Abstract

Three-part differential white blood cell counts are used for disease diagnosis and monitoring at the point-of-care. A low-cost, miniature achromatic microscope was fabricated for identification of lymphocytes, monocytes, and granulocytes in samples of whole blood stained with acridine orange. The microscope was manufactured using rapid prototyping techniques of diamond turning and 3D printing and is intended for use at the point-of-care in low-resource settings. The custom-designed microscope requires no manual adjustment between samples and was successfully able to classify three white blood cell types (lymphocytes, granulocytes, and monocytes) using samples of peripheral whole blood stained with acridine orange.

© 2015 Optical Society of America

Full Article  |  PDF Article
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References

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2015 (1)

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

2014 (3)

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

2013 (2)

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

W. Shi, L. Guo, H. Kasdan, and Y. C. Tai, “Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay,” Lab Chip 13(7), 1257–1265 (2013).
[Crossref] [PubMed]

2012 (2)

C. Briggs, S. Kimber, and L. Green, “Where are we at with point-of-care testing in haematology?” Br. J. Haematol. 158(6), 679–690 (2012).
[Crossref] [PubMed]

G. Wu and M. H. Zaman, “Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings,” Bull. World Health Organ. 90(12), 914–920 (2012).
[Crossref] [PubMed]

2011 (1)

2010 (2)

R. J. Leguit and J. G. van den Tweel, “The pathology of Bone marrow failure,” Histopathology 57(5), 655–670 (2010).
[Crossref] [PubMed]

L. Paladino, R. A. Subramanian, E. Bonilla, and R. H. Sinert, “Leukocytosis as prognostic indicator of major injury,” West. J. Emerg. Med. 11(5), 450–455 (2010).
[PubMed]

2009 (1)

A. Osei-Bimpong, C. Jury, R. McLean, and S. M. Lewis, “Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device,” Int. J. Lab. Hematol. 31(6), 657–664 (2009).
[Crossref] [PubMed]

2008 (4)

M. Buttarello and M. Plebani, “Automated blood cell counts: state of the art,” Am. J. Clin. Pathol. 130(1), 104–116 (2008).
[Crossref] [PubMed]

J. R. Casey and M. E. Pichichero, “A comparison of 2 white blood cell count devices to aid judicious antibiotic prescribing,” Clin. Pediatr. (Phila.) 48(3), 291–294 (2008).
[Crossref] [PubMed]

M. Zheng, J. C. Lin, H. Kasdan, and Y. Tai, “Fluorescent labeling, sensing, and differentiation of leukocytes from undiluted whole blood samples,” Sens. Actuators B Chem. 132(2), 558–567 (2008).
[Crossref]

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

2005 (1)

B. A. Ekberg, U. D. Larsen, and N. F. Andersen, “A real point-of-care system for complete blood counting,” Point Care 4(1), 64–65 (2005).
[Crossref]

2004 (1)

H. M. Shapiro, “Cellular astronomy--a foreseeable future in cytometry,” Cytometry A 60(2), 115–124 (2004).
[Crossref] [PubMed]

2002 (1)

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

2001 (1)

B. Houwen, “The differential cell count,” Lab. Hematol. 7, 89–100 (2001).

1986 (1)

J. D. Hare and D. W. Bahler, “Analysis of Plasmodium falciparum growth in culture using acridine orange and flow cytometry,” J. Histochem. Cytochem. 34(2), 215–220 (1986).
[Crossref] [PubMed]

1985 (1)

S. Charache, L. Nelson, E. Keyser, and P. Metzger, “A Clinical Trial of Three-Part Electronic Differential White Blood Cell Counts,” Arch. Intern. Med. 145(10), 1852–1855 (1985).
[Crossref] [PubMed]

1984 (1)

A. Kobayashi and K. Hirakawa, “Ultraprecision machining of plastics. Par 1 Polymethylmethacrylate,” Polym. Plast. Technol. Eng. 22(1), 15–25 (1984).
[Crossref]

Andersen, N. F.

B. A. Ekberg, U. D. Larsen, and N. F. Andersen, “A real point-of-care system for complete blood counting,” Point Care 4(1), 64–65 (2005).
[Crossref]

Baggett, B. K.

Bahler, D. W.

