1932

Abstract

Superresolution localization microscopy methods produce nanoscale images via a combination of intermittently active fluorescent probes and algorithms that can precisely determine the positions of these probes from single-molecule or few-molecule images. These algorithms vary widely in their underlying principles, complexity, and accuracy. In this review, we begin by surveying the principles of localization microscopy and describing the fundamental limits to localization precision. We then examine several different families of fluorophore localization algorithms, comparing their complexity, performance, and range of applicability (e.g., whether they require particular types of experimental information, are optimized for specific situations, or are more general). Whereas our focus is on the localization of single isotropic emitters in two dimensions, we also consider oriented dipoles, three-dimensional localization, and algorithms that can handle overlapping images of several nearby fluorophores. Throughout the review, we try to highlight practical advice for users of fluorophore localization algorithms, as well as open questions.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physchem-040513-103735
2014-04-01
2024-06-20
Loading full text...

Full text loading...

/deliver/fulltext/physchem/65/1/annurev-physchem-040513-103735.html?itemId=/content/journals/10.1146/annurev-physchem-040513-103735&mimeType=html&fmt=ahah

Literature Cited

  1. Stetson PB. 1.  1987. DAOPHOT: a computer program for crowded-field stellar photometry. Publ. Astron. Soc. Pac. 99:191–222 [Google Scholar]
  2. Sainis SK, Germain V, Dufresne ER. 2.  2007. Statistics of particle trajectories at short time intervals reveal fN-scale colloidal forces. Phys. Rev. Lett. 99:018303 [Google Scholar]
  3. Park H, Toprak E, Selvin PR. 3.  2007. Single-molecule fluorescence to study molecular motors. Q. Rev. Biophys. 40:87–111 [Google Scholar]
  4. Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S. 4.  et al. 2006. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313:1642–45 [Google Scholar]
  5. Hess ST, Girirajan TPK, Mason MD. 5.  2006. Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys. J. 91:4258–72 [Google Scholar]
  6. Rust MJ, Bates M, Zhuang X. 6.  2006. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3:793–96 [Google Scholar]
  7. Sengupta P, Van Engelenburg S, Lippincott-Schwartz J. 7.  2012. Visualizing cell structure and function with point-localization superresolution imaging. Dev. Cell 23:1092–102 [Google Scholar]
  8. Huang B, Bates M, Zhuang X. 8.  2009. Super-resolution fluorescence microscopy. Annu. Rev. Biochem. 78:993–1016 [Google Scholar]
  9. Fernández-Suárez M, Ting AY. 9.  2008. Fluorescent probes for super-resolution imaging in living cells. Nat. Rev. Mol. Cell Biol. 9:929–43 [Google Scholar]
  10. Patterson G, Davidson M, Manley S, Lippincott-Schwartz J. 10.  2010. Superresolution imaging using single-molecule localization. Annu. Rev. Phys. Chem. 61:345–67 [Google Scholar]
  11. Crocker JC, Hoffman BD. 11.  2007. Multiple-particle tracking and two-point microrheology in cells. Methods Cell Biol. 83:141–78 [Google Scholar]
  12. Betzig E. 12.  1995. Proposed method for molecular optical imaging. Opt. Lett. 20:237–39 [Google Scholar]
  13. Lidke K, Rieger B, Jovin T, Heintzmann R. 13.  2005. Superresolution by localization of quantum dots using blinking statistics. Opt. Express 13:7052–62 [Google Scholar]
  14. Sharonov A, Hochstrasser RM. 14.  2006. Wide-field subdiffraction imaging by accumulated binding of diffusing probes. Proc. Natl. Acad. Sci. USA 103:18911–16 [Google Scholar]
