Abstract

An endoscopic confocal microscope requires a high-performance, miniaturized microscope objective. We present the design of a miniature water-immersion microscope objective that is approximately 10 times smaller in length than a typical commercial objective. The miniature objective is 7 mm in outer diameter and 21 mm in length (from object to image). It is used in a fiber confocal reflectance microscope. The miniature microscope objective has a numerical aperture of 1.0, a field of view of 250 µm, and a working distance of 450 µm. It delivers diffraction-limited performance at λ = 1064 nm. Micro-meter-level resolution has been experimentally demonstrated.

© 2002 Optical Society of America

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References

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  1. C. Liang, K. B. Sung, R. Richards-Kortum, M. R. Descour, “Fiber confocal reflectance microscope (FCRM) for in-vivo imaging,” Opt. Express 9, 821–830 (2001), http://www.opticsexpress.org .
    [CrossRef] [PubMed]
  2. C. Williams, Cancer Biology and Management: An Introduction (Wiley, West Sussex, England, 1990).
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    [CrossRef] [PubMed]
  4. K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).
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    [CrossRef] [PubMed]
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    [CrossRef]
  7. C. L. Smithpeter, A. K. Dunn, A. J. Welch, R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” Appl. Opt. 37, 2749–2754 (1998).
    [CrossRef]
  8. K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).
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    [CrossRef]
  15. Optics Technology, Inc., Pittsford, N. Y., http://opticstechnology.com .
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2001 (3)

2000 (1)

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

1998 (1)

1996 (1)

1993 (1)

Azia, D.

Brookner, C.

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

Buess, G.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188, 267–273 (2001).
[CrossRef]

Collier, T.

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

Day, D.

Descour, M. R.

C. Liang, K. B. Sung, R. Richards-Kortum, M. R. Descour, “Fiber confocal reflectance microscope (FCRM) for in-vivo imaging,” Opt. Express 9, 821–830 (2001), http://www.opticsexpress.org .
[CrossRef] [PubMed]

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

Drezek, R.

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

Dunn, A. K.

Follen, M.

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

Gmitro, A. F.

Goodman, J. W.

J. W. Goodman, Introduction to Fourier Optics, 2nd ed. (McGraw-Hill, New York, 1996).

Gu, M.

Knittel, J.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188, 267–273 (2001).
[CrossRef]

Kumar, G.

Laikin, M.

M. Laikin, Lens design, 2nd ed. (Mercel Dekker, New York, 1995).

Liang, C.

C. Liang, K. B. Sung, R. Richards-Kortum, M. R. Descour, “Fiber confocal reflectance microscope (FCRM) for in-vivo imaging,” Opt. Express 9, 821–830 (2001), http://www.opticsexpress.org .
[CrossRef] [PubMed]

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

Lotan, R.

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

Malpica, A.

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

Messerschmidt, B.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188, 267–273 (2001).
[CrossRef]

Possner, T.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188, 267–273 (2001).
[CrossRef]

Richards-Kortum, R.

C. Liang, K. B. Sung, R. Richards-Kortum, M. R. Descour, “Fiber confocal reflectance microscope (FCRM) for in-vivo imaging,” Opt. Express 9, 821–830 (2001), http://www.opticsexpress.org .
[CrossRef] [PubMed]

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

C. L. Smithpeter, A. K. Dunn, A. J. Welch, R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” Appl. Opt. 37, 2749–2754 (1998).
[CrossRef]

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

Schmitt, J. M.

Schnieder, L.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188, 267–273 (2001).
[CrossRef]

Shannon, R. R.

R. R. Shannon, The Art and Science of Optical Design (Cambridge U. Press, Cambridge, 1997).
[CrossRef]

Smith, W. J.

W. J. Smith, Modern Lens Design: A Resource Manual (McGraw-Hill, New York, 1996).

Smithpeter, C. L.

Sung, K. B.

C. Liang, K. B. Sung, R. Richards-Kortum, M. R. Descour, “Fiber confocal reflectance microscope (FCRM) for in-vivo imaging,” Opt. Express 9, 821–830 (2001), http://www.opticsexpress.org .
[CrossRef] [PubMed]

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

Welch, A. J.