J. D. Hare and D. W. Bahler, “Analysis of Plasmodium falciparum growth in culture using acridine orange and flow cytometry,” J. Histochem. Cytochem. 34(2), 215–220 (1986).
[Crossref] [PubMed]

Bonilla, E.

L. Paladino, R. A. Subramanian, E. Bonilla, and R. H. Sinert, “Leukocytosis as prognostic indicator of major injury,” West. J. Emerg. Med. 11(5), 450–455 (2010).
[PubMed]

Briggs, C.

C. Briggs, S. Kimber, and L. Green, “Where are we at with point-of-care testing in haematology?” Br. J. Haematol. 158(6), 679–690 (2012).
[Crossref] [PubMed]

Buttarello, M.

M. Buttarello and M. Plebani, “Automated blood cell counts: state of the art,” Am. J. Clin. Pathol. 130(1), 104–116 (2008).
[Crossref] [PubMed]

Casey, J. R.

J. R. Casey and M. E. Pichichero, “A comparison of 2 white blood cell count devices to aid judicious antibiotic prescribing,” Clin. Pediatr. (Phila.) 48(3), 291–294 (2008).
[Crossref] [PubMed]

Charache, S.

S. Charache, L. Nelson, E. Keyser, and P. Metzger, “A Clinical Trial of Three-Part Electronic Differential White Blood Cell Counts,” Arch. Intern. Med. 145(10), 1852–1855 (1985).
[Crossref] [PubMed]

Chu, K.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Connor, D.

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

DE Haan, G.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

de Wijs, K.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Delahunt, C. B.

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

Descour, M. R.

Dusa, A.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Dwyre, D. M.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Ekberg, B. A.

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

B. A. Ekberg, U. D. Larsen, and N. F. Andersen, “A real point-of-care system for complete blood counting,” Point Care 4(1), 64–65 (2005).
[Crossref]

Gao, T.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Garing, S. H.

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

Green, L.

C. Briggs, S. Kimber, and L. Green, “Where are we at with point-of-care testing in haematology?” Br. J. Haematol. 158(6), 679–690 (2012).
[Crossref] [PubMed]

Guo, L.

W. Shi, L. Guo, H. Kasdan, and Y. C. Tai, “Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay,” Lab Chip 13(7), 1257–1265 (2013).
[Crossref] [PubMed]

Hare, J. D.

J. D. Hare and D. W. Bahler, “Analysis of Plasmodium falciparum growth in culture using acridine orange and flow cytometry,” J. Histochem. Cytochem. 34(2), 215–220 (1986).
[Crossref] [PubMed]

Hasan, M. U.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

Heifetz, L.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Hirakawa, K.

A. Kobayashi and K. Hirakawa, “Ultraprecision machining of plastics. Par 1 Polymethylmethacrylate,” Polym. Plast. Technol. Eng. 22(1), 15–25 (1984).
[Crossref]

Hood, J.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Horning, M. P.

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

Houwen, B.

B. Houwen, “The differential cell count,” Lab. Hematol. 7, 89–100 (2001).

Jakubiak, F.

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

Jaslove, J. M.

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

Jury, C.

A. Osei-Bimpong, C. Jury, R. McLean, and S. M. Lewis, “Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device,” Int. J. Lab. Hematol. 31(6), 657–664 (2009).
[Crossref] [PubMed]

Kasdan, H.

W. Shi, L. Guo, H. Kasdan, and Y. C. Tai, “Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay,” Lab Chip 13(7), 1257–1265 (2013).
[Crossref] [PubMed]

M. Zheng, J. C. Lin, H. Kasdan, and Y. Tai, “Fluorescent labeling, sensing, and differentiation of leukocytes from undiluted whole blood samples,” Sens. Actuators B Chem. 132(2), 558–567 (2008).
[Crossref]

Keiser, J.

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

Keyser, E.

S. Charache, L. Nelson, E. Keyser, and P. Metzger, “A Clinical Trial of Three-Part Electronic Differential White Blood Cell Counts,” Arch. Intern. Med. 145(10), 1852–1855 (1985).
[Crossref] [PubMed]

Kimber, S.

C. Briggs, S. Kimber, and L. Green, “Where are we at with point-of-care testing in haematology?” Br. J. Haematol. 158(6), 679–690 (2012).
[Crossref] [PubMed]

Kobayashi, A.

