Bibliography of Confocal Microscopes

  • Robert H. Webb

Abstract

This is a selected bibliography, as of early 1994, of accessible papers on confocal microscopy. Not included are conference reports and other documents not likely to be available in most technical libraries. I have tried to include a note as to the content— often taken from the abstract.

Keywords

Confocal Microscopy Confocal Scanning Fluorescence Correlation Spectroscopy Spherical Aberration Optical Transfer Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

Books and Review Articles

  1. Baxes, G.A., 1984, Digital Image Processing: A Practical Primer, Prentice-Hall, Englewood Cliffs, New Jersey. Also (1988) from Cascade Press, P.O. Box 27631, Denver, CO 80227. Truly a “practical primer.”Google Scholar
  2. Boyde, A., 1994, Bibliography on confocal microscopy and its applications, Scanning 16:33–56. Some overlap with this chapter, but not a direct mapping.Google Scholar
  3. Boyde, A., Jones, S.J., Taylor, M.L., Wolfe, L.A., and Watson, T.F., 1990, Fluorescence in the tandem scanning microscope, J. Microsc. 157:39–49. TSMs and CSMs.PubMedCrossRefGoogle Scholar
  4. Brelje, T.C., Wessendorf, M.W., and Sorenson, R.L., 1993, Multi-color laser scanning confocal immunofluorescence microscopy: Practical application and limitations, Methods Cell Biol. 38:98–182. A review of the dyes and the techniques for using them. Very specific. Complete.Google Scholar
  5. Cagnet, M., Françon, M., and Thrierr, J.C., 1962, Atlas of Optical Phenomena, Springer-Verlag, Berlin. See p. 23 for a beautiful through-focus display.Google Scholar
  6. Castleman, K.R., 1979, Digital Image Processing, Prentice-Hall, Englewood Cliffs, New Jersey. A standard reference on this subject.Google Scholar
  7. Inoué, S., 1986, Video Microscopy, Plenum Press, New York. A very complete basic book.Google Scholar
  8. Inoué, S, and Oldenbourg, R., 1994, Optical instruments: Microscopes. In: Handbook of Optics (M. Bass, ed.), 2nd ed., Vol. 2, Chap. 17, McGraw-Hill, New York. An up-to-date general reference.Google Scholar
  9. Kino, G.S., and Corle, T.R., 1989, Confocal scanning optical microscopy, Phys. Today 42:55–62. A review article for nonspecialist physicists.CrossRefGoogle Scholar
  10. Oppenheim, A.V., Willsky, A.S., and Young, LT., 1983, Signals and Systems, Prentice-Hall, Englewood Cliffs, New Jersey. Chapter 8 describes sampling theory very well.Google Scholar
  11. Pawley, J.B., 1991, Fundamental and practical limits in confocal light microscopy, Scanning 13:184–198. A general review of some of the choices we all make, with attention to photobleaching problems, optimization of optics, and pinholes.CrossRefGoogle Scholar
  12. Petran, M., Hadravsky, M., and Boyde, A., 1985 The tandem scanning reflected light microscope, Scanning 7:97–108. Summarizes the TSM.CrossRefGoogle Scholar
  13. Pratt, W.K., 1978, Digital Image Processing, Wiley, New York. A standard reference in this field.Google Scholar
  14. Shotton, D., ed., 1993, Electronic Light Microscopy—Techniques in Modem Biomedical Microscopy, Wiley-Liss, New York. Many of the usual suspects have contributed chapters, with some further chapters on display, video and sample preparation. A good companion to this volume.Google Scholar
  15. Slater, E.M., and Slater, H.S., 1993, Light and Electron Microscopy, Cambridge University Press, London. A fine general book on microscopes.Google Scholar
  16. Stevens, J.K., Mills, L.R., and Trogadis, J., eds., 1993, Three-Dimensional Confocal Microscopy, Academic Press, New York. A recent addition.Google Scholar
  17. Webb, R.H., 1991, Confocal microscopes, Optics & Photonics News 2:8–13. A review for optical scientists who do not specialize in microscopes.CrossRefGoogle Scholar
  18. White, J.G., and Amos, W.B., 1987, Confocal microscopy comes of age, Nature 328:183. General article by two of the early users of the CSM.CrossRefGoogle Scholar
  19. Wilson, T., 1980, Imaging properties and applications of scanning optical microscopes, Appl. Phys. (Germany) 22:119–128. A review paper, with 57 references.CrossRefGoogle Scholar
  20. Wilson, T., 1985, Scanning optical microscopy, Scanning 7:79–87. Summary article.CrossRefGoogle Scholar
  21. Wilson, T., ed., 1990, Confocal Microscopy, Academic Press, New York. Chapters by many of the usual folk. Much of the thinking of the 1980s summarized and updated.Google Scholar
  22. Wilson, T., and Sheppard, C.J.R., 1984, Theory and Practice ofScanning Optical Microscopy, Academic Press, New York. Reprints some of their early papers.Google Scholar