  15. Burnette DT, Sengupta P, Dai Y, Lippincott-Schwartz J, Kachar B. 15.  2011. Bleaching/blinking assisted localization microscopy for superresolution imaging using standard fluorescent molecules. Proc. Natl. Acad. Sci. USA 108:21081–86 [Google Scholar]
  16. Fölling J, Bossi M, Bock H, Medda R, Wurm CA. 16.  et al. 2008. Fluorescence nanoscopy by ground-state depletion and single-molecule return. Nat. Methods 5:943–45 [Google Scholar]
  17. Brown TA, Tkachuk AN, Shtengel G, Kopek BG, Bogenhagen DF. 17.  et al. 2011. Superresolution fluorescence imaging of mitochondrial nucleoids reveals their spatial range, limits, and membrane interaction. Mol. Cell. Biol. 31:4994–5010 [Google Scholar]
  18. Greenfield D, McEvoy AL, Shroff H, Crooks GE, Wingreen NS. 18.  et al. 2009. Self-organization of the Escherichia coli chemotaxis network imaged with super-resolution light microscopy. PLoS Biol. 7:e1000137 [Google Scholar]
  19. Shroff H, Galbraith CG, Galbraith JA, White H, Gillette J. 19.  et al. 2007. Dual-color superresolution imaging of genetically expressed probes within individual adhesion complexes. Proc. Natl. Acad. Sci. USA 104:20308–13 [Google Scholar]
  20. Hell SW. 20.  2007. Far-field optical nanoscopy. Science 316:1153–58 [Google Scholar]
  21. Willig KI, Harke B, Medda R, Hell SW. 21.  2007. STED microscopy with continuous wave beams. Nat. Methods 4:915–18 [Google Scholar]
  22. Gustafsson MG. 22.  2000. Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy. J. Microsc. 198:82–87 [Google Scholar]
  23. Gustafsson MG. 23.  2005. Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc. Natl. Acad. Sci. USA 102:13081–86 [Google Scholar]
  24. Ober RJ, Ram S, Ward ES. 24.  2004. Localization accuracy in single-molecule microscopy. Biophys. J. 86:1185–200 [Google Scholar]
  25. Kay S. 25.  1993. Fundamentals of Statistical Signal Processing I Estimation Theory Englewood Cliffs, NJ: Prentice Hall [Google Scholar]
  26. Ward ES, Ober RJ. 26.  2012. FandPLimitTool. GUI-Based Software Module. http://www.wardoberlab.com/software/fandplimittool/ [Google Scholar]
  27. Abraham AV, Ram S, Chao J, Ward ES, Ober RJ. 27.  2009. Quantitative study of single molecule location estimation techniques. Opt. Express 17:23352–73 [Google Scholar]
  28. Snyder DL, Helstrom CW, Lanterman AD, Faisal M, White RL. 28.  1995. Compensation for readout noise in CCD images. J. Opt. Soc. Am. 12:272–83 [Google Scholar]
  29. Holden SJ, Uphoff S, Kapanidis AN. 29.  2011. DAOSTORM: an algorithm for high-density super-resolution microscopy. Nat. Methods 8:279–80 [Google Scholar]
  30. Huang F, Schwartz SL, Byars JM, Lidke KA. 30.  2011. Simultaneous multiple-emitter fitting for single molecule super-resolution imaging. Biomed. Opt. Express 2:1377–93 [Google Scholar]
  31. Parthasarathy R. 31.  2012. Rapid, accurate particle tracking by calculation of radial symmetry centers. Nat. Methods 9:724–26 [Google Scholar]
  32. Křížek P, Raška I, Hagen GM. 32.  2011. Minimizing detection errors in single molecule localization microscopy. Opt. Express 19:3226–35 [Google Scholar]
  33. Smith CS, Joseph N, Rieger B, Lidke KA. 33.  2010. Fast, single-molecule localization that achieves theoretically minimum uncertainty. Nat. Methods 7:373–75 [Google Scholar]
  34. Small AR, Starr R, Stahlheber S. 34.  2013. molecule-localization-plugin; M2LE: a molecule localization plug-in for ImageJ. Software Plug-in. https://code.google.com/p/molecule-localization-plugin/ [Google Scholar]
  35. Lagerholm BC, Averett L, Weinreb GE, Jacobson K, Thompson NL. 35.  2006. Analysis method for measuring submicroscopic distances with blinking quantum dots. Biophys. J. 91:3050–60 [Google Scholar]
  36. Small AR. 36.  2009. Theoretical limits on errors and acquisition rates in localizing switchable fluorophores. Biophys. J. 96:L16–18 [Google Scholar]
