegler and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Tunnelling current

The current created from electrons tunnelling through a finite barrier that is forbidden in the classic regime.

Raster-scanning

A rectangular pattern of image capture and reconstruction.

Tip–sample junction

The tunnelling junction between the tip and the sample where electrons tunnel through a finite barrier in between.

Piezoelectric effect

The effect showing a finite induced voltage on both sides of a material when a specific pressure is applied on it.

Biased voltage

The DC voltage applied to the tunnelling junction, either on the sample or on the tip.

Eddy current

Loops of electrical current induced within a conductor by changing the magnetic field through this conductor based on Faraday’s law of induction.

Mechanical resonance frequency

The frequency at which a mechanical system vibrates with greater amplitude than it does at other frequencies, generally determined by the stiffness and mass of this mechanical system.

Quantum corrals

The barriers constructed by individually positioning the iron adatom through the scanning tunnelling microscopy tip.

Local force

The local interaction between the atoms on the tip apex and the surface within a volume of several cubic nanometres.

Dynamical AFM

A type of atomic force microscopy (AFM) where an oscillator (for example, cantilever, tuning fork) works at its resonance frequency, detecting interactions between the tip and the sample through the changes of frequency, amplitude and energy compensation of this oscillator.

Temporal resolution

The duration of time for acquisition or capture of a single event in measurements.

Functionalized tips

Modified tips with a single molecule or specific clusters in order to make the tip adapted for specific applications.

Quality factor

The dimensionless factor describing the dissipation and damping of the mechanical oscillator during a single oscillating cycle.

Thermal drift

The steady and monotonic changes of the specific location or parameter with time resulting from the changed temperature.

Young’s modulus

A mechanical property that quantifies the relationship between tensile stress and axial strain, which reflects the tensile stiffness of a solid material.

CO-functionalized tip

Modification of the tip with a single CO molecule in order to enhance the spatial resolution of scanning probe microscopy.

Hall probe

A micron-sized device for detecting the external magnetic field through the Hall effect.

Bipotentiostat

An electronic system capable of controlling two potentiostats, which include two working electrodes, one shared reference electrode and one shared counter electrode for electrochemical measurements.

Scanning gate microscopy

A kind of scanning probe microscopy capable of probing electrical transport at the nanoscale, where a conductive tip is used as the local gate capacitively coupled to the sample.

Kondo effect

An effect describing the scattering of conduction electrons caused by the magnetic impurities within a tunnelling junction, leading to a characteristic change in the electric conductivity at low temperature.

Yu–Shiba–Rusinov excitations

A pair of bound states inside the superconducting energy gap caused by the coupling between the superconductor and a magnetic impurity.

Cooper pairs

Pairs of electrons bound together through electron–phonon couplings, which are responsible for explaining superconductivity.

Quasiparticle interference

(QPI). Interference caused by the coherence of quasiparticles, inherently a kind of collective disturbance that behaves as a single particle.

QPI imaging

Imaging showing the quasiparticle interference (QPI).

Cantilever array technologies

Technologies using arrays of cantilevers for detecting the chemical reactions and nanomechanical motion of biomolecules with high sensitivity.

S/T parameters

Scattering/scattering transfer parameters describing the behaviours of incident and reflected waves during propagation through microwave electronics.

Quantum coherence

The status of a quantum state or wave function that has well-defined amplitude and phase, resulting from the principle of superposition.

Universal fitting scheme

A fitting scheme universally applied for analysing and processing all of the relative data sets during automated structure discovery.

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Bian, K., Gerber, C., Heinrich, A.J. et al. Scanning probe microscopy. Nat Rev Methods Primers 1, 36 (2021). https://doi.org/10.1038/s43586-021-00033-2

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