Historical Interest

  1. Some of the original articles, mostly now superseded by later work—often of the same authors. I have tried to avoid the “gee whiz” articles.Google Scholar
  2. Amos, W.B., White, J.G., and Fordham, M., 1987, Use of confocal imaging in the study of biological structures, Appl. Optics 26:3239–3243. A good general review, and an early description of the MRC (Biorad) microscope.CrossRefGoogle Scholar
  3. Åslund, N., Liljeborg, A., Forsgren, P.-O., and Wahlsten, S., 1987, Three-dimensional digital microscopy using the PHOIBOS scanner, Scanning 9:227–235. Consecutive optical sections to generate digital three-dimensional microscopy.CrossRefGoogle Scholar
  4. Baer, S.C., 1970, Optical apparatus providing focal-plane specific information, U.S. Patent 3,547,512. An early CSM idea, largely ignored for 17 years.Google Scholar
  5. Brakenhoff, G.J., Blom, P., and Barends, P., 1979, Confocal scanning light microscopy with high aperture immersion lenses, J. Microsc. 117:219–232. For point objects the theoretically expected factor of 1.4 can be realized. A further improvement by a factor of 1.25 after apodization with an annular aperture.CrossRefGoogle Scholar
  6. Brakenhoff, G.J., van der Voort, H.T.M., van Spronsen, E.A., Linnemans, W.A.M., and Nanninga, N., 1985, Three-dimensional chromatin distribution in neuroblastoma nuclei shown by confocal scanning laser microscopy, Nature 317:748–749. An early use of optical sectioning and higher resolution for studying the three-dimensional morphology of biological structures.PubMedCrossRefGoogle Scholar
  7. Chou, C.-H., and Kino, G.S., 1987, The evaluation of V(z) in a type II reflection microscope, IEEE Trans. Ultrason. Ferroelectr. Freq. Control 34:341–345. Theory: V(z) of an acoustic microscope, nonparaxial and finite pinhole and the asymmetry of the V(z) curve for a perfect reflector.PubMedCrossRefGoogle Scholar
  8. Davidovits, P., and Egger, M.D., 1971, Scanning laser microscope for biological investigations, Appl. Optics 10:1615–1619. Also: Davidovits, P., and Egger, M.D., 1969, Scanning laser microscope. Nature 223:831. Two seminal papers of historical interest.CrossRefGoogle Scholar
  9. Egger, M.D., and Petráň, M., 1967, New reflected-light microscope for viewing unstained brain and ganglion cells, Science 157:305–307. A largely unnoticed description of the TSM, but it was all therePubMedCrossRefGoogle Scholar
  10. Hamilton, D.K., and Wilson, T., 1982, Three-dimensional surface measurement using the confocal scanning microscope, Appl. Phys. B 27:211–213. Early profilometry on semiconductors, to 0.1 p. m.CrossRefGoogle Scholar
  11. Hamilton, D.K., Wilson, T., and Sheppard, C.J.R., 1981, Experimental observations of the depth-discrimination properties of scanning microscopes, Opt. Lett. 6:625–626. Optical sectioning.PubMedCrossRefGoogle Scholar
  12. Maurice, D.M., 1973, A scanning slit optical microscope, Invest. Ophthalmol. 13:1033–1037. A pioneer paper describing an early form of confocal microscopy for imaging layers in the cornea of the eye. This system used a scanning slit 3 μm wide to give depth definition, and scanning was carried out by moving a photographic film and the specimen in opposite directions. High-quality images of the cornea were obtained, which took about 20 minutes to form.Google Scholar
  13. Minsky, M., 1988, Memoir on inventing the CSM, Scanning 10:128–138. A valuable historical document, and enjoyable reading. Minsky’s patent ran out before the world was ready for the idea, but his early ideas have all proved out well. See Minsky, M., 1961, Microscopy apparatus, U.S. Patent 3,013,467.CrossRefGoogle Scholar
  14. Petráň, M., and Hadravsky, M., 1967, Method and arrangement for improving the resolving power and contrast, U.S. Patent 3,517,980, filed 4–12-67, granted 30–6–70.Google Scholar
  15. Petráň, M., and Hadravsky, M., 1968, Tandem-scanning reflected-light microscope, J. Opt. Soc. Am. 58:661–664. Source paper on TSM. See also Petráň, M., Hadravsky, M., Benes, J., Kucera, R., and Boy de, A., 1985, The tandem scanning reflected light microscope. Part 1—The principle, and its design, Proc. R. Microsc. Soc. 20:125–129.CrossRefGoogle Scholar
  16. Ploem, J.S., 1987, Laser scanning fluorescence microscopy, Appl. Optics 26 3226–3231. Another general description of CSM.CrossRefGoogle Scholar
  17. Sheppard, C.J.R., and Choudhury, A., 1977, Image formation in the scanning microscope, Opt. Acta 24:1051–1073. Fourier imaging in microscopes of type 1 (conventional) and type 2 (confocal). Single- and two-point resolution, response to a straight edge, annular pupil functions.CrossRefGoogle Scholar
  18. Sheppard, C.J.R., and Wilson, T., 1978, Depth of field in the scanning microscope, Opt. Lett. 3:115–117. Various definitions of depth of field in the microscope are discussed.PubMedCrossRefGoogle Scholar
  19. Toraldo di Francia, G., 1955, Resolving power and information, J. Opt. Soc. Am. 45:497–501. Two-point resolution is impossible unless the observer has a priori an infinite amount of information about the object.CrossRefGoogle Scholar
  20. Welford, W.T., 1972, On the relationship between the modes of image formation in scanning microscopy and conventional microscopy, J. Microsc. 96:105–107.PubMedCrossRefGoogle Scholar
  21. White, J.G., Amos, W.B., and Fordham, M., 1987, An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy, J. Cell Biol. 105–41-48. An early general article which helped introduce the technique.PubMedCrossRefGoogle Scholar
  22. Wilke, V., 1985, Optical scanning microscopy—The laser scan microscope, Scanning 7:88–96. The Zeiss CSM.CrossRefGoogle Scholar
  23. Wilson, T., and Hamilton, D.K., 1982, Dynamic focusing in the confocal scanning microscopes, J. Microsc. 128:139–143. Image built up as each section of the object passes through the focal plane.CrossRefGoogle Scholar