Williams, C.

C. Williams, Cancer Biology and Management: An Introduction (Wiley, West Sussex, England, 1990).

Am. J. Obstet. Gynecol. (1)

R. Drezek, T. Collier, C. Brookner, A. Malpica, R. Lotan, R. Richards-Kortum, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol. 182, 1135–1139 (2000).
[CrossRef] [PubMed]

Appl. Opt. (1)

J. Opt. Soc. Am. A (1)

Opt. Commun. (1)

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun. 188, 267–273 (2001).
[CrossRef]

Opt. Express (1)

Opt. Lett. (2)

Other (9)

C. Williams, Cancer Biology and Management: An Introduction (Wiley, West Sussex, England, 1990).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Near real time in-vivo fiber optic confocal microscope: sub-cellular structure resolved,” J. Microsc. (to be published).

K. B. Sung, C. Liang, M. R. Descour, T. Collier, M. Follen, R. Richards-Kortum, “Fiber optics confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng. (to be published).

J. W. Goodman, Introduction to Fourier Optics, 2nd ed. (McGraw-Hill, New York, 1996).

W. J. Smith, Modern Lens Design: A Resource Manual (McGraw-Hill, New York, 1996).

Schott Glass Technologies Inc., Duryea, Pa. http://www.us.shott.com .

R. R. Shannon, The Art and Science of Optical Design (Cambridge U. Press, Cambridge, 1997).
[CrossRef]

Optics Technology, Inc., Pittsford, N. Y., http://opticstechnology.com .

M. Laikin, Lens design, 2nd ed. (Mercel Dekker, New York, 1995).

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Figures (8)

Fig. 1
Fig. 1

Schematic of the FCRM. The miniature microscope objective is attached to the distal end of the coherent fiber bundle. APD, avalanche photodiode.

Fig. 2
Fig. 2

Design by halves. (a) Optical layout for the high-NA half-system (NA, 1.0) with water-filled image space. (b) Optical layout for the low-NA half-system (NA, 0.3) with index-matching-oil-filled image space. Scales in (a) and (b) are not the same.

Fig. 3
Fig. 3

Miniature microscope objective. (a) Optical layout of the miniature microscope objective. The maximum clear-aperture diameter is 4 mm. (b) Photograph of the miniature microscope objective placed next to a U.S. penny and a U.S. dime to show perspective. The brass barrel of the miniature microscope objective measures 7 mm in diameter.

Fig. 4
Fig. 4

Predicted performance of the miniature-microscope-objective design of Fig. 3(a). (a) Geometric spot diagrams for three radial distances from the optical axis at the object surface. The radial distances are denoted h. (b) Distortion plot for the miniature-microscope-objective design. (c) The modulational transfer function plots. See text for discussion.

Fig. 5
Fig. 5

Resolution measurement test setup for the miniature microscope objective.

Fig. 6
Fig. 6

Images of a standard U.S. Air Force resolution test target obtained with the setup shown in Fig. 5. Bar patterns in (a) have a line width and spacing of 1.8 µm; those in (b) have a line width and spacing of 1.2 µm, and those in (c) have a line width and spacing of 0.93 µm.

Fig. 7
Fig. 7

Image of polystyrene microspheres suspended in water. Seven microspheres are within the FOV. The average size of a microsphere is 4.3 µm, and the index of refraction is approximately 1.57. The diameter of a single microsphere expands two to three fibers. White filled circle, approximately 4.3-µm diameter; arrows point to some of the highly visible microspheres.

Fig. 8
Fig. 8

In vivo images of the lower lip of one of the authors (K. B. Sung). The FOV measures 170 µm on a side. The arrows point to some visible nuclei. The 20-µm scale bar is approximate.

Tables (1)

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Table 1 Five Tightest Tolerance Parameters and Their Corresponding Tolerance Values

Equations (2)

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Lateral sampling = Fiber spacingmobj = 2.1 μm.
D=0.61 λNA.

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