Abstract

The most expensive aspects in producing high quality miniature optical systems are the component costs and long assembly process. A new approach for fabricating these systems that reduces both aspects through the implementation of self-aligning LIGA (German acronym for lithographie, galvanoformung, abformung, or x-ray lithography, electroplating, and molding) optomechanics with high volume plastic injection molded and off-the-shelf glass optics is presented. This zero alignment strategy has been incorporated into a miniature high numerical aperture (NA=1.0W) microscope objective for a fiber confocal reflectance microscope. Tight alignment tolerances of less than 10 μm are maintained for all components that reside inside of a small 9 gauge diameter hypodermic tubing. A prototype system has been tested using the slanted edge modulation transfer function technique and demonstrated to have a Strehl ratio of 0.71. This universal technology is now being developed for smaller, needle-sized imaging systems and other portable point-of-care diagnostic instruments.

© 2009 Optical Society of America

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References

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  1. C. Liang, K. B. Sung, R. Richards-Kortum, and 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. K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
    [CrossRef] [PubMed]
  3. A. R. Rouse, J. A. Udovich, and A. F. Gmitro, “In-vivo multi-spectral confocal microscopy,” Proc. SPIE 5701, 73-84(2005).
    [CrossRef]
  4. J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
    [CrossRef] [PubMed]
  5. W. Gobel, J. N. Kerr, A. Nimmerjahn, and F. Helmchen, “Miniaturized two-photon microscope based on a fexible coherent fiber bundle and a gradient-index lens objective,” Opt. Lett. 29, 2521-2523 (2004).
    [CrossRef] [PubMed]
  6. H. Bao, J. Allen, R. Pattie, R. Vance, and M. Gu, “Fast handheld two-photon fluorescence microendoscope with a 475 μm×475 μm field of view for in vivo imaging,” Opt. Lett. 33, 1333-1335 (2008).
    [CrossRef] [PubMed]
  7. M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
    [CrossRef]
  8. N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
    [CrossRef] [PubMed]
  9. X. Li, C. Chudoba, T. Ko, C. Pitris, and J. G. Fujimoto, “Imaging needle for optical coherence tomography,” Opt. Lett. 25, 1520-1522 (2000).
    [CrossRef]
  10. ZEMAX Development Corporation: http://www.zemax.com.
  11. W. B. Wetherall, “The calculation of image quality,” in Applied Optics and Optical Engineering, R. R. Shannon and J. C. Wyant, eds. (Academic, 1980), Vol. 8, pp. 171-316.
  12. M. J. Madou, Fundamentals of Microfabrication, 2nd ed. (CRC Press, 2002).
  13. R. T. Kester, T. S. Tkaczyk, M. R. Descour, T. Christenson, and R. Richards-Kortum, “High numerical aperture microendoscope objective for a fiber confocal reflectance microscope,” Opt. Express 15, 2409-2420 (2007).
    [CrossRef] [PubMed]
  14. M. D. Chidley, K. Carlson, M. R. Descour, and R. Richards-Kortum, “Design, assembly, and optical bench testing of a high numerical aperture miniature injection-molded objective for fiber-optic confocal reflectance microscopy,” Appl. Opt. 45, 2545-2554 (2006).
    [CrossRef] [PubMed]
  15. C. Liang, K. B. Sung, R. Richards-Kortum, and M. R. Descour, “Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope,” Appl. Opt. 41, 4603-4610 (2002).
    [CrossRef] [PubMed]
  16. P. D. Burns, “Slanted-edge MTF for digital camera and scanner analysis,” Proceedings of the Society for Imaging Science & Technology 2000 PICS Conference (IEEE, 2000), pp. 135-138.

2008 (2)

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

H. Bao, J. Allen, R. Pattie, R. Vance, and M. Gu, “Fast handheld two-photon fluorescence microendoscope with a 475 μm×475 μm field of view for in vivo imaging,” Opt. Lett. 33, 1333-1335 (2008).
[CrossRef] [PubMed]

2007 (1)

2006 (1)

2005 (2)

A. R. Rouse, J. A. Udovich, and A. F. Gmitro, “In-vivo multi-spectral confocal microscopy,” Proc. SPIE 5701, 73-84(2005).
[CrossRef]

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

2004 (2)

M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
[CrossRef]

W. Gobel, J. N. Kerr, A. Nimmerjahn, and F. Helmchen, “Miniaturized two-photon microscope based on a fexible coherent fiber bundle and a gradient-index lens objective,” Opt. Lett. 29, 2521-2523 (2004).
[CrossRef] [PubMed]

2002 (2)

K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
[CrossRef] [PubMed]

C. Liang, K. B. Sung, R. Richards-Kortum, and M. R. Descour, “Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope,” Appl. Opt. 41, 4603-4610 (2002).
[CrossRef] [PubMed]

2001 (1)

2000 (1)

Ali, M. F.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Allen, J.