Theory (Mostly)

  1. Bertero, B., De Mol, C., and Pike, E.R., 1987, Analytic inversion formula for confocal scanning microscopy, J. Opt. Soc. Am. A 4:1748–1750. A simple analytic expression for the inverse problem in CSMs.CrossRefGoogle Scholar
  2. Carlsson, K., 1991, The influence of specimen refractive index, detector signal integration, and non-uniform scan speed on the imaging properties in confocal microscopy, J. Microsc. 163:2, 167–178. Index mismatch causes spherical aberrations, which affect axial resolution most.CrossRefGoogle Scholar
  3. Cogswell, C.J., and Sheppard, C.J.R., 1992, Confocal differential interference contrast (DIC) microscopy: Including a theoretical analysis of conventional and confocal DIC imaging, J. Microsc. 165:81–101. DIC with a CSM is compared to existing confocal differential phase contrast (DPC) techniques and to conventional Nomarski DIC. A theoretical treatment of DIC imaging is presented, which takes into account vignetting by the lens pupils.CrossRefGoogle Scholar
  4. Corle, T.R., and Kino, G.S., 1990, Differential interference contrast imaging on a real time confocal scanning optical microscope, Appl. Optics 29:3769–3774. The advantage of DIC in a CSM is that both the height and width of an edge can be measured without ambiguity, even if the edge is taller than half a wavelength.CrossRefGoogle Scholar
  5. Cox, I.J., and Sheppard, C.J.R., 1986, Information capacity and resolution in an optical system, J. Opt. Soc. Am. 3:1152–1158. A nonstandard approach that gives useful general results without major math.CrossRefGoogle Scholar
  6. Cox, I.J., Sheppard, C.J.R., and Wilson, T., 1981, Improvement in resolution by nearly confocal microscopy: The theory of the direct-view confocal microscope, J. Microsc. 124:107–117. Resolution increased by offsetting the pinhole. Dark-field conditions are produced with the pinhole over the first dark ring in the Airy disk. Theory for conventional and scanning microscopes, partial coherence and TSMs.CrossRefGoogle Scholar
  7. Drazic, V., 1992, Three-dimensional transfer function of coherent confocal microscopes with extended source and detector, J. Mod. Opt. 39:1777–1790. The effect of finite size of the source and detector on the three-dimensional transfer function of an incident light coherent CSM.CrossRefGoogle Scholar
  8. Gu, M., and Sheppard, C.J.R., 1992, Confocal fluorescent microscopy with a finite-sized circular detector, J. Opt. Soc. Am. A, Opt. Image Sci. 9:151–153. OTF has negative values when the detector radius exceeds certa in magnitudes.CrossRefGoogle Scholar
  9. Gu, M., and Sheppard, C.J.R., 1992, Three-dimensional optical transfer function in a fiber-optical confocal fluorescence microscope using annular lenses, J. Opt. Soc. Am. A, Opt. Image Sci. 9:1991–1999. Annular lenses in a system with optical fibers can result in improved resolution in both transverse and axial directions.CrossRefGoogle Scholar
  10. Gu, M., and Sheppard, C.J.R., 1992, Effects of defocus and primary spherical aberration on three-dimensional coherent transfer functions in confocal microscopes, Appl. Optics 31:2541–2549. Three-dimensional confocal imaging is strongly degraded if the amount of aberration is larger than a quarter wavelength. Spherical aberration compensated by defocus.CrossRefGoogle Scholar
  11. Hamilton, D.K., and Wilson, T., 1984, Two-dimensional phase imaging in the scanning optical microscope, Appl. Optics 23:348–352. Early split-detector phase imaging.CrossRefGoogle Scholar
  12. Hegedus, Z.S., 1985, Annular pupil arrays. Application to confocal scanning, Opt. Acta 32:815–826. Radially symmetrical pupil masks with a continuously varying transmittance can be made by vacuum deposition or photographic integration, or a binary mask of a concentric array of annuli.CrossRefGoogle Scholar
  13. Hell, S., Reiner, G., Cremer, C., and Stelzer, E.H.K., 1993, Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index, J. Microsc. 169:391–405. An extensive and readable analysis of this frequent topic. Scaling factors for correction are given.CrossRefGoogle Scholar
