We present a combination of self-interference microscopy with lateral super-resolution microscopy and introduce a novel approach for localizing a single nano-emitter to within a few nanometers in all three dimensions over a large axial range. We demonstrate nanometer displacements of quantum dots placed on top of polymer bilayers that undergo swelling when changing from an air to a water environment, achieving standard deviations below 10 nm for axial and lateral localization.

© 2010 Optical Society of America

1. G. Donnert, J. Keller, R. Medda, M. A. Andrei, S. O. Rizzoli, R. Lührmann, R. Jahn, C. Eggeling, and S. W. Hell, “Macromolecular-scale resolution in biological fluorescence microscopy,” Proc. Natl. Acad. Sci. USA 103, 11440–11445 (2006). [CrossRef] [PubMed]
2. B. Hein, K. I. Willig, and S. W. Hell, “Stimulated emission depletion (sted) nanoscopy of a fluorescent protein-labeled organelle inside a living cell,” Proc. Natl. Acad. Sci. USA 105, 14271–14276 (2008). [CrossRef] [PubMed]
3. R. Schmidt, C. A. Wurm, S. Jakobs, J. Engelhardt, A. Egner, and S. W. Hell, “Spherical nanosized focal spot unravels the interior of cells,” Nat. Methods 5, 539–544 (2008). [CrossRef] [PubMed]
4. V. Westphal, S. O. Rizzoli, M. A. Lauterbach, D. Kamin, R. Jahn, and S. W. Hell, “Video-rate far-field optical nanoscopy dissects synaptic vesicle movement,” Science 320, 246–249 (2008). [CrossRef] [PubMed]
5. E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006). [CrossRef] [PubMed]
6. B. Huang, S. Jones, B. Brandenburg, and X. Zhuang, “Whole-cell 3D storm reveals interactions between cellular structures with nanometer-scale resolution,” Nat. Methods 5, 1047–1052 (2008). [CrossRef] [PubMed]
7. J. S. Biteen, M. A. Thompson, N. K. Tselentis, G. R. Bowman, and L. Shapiro, “andW. E.Moerner, “Super-resolution imaging in live caulobacter crescentus cells using photoswitchable eyfp,” Nat. Methods 5, 947–949 (2008). [CrossRef] [PubMed]
8. J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Controlling the fluorescence of ordinary oxazine dyes for single-molecule switching and superresolution microscopy,” Proc. Natl. Acad. Sci. USA 106, 8107–8112 (2009). [CrossRef] [PubMed]
9. B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super- resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008). [CrossRef] [PubMed]
10. S. R. P. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Appl. Phys. Lett. 106, 2995–2999 (2009).
11. P. V. Ganesan, and S. G. Boxer, “A membrane interferometer,” Proc. Natl. Acad. Sci. USA 106, 5627–5632 (2009). [CrossRef] [PubMed]
12. L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “Dna conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A. 103, 2623–2628 (2006). [CrossRef] [PubMed]
13. G. Shtengel, J. Galbraith, C. Galbraith, J. Lippincott-Schwartz, J. Gillette, S. Manley, R. Sougrat, C. Waterman, P. Kanchanawong, M. Davidson, R. Fetter, and H. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A. 106, 3125–3130 (2009). [CrossRef] [PubMed]
14. A. Swan, L. Moiseev, C. Cantor, and B. Davis, “Toward nanometer-scale resolution in fluorescence microscopy using spectral self-interference,” IEEE J. Sel. Top. Quantum Electron. 9, 294–300 (2003). [CrossRef]
15. F. Aguet, S. Geissbuehler, I. Maerki, T. Lasser, and M. Unser, “Super-resolution orientation estimation and localization of fluorescent dipoles using 3-d steerable filters,” Opt. Express 17, 6829–6848 (2009). [CrossRef] [PubMed]
16. G. Decher, “Fuzzy nanoassemblies: toward layered polymeric multicomposites,” Science 277, 1232–1237 (1997). [CrossRef]
