Abstract

We have developed a low-cost, near-infrared (NIR) reflectance confocal microscope (RCM) to overcome challenges in the imaging depth and speed found in our previously-reported smartphone confocal microscope. In the new NIR RCM device, we have used 840 nm superluminescent LED (sLED) to increase the tissue imaging depth and speed. A new confocal detection optics has been developed to maintain high lateral resolution even when a relatively large slit width was used. The material cost of the NIR RCM device was still low, ~$5,200. The lateral resolution was 1.1 µm and 1.3 µm along the vertical and horizontal directions, respectively. Axial resolution was measured as 11.2 µm. In vivo confocal images of human forearm skin obtained at the imaging speed of 203 frames/sec clearly visualized characteristic epidermal and dermal cellular features of the human skin.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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2018 (1)

2017 (4)

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

2015 (2)

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

2014 (2)

S. A. Lee and C. Yang, “A smartphone-based chip-scale microscope using ambient illumination,” Lab Chip 14(16), 3056–3063 (2014).
[Crossref] [PubMed]

A. Ozcan, “Mobile phones democratize and cultivate next-generation imaging, diagnostics and measurement tools,” Lab Chip 14(17), 3187–3194 (2014).
[Crossref] [PubMed]

2012 (1)

C. Glazowski and M. Rajadhyaksha, “Optimal detection pinhole for lowering speckle noise while maintaining adequate optical sectioning in confocal reflectance microscopes,” J. Biomed. Opt. 17(8), 085001 (2012).
[Crossref] [PubMed]

2011 (1)

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

2010 (2)

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

2007 (1)

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

2006 (1)

2002 (1)

S. González and Z. Tannous, “Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma,” J. Am. Acad. Dermatol. 47(6), 869–874 (2002).
[Crossref] [PubMed]

Ahlford, A.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Anderson, R. R.

Araújo Pinto, L.

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Ardigò, M.

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Arena, E. T.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Avila-Wallace, M.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Avramidis, M.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Bashir, R.

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Borges, V.

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

Boudoux, C.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Bouma, B. E.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Buffon, R. B.

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Carrera, C.

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

Carruth, R. W.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Castro, C. M.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Chen, W.

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Cota, C.

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Cunningham, B. T.

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Damhorst, G. L.

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Darai, E.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

DeZonia, B. E.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Duarte-Guevara, C.

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Eliceiri, K. W.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Fexon, L.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Freeman, E. E.

Ghonge, T.

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Glazowski, C.

C. Glazowski and M. Rajadhyaksha, “Optimal detection pinhole for lowering speckle noise while maintaining adequate optical sectioning in confocal reflectance microscopes,” J. Biomed. Opt. 17(8), 085001 (2012).
[Crossref] [PubMed]

González, S.

Grant, C. N.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Grazziotin, T. C.

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Guitera, P.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Gweon, D.

Halpern, A. C.

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

Hernández-Neuta, I.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Hiner, M. C.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Im, H.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Kang, D.

E. E. Freeman, A. Semeere, H. Osman, G. Peterson, M. Rajadhyaksha, S. González, J. N. Martin, R. R. Anderson, G. J. Tearney, and D. Kang, “Smartphone confocal microscopy for imaging cellular structures in human skin in vivo,” Biomed. Opt. Express 9(4), 1906–1915 (2018).
[Crossref] [PubMed]

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

J. Kim, D. Kang, and D. Gweon, “Spectrally Encoded Slit Confocal Microscopy,” Opt. Lett. 31(11), 1687–1689 (2006).
[Crossref] [PubMed]

Kim, J.

Kim, M.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Kühnemund, M.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Latini, A.

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Lauwers, G. Y.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Lecha, M.

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

Lee, H.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Lee, S. A.

S. A. Lee and C. Yang, “A smartphone-based chip-scale microscope using ambient illumination,” Lab Chip 14(16), 3056–3063 (2014).
[Crossref] [PubMed]

Liong, M.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Longo, C.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Magaoay, B.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Malvehy, J.

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

Marghoob, A.

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

Martin, J. N.