  14. Hobbs, P.C.D., and Kino, G.S., 1990, Generalizing the confocal microscope via heterodyne interferometry and digital filtering, J. Microsc. 160:245–264. A true heterodyne CSM, yielding both phase and amplitude.CrossRefGoogle Scholar
  15. Inoué, S., 1989, Imaging of unresolved objects, superresolution, and precision of distance measurement with video microscopy, Methods Cell Biol. 30:85–112.PubMedCrossRefGoogle Scholar
  16. Mendez, E.R., 1986, Speckle contrast variation in the CSM. Hard-edged apertures, Opt. Acta 33:269–278. Speckle contrast variation as a function of defocus, and the statistical properties of random diffusing objects.CrossRefGoogle Scholar
  17. Ooki, H., and Iwasaki, J., 1991, A novel type of laser scanning microscope: Theoretical considerations, Opt. Commun. 85:177–182. Differential interference contrast by means of mode interference in a waveguide device. Phase and amplitude separately.CrossRefGoogle Scholar
  18. Sandison, D.R., and Webb, W.W., 1994, Background rejection and signal-to-noise optimization in the confocal and alternative fluorescence microscopes, Applied Optics 33:603. A complete analysis of signal, background and noise in the family of confocal microscopes.PubMedCrossRefGoogle Scholar
  19. Sheppard, C.J.R., 1988, Aberrations in high aperture conventional and confocal imaging systems, Appl. Optics 27:4782–4786. In an aberration function for high numerical aperture the effects on the defocus signal of a confocal imaging system of aberrations, high aperture, finite Fresnel number, system configuration, and surface tilt are discussed.CrossRefGoogle Scholar
  20. Sheppard, C.J.R., and Cogswell, C.J., 1990, Three-dimensional image formation in confocal microscopy, J. Microsc. 159:179–194. 3D imaging in terms of 3D transfer functions.CrossRefGoogle Scholar
  21. Sheppard, C.J.R., and Wilson, T., 1981, The theory of the direct-view confocal microscope, J. Microsc. 124:107–117. Theory embracing conventional microscopes with partially coherent source and scanning microscopes with partially coherent effective source and detector, including confocal microscopes and the TSM of Petráň.PubMedCrossRefGoogle Scholar
  22. Sheppard, C.J.R., and Wilson, T., 1986, Reciprocity and equivalence in scanning microscopes, J. Opt. Soc. Am. A 3:755–756. The principle of reciprocity and methods of Fourier optics in conventional and scanning microscopes: their behavior is identical even for objects thick enough for multiple scattering to occur, provided that there is no inelastic scattering or birefringence present.CrossRefGoogle Scholar
  23. Sheppard, C.J.R., Cogswell, C.J., and Gu, M., 1991, Signal strength and noise in confocal microscopy: Factors influencing selection of an optimum detector aperture, Scanning 13:233–240.CrossRefGoogle Scholar
  24. van der Voort, H.T.M., and Brakenhoff, G.J., 1990, 3-D image formation in high-aperture fluorescence confocal microscopy: A numerical analysis, J. Microsc. 158:43–54. Electromagnetic diffraction theory of the field near focus as developed by Richards and Wolf is used to compute the optical properties of the model.CrossRefGoogle Scholar
  25. Visser, T.D., Groen, F.C.A., and Brakenhoff, G.J., 1991, Absorption and scattering correction in fluorescence confocal microscopy, J. Microsc. 163:189–200. With one space-dependent extinction coefficient, the total attenuation process can be calculated to the deeper layers.CrossRefGoogle Scholar
  26. Wilson, T., 1991, Comment on “Image formation in a superresolution phase conjugate scanning microscope,” Appl. Phys. Lett. 58:314. Johnson, Cathey, and Mao, 1989, Appl. Phys. Lett. 55:1707, proposed using a phase conjugate mirror to exhibit superresolution. A phase conjugate mirror is not strictly necessary and a similar, or even enhanced, effect may be obtained by processing the image from a standard confocal microscope in an extremely simple way.CrossRefGoogle Scholar
  27. Wilson, T., and Carlini, A.R., 1987, Size of the detector in confocal imaging systems, Opt. Lett. 12:227–229. Original of many familiar figures.PubMedCrossRefGoogle Scholar
  28. Wilson, T., Carlini, A.R., 1989, The effect of aberrations on the axial response of confocal imaging systems, J. Microsc. 154:243–256. Aberrations are diminished by smaller pinholes.CrossRefGoogle Scholar

