Abstract

We demonstrate a hyperspectral and depth sensitive diffuse optical imaging microsystem, where fast scanning is provided by a CMOS compatible 2-axis MEMS mirror. By using lissajous scanning patterns, large field-of-view (FOV) of 1.2cm x 1.2cm images with lateral resolution of 100µm can be taken at 1.3 frames-per-second (fps). Hyperspectral and depth-sensitive images were acquired on tissue simulating phantom samples containing quantum dots (QDs) patterned at various depths in Polydimethylsiloxane (PDMS). Device performance delivers 6 nm spectral resolution and 0.43 wavelengths per second acquisition speed. A sample of porcine epithelium with subcutaneously placed QDs was also imaged. Images of the biological sample were processed by spectral unmixing in order to qualitatively separate chromophores in the final images and demonstrate spectral performance of the imaging system.

© 2010 OSA

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  1. Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
    [CrossRef] [PubMed]
  2. N. Rajaram, T. J. Aramil, K. Lee, J. S. Reichenberg, T. H. Nguyen, and J. W. Tunnell, “Design and validation of a clinical instrument for spectral diagnosis of cutaneous malignancy,” Appl. Opt. 49(2), 142–152 (2010).
    [CrossRef] [PubMed]
  3. 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]
  4. K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
    [CrossRef]
  5. K. Kumar, R. Avritscher, D. Madoff, and X. Zhang, Handheld Single-Cell-Layer Optical Sectioning Reflectance Confocal Microscope for Interventional Imaging, p 1¨C5. (format).
  6. G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
    [CrossRef]
  7. S. A. Burgess, M. B. Bouchard, B. Yuan, and E. M. Hillman, “Simultaneous multiwavelength laminar optical tomography,” Opt. Lett. 33(22), 2710–2712 (2008).
    [CrossRef] [PubMed]

2010

N. Rajaram, T. J. Aramil, K. Lee, J. S. Reichenberg, T. H. Nguyen, and J. W. Tunnell, “Design and validation of a clinical instrument for spectral diagnosis of cutaneous malignancy,” Appl. Opt. 49(2), 142–152 (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]

2008

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
[CrossRef]

S. A. Burgess, M. B. Bouchard, B. Yuan, and E. M. Hillman, “Simultaneous multiwavelength laminar optical tomography,” Opt. Lett. 33(22), 2710–2712 (2008).
[CrossRef] [PubMed]

2007

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

Aramil, T. J.

Aranda, I.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

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]

Bouchard, M. B.

Burgess, S. A.

Condit, J.

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

Fedder, G. K.

G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
[CrossRef]

Halpern, A. C.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

Hillman, E. M.

Hoshino, K.

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

Howe, R. T.

G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
[CrossRef]

Kemp, N.

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

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]

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

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]

Lee, K.

Li, Y.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

Liu, T.-J. K.

G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
[CrossRef]

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]

McElroy, A.

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

Milner, T.

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

Nehal, K. S.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

Nguyen, T. H.

Patel, Y. G.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

Quevy, E. P.

G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
[CrossRef]

Rajadhyaksha, M.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

Rajaram, N.

Reichenberg, J. S.

Tunnell, J. W.

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]

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]

Yu, T. 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]

Yuan, B.

Zhang, X.

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]

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

Appl. Opt.

Biomed. Microdevices

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]

J. Biomed. Opt.

Y. G. Patel, K. S. Nehal, I. Aranda, Y. Li, A. C. Halpern, and M. Rajadhyaksha, “Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions,” J. Biomed. Opt. 12(3), 034027 (2007).
[CrossRef] [PubMed]

J. Opt. A, Pure Appl. Opt.

K. Kumar, J. Condit, A. McElroy, N. Kemp, K. Hoshino, T. Milner, and X. Zhang, “Fast 3D in vivo swept-source optical coherence tomography using a two-axis MEMS scanning micromirror,” J. Opt. A, Pure Appl. Opt. 10(4), 044013 (2008).
[CrossRef]

Opt. Lett.

Proc. IEEE

G. K. Fedder, R. T. Howe, T.-J. K. Liu, and E. P. Quevy, “Technologies for Cofabricating MEMS and Electronics,” Proc. IEEE 96(2), 306–322 (2008).
[CrossRef]

Other

K. Kumar, R. Avritscher, D. Madoff, and X. Zhang, Handheld Single-Cell-Layer Optical Sectioning Reflectance Confocal Microscope for Interventional Imaging, p 1¨C5. (format).

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Figures (8)

Fig. 1
Fig. 1

Schematic of the MEMS HSI system.

Fig. 2
Fig. 2

SEMs of CMOS compatible microscanner. (a) Scanning electron micrograph of micromirror.(b) Roughness measurement showing a 8nm roughness in average (split in to two figures, one on SEM + deflection + f, one on surface characterizations)

Fig. 3
Fig. 3

Experiment measurement of the optical performance of the FSI system. Left: Image of the elements of group 7 of a USAF 1951 standard resolution target. Field of view: 1.2cm by 1.2cm Right: Image of the USAF target using Leica EZ4DMicroscope image of a USAF target. Scale bars are 2mm.

Fig. 4
Fig. 4

Schematic of the μCP fabricated QDs multilayer PDMS sample. Left: Isometric View. Right: Side View.

Fig. 5
Fig. 5

MEMS HSI for PDMS-QD phantom imaging. (a) PDMS sample imaged under 12 selected wavelengths from the 30 total acquired wavelengths. (b) Normalized spectrum of 3 featured positions on the PDMS sample.

Fig. 6
Fig. 6

Comparison of images acquired using MEMS HSI and Olympus microscope. (a) Pseudocolor image merged from 3 peak wavelength images. (b) Microscope image using Olympus BX51 microscope. Scale bars are 1mm.

Fig. 7
Fig. 7

(a)-(d): Depth sampled images for four different SD separations. Fluorescence intensities within selected regions of the image were calculated to obtain ratios of shallow to deep intensities. Red and yellow outlined regions contain shallow (200μm) and deep (600μm) QDs respectively. (e) Mean intensity ratios of shallow vs. deep quantum dot stamps over 0 to 399μm SD separations. Scale bar is 1mm.

Fig. 8
Fig. 8

Biological Sample of porcine epithelium with QDs placed underneath the surface, with SD separation being zero (essentially, the confocal configuration). (a) Camera image of sample, MEMS HSI scan area is delineated by the white box. (b) Emission spectrum of quantum dots used. Bold curve derived using USB4000 spectrometer, broken line curves derived from the hyperspectral imaging system (25 points from 550 to 700nm). (c)-(d) De-mixed image acquired at the peak wavelength of orange and red QDs. (e) Pseudocolor image merged from (c), (d) after thresholding despeckling denoise.

Equations (1)

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I Q D _ s h a l l o w I Q D _ d e e p 1 σ

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