Mathot, L.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Menzies, S.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Min, C.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Mino-Kenudson, M.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Nehal, K. S.

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

Nilsson, M.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Nishioka, N. S.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Osman, H.

Ozcan, A.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

A. Ozcan, “Mobile phones democratize and cultivate next-generation imaging, diagnostics and measurement tools,” Lab Chip 14(17), 3187–3194 (2014).
[Crossref] [PubMed]

Pathania, D.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Pellacani, G.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Peterson, G.

Pivovarov, M.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Puig, S.

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

Puricelli, W. P.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Rajadhyaksha, M.

E. E. Freeman, A. Semeere, H. Osman, G. Peterson, M. Rajadhyaksha, S. González, J. N. Martin, R. R. Anderson, G. J. Tearney, and D. Kang, “Smartphone confocal microscopy for imaging cellular structures in human skin in vivo,” Biomed. Opt. Express 9(4), 1906–1915 (2018).
[Crossref] [PubMed]

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

C. Glazowski and M. Rajadhyaksha, “Optimal detection pinhole for lowering speckle noise while maintaining adequate optical sectioning in confocal reflectance microscopes,” J. Biomed. Opt. 17(8), 085001 (2012).
[Crossref] [PubMed]

Rho, J.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Rosenberg, M.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Rossi, A.

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

Rueden, C. T.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Schindelin, J.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Schlachter, S. C.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Segura, S.

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

Seidenari, S.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Semeere, A.

Shao, H.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Sjöblom, T.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Song, J.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Soomro, A. R.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Suter, M. J.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Tabatabaei, N.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Tambouret, R. H.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Tannous, Z.

S. González and Z. Tannous, “Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma,” J. Am. Acad. Dermatol. 47(6), 869–874 (2002).
[Crossref] [PubMed]

Tearney, G. J.

E. E. Freeman, A. Semeere, H. Osman, G. Peterson, M. Rajadhyaksha, S. González, J. N. Martin, R. R. Anderson, G. J. Tearney, and D. Kang, “Smartphone confocal microscopy for imaging cellular structures in human skin in vivo,” Biomed. Opt. Express 9(4), 1906–1915 (2018).
[Crossref] [PubMed]

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Tseng, D.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Walter, A. E.

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Wang, Y.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Wei, Q.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Weissleder, R.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Wu, T.

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Yachimski, P. S.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Yang, C.

S. A. Lee and C. Yang, “A smartphone-based chip-scale microscope using ambient illumination,” Lab Chip 14(16), 3056–3063 (2014).
[Crossref] [PubMed]

Yang, Z.

M. Kühnemund, Q. Wei, E. Darai, Y. Wang, I. Hernández-Neuta, Z. Yang, D. Tseng, A. Ahlford, L. Mathot, T. Sjöblom, A. Ozcan, and M. Nilsson, “Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy,” Nat. Commun. 8(1), 13913 (2017).
[Crossref] [PubMed]

Yoo, H.

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

Zurkiya, O.

H. Im, C. M. Castro, H. Shao, M. Liong, J. Song, D. Pathania, L. Fexon, C. Min, M. Avila-Wallace, O. Zurkiya, J. Rho, B. Magaoay, R. H. Tambouret, M. Pivovarov, R. Weissleder, and H. Lee, “Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone,” Proc. Natl. Acad. Sci. U.S.A. 112(18), 5613–5618 (2015).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

BMC Bioinformatics (1)

C. T. Rueden, J. Schindelin, M. C. Hiner, B. E. DeZonia, A. E. Walter, E. T. Arena, and K. W. Eliceiri, “ImageJ2: ImageJ for the next generation of scientific image data,” BMC Bioinformatics 18(1), 529 (2017).
[Crossref] [PubMed]

Dermatology (Basel) (1)

T. C. Grazziotin, C. Cota, R. B. Buffon, L. Araújo Pinto, A. Latini, and M. Ardigò, “Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma,” Dermatology (Basel) 220(4), 346–354 (2010).
[Crossref] [PubMed]

Engineering (Beijing) (1)

