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Resolution and contrast enhancements of optical microscope based on point spread function engineering

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Abstract

Point spread function (PSF) engineering-based methods to enhance resolution and contrast of optical microscopes have experienced great achievements in the last decades. These techniques include: stimulated emission depletion (STED), time-gated STED (g-STED), ground-state depletion microscopy (GSD), difference confocal microscopy, fluorescence emission difference microscopy (FED), switching laser mode (SLAM), virtual adaptable aperture system (VAAS), etc. Each affords unique strengths in resolution, contrast, speed and expenses. We explored how PSF engineering generally could be used to break the diffraction limitation, and concluded that the common target of PSF engineering-based methods is to get a sharper PSF. According to their common or distinctive principles to reshape the PSF, we divided all these methods into three categories, nonlinear PSF engineering, linear PSF engineering, and linear-based nonlinear PSF engineering and expounded these methods in classification. Nonlinear effect and linear subtraction is the core techniques described in this paper from the perspective of PSF reconstruction. By comparison, we emphasized each method’s strengths, weaknesses and biologic applications. In the end, we promote an expectation of prospective developing trend for PSF engineering.

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References

  1. Martinez-Corral M, Caballero M T, Stelzer E H K, Swoger J. Tailoring the axial shape of the point spread function using the Toraldo concept. Optics Express, 2002, 10(1): 98–103

    Article  Google Scholar 

  2. Köhler H. On Abbe’s theory of image formation in the microscope. Journal of Modern Optics, 1981, 28(12): 1691–1701

    Google Scholar 

  3. Toomre D, Bewersdorf J. A new wave of cellular imaging. Annual Review of Cell and Developmental Biology, 2010, 26(1): 285–314

    Article  Google Scholar 

  4. Bloembergen N. Nonlinear Optics. New York: Benjamin, 1965

    Google Scholar 

  5. Hell S W. Increasing the resolution of far-field fluorescence light microscopy by point-spread-function engineering. In: Lakowicz J R, ed. Topics in Fluorescence Spectroscopy. New York: Springer US, 2002, 361–426

    Chapter  Google Scholar 

  6. Hell S W, Wichmann J. Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Optics Letters, 1994, 19(11): 780–782

    Article  Google Scholar 

  7. Hell S W, Kroug M. Ground-state-depletion fluorscence microscopy: a concept for breaking the diffraction resolution limit. Applied Physics B, Lasers and Optics, 1995, 60(5): 495–497

    Article  Google Scholar 

  8. Irvine S E, Staudt T, Rittweger E, Engelhardt J, Hell S W. Direct light-driven modulation of luminescence from Mn-doped ZnSe quantum dots. Angewandte Chemie (International ed. in English), 2008, 120(14): 2725–2728

    Google Scholar 

  9. Hofmann M, Eggeling C, Jakobs S, Hell S W. Breaking the diffraction barrier in fluorescence microscopy at low light intensities by using reversibly photoswitchable proteins. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(49): 17565–17569

    Article  Google Scholar 

  10. Bossi M, Belov V, Polyakova S, Hell S W. Reversible red fluorescent molecular switches. Angewandte Chemie (International ed. in English), 2006, 45(44): 7462–7465

    Article  Google Scholar 

  11. Hao X, Kuang C, Li Y, Liu X. Reversible saturable optical transitions based fluorescence nanoscopy. Laser & Optoelectronic Progress, 2012, 49(3): 34–42

    Google Scholar 

  12. Sauer M. Reversible molecular photoswitches: a key technology for nanoscience and fluorescence imaging. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(27): 9433–9434

    Article  Google Scholar 

  13. Hell S W, Dyba M, Jakobs S. Concepts for nanoscale resolution in fluorescence microscopy. Current Opinion in Neurobiology, 2004, 14(5): 599–609

    Article  Google Scholar 

  14. Kuang C, Li S, Liu W, Hao X, Gu Z, Wang Y, Ge J, Li H, Liu X. Breaking the diffraction barrier using fluorescence emission difference microscopy. Scientific Reports, 2013, 3: 1441

    Article  Google Scholar 

  15. Farahani J N, Schibler M J, Bentolila L A. Stimulated emission depletion (STED) microscopy: from theory to practice. Microscopy: Science, Technology, Applications and Education, 2010, 2: 1539–1547

    Google Scholar 

  16. Hewlett S J, Wilson T. Resolution enhancement in threedimensional confocal microscopy. Machine Vision and Applications, 1991, 4(4): 233–242