17. L. Moiseev, C. Cantor, M. Aksun, M. Dogan, B. Goldberg, A. Swan, and M. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys. 96, 5311–5315 (2004). [CrossRef]
18. M. Born, and E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light (7th ed.) (Cambridge University Press, 1999). [PubMed]
19. S. Gibson, and F. Lanni, “Experimental test of an analytical model of aberration in an oil-immersion objective lens used in 3-dimensional light-microscopy,” J. Opt. Soc. Am. A 8, 1601–1613 (1991). [CrossRef]
20. M. K. Cheezum, W. F. Walker, and W. H. Guilford, “Quantitative comparison of algorithms for tracking single fluorescent particles,” Biophys. J. 81, 2378–2388 (2001). [CrossRef] [PubMed]
21. D. Patra, I. Gregor, J. Enderlein, and M. Sauer, “Defocused imaging of quantum-dot angular distribution of radiation,” Appl. Phys. Lett. 87, 101103 (2005). [CrossRef]
22. B. Richards, and E. Wolf, “Electromagnetic diffraction in optical systems. 2. Structure of the image field in an aplanatic system,” Proc. R. Soc. Lond. A 253, 358–379 (1959). [CrossRef]
23. M. Dogan, A. Yalcin, S. Jain, M. B. Goldberg, A. K. Swan, M. S. Unlu, and B. B. Goldberg, “Spectral self-interference fluorescence microscopy for subcellular imaging,” IEEE J. Sel. Top. Quantum Electron. 14, 217–225 (2008). [CrossRef]
24. A. Swan, L. Moiseev, C. Cantor, B. Davis, S. Ippolito, W. Karl, B. Goldberg, and M. Unlu, “Toward nanometer-scale resolution in fluorescence microscopy using spectral self-interference,” IEEE J. Sel. Top. Quantum Electron. 9, 294–300 (2003). [CrossRef]
25. A. Bilenca, A. Ozcan, B. Bouma, and G. Tearney, “Fluorescence coherence tomography,” Opt. Express 14, 7134–7143 (2006). [CrossRef] [PubMed]
26. W. Barnes, “Fluorescence near interfaces: the role of photonic mode density,” J. Mod. Opt. 45, 661–699 (1998). [CrossRef]
27. J. Antelman, C. Wilking-Chang, S. Weiss, and X. Michalet, “Nanometer distance measurements between multicolor quantum dots,” Nano Lett. 9, 2199–2205 (2009). [CrossRef] [PubMed]
28. B. J. Davis, A. K. Swan, M. S. Unlü, W. C. Karl, B. B. Goldberg, J. C. Schotland, and P. S. Carney, “Spectral self-interference microscopy for low-signal nanoscale axial imaging,” J. Opt. Soc. Am. A 24, 3587–3599 (2007). [CrossRef]
29. G. Decher, and J. Schmitt, “Fine-tuning of the film thickness of ultrathin multilayer films composed of consecutively alternating layers of anionic and cationic polyelectrolytes,” Prog. Colloid Polym. Sci. 89, 160–164 (1992). [CrossRef]
30. K. Vasilev, W. Knoll, and M. Kreiter, “Fluorescence intensities of chromophores in front of a thin metal film,” J. Chem. Phys. 120, 3439–3445 (2004). [CrossRef] [PubMed]
31. K. Vasilev, F. Stefani, V. Jacobsen, W. Knoll, and M. Kreiter, “Reduced photobleaching of chromophores close to a metal surface,” J. Chem. Phys. 120, 6701–6704 (2004). [CrossRef] [PubMed]
32. N. L. Bocchio, A. Unger, and M. Alvarez, “andM. Kreiter, “Thin layer sensing with multipolar plasmonic resonances,” J. Phys. Chem. C 112, 14355–14359 (2008). [CrossRef]
33. A. Yalçin, F. Damin, E. Ozkumur, G. di Carlo, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Direct observation of conformation of a polymeric coating with implications in microarray applications,” Anal. Chem. 81, 625–630 (2009). [CrossRef]

Anal. Chem.

• A. Yalçin, F. Damin, E. Ozkumur, G. di Carlo, B. B. Goldberg, M. Chiari, and M. S. Unlü, “Direct observation of conformation of a polymeric coating with implications in microarray applications,” Anal. Chem. 81, 625–630 (2009). [CrossRef]

Appl. Phys. Lett.