Technical

  1. Aikens, R.S., Agard, D.A., and Sedat, J.W., 1989, Solid state imagers for microscopy, Methods Cell Biol. 29:291–313. A complete discussion of the detector of choice in many disk-scanning and wide-field microscopes.PubMedCrossRefGoogle Scholar
  2. Art, J.J., and Goodman, M.B., 1993, Rapid scanning confocal microscopy, Methods Cell Biol. 38. Includes the NORAN Odyssey instrument.Google Scholar
  3. Benedetti, P.A., Evangelista, V., Guidarini, D., and Vestri, S., 1992, Confocal-line microscopy, J. Microsc. 165:119–129. Confocal in one dimension, no moving parts. Linear imagers permit transmission, reflection, and emission images simultaneously.PubMedCrossRefGoogle Scholar
  4. Bliton, C., Lechleiter, J., and Clapham, D.E., 1993, Optical modifications enabling simultaneous confocal imaging with dyes excited by ultra-violet and visible-wavelength light, J. Microsc. 169:15–26. Modifications to a BioRad MRC 600.CrossRefGoogle Scholar
  5. Boyde, A., Xiao, G.Q., Corle, T., Watson, T.F., and Kino, G.S., 1990, An evaluation of unilateral TSM for biological applications, Scanning 12:273–279. Two designs of tandem scanning reflected light microscopes, due to Petráň and to Kino.CrossRefGoogle Scholar
  6. Brakenhoff, G.J., and Visscher, K., 1992, Confocal imaging with bilateral scanning and array detectors, J. Microsc. 165:139–146. A hybrid CSM/TSM using an array detector such as a CCD for confocal image collection and a double-sided scanning mirror to scan and collect data. This is the scheme implemented by Meridian.CrossRefGoogle Scholar
  7. Brakenhoff, G.J., and Visscher, K., 1993, Imaging modes for bilateral confocal scanning microscopy, J. Microsc. 171:17–26. Details of the double-sided mirror rescanning system. The remitted light traverses the confocal pinhole to yet another scanning mirror (the second side of the original one) to be spread again into an image viewable by eye or camera. See the Koester papers for earlier implementations. This is the scheme implemented by Meridian.CrossRefGoogle Scholar
  8. Buurman, E.P., Sanders, R., Draaijer, A., Gerritsen, H.C., Van Veer, J.J.F., Haupt, P.M., and Levine, Y.K., 1992, Fluorescence lifetime imaging using a confocal laser scanning microscope, Scanning 14:155–159. Fluorescence lifetime imaging method in a CSM uses a low-power CW argon laser chopped to 25-MHz nanosecond pulses. Time-gated detection measures the lifetime of a pixel in 40 μ sec.CrossRefGoogle Scholar
  9. Carlsson, K., and Åslund, N., 1987 Confocal imaging or 3-D digital microscopy, Appl. Optics 26:3232–3238. This is the Phoibos instrument of Sarastro, now of Molecular Dynamics.CrossRefGoogle Scholar
  10. Cogswell, C.J., Hamilton, D.K., and Sheppard, C.J.R., 1992, Colour confocal reflection microscopy using red, green and blue lasers, J. Microsc. 165:103–117. Lasers: HeNe (633 nm); NdYAG (532 nm); HeCd (442 nm) and three photomultiplier detectors.CrossRefGoogle Scholar
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  12. Dixon, A.E., Damaskinos, S., and Atkinson, M.R., 1991, Transmission and double-reflection scanning stage confocal microscope, Scanning 13:299–306. A stage-scanning transmitted- and reflected-light laser microscope is described.CrossRefGoogle Scholar
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  14. Fricker, M.D., and White, N.S., 1992, Wavelength considerations in confocal microscopy of botanical specimens, J. Microsc. 166:29–42. Some of the problems associated with multiple wavelengths. CSMs make severe demands on achromatized optics.CrossRefGoogle Scholar
  15. Glass, M., and Dabbs, T., 1991, The experimental effect of detector size on confocal lateral resolution, J. Microsc. 164:153–158. The discrepancy between data and theory attributed to apodization from multielement thick lenses and a nonideal, truncated Gaussian beam profile.CrossRefGoogle Scholar