  37. Papoulis A. 37.  1991. Probability, Random Variables, and Stochastic Processes New York: McGraw-Hill [Google Scholar]
  38. Mortensen KI, Churchman LS, Spudich JA, Flyvbjerg H. 38.  2010. Optimized localization analysis for single-molecule tracking and super-resolution microscopy. Nat. Methods 7:377–81 [Google Scholar]
  39. Chao J, Ram S, Ward ES, Ober RJ. 39.  2013. Ultrahigh accuracy imaging modality for super-localization microscopy. Nat. Methods 10:335–38 [Google Scholar]
  40. Huang F, Hartwich TMP, Rivera-Molina FE, Lin Y, Duim WC. 40.  et al. 2013. Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms. Nat. Methods 10:653–58 [Google Scholar]
  41. Starr R, Stahlheber S, Small A. 41.  2012. Fast maximum likelihood algorithm for localization of fluorescent molecules. Opt. Lett. 37:413–15 [Google Scholar]
  42. Wolter S, Löschberger A, Holm T, Aufmkolk S, Dabauvalle M-C. 42.  et al. 2012. rapidSTORM: accurate, fast open-source software for localization microscopy. Nat. Methods 9:1040–41 [Google Scholar]
  43. Mlodzianoski MJ, Schreiner JM, Callahan SP, Smolková K, Dlasková A. 43.  et al. 2011. Sample drift correction in 3D fluorescence photoactivation localization microscopy. Opt. Express 19:15009–19 [Google Scholar]
  44. Thompson RE, Larson DR, Webb WW. 44.  2002. Precise nanometer localization analysis for individual fluorescent probes. Biophys. J. 82:2775–83 [Google Scholar]
  45. Anthony SM, Granick S. 45.  2009. Image analysis with rapid and accurate two-dimensional Gaussian fitting. Langmuir 25:8152–60 [Google Scholar]
  46. Zhu H, Yaglidere O, Su T-W, Tseng D, Ozcan A. 46.  2011. Cost-effective and compact wide-field fluorescent imaging on a cell-phone. Lab. Chip 11:315–22 [Google Scholar]
  47. Berglund AJ, McMahon MD, McClelland JJ, Liddle JA. 47.  2008. Fast, bias-free algorithm for tracking single particles with variable size and shape. Opt. Express 16:14064–75 [Google Scholar]
  48. Cheezum MK, Walker WF, Guilford WH. 48.  2001. Quantitative comparison of algorithms for tracking single fluorescent particles. Biophys. J. 81:2378–88 [Google Scholar]
  49. Crocker JC, Grier DG. 49.  1996. Methods of digital video microscopy for colloidal studies. J. Colloid Interface Sci. 179:298–310 [Google Scholar]
  50. Ma H, Kawai H, Toda E, Zeng S, Huang Z-L. 50.  2013. Localization-based super-resolution microscopy with an sCMOS camera part III: Camera embedded data processing significantly reduces the challenges of massive data handling. Opt. Lett. 38:1769–71 [Google Scholar]
  51. Wang Y, Quan T, Zeng S, Huang Z-L. 51.  2012. PALMER: a method capable of parallel localization of multiple emitters for high-density localization microscopy. Opt. Express 20:16039–49 [Google Scholar]
  52. Quan T, Zhu H, Liu X, Liu Y, Ding J. 52.  et al. 2011. High-density localization of active molecules using structured sparse model and Bayesian information criterion. Opt. Express 19:16963–74 [Google Scholar]
  53. Babcock H, Sigal YM, Zhuang X. 53.  2012. A high-density 3D localization algorithm for stochastic optical reconstruction microscopy. Opt. Nanoscopy 1:6 [Google Scholar]
  54. Mukamel EA, Babcock H, Zhuang X. 54.  2012. Statistical deconvolution for superresolution fluorescence microscopy. Biophys. J. 102:2391–400 [Google Scholar]
  55. Zhu L, Zhang W, Elnatan D, Huang B. 55.  2012. Faster STORM using compressed sensing. Nat. Methods 9:721–23 [Google Scholar]
  56. Cox S, Rosten E, Monypenny J, Jovanovic-Talisman T, Burnette DT. 56.  et al. 2012. Bayesian localization microscopy reveals nanoscale podosome dynamics. Nat. Methods 9:195–200 [Google Scholar]
  57. Hu YS, Nan X, Sengupta P, Lippincott-Schwartz J, Cang H. 57.  2013. Accelerating 3B single-molecule super-resolution microscopy with cloud computing. Nat. Methods 10:96–97 [Google Scholar]
