Abstract

Quantification of optical absorption gaps in nailfold capillaries has recently shown promise as a non-invasive technique for neutropenia screening. Here we demonstrate a low-cost, portable attachment to a mobile phone that can resolve optical absorption gaps in nailfold capillaries using a reverse lens technique and oblique 520nm illumination. Resolution <4μm within a 1mm2 on-axis region is demonstrated, and wide field of view (3.5mm × 4.8mm) imaging is achieved with resolution <6μm in the periphery. Optical absorption gaps (OAGs) are visible in superficial capillary loops of a healthy human participant by an ∼8-fold difference in contrast-to-noise ratio with respect to red blood cell absorption contrast. High speed video capillaroscopy up to 240 frames per second (fps) is possible, though 60fps is sufficient to resolve an average frequency of 37 OAGs/minute passing through nailfold capillaries. The simplicity and portability of this technique may enable the development of an effective non-invasive tool for white blood cell screening in point-of-care and global health settings.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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2019 (1)

A. Pablo-Trinidad, I. Butterworth, M. J. Ledesma-Carbayo, T. Vettenburg, A. Sanchez-Ferro, L. Soenksen, N. J. Durr, A. Munoz-Barrutia, C. Cerrato, K. Humala, M. F. Urdiol, C. Del Rio, B. Valles, Y.-B. Chen, E. P. Hochberg, C. Castro-González, and A. Bourquard, “Automated detection of neutropenia using noninvasive video microscopy of superficial capillaries,” Am. J. Hematol. 94(8), E219–E222 (2019).
[Crossref]

2018 (3)

I. Gurov, M. Volkov, N. Margaryants, A. Pimenov, and A. Potemkin, “High-speed video capillaroscopy method for imaging and evaluation of moving red blood cells,” Opt. Lasers Eng. 104, 244–251 (2018).
[Crossref]

A. Bourquard, A. Pablo-Trinidad, I. Butterworth, Á. Sánchez-Ferro, C. Cerrato, K. Humala, M. F. Urdiola, C. D. Rio, B. Valles, J. M. Tucker-Schwartz, E. S. Lee, B. J. Vakoc, T. P. Padera, M. J. Ledesma-Carbayo, Y.-B. Chen, E. P. Hochberg, M. L. Gray, and C. Castro-González, “Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation,” Sci. Rep. 8(1), 5301 (2018).
[Crossref]

R. G. Mannino, D. R. Myers, E. A. Tyburski, C. Caruso, J. Boudreaux, T. Leong, G. D. Clifford, and W. A. Lam, “Smartphone app for non-invasive detection of anemia using only patient-sourced photos,” Nat. Commun. 9(1), 4924 (2018).
[Crossref]

2017 (1)

E. Tai, G. P. Guy Jr., A. Dunbar, and L. C. Richardson, “Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States 2012,” J. Oncol. Pract. 13(6), e552–e561 (2017).
[Crossref]

2016 (2)

T. Honda, T. Uehara, G. Matsumoto, S. Arai, and M. Sugano, “Neutrophil left shift and white blood cell count as markers of bacterial infection,” Clin. Chim. Acta 457, 46–53 (2016).
[Crossref]

K. M. Rappaport, C. C. McCracken, J. Beniflah, W. K. Little, D. A. Fletcher, W. A. Lam, and A. L. Shane, “Assessment of a Smartphone Otoscope Device for the Diagnosis and Management of Otitis Media,” Clin. Pediatr. (Philadelphia) 55(9), 800–810 (2016).
[Crossref]

2015 (2)

K. J. Ciuffreda and M. Rosenfield, “Evaluation of the SVOne: A Handheld, Smartphone-Based Autorefractor,” Optom. Vis. Sci. 92(12), 1133–1139 (2015).
[Crossref]

U. Baran, L. Shi, and R. K. Wang, “Capillary blood flow imaging within human finger cuticle using optical microangiography,” J. Biophotonics 8(1-2), 46–51 (2015).
[Crossref]

2014 (3)

A. Skandarajah, C. D. Reber, N. A. Switz, and D. A. Fletcher, “Quantitative Imaging with a Mobile Phone Microscope,” PLoS One 9(5), e96906 (2014).
[Crossref]

