Abstract

This paper presents a confocal microscanner for direct vertical optical sectioning of biological samples. Confocal imaging is performed by transverse (X-axis) and axial (Z-axis) scanning of a focused laser beam using an optical fiber and a microlens respectively. The actuators are fabricated by laser micromachining techniques and are driven by electromagnetic forces. Optical and mechanical performance of the system is predicted by simulation software packages and characterized by experimental measurements. The scanner has lateral resolution of 3.87 µm and axial resolution of 10.68 µm with a field of view of 145 µm in X and 190 µm in Z directions. Confocal imaging of a polymer layer deposited on a silicon wafer and onion epidermal cells is demonstrated.

© 2011 OSA

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    [CrossRef] [PubMed]

2011

H. Mansoor, H. Zeng, and M. Chiao, “A micro-fabricated optical scanner for rapid non-contact thickness measurement of transparent films,” Sens. Actuators A Phys. 167(1), 91–96 (2011).
[CrossRef]

H. Mansoor, H. Zeng, and M. Chiao, “Real-time thickness measurement of biological tissues using a microfabricated magnetically-driven lens actuator,” Biomed. Microdevices 13(4), 641–649 (2011).
[CrossRef] [PubMed]

E. J. Min, J. G. Shin, Y. Kim, and B. H. Lee, “Two-dimensional scanning probe driven by a solenoid-based single actuator for optical coherence tomography,” Opt. Lett. 36(11), 1963–1965 (2011).
[CrossRef] [PubMed]

2010

C. L. Arrasmith, D. L. Dickensheets, and A. Mahadevan-Jansen, “MEMS-based handheld confocal microscope for in-vivo skin imaging,” Opt. Express 18(4), 3805–3819 (2010).
[CrossRef] [PubMed]

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

2008

2007

2006

2005

A. Jain and H. Xie, “An electrothermal microlens scanner with low-voltage large-vertical-displacement actuation,” IEEE Photon. Technol. Lett. 17(9), 1971–1973 (2005).
[CrossRef]

2004

K. Venkateswaran, A. Roorda, and F. Romero-Borja, “Theoretical modeling and evaluation of the axial resolution of the adaptive optics scanning laser ophthalmoscope,” J. Biomed. Opt. 9(1), 132–138 (2004).
[CrossRef] [PubMed]

2003

T. D. Wang, C. H. Contag, M. J. Mandella, N. Y. Chan, and G. S. Kino, “Dual-axes confocal microscopy with post-objective scanning and low-coherence heterodyne detection,” Opt. Lett. 28(20), 1915–1917 (2003).
[CrossRef] [PubMed]

K. Koenig and I. Riemann, “High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution,” J. Biomed. Opt. 8(3), 432–439 (2003).
[CrossRef] [PubMed]

1999

N. Callamaras and I. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium 26(6), 271–279 (1999).
[CrossRef] [PubMed]

M. Rajadhyaksha, R. R. Anderson, and R. H. Webb, “Video-rate confocal scanning laser microscope for imaging human tissues in vivo,” Appl. Opt. 38(10), 2105–2115 (1999).
[CrossRef] [PubMed]

M. D. Sharma and C. J. R. Sheppard, “Effects of system geometry on the axial response of the fibre optical confocal microscope,” J. Mod. Opt. 46(4), 605–621 (1999).

1995

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

1991

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

M. Gu, C. J. R. Sheppard, and X. Gan, “Image formation in a fiber-optical confocal scanning microscope,” J. Opt. Soc. Am. A 8(11), 1755–1761 (1991).
[CrossRef]

1990

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1987

Anderson, R. R.

M. Rajadhyaksha, R. R. Anderson, and R. H. Webb, “Video-rate confocal scanning laser microscope for imaging human tissues in vivo,” Appl. Opt. 38(10), 2105–2115 (1999).
[CrossRef] [PubMed]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Arrasmith, C. L.

Avritscher, R.

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

Booth, M. J.