G. L. Damhorst, C. Duarte-Guevara, W. Chen, T. Ghonge, B. T. Cunningham, and R. Bashir, “Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood,” Engineering (Beijing) 1(3), 324–335 (2015).
[Crossref] [PubMed]

Gastrointest. Endosc. (1)

D. Kang, M. J. Suter, C. Boudoux, H. Yoo, P. S. Yachimski, W. P. Puricelli, N. S. Nishioka, M. Mino-Kenudson, G. Y. Lauwers, B. E. Bouma, and G. J. Tearney, “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy,” Gastrointest. Endosc. 71(1), 35–43 (2010).
[Crossref] [PubMed]

J. Am. Acad. Dermatol. (1)

S. González and Z. Tannous, “Real-time, in vivo confocal reflectance microscopy of basal cell carcinoma,” J. Am. Acad. Dermatol. 47(6), 869–874 (2002).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

C. Glazowski and M. Rajadhyaksha, “Optimal detection pinhole for lowering speckle noise while maintaining adequate optical sectioning in confocal reflectance microscopes,” J. Biomed. Opt. 17(8), 085001 (2012).
[Crossref] [PubMed]

J. Eur. Acad. Dermatol. Venereol. (1)

S. Segura, S. Puig, C. Carrera, M. Lecha, V. Borges, and J. Malvehy, “Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: A role for confocal microscopy and photodynamic therapy,” J. Eur. Acad. Dermatol. Venereol. 25(7), 819–827 (2011).
[Crossref] [PubMed]

J. Invest. Dermatol. (1)

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[Crossref] [PubMed]

Lab Chip (2)

S. A. Lee and C. Yang, “A smartphone-based chip-scale microscope using ambient illumination,” Lab Chip 14(16), 3056–3063 (2014).
[Crossref] [PubMed]

A. Ozcan, “Mobile phones democratize and cultivate next-generation imaging, diagnostics and measurement tools,” Lab Chip 14(17), 3187–3194 (2014).
[Crossref] [PubMed]

Lasers Surg. Med. (2)

M. Rajadhyaksha, A. Marghoob, A. Rossi, A. C. Halpern, and K. S. Nehal, “Reflectance confocal microscopy of skin in vivo: From bench to bedside,” Lasers Surg. Med. 49(1), 7–19 (2017).
[Crossref] [PubMed]

D. Kang, S. C. Schlachter, R. W. Carruth, M. Kim, T. Wu, N. Tabatabaei, A. R. Soomro, C. N. Grant, M. Rosenberg, N. S. Nishioka, and G. J. Tearney, “Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo,” Lasers Surg. Med. 49(3), 233–239 (2017).
[Crossref] [PubMed]

Nat. Commun. (1)

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Supplementary Material (1)

NameDescription
» Visualization 1       Visualizaiton 1 Movie of en face confocal images obtained by axial scanning and 3D rendering of volumetric confocal data at 10 different locations.

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Figures (6)

Fig. 1
Fig. 1 Schematic of the low-cost NIR RCM device.
Fig. 2
Fig. 2 Different approaches for confocal detections optics. a – detection optics used in the previous, smartphone confocal microscope; and b – detection optics used in the present confocal microscope.
Fig. 3
Fig. 3 Simulated PSFs of the previous and current confocal detection optics for a range of slit widths and lateral and axial FWHMs of PSFs. All FWHM values are shown in µm.
Fig. 4
Fig. 4 Photo of the low-cost NIR RCM device.
Fig. 5
Fig. 5 Resolution measurement. A – Lateral resolution measurement with a USAF resolution target; and B – Axial response curve.
Fig. 6
Fig. 6 In vivo confocal images of human forearm obtained at the imaging depth of 25 µm (A), 60 µm (B), 80µm (C), 125 µm (D), 195 µm (E), and 265 µm (F). arrows – keratinocytes; arrowheads – melanocytes or melanin-containing basal cells; yellow asterisks - dermal papillae; white asterisks – blood vessels; and dotted line – a cluster of melanocytes of melanin-containing basal cells. Scale bar = 100 µm.

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