N. A. Switz, M. V. D’Ambrosio, and D. A. Fletcher, “Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens,” PLoS One 9(5), e95330 (2014).
[Crossref]

D. S. Chabot-Richards and T. I. George, “Leukocytosis,” Int. Jnl. Lab. Hem. 36(3), 279–288 (2014).
[Crossref]

2013 (2)

I. I. Bogoch, J. R. Andrews, B. Speich, J. Utzinger, S. M. Ame, S. M. Ali, and J. Keiser, “Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study,” Am. J. Trop. Med. Hyg. 88(4), 626–629 (2013).
[Crossref]

P. Jung and F. Trautinger, “Capillaroscopy,” J. Ger. Soc. Dermatol. 11(8), 731–736 (2013).
[Crossref]

2012 (2)

A. Uji, M. Hangai, S. Ooto, K. Takayama, N. Arakawa, H. Imamura, K. Nozato, and N. Yoshimura, “The Source of Moving Particles in Parafoveal Capillaries Detected by Adaptive Optics Scanning Laser Ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 53(1), 171–178 (2012).
[Crossref]

M. B. Lustberg, “Management of Neutropenia in Cancer Patients,” Clin. Adv. Hematol. & Oncol. 10, 825–826 (2012).

2011 (2)

H. Zhu, O. Yaglidere, T.-W. Su, D. Tseng, and A. Ozcan, “Cost-effective and compact wide-field fluorescent imaging on a cell-phone,” Lab Chip 11(2), 315–322 (2011).
[Crossref]

Z. J. Smith, K. Chu, A. R. Espenson, M. Rahimzadeh, A. Gryshuk, M. Molinaro, D. M. Dwyre, S. Lane, D. Matthews, and S. Wachsmann-Hogiu, “Cell-Phone-Based Platform for Biomedical Device Development and Education Applications,” PLoS One 6(3), e17150 (2011).
[Crossref]

2009 (1)

D. N. Breslauer, R. N. Maamari, N. A. Switz, W. A. Lam, and D. A. Fletcher, “Mobile Phone Based Clinical Microscopy for Global Health Applications,” PLoS One 4(7), e6320 (2009).
[Crossref]

2008 (1)

E. J. Botcherby, R. Juskaitis, M. J. Booth, and T. Wilson, “An optical technique for remote focusing in microscopy,” Opt. Commun. 281(4), 880–887 (2008).
[Crossref]

2004 (1)

J. Crawford, D. C. Dale, and G. H. Lyman, “Chemotherapy-Induced Neutropenia. Risks, consequences, and new directions for its management,” Cancer 100(2), 228–237 (2004).
[Crossref]

1999 (1)

C. E. Curtis, W. G. Iacono, and M. Beiser, “Relationship between Nailfold Plexus Visibility and Clinical, Neuropsychological, and Brain Structural Measures in Schizoprenia,” Biol. Psychiatry 46(1), 102–109 (1999).
[Crossref]

1997 (1)

C.-H. Chang, R.-K. Tsai, W.-C. Wu, S.-L. Kuo, and H.-S. Yu, “Use of Dynamic Capillaroscopy for Studying Cutaneous Microcirculation in Patients with Diabetes Mellitus,” Microvasc. Res. 53(2), 121–127 (1997).
[Crossref]

1996 (1)

K. M. Syed and R. S. Pinals, “Leukocytosis in Rheumatoid Arthritis,” J. Clin. Rheumatol. 2(4), 197–202 (1996).
[Crossref]

1989 (1)

S. H. Sinclair, M. Azar-Cavanagh, K. A. Soper, R. F. Tuma, and H. N. Mayrovitz, “Investigation of the Source of the Blue Field Entoptic Phenomenon,” Investig. Ophthalmol. Vis. Sci. 30(4), 668–673 (1989).