M. J. Booth, R. Juškaitis, and T. Wilson, “Spectral confocal reflection microscopy using a white light source,” J. Eur. Opt. Rapid Publ. 3, 08026 (2008).
[CrossRef]

Boppart, S. A.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

Callamaras, N.

N. Callamaras and I. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium 26(6), 271–279 (1999).
[CrossRef] [PubMed]

Carlini, A. R.

Chan, N. Y.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chiao, J.-C.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Chiao, M.

H. Mansoor, H. Zeng, and M. Chiao, “A micro-fabricated optical scanner for rapid non-contact thickness measurement of transparent films,” Sens. Actuators A Phys. 167(1), 91–96 (2011).
[CrossRef]

H. Mansoor, H. Zeng, and M. Chiao, “Real-time thickness measurement of biological tissues using a microfabricated magnetically-driven lens actuator,” Biomed. Microdevices 13(4), 641–649 (2011).
[CrossRef] [PubMed]

Contag, C. H.

Dave, D.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Dhaubanjar, N.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Dickensheets, D. L.

Esterowitz, D.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gan, X.

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Grossman, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Gu, M.

Hardy, J.

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hsiung, P.-L.

Hu, H.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Jain, A.

A. Jain and H. Xie, “An electrothermal microlens scanner with low-voltage large-vertical-displacement actuation,” IEEE Photon. Technol. Lett. 17(9), 1971–1973 (2005).
[CrossRef]

Juškaitis, R.

M. J. Booth, R. Juškaitis, and T. Wilson, “Spectral confocal reflection microscopy using a white light source,” J. Eur. Opt. Rapid Publ. 3, 08026 (2008).
[CrossRef]

Kim, Y.

Kino, G. S.

Koenig, K.

K. Koenig and I. Riemann, “High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution,” J. Biomed. Opt. 8(3), 432–439 (2003).
[CrossRef] [PubMed]

Kumar, K.

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

Lane, N.

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

Lee, B. H.

Lee, D.

Li, X.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Liu, J. T. C.

MacDonald, D. J.

Madoff, D. C.

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

Mahadevan-Jansen, A.

Maitland, K. C.

Mandella, M. J.

Mansoor, H.

H. Mansoor, H. Zeng, and M. Chiao, “A micro-fabricated optical scanner for rapid non-contact thickness measurement of transparent films,” Sens. Actuators A Phys. 167(1), 91–96 (2011).
[CrossRef]

H. Mansoor, H. Zeng, and M. Chiao, “Real-time thickness measurement of biological tissues using a microfabricated magnetically-driven lens actuator,” Biomed. Microdevices 13(4), 641–649 (2011).
[CrossRef] [PubMed]

Marks, D. L.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

Min, E. J.

Myaing, M. T.

Nguyen, F. T.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

Oldenburg, A. L.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

Parker, I.

N. Callamaras and I. Parker, “Construction of a confocal microscope for real-time x-y and x-z imaging,” Cell Calcium 26(6), 271–279 (1999).
[CrossRef] [PubMed]

Phuyal, P.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Piyawattanametha, W.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Ra, H.

Rajadhyaksha, M.

M. Rajadhyaksha, R. R. Anderson, and R. H. Webb, “Video-rate confocal scanning laser microscope for imaging human tissues in vivo,” Appl. Opt. 38(10), 2105–2115 (1999).
[CrossRef] [PubMed]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Richards-Kortum, R.

Riemann, I.

K. Koenig and I. Riemann, “High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution,” J. Biomed. Opt. 8(3), 432–439 (2003).
[CrossRef] [PubMed]

Romero-Borja, F.

K. Venkateswaran, A. Roorda, and F. Romero-Borja, “Theoretical modeling and evaluation of the axial resolution of the adaptive optics scanning laser ophthalmoscope,” J. Biomed. Opt. 9(1), 132–138 (2004).
[CrossRef] [PubMed]

Roorda, A.

K. Venkateswaran, A. Roorda, and F. Romero-Borja, “Theoretical modeling and evaluation of the axial resolution of the adaptive optics scanning laser ophthalmoscope,” J. Biomed. Opt. 9(1), 132–138 (2004).
[CrossRef] [PubMed]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Sharma, M. D.