A. Kobayashi and K. Hirakawa, “Ultraprecision machining of plastics. Par 1 Polymethylmethacrylate,” Polym. Plast. Technol. Eng. 22(1), 15–25 (1984).
[Crossref]

Kyrish, M.

Lagae, L.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Lane, S. M.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Larsen, U. D.

B. A. Ekberg, U. D. Larsen, and N. F. Andersen, “A real point-of-care system for complete blood counting,” Point Care 4(1), 64–65 (2005).
[Crossref]

Laubscher, M.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

Leguit, R. J.

R. J. Leguit and J. G. van den Tweel, “The pathology of Bone marrow failure,” Histopathology 57(5), 655–670 (2010).
[Crossref] [PubMed]

Lewis, S. M.

A. Osei-Bimpong, C. Jury, R. McLean, and S. M. Lewis, “Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device,” Int. J. Lab. Hematol. 31(6), 657–664 (2009).
[Crossref] [PubMed]

Lin, J. C.

M. Zheng, J. C. Lin, H. Kasdan, and Y. Tai, “Fluorescent labeling, sensing, and differentiation of leukocytes from undiluted whole blood samples,” Sens. Actuators B Chem. 132(2), 558–567 (2008).
[Crossref]

Liu, C.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Majors, C. E.

C. E. Majors, M. E. Pawlowski, T. Tkaczyk, and R. R. Richards-Kortum, “Low - Cost Disposable Cartridge for Performing a White Blood Cell Count and Partial Differential at the Point - of - Care,” in Health Innovations and Point-of-Care Technologies Conference, Seattle, WA, 2014, pp. 10–13.
[Crossref]

Matthews, D. L.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Maude, R. J.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

McLean, R.

A. Osei-Bimpong, C. Jury, R. McLean, and S. M. Lewis, “Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device,” Int. J. Lab. Hematol. 31(6), 657–664 (2009).
[Crossref] [PubMed]

Metzger, P.

S. Charache, L. Nelson, E. Keyser, and P. Metzger, “A Clinical Trial of Three-Part Electronic Differential White Blood Cell Counts,” Arch. Intern. Med. 145(10), 1852–1855 (1985).
[Crossref] [PubMed]

Nelson, L.

S. Charache, L. Nelson, E. Keyser, and P. Metzger, “A Clinical Trial of Three-Part Electronic Differential White Blood Cell Counts,” Arch. Intern. Med. 145(10), 1852–1855 (1985).
[Crossref] [PubMed]

Nichols, K. P.

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

Osei-Bimpong, A.

A. Osei-Bimpong, C. Jury, R. McLean, and S. M. Lewis, “Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device,” Int. J. Lab. Hematol. 31(6), 657–664 (2009).
[Crossref] [PubMed]

Paladino, L.

L. Paladino, R. A. Subramanian, E. Bonilla, and R. H. Sinert, “Leukocytosis as prognostic indicator of major injury,” West. J. Emerg. Med. 11(5), 450–455 (2010).
[PubMed]

Pawlowski, M. E.

C. E. Majors, M. E. Pawlowski, T. Tkaczyk, and R. R. Richards-Kortum, “Low - Cost Disposable Cartridge for Performing a White Blood Cell Count and Partial Differential at the Point - of - Care,” in Health Innovations and Point-of-Care Technologies Conference, Seattle, WA, 2014, pp. 10–13.
[Crossref]

Peumans, P.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Pichichero, M. E.

J. R. Casey and M. E. Pichichero, “A comparison of 2 white blood cell count devices to aid judicious antibiotic prescribing,” Clin. Pediatr. (Phila.) 48(3), 291–294 (2008).
[Crossref] [PubMed]

Pierce, M. C.

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

Plebani, M.

M. Buttarello and M. Plebani, “Automated blood cell counts: state of the art,” Am. J. Clin. Pathol. 130(1), 104–116 (2008).
[Crossref] [PubMed]

Premji, Z.

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

Prodanov, D.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Rao, L. V.

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

Richards-Kortum, R.

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

Richards-Kortum, R. R.

C. E. Majors, M. E. Pawlowski, T. Tkaczyk, and R. R. Richards-Kortum, “Low - Cost Disposable Cartridge for Performing a White Blood Cell Count and Partial Differential at the Point - of - Care,” in Health Innovations and Point-of-Care Technologies Conference, Seattle, WA, 2014, pp. 10–13.
[Crossref]

Shapiro, H. M.