1988 (1)

T. Rimmer, E. M. Kohner, and J. M. Goldman, “Retinal Blood Velocity in Patients with Leukocyte Disorders,” Arch. Ophthalmol. 106(11), 1548 (1988).
[Crossref]

1986 (1)

F. Lefford and J. Edwards, “Nailfold capillary microscopy in connective tissue disease: a quantitative morphological analysis,” Ann. Rheum. Dis. 45(9), 741–749 (1986).
[Crossref]

1980 (1)

G. W. Schmid-Schonbein, S. Usami, R. Skalak, and S. Chien, “The Interaction of Leukocytes and Erythrocytes Capillary and Postcapillary Vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[Crossref]

1974 (1)

A. Bollinger, P. Butti, J. P. Barras, H. Trachsler, and W. Siegenthaler, “Red blood cell velocity in nailfold capillaries of man measured by a television microscopy technique,” Microvasc. Res. 7(1), 61–72 (1974).
[Crossref]

1925 (1)

G. E. Brown, “The Skin Capillaries in Raynaud’s Disease,” Arch. Intern. Med. 35(1), 56–73 (1925).
[Crossref]

Ali, S. M.

I. I. Bogoch, J. R. Andrews, B. Speich, J. Utzinger, S. M. Ame, S. M. Ali, and J. Keiser, “Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study,” Am. J. Trop. Med. Hyg. 88(4), 626–629 (2013).
[Crossref]

Ame, S. M.

I. I. Bogoch, J. R. Andrews, B. Speich, J. Utzinger, S. M. Ame, S. M. Ali, and J. Keiser, “Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study,” Am. J. Trop. Med. Hyg. 88(4), 626–629 (2013).
[Crossref]

Andrews, J. R.

I. I. Bogoch, J. R. Andrews, B. Speich, J. Utzinger, S. M. Ame, S. M. Ali, and J. Keiser, “Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study,” Am. J. Trop. Med. Hyg. 88(4), 626–629 (2013).
[Crossref]

Arai, S.

T. Honda, T. Uehara, G. Matsumoto, S. Arai, and M. Sugano, “Neutrophil left shift and white blood cell count as markers of bacterial infection,” Clin. Chim. Acta 457, 46–53 (2016).
[Crossref]

Arakawa, N.

A. Uji, M. Hangai, S. Ooto, K. Takayama, N. Arakawa, H. Imamura, K. Nozato, and N. Yoshimura, “The Source of Moving Particles in Parafoveal Capillaries Detected by Adaptive Optics Scanning Laser Ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 53(1), 171–178 (2012).
[Crossref]

Azar-Cavanagh, M.

S. H. Sinclair, M. Azar-Cavanagh, K. A. Soper, R. F. Tuma, and H. N. Mayrovitz, “Investigation of the Source of the Blue Field Entoptic Phenomenon,” Investig. Ophthalmol. Vis. Sci. 30(4), 668–673 (1989).

Baran, U.

U. Baran, L. Shi, and R. K. Wang, “Capillary blood flow imaging within human finger cuticle using optical microangiography,” J. Biophotonics 8(1-2), 46–51 (2015).
[Crossref]

Barras, J. P.

A. Bollinger, P. Butti, J. P. Barras, H. Trachsler, and W. Siegenthaler, “Red blood cell velocity in nailfold capillaries of man measured by a television microscopy technique,” Microvasc. Res. 7(1), 61–72 (1974).
[Crossref]

Beiser, M.

C. E. Curtis, W. G. Iacono, and M. Beiser, “Relationship between Nailfold Plexus Visibility and Clinical, Neuropsychological, and Brain Structural Measures in Schizoprenia,” Biol. Psychiatry 46(1), 102–109 (1999).
[Crossref]

Beniflah, J.

K. M. Rappaport, C. C. McCracken, J. Beniflah, W. K. Little, D. A. Fletcher, W. A. Lam, and A. L. Shane, “Assessment of a Smartphone Otoscope Device for the Diagnosis and Management of Otitis Media,” Clin. Pediatr. (Philadelphia) 55(9), 800–810 (2016).
[Crossref]

Bobrow, T. L.

G. N. McKay, T. L. Bobrow, S. Kalyan, S. C. Hur, and N. J. Durr, “Optimizing white blood cell contrast in graded-field capillaroscopy using capillary tissue phantoms,” in Proc. SPIE 11243, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVIII, (2020).