M. D. Sharma and C. J. R. Sheppard, “Effects of system geometry on the axial response of the fibre optical confocal microscope,” J. Mod. Opt. 46(4), 605–621 (1999).

Sheppard, C. J. R.

M. D. Sharma and C. J. R. Sheppard, “Effects of system geometry on the axial response of the fibre optical confocal microscope,” J. Mod. Opt. 46(4), 605–621 (1999).

M. Gu, C. J. R. Sheppard, and X. Gan, “Image formation in a fiber-optical confocal scanning microscope,” J. Opt. Soc. Am. A 8(11), 1755–1761 (1991).
[CrossRef]

Shin, H. J.

Shin, J. G.

Sin, J.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Solgaard, O.

Stephanou, H.

N. Dhaubanjar, H. Hu, D. Dave, P. Phuyal, J. Sin, H. Stephanou, and J.-C. Chiao, “A compact optical fiber scanner for medical imaging,” Proc. SPIE 6414, 64141Z (2006).
[CrossRef]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Uhr, J. W.

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

Venkateswaran, K.

K. Venkateswaran, A. Roorda, and F. Romero-Borja, “Theoretical modeling and evaluation of the axial resolution of the adaptive optics scanning laser ophthalmoscope,” J. Biomed. Opt. 9(1), 132–138 (2004).
[CrossRef] [PubMed]

Wang, T. D.

Wang, Y.

K. Kumar, R. Avritscher, Y. Wang, N. Lane, D. C. Madoff, T.-K. Yu, J. W. Uhr, and X. Zhang, “Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging,” Biomed. Microdevices 12(2), 223–233 (2010).
[CrossRef] [PubMed]

Webb, R. H.

M. Rajadhyaksha, R. R. Anderson, and R. H. Webb, “Video-rate confocal scanning laser microscope for imaging human tissues in vivo,” Appl. Opt. 38(10), 2105–2115 (1999).
[CrossRef] [PubMed]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Webb, W. W.

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Figures (12)

Fig. 1
Fig. 1

(a) Optical configuration of the 2-axis confocal scanner. The optical fiber and objective lens are capable of scanning in transverse (X-axis) and axial (Z-axis) directions respectively. (b) Schematic diagram of the experimental setup.

Fig. 2
Fig. 2

(a) Deflection diagram of cantilever/fiber actuator for transverse scanning. (b) Deflection diagram of one of the four folded beams for axial scanning of a lens.

Fig. 3
Fig. 3

Photo of (a) Fiber optic actuator, and (b) Lens actuator, fabricated by laser micromachining of nickel foils.

Fig. 4
Fig. 4

Cross-sectional drawing of 2-axis confocal scanner.

Fig. 5
Fig. 5

Measured, predicted and calculated resonant frequencies of the nickel flexure.

Fig. 6
Fig. 6

Two-dimensional layout of confocal scanner optical configuration.

Fig. 7
Fig. 7

Full field spot diagram of the confocal scanner demonstrating the lateral resolution.

Fig. 8
Fig. 8

Plot of modulation transfer function (MTF) for three fiber positions.

Fig. 9
Fig. 9

Through focus spot diagram of 2-axis confocal scanner at three fiber positions.

Fig. 10
Fig. 10

Experimental measurement of (a) Axial and (b) Lateral resolutions of 2-axis confocal scanner.

Fig. 11
Fig. 11

(a) Confocal image of SU-8 channel cross-section. (b) Optical profile of the channel measured by an optical profiler.

Fig. 12
Fig. 12

(a) Microscopic image of an onion transverse section stained with Alcian blue. (b), (c), and (d) Confocal vertical optical section images of onion epidermis.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

F mag = μ 0 A N 2 2 g 2 i max 2 sin 2 ωt
d x = F mag a 2 6EI (a3 l f )
d z = F mag k 1 { [ 1 ( 2ω ω n ) 2 ] 2 + [ 2ζ 2ω ω n ] 2 } 1 2
k= 192EI l b 3

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