  58. Rosenberg SA, Quinlan ME, Forkey JN, Goldman YE. 58.  2005. Rotational motions of macromolecules by single-molecule fluorescence microscopy. Acc. Chem. Res. 38:583–93 [Google Scholar]
  59. Backlund MP, Lew MD, Backer AS, Sahl SJ, Grover G. 59.  et al. 2012. Simultaneous, accurate measurement of the 3D position and orientation of single molecules. Proc. Natl. Acad. Sci. USA 109:19087–92 [Google Scholar]
  60. Enderlein J, Toprak E, Selvin PR. 60.  2006. Polarization effect on position accuracy of fluorophore localization. Opt. Express 14:8111–20 [Google Scholar]
  61. Engelhardt J, Keller J, Hoyer P, Reuss M, Staudt T, Hell SW. 61.  2011. Molecular orientation affects localization accuracy in superresolution far-field fluorescence microscopy. Nano Lett. 11:209–13 [Google Scholar]
  62. Aguet F, Geissbühler S, Märki I, Lasser T, Unser M. 62.  2009. Super-resolution orientation estimation and localization of fluorescent dipoles using 3-D steerable filters. Opt. Express 17:6829–48 [Google Scholar]
  63. Pavani SR, Thompson MA, Biteen JS, Lord SJ, Liu N. 63.  et al. 2009. Three-dimensional, single-molecule fluorescence imaging beyond the diffraction limit by using a double-helix point spread function. Proc. Natl. Acad. Sci. USA 106:2995–99 [Google Scholar]
  64. Stallinga S, Rieger B. 64.  2012. Position and orientation estimation of fixed dipole emitters using an effective Hermite point spread function model. Opt. Express 20:5896–921 [Google Scholar]
  65. Huang B, Jones SA, Brandenburg B, Zhuang X. 65.  2008. Whole-cell 3D STORM reveals interactions between cellular structures with nanometer-scale resolution. Nat. Methods 5:1047–52 [Google Scholar]
  66. Juette MF, Gould TJ, Lessard MD, Mlodzianoski MJ, Nagpure BS. 66.  et al. 2008. Three-dimensional sub–100 nm resolution fluorescence microscopy of thick samples. Nat. Methods 5:527–29 [Google Scholar]
  67. Mlodzianoski MJ, Juette MF, Beane GL, Bewersdorf J. 67.  2009. Experimental characterization of 3D localization techniques for particle-tracking and super-resolution microscopy. Opt. Express 17:8264–77 [Google Scholar]
  68. Badieirostami M, Lew MD, Thompson MA, Moerner WE. 68.  2010. Three-dimensional localization precision of the double-helix point spread function versus astigmatism and biplane. Appl. Phys. Lett. 97:161103 [Google Scholar]
  69. Grover G, Pavani SRP, Piestun R. 69.  2010. Performance limits on three-dimensional particle localization in photon-limited microscopy. Opt. Lett. 35:3306–8 [Google Scholar]
  70. Sage D, Pengo T, Kirshner H, Stuurman N, Min J, Manley S. 70.  2012. Localization microscopy: ISBI 2013 challenge http://bigwww.epfl.ch/smlm/challenge2013 [Google Scholar]
  71. Baddeley D, Cannell MB, Soeller C. 71.  2010. Visualization of localization microscopy data. Microsc. Microanal. 16:64–72 [Google Scholar]
  72. Shroff H, Galbraith CG, Galbraith JA, Betzig E. 72.  2008. Live-cell photoactivated localization microscopy of nanoscale adhesion dynamics. Nat. Methods 5:417–23 [Google Scholar]
  73. Egner A, Geisler C, von Middendorff C, Bock H, Wenzel D. 73.  et al. 2007. Fluorescence nanoscopy in whole cells by asynchronous localization of photoswitching emitters. Biophys. J. 93:3285–90 [Google Scholar]
  74. Huang Z-L, Zhu H, Long F, Ma H, Qin L. 74.  et al. 2011. Localization-based super-resolution microscopy with an sCMOS camera. Opt. Express 19:19156–68 [Google Scholar]
  75. Saurabh S, Maji S, Bruchez MP. 75.  2012. Evaluation of sCMOS cameras for detection and localization of single Cy5 molecules. Opt. Express 20:7338–49 [Google Scholar]
/content/journals/10.1146/annurev-physchem-040513-103735
Loading
/content/journals/10.1146/annurev-physchem-040513-103735
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error