Bogoch, I. I.

I. I. Bogoch, J. R. Andrews, B. Speich, J. Utzinger, S. M. Ame, S. M. Ali, and J. Keiser, “Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study,” Am. J. Trop. Med. Hyg. 88(4), 626–629 (2013).
[Crossref]

Bollinger, A.

A. Bollinger, P. Butti, J. P. Barras, H. Trachsler, and W. Siegenthaler, “Red blood cell velocity in nailfold capillaries of man measured by a television microscopy technique,” Microvasc. Res. 7(1), 61–72 (1974).
[Crossref]

Booth, M. J.

E. J. Botcherby, R. Juskaitis, M. J. Booth, and T. Wilson, “An optical technique for remote focusing in microscopy,” Opt. Commun. 281(4), 880–887 (2008).
[Crossref]

Botcherby, E. J.

E. J. Botcherby, R. Juskaitis, M. J. Booth, and T. Wilson, “An optical technique for remote focusing in microscopy,” Opt. Commun. 281(4), 880–887 (2008).
[Crossref]

Boudreaux, J.

R. G. Mannino, D. R. Myers, E. A. Tyburski, C. Caruso, J. Boudreaux, T. Leong, G. D. Clifford, and W. A. Lam, “Smartphone app for non-invasive detection of anemia using only patient-sourced photos,” Nat. Commun. 9(1), 4924 (2018).
[Crossref]

Bourquard, A.

A. Pablo-Trinidad, I. Butterworth, M. J. Ledesma-Carbayo, T. Vettenburg, A. Sanchez-Ferro, L. Soenksen, N. J. Durr, A. Munoz-Barrutia, C. Cerrato, K. Humala, M. F. Urdiol, C. Del Rio, B. Valles, Y.-B. Chen, E. P. Hochberg, C. Castro-González, and A. Bourquard, “Automated detection of neutropenia using noninvasive video microscopy of superficial capillaries,” Am. J. Hematol. 94(8), E219–E222 (2019).
[Crossref]

A. Bourquard, A. Pablo-Trinidad, I. Butterworth, Á. Sánchez-Ferro, C. Cerrato, K. Humala, M. F. Urdiola, C. D. Rio, B. Valles, J. M. Tucker-Schwartz, E. S. Lee, B. J. Vakoc, T. P. Padera, M. J. Ledesma-Carbayo, Y.-B. Chen, E. P. Hochberg, M. L. Gray, and C. Castro-González, “Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation,” Sci. Rep. 8(1), 5301 (2018).
[Crossref]

Breslauer, D. N.

D. N. Breslauer, R. N. Maamari, N. A. Switz, W. A. Lam, and D. A. Fletcher, “Mobile Phone Based Clinical Microscopy for Global Health Applications,” PLoS One 4(7), e6320 (2009).
[Crossref]

Brown, G. E.

G. E. Brown, “The Skin Capillaries in Raynaud’s Disease,” Arch. Intern. Med. 35(1), 56–73 (1925).
[Crossref]

Butterworth, I.

A. Pablo-Trinidad, I. Butterworth, M. J. Ledesma-Carbayo, T. Vettenburg, A. Sanchez-Ferro, L. Soenksen, N. J. Durr, A. Munoz-Barrutia, C. Cerrato, K. Humala, M. F. Urdiol, C. Del Rio, B. Valles, Y.-B. Chen, E. P. Hochberg, C. Castro-González, and A. Bourquard, “Automated detection of neutropenia using noninvasive video microscopy of superficial capillaries,” Am. J. Hematol. 94(8), E219–E222 (2019).
[Crossref]

A. Bourquard, A. Pablo-Trinidad, I. Butterworth, Á. Sánchez-Ferro, C. Cerrato, K. Humala, M. F. Urdiola, C. D. Rio, B. Valles, J. M. Tucker-Schwartz, E. S. Lee, B. J. Vakoc, T. P. Padera, M. J. Ledesma-Carbayo, Y.-B. Chen, E. P. Hochberg, M. L. Gray, and C. Castro-González, “Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation,” Sci. Rep. 8(1), 5301 (2018).
[Crossref]

Butti, P.