    Article  Google Scholar 

  17. Heintzmann R, Sarafis V, Munroe P, Nailon J, Hanley Q S, Jovin T M. Resolution enhancement by subtraction of confocal signals taken at different pinhole sizes. Micron, 2003, 34(6-7): 293–300

    Article  Google Scholar 

  18. Wilson T, Hamilton D K. Difference confocal scanning microscopy. Optica Acta: International Journal of Optics, 1984, 31(4): 453–465

    Article  Google Scholar 

  19. Sheppard C J R, Cogswell C J. Confocal microscopy with detector arrays. Journal of Modern Optics, 1990, 37(2): 267–279

    Article  Google Scholar 

  20. Dehez H, Piché M, Koninck Y D. High resolution imaging with TM01 laser beams. International Society for Optics and Photonics, 2009, 7386: 738606

    Google Scholar 

  21. Dehez H, Piché M, De Koninck Y. Resolution and contrast enhancement in laser scanning microscopy using dark beam imaging. Optics Express, 2013, 21(13): 15912–15925

    Article  Google Scholar 

  22. Fang Y, Wang Y, Kuang C, Liu X. Enhancing the resolution and contrast in CW-STED microscopy. Optics Communications, 2014, 322: 169–174

    Article  Google Scholar 

  23. Hao X, Kuang C, Gu Z, Li S, Ge J, Liu X. Optical super-resolution by subtraction of time-gated images. Optics Letters, 2013, 38(6): 1001–1003

    Article  Google Scholar 

  24. Horrocks M H, Palayret M, Klenerman D, Lee S F. The changing point-spread function: single-molecule-based super-resolution imaging. Histochemistry and Cell Biology, 2014, 141(6): 577–585

    Article  Google Scholar 

  25. Pawley J. Handbook of Biological Confocal Microscopy. Berlin: Springer, 2010

    Google Scholar 

  26. Juette M F, Gould T J, Lessard M D, Mlodzianoski M J, Nagpure B S, Bennett B T, Hess S T, Bewersdorf J. Three-dimensional sub-100 nm resolution fluorescence microscopy of thick samples. Nature Methods, 2008, 5(6): 527–529

    Article  Google Scholar 

  27. Zahreddine R N, Cormack R H, Cogswell C J. Simultaneous quantitative depth mapping and extended depth of field for 4D microscopy through PSF engineering. International Society for Optics and Photonics, 2012, 8227: 822705

    Google Scholar 

  28. Martínez-Corral M. Point spread function engineering in confocal scanning microscopy. International Society for Optics and Photonics, 2003, 5182: 112–122

    Google Scholar 

  29. Hell S W. Toward fluorescence nanoscopy. Nature Biotechnology, 2003, 21(11): 1347–1355

    Article  Google Scholar 

  30. Keller J. Optimal de-excitation patterns for RESOLFT-microscopy. 2006, http://www.ub.uni-heidelberg.de/archiv/7163

    Google Scholar 

  31. Ding Y, Xi P, Ren Q. Hacking the optical diffraction limit: review on recent developments of fluorescence nanoscopy. Chinese Science Bulletin, 2011, 56(18): 1857–1876

    Article  Google Scholar 

  32. Hell SW, Jakobs S, Kastrup L. Imaging and writing at the nanoscale with focused visible light through saturable optical transitions. Applied Physics A, Materials Science & Processing, 2003, 77(7): 859–860

    Article  Google Scholar 

  33. Vicidomini G, Schönle A, Ta H, Han K Y, Moneron G, Eggeling C, Hell S W. STED nanoscopy with time-gated detection: theoretical and experimental aspects. PLOS ONE, 2013, 8(1): e54421

    Article  Google Scholar 

  34. Vicidomini G, Moneron G, Han K Y, Westphal V, Ta H, Reuss M, Engelhardt J, Eggeling C, Hell S W. Sharper low-power STED nanoscopy by time gating. Nature Methods, 2011, 8(7): 571–573

    Article  Google Scholar 

  35. Wang Y, Kuang C, Gu Z, Xu Y, Li S, Hao X, Liu X. Time-gated stimulated emission depletion nanoscopy. Optical Engineering (Redondo Beach, Calif), 2013, 52(9): 093107-1–093107-8

    Google Scholar 

  36. Boyer G, Sarafis V. Two pinhole superresolution using spatial filters. Optik-International Journal for Light and Electron Optics, 2001, 112(4): 177–179