H. M. Shapiro, “Cellular astronomy--a foreseeable future in cytometry,” Cytometry A 60(2), 115–124 (2004).
[Crossref] [PubMed]

Shi, W.

W. Shi, L. Guo, H. Kasdan, and Y. C. Tai, “Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay,” Lab Chip 13(7), 1257–1265 (2013).
[Crossref] [PubMed]

Silamut, K.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

Sinert, R. H.

L. Paladino, R. A. Subramanian, E. Bonilla, and R. H. Sinert, “Leukocytosis as prognostic indicator of major injury,” West. J. Emerg. Med. 11(5), 450–455 (2010).
[PubMed]

Singer, B. H.

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

Singh, S. R.

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

Smith, Z. J.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Snyder, M.

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

Stahl, R.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Subramanian, R. A.

L. Paladino, R. A. Subramanian, E. Bonilla, and R. H. Sinert, “Leukocytosis as prognostic indicator of major injury,” West. J. Emerg. Med. 11(5), 450–455 (2010).
[PubMed]

Tai, Y.

M. Zheng, J. C. Lin, H. Kasdan, and Y. Tai, “Fluorescent labeling, sensing, and differentiation of leukocytes from undiluted whole blood samples,” Sens. Actuators B Chem. 132(2), 558–567 (2008).
[Crossref]

Tai, Y. C.

W. Shi, L. Guo, H. Kasdan, and Y. C. Tai, “Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay,” Lab Chip 13(7), 1257–1265 (2013).
[Crossref] [PubMed]

Tatsukawa, K.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Tkaczyk, T.

C. E. Majors, M. E. Pawlowski, T. Tkaczyk, and R. R. Richards-Kortum, “Low - Cost Disposable Cartridge for Performing a White Blood Cell Count and Partial Differential at the Point - of - Care,” in Health Innovations and Point-of-Care Technologies Conference, Seattle, WA, 2014, pp. 10–13.
[Crossref]

Tkaczyk, T. S.

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

M. Kyrish, U. Utzinger, M. R. Descour, B. K. Baggett, and T. S. Tkaczyk, “Ultra-slim plastic endomicroscope objective for non-linear microscopy,” Opt. Express 19(8), 7603–7615 (2011).
[Crossref] [PubMed]

Utzinger, J.

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

Utzinger, U.

Vallaro, G. M.

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

van den Tweel, J. G.

R. J. Leguit and J. G. van den Tweel, “The pathology of Bone marrow failure,” Histopathology 57(5), 655–670 (2010).
[Crossref] [PubMed]

Vanmeerbeeck, G.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Vercruysse, D.

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

Vink, J. P.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

Vlutters, R.

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

Wachsmann-Hogiu, S.

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Weigum, S. E.

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

Wu, G.

G. Wu and M. H. Zaman, “Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings,” Bull. World Health Organ. 90(12), 914–920 (2012).
[Crossref] [PubMed]

Yamagata, Y.

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

Zaman, M. H.

G. Wu and M. H. Zaman, “Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings,” Bull. World Health Organ. 90(12), 914–920 (2012).
[Crossref] [PubMed]

Zheng, M.

M. Zheng, J. C. Lin, H. Kasdan, and Y. Tai, “Fluorescent labeling, sensing, and differentiation of leukocytes from undiluted whole blood samples,” Sens. Actuators B Chem. 132(2), 558–567 (2008).
[Crossref]

Am. J. Clin. Pathol. (1)

M. Buttarello and M. Plebani, “Automated blood cell counts: state of the art,” Am. J. Clin. Pathol. 130(1), 104–116 (2008).
[Crossref] [PubMed]

Ann. Biomed. Eng. (1)

M. C. Pierce, S. E. Weigum, J. M. Jaslove, R. Richards-Kortum, and T. S. Tkaczyk, “Optical systems for point-of-care diagnostic instrumentation: analysis of imaging performance and cost,” Ann. Biomed. Eng. 42(1), 231–240 (2014).
[Crossref] [PubMed]

Ann. Trop. Med. Parasitol. (1)

J. Keiser, J. Utzinger, Z. Premji, Y. Yamagata, and B. H. Singer, “Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control,” Ann. Trop. Med. Parasitol. 96(7), 643–654 (2002).
[Crossref] [PubMed]

Arch. Intern. Med. (1)