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G. N. McKay, T. L. Bobrow, S. Kalyan, S. C. Hur, and N. J. Durr, “Optimizing white blood cell contrast in graded-field capillaroscopy using capillary tissue phantoms,” in Proc. SPIE 11243, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVIII, (2020).

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C. E. Curtis, W. G. Iacono, and M. Beiser, “Relationship between Nailfold Plexus Visibility and Clinical, Neuropsychological, and Brain Structural Measures in Schizoprenia,” Biol. Psychiatry 46(1), 102–109 (1999).
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C.-H. Chang, R.-K. Tsai, W.-C. Wu, S.-L. Kuo, and H.-S. Yu, “Use of Dynamic Capillaroscopy for Studying Cutaneous Microcirculation in Patients with Diabetes Mellitus,” Microvasc. Res. 53(2), 121–127 (1997).
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R. G. Mannino, D. R. Myers, E. A. Tyburski, C. Caruso, J. Boudreaux, T. Leong, G. D. Clifford, and W. A. Lam, “Smartphone app for non-invasive detection of anemia using only patient-sourced photos,” Nat. Commun. 9(1), 4924 (2018).
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Z. J. Smith, K. Chu, A. R. Espenson, M. Rahimzadeh, A. Gryshuk, M. Molinaro, D. M. Dwyre, S. Lane, D. Matthews, and S. Wachsmann-Hogiu, “Cell-Phone-Based Platform for Biomedical Device Development and Education Applications,” PLoS One 6(3), e17150 (2011).
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A. Bourquard, A. Pablo-Trinidad, I. Butterworth, Á. Sánchez-Ferro, C. Cerrato, K. Humala, M. F. Urdiola, C. D. Rio, B. Valles, J. M. Tucker-Schwartz, E. S. Lee, B. J. Vakoc, T. P. Padera, M. J. Ledesma-Carbayo, Y.-B. Chen, E. P. Hochberg, M. L. Gray, and C. Castro-González, “Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation,” Sci. Rep. 8(1), 5301 (2018).
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R. G. Mannino, D. R. Myers, E. A. Tyburski, C. Caruso, J. Boudreaux, T. Leong, G. D. Clifford, and W. A. Lam, “Smartphone app for non-invasive detection of anemia using only patient-sourced photos,” Nat. Commun. 9(1), 4924 (2018).
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K. M. Rappaport, C. C. McCracken, J. Beniflah, W. K. Little, D. A. Fletcher, W. A. Lam, and A. L. Shane, “Assessment of a Smartphone Otoscope Device for the Diagnosis and Management of Otitis Media,” Clin. Pediatr. (Philadelphia) 55(9), 800–810 (2016).
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D. N. Breslauer, R. N. Maamari, N. A. Switz, W. A. Lam, and D. A. Fletcher, “Mobile Phone Based Clinical Microscopy for Global Health Applications,” PLoS One 4(7), e6320 (2009).
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I. Gurov, M. Volkov, N. Margaryants, A. Pimenov, and A. Potemkin, “High-speed video capillaroscopy method for imaging and evaluation of moving red blood cells,” Opt. Lasers Eng. 104, 244–251 (2018).
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T. Honda, T. Uehara, G. Matsumoto, S. Arai, and M. Sugano, “Neutrophil left shift and white blood cell count as markers of bacterial infection,” Clin. Chim. Acta 457, 46–53 (2016).
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K. M. Rappaport, C. C. McCracken, J. Beniflah, W. K. Little, D. A. Fletcher, W. A. Lam, and A. L. Shane, “Assessment of a Smartphone Otoscope Device for the Diagnosis and Management of Otitis Media,” Clin. Pediatr. (Philadelphia) 55(9), 800–810 (2016).
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G. N. McKay, T. L. Bobrow, S. Kalyan, S. C. Hur, and N. J. Durr, “Optimizing white blood cell contrast in graded-field capillaroscopy using capillary tissue phantoms,” in Proc. SPIE 11243, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVIII, (2020).