• D. Patra, I. Gregor, J. Enderlein, and M. Sauer, “Defocused imaging of quantum-dot angular distribution of radiation,” Appl. Phys. Lett. 87, 101103 (2005). [CrossRef]
• S. R. P. Pavani, M. A. Thompson, J. S. Biteen, S. J. Lord, N. Liu, R. J. Twieg, R. Piestun, and W. E. Moerner, “Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function,” Appl. Phys. Lett. 106, 2995–2999 (2009).

Biophys. J.

• M. K. Cheezum, W. F. Walker, and W. H. Guilford, “Quantitative comparison of algorithms for tracking single fluorescent particles,” Biophys. J. 81, 2378–2388 (2001). [CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron.

• M. Dogan, A. Yalcin, S. Jain, M. B. Goldberg, A. K. Swan, M. S. Unlu, and B. B. Goldberg, “Spectral self-interference fluorescence microscopy for subcellular imaging,” IEEE J. Sel. Top. Quantum Electron. 14, 217–225 (2008). [CrossRef]
• A. Swan, L. Moiseev, C. Cantor, B. Davis, S. Ippolito, W. Karl, B. Goldberg, and M. Unlu, “Toward nanometer-scale resolution in fluorescence microscopy using spectral self-interference,” IEEE J. Sel. Top. Quantum Electron. 9, 294–300 (2003). [CrossRef]
• A. Swan, L. Moiseev, C. Cantor, and B. Davis, “Toward nanometer-scale resolution in fluorescence microscopy using spectral self-interference,” IEEE J. Sel. Top. Quantum Electron. 9, 294–300 (2003). [CrossRef]

J. Appl. Phys.

• L. Moiseev, C. Cantor, M. Aksun, M. Dogan, B. Goldberg, A. Swan, and M. Unlu, “Spectral self-interference fluorescence microscopy,” J. Appl. Phys. 96, 5311–5315 (2004). [CrossRef]

J. Chem. Phys.

• K. Vasilev, W. Knoll, and M. Kreiter, “Fluorescence intensities of chromophores in front of a thin metal film,” J. Chem. Phys. 120, 3439–3445 (2004). [CrossRef] [PubMed]
• K. Vasilev, F. Stefani, V. Jacobsen, W. Knoll, and M. Kreiter, “Reduced photobleaching of chromophores close to a metal surface,” J. Chem. Phys. 120, 6701–6704 (2004). [CrossRef] [PubMed]

J. Mod. Opt.

• W. Barnes, “Fluorescence near interfaces: the role of photonic mode density,” J. Mod. Opt. 45, 661–699 (1998). [CrossRef]

J. Opt. Soc. Am. A

• S. Gibson, and F. Lanni, “Experimental test of an analytical model of aberration in an oil-immersion objective lens used in 3-dimensional light-microscopy,” J. Opt. Soc. Am. A 8, 1601–1613 (1991). [CrossRef]
• B. J. Davis, A. K. Swan, M. S. Unlü, W. C. Karl, B. B. Goldberg, J. C. Schotland, and P. S. Carney, “Spectral self-interference microscopy for low-signal nanoscale axial imaging,” J. Opt. Soc. Am. A 24, 3587–3599 (2007). [CrossRef]

J. Phys. Chem. C

• N. L. Bocchio, A. Unger, and M. Alvarez, “andM. Kreiter, “Thin layer sensing with multipolar plasmonic resonances,” J. Phys. Chem. C 112, 14355–14359 (2008). [CrossRef]

Nano Lett.

• J. Antelman, C. Wilking-Chang, S. Weiss, and X. Michalet, “Nanometer distance measurements between multicolor quantum dots,” Nano Lett. 9, 2199–2205 (2009). [CrossRef] [PubMed]

Nat. Methods

• R. Schmidt, C. A. Wurm, S. Jakobs, J. Engelhardt, A. Egner, and S. W. Hell, “Spherical nanosized focal spot unravels the interior of cells,” Nat. Methods 5, 539–544 (2008). [CrossRef] [PubMed]
• B. Huang, S. Jones, B. Brandenburg, and X. Zhuang, “Whole-cell 3D storm reveals interactions between cellular structures with nanometer-scale resolution,” Nat. Methods 5, 1047–1052 (2008). [CrossRef] [PubMed]
• J. S. Biteen, M. A. Thompson, N. K. Tselentis, G. R. Bowman, and L. Shapiro, “andW. E.Moerner, “Super-resolution imaging in live caulobacter crescentus cells using photoswitchable eyfp,” Nat. Methods 5, 947–949 (2008). [CrossRef] [PubMed]