S. Charache, L. Nelson, E. Keyser, and P. Metzger, “A Clinical Trial of Three-Part Electronic Differential White Blood Cell Counts,” Arch. Intern. Med. 145(10), 1852–1855 (1985).
[Crossref] [PubMed]

Br. J. Haematol. (1)

C. Briggs, S. Kimber, and L. Green, “Where are we at with point-of-care testing in haematology?” Br. J. Haematol. 158(6), 679–690 (2012).
[Crossref] [PubMed]

Bull. World Health Organ. (1)

G. Wu and M. H. Zaman, “Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings,” Bull. World Health Organ. 90(12), 914–920 (2012).
[Crossref] [PubMed]

Clin. Chim. Acta (1)

L. V. Rao, B. A. Ekberg, D. Connor, F. Jakubiak, G. M. Vallaro, and M. Snyder, “Evaluation of a new point of care automated complete blood count (CBC) analyzer in various clinical settings,” Clin. Chim. Acta 389(1-2), 120–125 (2008).
[Crossref] [PubMed]

Clin. Pediatr. (Phila.) (1)

J. R. Casey and M. E. Pichichero, “A comparison of 2 white blood cell count devices to aid judicious antibiotic prescribing,” Clin. Pediatr. (Phila.) 48(3), 291–294 (2008).
[Crossref] [PubMed]

Cytometry A (1)

H. M. Shapiro, “Cellular astronomy--a foreseeable future in cytometry,” Cytometry A 60(2), 115–124 (2004).
[Crossref] [PubMed]

Histopathology (1)

R. J. Leguit and J. G. van den Tweel, “The pathology of Bone marrow failure,” Histopathology 57(5), 655–670 (2010).
[Crossref] [PubMed]

Int. J. Lab. Hematol. (1)

A. Osei-Bimpong, C. Jury, R. McLean, and S. M. Lewis, “Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device,” Int. J. Lab. Hematol. 31(6), 657–664 (2009).
[Crossref] [PubMed]

J. Histochem. Cytochem. (1)

J. D. Hare and D. W. Bahler, “Analysis of Plasmodium falciparum growth in culture using acridine orange and flow cytometry,” J. Histochem. Cytochem. 34(2), 215–220 (1986).
[Crossref] [PubMed]

J. Microsc. (1)

J. P. Vink, M. Laubscher, R. Vlutters, K. Silamut, R. J. Maude, M. U. Hasan, and G. DE Haan, “An automatic vision-based malaria diagnosis system,” J. Microsc. 250(3), 166–178 (2013).
[Crossref] [PubMed]

Lab Chip (4)

M. P. Horning, C. B. Delahunt, S. R. Singh, S. H. Garing, and K. P. Nichols, “A paper microfluidic cartridge for automated staining of malaria parasites with an optically transparent microscopy window,” Lab Chip 14(12), 2040–2046 (2014).
[Crossref] [PubMed]

D. Vercruysse, A. Dusa, R. Stahl, G. Vanmeerbeeck, K. de Wijs, C. Liu, D. Prodanov, P. Peumans, and L. Lagae, “Three-part differential of unlabeled leukocytes with a compact lens-free imaging flow cytometer,” Lab Chip 15(4), 1123–1132 (2015).
[Crossref] [PubMed]

W. Shi, L. Guo, H. Kasdan, and Y. C. Tai, “Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay,” Lab Chip 13(7), 1257–1265 (2013).
[Crossref] [PubMed]

Z. J. Smith, T. Gao, K. Chu, S. M. Lane, D. L. Matthews, D. M. Dwyre, J. Hood, K. Tatsukawa, L. Heifetz, and S. Wachsmann-Hogiu, “Single-step preparation and image-based counting of minute volumes of human blood,” Lab Chip 14(16), 3029–3036 (2014).
[Crossref] [PubMed]

Lab. Hematol. (1)

B. Houwen, “The differential cell count,” Lab. Hematol. 7, 89–100 (2001).

Opt. Express (1)

Point Care (1)

B. A. Ekberg, U. D. Larsen, and N. F. Andersen, “A real point-of-care system for complete blood counting,” Point Care 4(1), 64–65 (2005).
[Crossref]

Polym. Plast. Technol. Eng. (1)

A. Kobayashi and K. Hirakawa, “Ultraprecision machining of plastics. Par 1 Polymethylmethacrylate,” Polym. Plast. Technol. Eng. 22(1), 15–25 (1984).
[Crossref]