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Z. J. Smith, K. Chu, A. R. Espenson, M. Rahimzadeh, A. Gryshuk, M. Molinaro, D. M. Dwyre, S. Lane, D. Matthews, and S. Wachsmann-Hogiu, “Cell-Phone-Based Platform for Biomedical Device Development and Education Applications,” PLoS One 6(3), e17150 (2011).
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Myers, D. R.

R. G. Mannino, D. R. Myers, E. A. Tyburski, C. Caruso, J. Boudreaux, T. Leong, G. D. Clifford, and W. A. Lam, “Smartphone app for non-invasive detection of anemia using only patient-sourced photos,” Nat. Commun. 9(1), 4924 (2018).
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A. Uji, M. Hangai, S. Ooto, K. Takayama, N. Arakawa, H. Imamura, K. Nozato, and N. Yoshimura, “The Source of Moving Particles in Parafoveal Capillaries Detected by Adaptive Optics Scanning Laser Ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 53(1), 171–178 (2012).
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A. Uji, M. Hangai, S. Ooto, K. Takayama, N. Arakawa, H. Imamura, K. Nozato, and N. Yoshimura, “The Source of Moving Particles in Parafoveal Capillaries Detected by Adaptive Optics Scanning Laser Ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 53(1), 171–178 (2012).
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H. Zhu, O. Yaglidere, T.-W. Su, D. Tseng, and A. Ozcan, “Cost-effective and compact wide-field fluorescent imaging on a cell-phone,” Lab Chip 11(2), 315–322 (2011).
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K. M. Syed and R. S. Pinals, “Leukocytosis in Rheumatoid Arthritis,” J. Clin. Rheumatol. 2(4), 197–202 (1996).
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A. Bourquard, A. Pablo-Trinidad, I. Butterworth, Á. Sánchez-Ferro, C. Cerrato, K. Humala, M. F. Urdiola, C. D. Rio, B. Valles, J. M. Tucker-Schwartz, E. S. Lee, B. J. Vakoc, T. P. Padera, M. J. Ledesma-Carbayo, Y.-B. Chen, E. P. Hochberg, M. L. Gray, and C. Castro-González, “Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation,” Sci. Rep. 8(1), 5301 (2018).
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A. Bollinger, P. Butti, J. P. Barras, H. Trachsler, and W. Siegenthaler, “Red blood cell velocity in nailfold capillaries of man measured by a television microscopy technique,” Microvasc. Res. 7(1), 61–72 (1974).
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G. W. Schmid-Schonbein, S. Usami, R. Skalak, and S. Chien, “The Interaction of Leukocytes and Erythrocytes Capillary and Postcapillary Vessels,” Microvasc. Res. 19(1), 45–70 (1980).
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I. I. Bogoch, J. R. Andrews, B. Speich, J. Utzinger, S. M. Ame, S. M. Ali, and J. Keiser, “Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study,” Am. J. Trop. Med. Hyg. 88(4), 626–629 (2013).
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A. Bourquard, A. Pablo-Trinidad, I. Butterworth, Á. Sánchez-Ferro, C. Cerrato, K. Humala, M. F. Urdiola, C. D. Rio, B. Valles, J. M. Tucker-Schwartz, E. S. Lee, B. J. Vakoc, T. P. Padera, M. J. Ledesma-Carbayo, Y.-B. Chen, E. P. Hochberg, M. L. Gray, and C. Castro-González, “Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation,” Sci. Rep. 8(1), 5301 (2018).
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C.-H. Chang, R.-K. Tsai, W.-C. Wu, S.-L. Kuo, and H.-S. Yu, “Use of Dynamic Capillaroscopy for Studying Cutaneous Microcirculation in Patients with Diabetes Mellitus,” Microvasc. Res. 53(2), 121–127 (1997).
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Am. J. Trop. Med. Hyg. (1)

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T. Honda, T. Uehara, G. Matsumoto, S. Arai, and M. Sugano, “Neutrophil left shift and white blood cell count as markers of bacterial infection,” Clin. Chim. Acta 457, 46–53 (2016).
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Clin. Pediatr. (Philadelphia) (1)