    Article  Google Scholar 

  37. Cox I J, Sheppard C J R, Wilson T. Reappraisal of arrays of concentric annuli as superresolving filters. Journal of the Optical Society of America, 1982, 72(9): 1287–1291

    Article  Google Scholar 

  38. Cox I J, Sheppard C J R. Information capacity and resolution in an optical system. Journal of the Optical Society of America A, 1986, 3(8): 1152–1158

    Article  Google Scholar 

  39. Wang Y, Kuang C, Gu Z, Liu X. Image subtraction method for improving lateral resolution and SNR in confocal microscopy. Optics & Laser Technology, 2013, 48: 489–494

    Article  Google Scholar 

  40. Okugawa H. A new imaging method for confocal microscopy. International Society for Optics and Photonics, 2008, 6860: 68600K-1–68600K-7

    Google Scholar 

  41. Gasecka A, Daradich A, Dehez H, Piché M, Côté D. Resolution and contrast enhancement in coherent anti-Stokes Raman-scattering microscopy. Optics Letters, 2013, 38(21): 4510–4513

    Article  Google Scholar 

  42. Xue Y, Kuang C, Li S, Gu Z, Liu X. Sharper fluorescent superresolution spot generated by azimuthally polarized beam in STED microscopy. Optics Express, 2012, 20(16): 17653–17666

    Article  Google Scholar 

  43. Li S, Kuang C, Hao X, Wang Y, Ge J, Liu X. Enhancing the performance of fluorescence emission difference microscopy using beam modulation. Journal of Optics, 2013, 15(12): 125708–125715

    Article  Google Scholar 

  44. Hao X, Kuang C, Wang T, Liu X. Effects of polarization on the deexcitation dark focal spot in STED microscopy. Journal of Optics, 2010, 12(11): 115707

    Article  Google Scholar 

  45. Rong Z, Li S, Kuang C, Xu Y, Liu X. Real-time super-resolution imaging by high-speed fluorescence emission difference microscopy. Journal of Modern Optics, 2014, 61(16): 1364–1371

    Article  Google Scholar 

  46. Chmyrov A, Keller J, Grotjohann T, Ratz M, d’Este E, Jakobs S, Eggeling C, Hell S W. Nanoscopy with more than 100,000 ‘doughnuts’. Nature Methods, 2013, 10(8): 737–740

    Article  Google Scholar 

Download references

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Correspondence to Xu Liu.

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Yue Fang is a master student in the Department of Optical Engineering at Zhejiang University in Hangzhou, Zhejiang, China. She received the bachelor degree in Chongqing University College of Optoelectronic Engineering in 2013. Her current research interests are in optical microscopy, nanoscopy and high-precision optical measurement.

Cuifang Kuang is an associate professor in the Department of Optical Engineering at Zhejiang University in Hangzhou, Zhejiang, China. He received the Ph.D. degree in School of Science of Beijing Jiaotong University in 2007. From January of 2006 to July of 2006, he went on an academic visit to University of Michigan funded by the Scholarship for Outstanding Doctoral Students. His current research interests are in optical microscopy, nanoscopy and high-precision optical measurement. He is the coauthor of about 60 international refereed journal papers.

Ye Ma is currently studying for his B. Eng. degree in the Department of Optical Engineering at Zhejiang University in Hangzhou, Zhejiang, China. He chiefly commits himself to the research on optical super-resolution imaging technology.

Yifan Wang is a Ph.D. candidate in the Department of Optical Engineering at Zhejiang University in Hangzhou, Zhejiang, China. He received the B.S. degree in Xidian University. His current research interests include optical superresolution and digital image processing.

Xu Liu obtained his B.S. and M.S. degrees from Zhejiang University in 1984 and 1986, respectively. He had his Ph.D. degree from Ecole Nationale Superieure de Physique de Marseille in France in 1990. He has been a professor in the Department of Optical Engineering of Zhejiang University since 1995. Currently, he is the Dean of Faculty of Information Technology of Zhejiang University, the Director of the State Key Laboratory of Modern Optical Instrumentation in China. His research fields are: thin film optics and coatings techniques, 3D display, optical imaging and instrumentation. He is the author and co-author of more than 200 journal papers in the above research fields.

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Fang, Y., Kuang, C., Ma, Y. et al. Resolution and contrast enhancements of optical microscope based on point spread function engineering. Front. Optoelectron. 8, 152–162 (2015). https://doi.org/10.1007/s12200-015-0479-x

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