  16. Hamilton, D.K., and Sheppard, C.J.R., 1986, Interferometric measurements of the complex amplitude of the defocus signal V(z) in the confocal scanning optical microscope, J. Appl. Phys. 60:2708–2712. A confocal interference microscope with electro-optic phase modulator makes simultaneous measurements of the in-phase and quadrature components of the confocal signal as a reflecting surface is scanned axially, the so-called V(z) response.CrossRefGoogle Scholar
  17. Hansen, E.W., Allen, R.D., Strohbehn, J.W., Chaffee, M.A., Farrington, D.L., Murray, W.J., Pillsbury, T.A., and Riley, M.F., 1985, Laser scanning phase modulation microscope, J. Microsc. 140:371–381. Quantitative polarized light imaging with a phase modulation feedback loop for precise measurement of birefringence.PubMedCrossRefGoogle Scholar
  18. Hell, S., Witting, S., Schickfus, M.V., and Neiger, M., 1991, A confocal beam scanning white-light microscope, J. Microsc. 163:179–187. CSM with a continuous Xe short-arc lamp operating in the visible spectrum. Resolution of the white-light microscope is equivalent to that of the scanning laser microscope, without artifacts caused by interference.CrossRefGoogle Scholar
  19. Highett, M.I., Rawlins, D.J., and Shaw, P.J., 1993, Different patterns of rDNA distribution in Pisum sativum nucleoli correlate with different levels of nucleolar activity, J. Cell Sci. 104:843–852. Compares CSM and decon-volution of wide-field images. Both together are best.Google Scholar
  20. Hong Qian, and Elson, E.L., 1991, Analysis of confocal laser-microscope optics for 3-D fluorescence correlation spectroscopy, Appl. Optics 30:1185–1195. Quantitative fluorescence correlation spectroscopy and fluorescence photobleaching recovery measurements.CrossRefGoogle Scholar
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  23. Mansfield, S.M., and Kino, G.S., 1990, Solid immersion microscope, Appl. Phys. Lett. 57:2615–2616. A real-time optical microscope with the liquid replaced by a solid lens of high-refractive-index material.CrossRefGoogle Scholar
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  29. Shaw, P.J., 1990, Three-dimensional optical microscopy using tilted views, J. Microsc. 158:165–172. Multiple tilted views increase the resolution in z. This technique was applied to metaphase chromosomes from intact embryos of Drosophila melanogaster. As determined from significant intensity in the Fourier transform, the resolution of the final reconstruction was about 0.25 μm in x andy, and 0.4 μm in z.PubMedCrossRefGoogle Scholar
  30. Shaw, P.J., and Rawlins, D.J., 1991, The point-spread function of a confocal microscope: Its measurement and use in deconvolution of 3-D data, J. Microsc. 163:151–165. PSF for an MRC-500 CSM using subresolution fluorescent beads. The resulting optical transfer functions were used in an iterative, constrained deconvolution procedure to get three-dimensional confocal data sets from a biological specimen.CrossRefGoogle Scholar
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  32. Sheppard, C.J.R., and Gu, M., 1991, Aberration compensation in confocal microscopy, Appl. Optics 30:3563–3568. Spherical aberration due to focusing deep within the specimen can be compensated by altering the effective tube length.CrossRefGoogle Scholar
  33. Sheppard, C.J.R., and Gu, M., 1992, Axial imaging through an aberrating layer of water in confocal microscopy, Opt. Commun. 88:180–190. The axial response modeled by a series of signals reflected from different interfaces. Altering the effective tube length for an optimum axial response, experimental results are well in agreement with theoretical predictions.CrossRefGoogle Scholar
  34. Sheppard, C.J.R., Hamilton, D.K., and Cox, I.J., 1982, Optical microscopy with extended depth of field: Observation of optical signatures of materials, Appl. Phys. Lett. 41:604–606. Depth of field may be extended while high-resolution, diffraction-limited imaging is retained. The technique is similar to one already used in acoustic microscopy.CrossRefGoogle Scholar
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Applications