Sens. Actuators B Chem. (1)

M. Zheng, J. C. Lin, H. Kasdan, and Y. Tai, “Fluorescent labeling, sensing, and differentiation of leukocytes from undiluted whole blood samples,” Sens. Actuators B Chem. 132(2), 558–567 (2008).
[Crossref]

West. J. Emerg. Med. (1)

L. Paladino, R. A. Subramanian, E. Bonilla, and R. H. Sinert, “Leukocytosis as prognostic indicator of major injury,” West. J. Emerg. Med. 11(5), 450–455 (2010).
[PubMed]

Other (4)

M. S. Blumenreich, Clinical Methods: The History, Physical, and Laboratory Examinations (Butterworths, 1990).

B. H. Estridge, A. P. Reynolds, and N. J. Walters, Basic Haematology (Delmar-Thompson Learning, 2000).

C. E. Majors, M. E. Pawlowski, T. Tkaczyk, and R. R. Richards-Kortum, “Low - Cost Disposable Cartridge for Performing a White Blood Cell Count and Partial Differential at the Point - of - Care,” in Health Innovations and Point-of-Care Technologies Conference, Seattle, WA, 2014, pp. 10–13.
[Crossref]

S. Baumer, Handbook of Plastic Optics, 2nd ed. (Wiley-VCH, 2005).

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Figures (8)

Fig. 1
Fig. 1 Optical schematic of the miniature achromatic objective.
Fig. 2
Fig. 2 Performance metrics of the miniature tunable fluorescent microscope for nominal working conditions: (a) modulation transfer function for expected performance at 525 nm, (b) modulation transfer function for expected performance at 650 nm, (c) spot diagram for expected performance at 525 nm (shown in blue) and 625 nm (shown in green). All plots are for image surface for design wavelength of 590nm, for following object points: 0.0mm, 0.25mm, 0.35mm, 0.45 mm, 0.50 mm, 0.55 mm, 0.6 mm. Airy disk radii for 525 nm and 650 nm: 4.179 and 5.126µm, respectively.
Fig. 3
Fig. 3 Assembled plastic objective inside brass tubing (left). 3D printed threaded objective holder (right).
Fig. 4
Fig. 4 Images of high resolution USAF target taken with the miniature 0.35 NA achromatic objective. (a) Image acquired at 525 nm, (b) Image acquired at 650 nm. Magnified inlays of the smallest resolvable elements are shown outlined in each image. Contrast has been enhanced for presentation purposes.
Fig. 5
Fig. 5 (a) Optomechanical schematic of the miniature WBC microscope, (b) cross-section through sample chamber with 3D printed microscope slide positioning springs, (c) details of the optomechanical assembly of the prototype of the WBC objective, (d) photograph of assembled 3D printed WBC microscope is shown on an optical bench. The spacing between the holes is 1 inch for reference.
Fig. 6
Fig. 6 (a) Schematic of measurement system used to evaluate sample insertion repeatability. (b) Slide insertion repeatability test: blue line – measured distance, black line – mean distance, red lines – ± 1σ standard deviation boarder lines.
Fig. 7
Fig. 7 (a) Image of acridine orange taken at 400 ms exposure stained white blood cells in whole blood. Image acquired with the miniature all-plastic objective. (b) Magnified image of granulocyte. (c) Magnified image of a lymphocyte. (d) Magnified image of a monocyte. Contrast has been enhanced for presentation purposes. Red-to-green ratios were calculated using raw data.
Fig. 8
Fig. 8 Cumulative percentage of samples falling within percent difference from gold standard measurement on AcT Diff2 hematology analyzer.

Tables (6)

Tables Icon

Table 1 Summary of optical parameters of miniature fluorescent microscope

Tables Icon

Table 2 Optical prescription data of miniature microscope Radii, thicknesses and semi-diameters are in units of [mm]

Tables Icon

Table 3 Measured vs. reported refractive index values for polystyrene and PMMA

Tables Icon

Table 4 Calculated vs. reported (in Zemax) Vd for polystyrene and PMMA

Tables Icon

Table 5 Tolerance parameters of the miniature fluorescent microscope

Tables Icon

Table 6 Cost of complete optical detection hardware for prototype device and conservative cost estimate for mass production

Equations (1)

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V d = n D 1 n F n C

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