Anslyn, E.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Bao, H.

Bernard, B.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Burns, P. D.

P. D. Burns, “Slanted-edge MTF for digital camera and scanner analysis,” Proceedings of the Society for Imaging Science & Technology 2000 PICS Conference (IEEE, 2000), pp. 135-138.

Carlson, K.

Chidley, M. D.

Christenson, T.

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

R. T. Kester, T. S. Tkaczyk, M. R. Descour, T. Christenson, and R. Richards-Kortum, “High numerical aperture microendoscope objective for a fiber confocal reflectance microscope,” Opt. Express 15, 2409-2420 (2007).
[CrossRef] [PubMed]

Christodoulides, N.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Chudoba, C.

Collier, T.

K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
[CrossRef] [PubMed]

Descour, M.

K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
[CrossRef] [PubMed]

Descour, M. R.

Dharshan, P.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Floriano, P. N.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Follen, M.

K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
[CrossRef] [PubMed]

Fox, P. C.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Fujimoto, J. G.

Gmitro, A. F.

A. R. Rouse, J. A. Udovich, and A. F. Gmitro, “In-vivo multi-spectral confocal microscopy,” Proc. SPIE 5701, 73-84(2005).
[CrossRef]

Gobel, W.

Gu, M.

Helmchen, F.

Karkainen, A. H. O.

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

Kasischke, D. A.

M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
[CrossRef]

Kerr, J. N.

Kester, R. T.

Ko, T.

Landau, S.

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

Langub, M. C.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Levene, M. J.

M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
[CrossRef]

Li, X.

Liang, C.

Madou, M. J.

M. J. Madou, Fundamentals of Microfabrication, 2nd ed. (CRC Press, 2002).

Malpica, A.

K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
[CrossRef] [PubMed]

McDevitt, J. T.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Miller, C. S.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Mohanty, S.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Molloy, K. A.

M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
[CrossRef]

Nimmerjahn, A.

Pattie, R.

Pitris, C.

Rahman, M. S.

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

Richards-Kortum, R.

Rogers, J. D.

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

Romanovicz, D.

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Rouse, A. R.

A. R. Rouse, J. A. Udovich, and A. F. Gmitro, “In-vivo multi-spectral confocal microscopy,” Proc. SPIE 5701, 73-84(2005).
[CrossRef]

Sung, K. B.

Tkaczyk, T. S.

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

R. T. Kester, T. S. Tkaczyk, M. R. Descour, T. Christenson, and R. Richards-Kortum, “High numerical aperture microendoscope objective for a fiber confocal reflectance microscope,” Opt. Express 15, 2409-2420 (2007).
[CrossRef] [PubMed]

Udovich, J. A.

A. R. Rouse, J. A. Udovich, and A. F. Gmitro, “In-vivo multi-spectral confocal microscopy,” Proc. SPIE 5701, 73-84(2005).
[CrossRef]

Vance, R.

Webb, W. W.

M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
[CrossRef]

Wetherall, W. B.

W. B. Wetherall, “The calculation of image quality,” in Applied Optics and Optical Engineering, R. R. Shannon and J. C. Wyant, eds. (Academic, 1980), Vol. 8, pp. 171-316.

Appl. Opt. (2)

J. Biomed. Opt. (1)

J. D. Rogers, S. Landau, T. S. Tkaczyk, M. R. Descour, M. S. Rahman, R. Richards-Kortum, A. H. O. Karkainen, and T. Christenson, “Imaging performance of a miniature integrated microendoscope,” J. Biomed. Opt. 13, 054020 (2008).
[CrossRef] [PubMed]

J. Microsc. (1)

K. B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, “Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved,” J. Microsc. 207, 137-145 (2002).
[CrossRef] [PubMed]

J. Neurophysiol. (1)

M. J. Levene, D. A. Kasischke, K. A. Molloy, and W. W. Webb, “in vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91, 1908-1912 (2004).
[CrossRef]

Lab Chip (1)

N. Christodoulides, S. Mohanty, C. S. Miller, M. C. Langub, P. N. Floriano, P. Dharshan, M. F. Ali, B. Bernard, D. Romanovicz, E. Anslyn, P. C. Fox, and J. T. McDevitt, “Application of microchip assay system for the measurement of C-reactive protein in human saliva,” Lab Chip 5, 261-269(2005).
[CrossRef] [PubMed]

Opt. Express (2)

Opt. Lett. (3)

Proc. SPIE (1)

A. R. Rouse, J. A. Udovich, and A. F. Gmitro, “In-vivo multi-spectral confocal microscopy,” Proc. SPIE 5701, 73-84(2005).
[CrossRef]

Other (4)

ZEMAX Development Corporation: http://www.zemax.com.