  1. Arndt-Jovin, D.J., Robert Nicoud, M., and Jovin, T.M., 1990, Probing DNA structure and function with a multi-wavelength fluorescence confocal laser microscope, J. Microsc. 157:61–72 Three levels of organization in DNA structure in the interphase cell nucleus are assessed by CSM..PubMedCrossRefGoogle Scholar
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  11. Montag, M., Kukulies, J., Jorgens, R., Gundlach, H., Trendelenburg, M.F., and Spring, H., 1991, Working with the confocal scanning UV-laser microscope: Specific DNA localization at high sensitivity and multiple-parameter fluorescence, J. Microsc. 163:201–210. Multiple-parameter studies and identification of the double-stranded DNA of lampbrush chromosome loops in germinal vesicles of amphibian oocytes.PubMedCrossRefGoogle Scholar
  12. Mossberg, K., and Ericsson, M., 1990, Detection of doubly stained fluorescence specimens using confocal microscopy, J. Microsc. 158:215–224. Lucifer Yellow, Texas Red, fluorescein isothiocyanate, and tetramethylrho-damine isothiocyanate.PubMedCrossRefGoogle Scholar
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  15. Smith, P.J., and Sykes, H.R., 1992, Simultaneous measurement of cell cycle phase position and ionizing radiation-induced DNA strand breakage in single human tumour cells using laser scanning confocal imaging, Int. J. Radial Biol. 61:553–560. Measurement of nucleoid relaxation in response to DNA damage. The volumes of spherical nucleoids and their relative DNA contents from ethidium bromide staining and equatorial sections of the nucleoids.CrossRefGoogle Scholar
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Variants on the Main Theme

  1. Bailey, B., Farkas, D.L., Taylor, D.L., and Lanni, F., 1993, Enhancement of axial resolution in fluorescence microscopy by standing-wave excitation, Nature 366:44–48. A means of increasing axial sectioning resolution at the expense of an uncertainty in choice of which standing wave plane is addressed. Combined with CSM, an improvement to 0.05μm is claimed, although the standing waves are λ/2ŋ apart (0.15 μm).PubMedCrossRefGoogle Scholar
  2. Benschop, J., and van Rosmalen, G., 1991, Confocal compact scanning optical microscope based on compact disc technology, Appl. Optics 30:1179–1184. A compact CSM based on the optics and mechanics of a compact disc (CD) player is equipped with automatic focusing. The laser in the CD player is replaced by the endface of a single-mode fiber which acts both as the emitting source and as a point detector.CrossRefGoogle Scholar
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  9. Denk W., Strickler J.H., and Webb W.W., 1990, Two-photon laser scanning fluorescence in microscopy, Science 248:73–76. Two infrared photons excite the same fluorescence as one ultraviolet photon, but there must be a lot of IR in one small volume. No confocal pinhole is necessary, since the requisite convolution of two J 1(r)2/r 2 functions comes from the two illuminations.PubMedCrossRefGoogle Scholar
  10. Draaijer, A., and Houpt, P.M., 1988, A standard video-rate confocal laser-scanning reflection and fluorescence microscope, Scanning 10:139–145. The CSM developed at TNO has standard video-rate imaging, and is capable of working in reflection and in fluorescence mode simultaneously.CrossRefGoogle Scholar
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  24. Sawatari, T., 1973, Optical heterodyne scanning microscope, Appl. Optics 12:2768–2772. Image similar to CSM because the same self convolution of the diffraction pattern is required. Ambient light effects eliminated. High contrast images from low-contrast objects.CrossRefGoogle Scholar
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Fiber Optic CSMs