K. M. Rappaport, C. C. McCracken, J. Beniflah, W. K. Little, D. A. Fletcher, W. A. Lam, and A. L. Shane, “Assessment of a Smartphone Otoscope Device for the Diagnosis and Management of Otitis Media,” Clin. Pediatr. (Philadelphia) 55(9), 800–810 (2016).
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A. Uji, M. Hangai, S. Ooto, K. Takayama, N. Arakawa, H. Imamura, K. Nozato, and N. Yoshimura, “The Source of Moving Particles in Parafoveal Capillaries Detected by Adaptive Optics Scanning Laser Ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 53(1), 171–178 (2012).
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Investig. Ophthalmol. Vis. Sci. (1)

S. H. Sinclair, M. Azar-Cavanagh, K. A. Soper, R. F. Tuma, and H. N. Mayrovitz, “Investigation of the Source of the Blue Field Entoptic Phenomenon,” Investig. Ophthalmol. Vis. Sci. 30(4), 668–673 (1989).

J. Biophotonics (1)

U. Baran, L. Shi, and R. K. Wang, “Capillary blood flow imaging within human finger cuticle using optical microangiography,” J. Biophotonics 8(1-2), 46–51 (2015).
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J. Clin. Rheumatol. (1)

K. M. Syed and R. S. Pinals, “Leukocytosis in Rheumatoid Arthritis,” J. Clin. Rheumatol. 2(4), 197–202 (1996).
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J. Ger. Soc. Dermatol. (1)

P. Jung and F. Trautinger, “Capillaroscopy,” J. Ger. Soc. Dermatol. 11(8), 731–736 (2013).
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J. Oncol. Pract. (1)

E. Tai, G. P. Guy Jr., A. Dunbar, and L. C. Richardson, “Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States 2012,” J. Oncol. Pract. 13(6), e552–e561 (2017).
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Lab Chip (1)

H. Zhu, O. Yaglidere, T.-W. Su, D. Tseng, and A. Ozcan, “Cost-effective and compact wide-field fluorescent imaging on a cell-phone,” Lab Chip 11(2), 315–322 (2011).
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Supplementary Material (2)

NameDescription
» Visualization 1       Reverse lens mobile phone microscopy of human nailfold capillaries. 60 frames-per-second, 50µm scale bar.
» Visualization 2       Reverse lens mobile phone microscopy of human nailfold capillaries. 60 frames-per-second, 200µm scale bar.

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Figures (4)

Fig. 1.
Fig. 1. Reverse lens capillaroscope design. (a) Image of mounted mobile phone capillaroscope prototype, (b) nailfold imaging with reverse lens technique, (c) contrast to red blood cells (RBCs) is generated due to absorption of green light by hemoglobin, leaving white blood cells or plasma gaps appearing bright.
Fig. 2.
Fig. 2. Capillaroscope resolution characterization. (a) Image of 1952 NBS Imaging Target. Numerical markings have units of line pairs per mm (lp/mm). (b) Magnified region of interest from (a) including three lines at a spatial frequency of 80 lp/mm. (c) Edge spread function used for 2550$\mu$m off axis MTF calculation (50$\mu$m scale bar). (d) Calculated MTFs for edge spread functions acquired at increasing distance from the optic axis. (e) Image of superficial capillaries in a microfluidic phantom demonstrates resolution of single red blood cell shadows (200 $\mu$m scale bar).
Fig. 3.
Fig. 3. (a)-(b) Raw nailfold capillary images at different time points ($\Delta$t = 500 ms) demonstrate imaging of optical absorption gaps in vivo. Scale bars are 250$\mu$m. (c)-(d) Boxed regions in (a) and (b), respectively, highlight a flowing absorption gap. Scale bars are 50$\mu$m. (e) Representative line profile through green and orange lines highlighted in (c) and (d).
Fig. 4.
Fig. 4. (a) Wide field of view nailfold capillaroscopy image, 200$\mu$m scale bar (see Visualization 1). (b)-(f) Boxed region of interest from (a) with temporally-separated images from a high speed video capillaroscopy acquisition at 60fps. Every 5th frame was selected from the video, with a temporal separation of 83ms. Scale bar is 50$\mu$m. (see Visualization 2).

Tables (1)

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Table 1. Comparison of Mobile Phone Capillaroscope Options

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