W. B. Wetherall, “The calculation of image quality,” in Applied Optics and Optical Engineering, R. R. Shannon and J. C. Wyant, eds. (Academic, 1980), Vol. 8, pp. 171-316.

M. J. Madou, Fundamentals of Microfabrication, 2nd ed. (CRC Press, 2002).

P. D. Burns, “Slanted-edge MTF for digital camera and scanner analysis,” Proceedings of the Society for Imaging Science & Technology 2000 PICS Conference (IEEE, 2000), pp. 135-138.

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Figures (11)

Fig. 1
Fig. 1

Optical design layout of miniature microscope objective.

Fig. 2
Fig. 2

Optical design performance of the NA = 1.0 (water immersion) miniature objective. (a) Modulation transfer function for three field locations: on axis, 0.707 field, and full field. (b) Field curvature for sagittal and tangential planes. (c) Spot diagrams for the same three field locations in MTF with diffraction limited Airy disk.

Fig. 3
Fig. 3

Drawing of the self-aligning concept as applied to this miniature objective. (a) Isometric view of critical objective components with lens barrel suppressed. (b) Sliced isometric view with lens components labeled. (c) Sliced side view of objective with actual light rays refracting through system from an on-axis field point. (d) Front view showing the six self-centering flexures on the periphery of the LIGA optomechanics.

Fig. 4
Fig. 4

Diagram of flexure design and analysis. Flexures were modeled as simple cantilevers to balance the force and stress equations.

Fig. 5
Fig. 5

Pictures of prototype LIGA fabricated optomechanical components: (a) nonoxidized parts with high scattering; (b) black oxidized parts with low scattering.

Fig. 6
Fig. 6

Lens barrel (hypodermic tubing) waviness measurements measured with a white light interferometer around four full length regions of the tubing. Below are actual 2D surface profiles taken from tube 1.

Fig. 7
Fig. 7

Decentration test setup and initial results. (a) 3D map of lens 1 and its LIGA layer tomography obtained by the WLI. (b) x-axis cross section through lens and LIGA layer. (c) Curve fit results for the x-axis cross section of the lens apex used to find the lens center.

Fig. 8
Fig. 8

Element tilt test setup and results. (1A) Gray scale image and (1B) WLI tomography results taken from region 1 (microscope slide). (2A) Gray scale image and (2B) WLI tomography results taken from region 2 (top of Lens 3) used to find tilt system components.

Fig. 9
Fig. 9

Assembled miniature objective prototypes (oxidized and nonoxidized) on a US penny for size comparison.

Fig. 10
Fig. 10

MTF test setup for evaluation of prototype objective imaging performance.

Fig. 11
Fig. 11

Imaging results for the prototype objective. (a) Objective can resolve the USAF resolution target group 7 element 6 ( 256 l i n e p a i r s / mm ) bars. (b) Image of a corner on the resolution target is used for calculating MTF based on the slanted-edge technique. (c) Objective MTF curves for horizontal and vertical edges (dash and dotted curves) shown with ideal MTF curve (solid black). The average for the horizontal and vertical edge is shown in dark gray. The objective has an average SR of 0.71.

Tables (5)

Tables Icon

Table 1 Miniature Microscope Objective Top Level Optical Design Requirements

Tables Icon

Table 2 Lens Prescription for Miniature Objective Optical Design

Tables Icon

Table 3 Optomechanical Tolerances and Tolerance Sensitivities Analysis

Tables Icon

Table 4 Lateral and Axial Measurements for Critical Features of the LIGA Optomechanics Taken with a White Light Interferometer

Tables Icon

Table 5 Hypodermic Tubing Waviness Characterization Results Taken with a White Light Interferometer a

Equations (3)

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

F = δ 3 E I l 3 ,
σ = F l h 2 I .
( x h ) 2 + ( y k ) 2 = r 2 ,

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