  1. Dabbs, T., and Glass, M., 1992, Single-mode fibers used as confocal microscope pinholes, Appl. Optics 31:705–706, and Dabbs, T., and Glass, M., 1992, Fiber-optic confocal microscope: FOCON, Appl. Optics 31:3030–3035. The beamsplitter is replaced by a fiber-optic splitter, and the core of a single-mode fiber takes the place of both the source and detector pinholes. Scanning in the x, y, and z directions is by moving the end of the optical fiber.CrossRefGoogle Scholar
  2. Gan, X., Gu, M., and Sheppard, C.J.R., 1992, Fluorescent image formation in the fibre-optical confocal scanning microscope, J. Mod. Opt. 39:825–834. Unlike a finite circular pinhole, there is no missing cone of spatial frequencies, and no negative tail in the transfer function.CrossRefGoogle Scholar
  3. Ghiggino, K.P., Harris, M.R., and Spizzirri, P.G., 1992, Fluorescence lifetime measurements using a novel fibre-optic laser scanning confocal microscope, Rev. Sci. Instrum. 63:2999–3002. A fiber-optic CSM with a mode-locked dye laser excitation source, avalanche photodiode detector, and time-correlated photon counting electronics, allows spatially resolved fluorescence decay profiles from fluorescent dyes in solution and polymer films.CrossRefGoogle Scholar
  4. Giniunas, L., Juskaitis, R., and Shatalin, S.V., 1991 Scanning fibre-optic microscope, Electron. Lett. 27:724–726. A phase-sensitive scanning fiber-optic microscope designed to be used as an endoscope. Confocal operation with single mode fiber yields 0.8 μm lateral resolution.CrossRefGoogle Scholar
  5. Gu, M., and Sheppard, C.J.R., 1991, Signal level of the fibre-optical CSM, J. Mod. Opt. 38:1621–1630. The efficiency of total power transformation and signal level of the fiber-optical CSM, including defocus effects.CrossRefGoogle Scholar
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  8. Juskaitis, R., and Wilson, T., 1992, Differential CSM with a two-mode optical fiber, Appl. Optics 31:898–902. Both the differential amplitude and the differential phase images can be obtained by adjusting the differential phase delay between the fiber modes.CrossRefGoogle Scholar
  9. Juskaitis, R., and Wilson, T., 1992, Imaging in reciprocal fibre-optic based CSMs, Opt. Commun. 92:315–325. Single- and two-mode fibers in a reciprocal scheme. Confocal, differential amplitude or phase contrast imaging and surface profilometry with reduced alignment tolerances.CrossRefGoogle Scholar
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Profilometry

  1. Corle, T.R., Fanton, J.T., and Kino, G.S., 1987, Distance measurements by differential confocal optical ranging, Appl. Optics 26:2416–2420. Dithering generates a differential measurement, placing a zero-crossing at the peak of the depth response. Sensitivities to surface vibrations of 0.01 nm and thin film measurements to 0.04 μmCrossRefGoogle Scholar
  2. Hamilton, D.K., and Matthews, H.J., 1985, The confocal interference microscope as a surface profilometer, Optik 71:31–34. A noncontacting high-resolution surface profiling technique, with feedback to maintain a constant phase relationship between the signal and the reference beams of a confocal interference microscope.Google Scholar
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  5. Matthews, H.J., Hamilton, D.K., and Sheppard, C.J.R., 1986, Surface profiling by phase-locked interferometry, Appl. Optics 25:2372–2374. 1-nm height resolution. A feedback arrangement keeps in quadrature the two arms of a confocal interference microscope by modulating the reference beam using an electro-optic phase modulator.CrossRefGoogle Scholar
  6. Toy, D.A., 1990, Confocal microscopy: The ups and downs of 3-D profiling. Semicond. Int. 13:120–123. Confocal techniques can solve the problems of depth of field versus resolution.Google Scholar

Display

  1. Carlsson, K., Danielsson, P.E., Lenz, R., Liljeborg, A., Majlof, L., and Åslund, N., 1985, Three-dimensional microscopy using a confocal laser scanning microscope, Opt. Lett. 10:53–55. Visualizes in stereo and rotation by making look-through projections of the digital data in different directions. Contrast enhanced by generating gradient volume to display the border surfaces between regions in opposing senses for the two images.PubMedCrossRefGoogle Scholar
  2. Conchello, J.A., and Hansen, E.W., 1990, Enhanced 3-D reconstruction from CSM images. I. Deterministic and maximum likelihood reconstructions, Appl. Optics 29:3795–3804. The feasibility of obtaining longitudinal resolution comparable to the lateral diffraction limit by posterior processing of confocal sections.CrossRefGoogle Scholar
  3. Dilworth, D.S., Leith, E.N., and Lopez, J.L., 1991, Three-dimensional confocal imaging of objects embedded within thick diffusing media, Appl. Optics 30:1796–1803. Exfoliative deconvolution to sharpen a volume image in which the blur is depth variant.CrossRefGoogle Scholar
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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Robert H. Webb
    • 1
  1. 1.Wellman LaboratoriesSchepens Eye Research Institute and MGH Laser CenterBostonUSA

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