Opt. Express

• F. Aguet, S. Geissbuehler, I. Maerki, T. Lasser, and M. Unser, “Super-resolution orientation estimation and localization of fluorescent dipoles using 3-d steerable filters,” Opt. Express 17, 6829–6848 (2009). [CrossRef] [PubMed]
• A. Bilenca, A. Ozcan, B. Bouma, and G. Tearney, “Fluorescence coherence tomography,” Opt. Express 14, 7134–7143 (2006). [CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

• L. Moiseev, M. S. Unlü, A. K. Swan, B. B. Goldberg, and C. R. Cantor, “Dna conformation on surfaces measured by fluorescence self-interference,” Proc. Natl. Acad. Sci. U.S.A. 103, 2623–2628 (2006). [CrossRef] [PubMed]
• G. Shtengel, J. Galbraith, C. Galbraith, J. Lippincott-Schwartz, J. Gillette, S. Manley, R. Sougrat, C. Waterman, P. Kanchanawong, M. Davidson, R. Fetter, and H. Hess, “Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure,” Proc. Natl. Acad. Sci. U.S.A. 106, 3125–3130 (2009). [CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA

• P. V. Ganesan, and S. G. Boxer, “A membrane interferometer,” Proc. Natl. Acad. Sci. USA 106, 5627–5632 (2009). [CrossRef] [PubMed]
• J. Vogelsang, T. Cordes, C. Forthmann, C. Steinhauer, and P. Tinnefeld, “Controlling the fluorescence of ordinary oxazine dyes for single-molecule switching and superresolution microscopy,” Proc. Natl. Acad. Sci. USA 106, 8107–8112 (2009). [CrossRef] [PubMed]
• G. Donnert, J. Keller, R. Medda, M. A. Andrei, S. O. Rizzoli, R. Lührmann, R. Jahn, C. Eggeling, and S. W. Hell, “Macromolecular-scale resolution in biological fluorescence microscopy,” Proc. Natl. Acad. Sci. USA 103, 11440–11445 (2006). [CrossRef] [PubMed]
• B. Hein, K. I. Willig, and S. W. Hell, “Stimulated emission depletion (sted) nanoscopy of a fluorescent protein-labeled organelle inside a living cell,” Proc. Natl. Acad. Sci. USA 105, 14271–14276 (2008). [CrossRef] [PubMed]

Proc. R. Soc. Lond. A

• B. Richards, and E. Wolf, “Electromagnetic diffraction in optical systems. 2. Structure of the image field in an aplanatic system,” Proc. R. Soc. Lond. A 253, 358–379 (1959). [CrossRef]

Prog. Colloid Polym. Sci.

• G. Decher, and J. Schmitt, “Fine-tuning of the film thickness of ultrathin multilayer films composed of consecutively alternating layers of anionic and cationic polyelectrolytes,” Prog. Colloid Polym. Sci. 89, 160–164 (1992). [CrossRef]

Science

• V. Westphal, S. O. Rizzoli, M. A. Lauterbach, D. Kamin, R. Jahn, and S. W. Hell, “Video-rate far-field optical nanoscopy dissects synaptic vesicle movement,” Science 320, 246–249 (2008). [CrossRef] [PubMed]
• E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006). [CrossRef] [PubMed]
• B. Huang, W. Wang, M. Bates, and X. Zhuang, “Three-dimensional super- resolution imaging by stochastic optical reconstruction microscopy,” Science 319, 810–813 (2008). [CrossRef] [PubMed]
• G. Decher, “Fuzzy nanoassemblies: toward layered polymeric multicomposites,” Science 277, 1232–1237 (1997). [CrossRef]

Other

• M. Born, and E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light (7th ed.) (Cambridge University Press, 1999). [PubMed]

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