Abstract

We report on the development of a technique for differentiating between biological micro-objects using a rigorous, full-wave model of OCT image formation. We model an existing experimental prototype which uses OCT to interrogate a microfluidic chip containing the blood cells. A full-wave model is required since the technique uses light back-scattered by a scattering substrate, rather than by the cells directly. The light back-scattered by the substrate is perturbed upon propagation through the cells, which flow between the substrate and imaging system’s objective lens. We present the key elements of the 3D, Maxwell equation-based computational model, the key findings of the computational study and a comparison with experimental results.

© 2017 Optical Society of America

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2016 (1)

2015 (3)

2014 (1)

2013 (3)

M. Szkulmowski and M. Wojtkowski, “Averaging techniques for OCT imaging,” Opt. Express 21(8), 9757–9773 (2013).
[Crossref] [PubMed]

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (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 (4)

R. L. Schoch, L. E. Kapinos, and R. Y. Lim, “Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes,” Proc. Natl. Acad. Sci. U.S.A. 109(42), 16911–16916 (2012).
[Crossref] [PubMed]

T.-F. Wu, Z. Mei, and Y.-H. Lo, “Optofluidic device for label-free cell classification from whole blood,” Lab Chip 12(19), 3791–3797 (2012).
[Crossref] [PubMed]

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

L. Golan, D. Yeheskely-Hayon, L. Minai, E. J. Dann, and D. Yelin, “Noninvasive imaging of flowing blood cells using label-free spectrally encoded flow cytometry,” Biomed. Opt. Express 3(6), 1455–1464 (2012).
[Crossref] [PubMed]

2011 (3)

J. Lim, H. Ding, M. Mir, R. Zhu, K. Tangella, and G. Popescu, “Born approximation model for light scattering by red blood cells,” Biomed. Opt. Express 2(10), 2784–2791 (2011).
[Crossref] [PubMed]

C. G. Hebert, A. Terray, and S. J. Hart, “Toward label-free optical fractionation of blood--optical force measurements of blood cells,” Anal. Chem. 83(14), 5666–5672 (2011).
[Crossref] [PubMed]

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

2010 (3)

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

2009 (2)

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

2008 (2)

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

P. Török, P. R. Munro, and E. E. Kriezis, “High numerical aperture vectorial imaging in coherent optical microscopes,” Opt. Express 16(2), 507–523 (2008).
[Crossref] [PubMed]

2007 (2)

M. A. Yurkin, K. A. Semyanov, V. P. Maltsev, and A. G. Hoekstra, “Discrimination of granulocyte subtypes from light scattering: theoretical analysis using a granulated sphere model,” Opt. Express 15(25), 16561–16580 (2007).
[Crossref] [PubMed]

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

2006 (1)

2005 (1)

2004 (1)

1997 (2)

J. Schmitt and A. Knüttel, “Model of optical coherence tomography of heterogeneous tissue,” J. Opt. Soc. Am. A 14(6), 1231–1242 (1997).
[Crossref]

Q. H. Liu, “The PSTD algorithm: A time‐domain method requiring only two cells per wavelength,” Microw. Opt. Technol. Lett. 15(3), 158–165 (1997).
[Crossref]

1995 (1)

1994 (1)

J. P. Berenger, “A perfectly matched layer for the absorption of electromagnetic waves,” J. Comput. Phys. 114(2), 185–200 (1994).
[Crossref]

1968 (1)

Y. C. Fung and P. Tong, “Theory of the sphering of red blood cells,” Biophys. J. 8(2), 175–198 (1968).
[Crossref] [PubMed]

1959 (1)

B. Richards and E. Wolf, “Electromagnetic diffraction in optical systems. II. Structure of the image field in an aplanatic system,” Proc. R. Soc. Lond. A Math. Phys. Sci. 253(1274), 358–379 (1959).
[Crossref]

Bang, H.

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

Bauer, M.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

Berenger, J. P.

J. P. Berenger, “A perfectly matched layer for the absorption of electromagnetic waves,” J. Comput. Phys. 114(2), 185–200 (1994).
[Crossref]

Birngruber, R.

Bishara, W.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Bocklitz, T.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

Boppart, S. A.

Brattke, K.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

Bukowska, D.

Carney, P. S.

Chang, J. K.

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

Chen, C. H.

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

Chernyshev, A. V.

Chin, C. D.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Chin, S. Y.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Cho, S. H.

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

Chung, C.

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

Coulter, W. H.

W. H. Coulter, “High speed automatic blood cell counter and cell size analyzer,” Proc. Natl. Electron. Conf.12, 1034–1040 (1956).

Dann, E. J.

Davies, D. E.

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[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]

Deane, S.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

Derzsi, L.

Dimitrov, S.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

Ding, H.

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]

Eljaszewicz, A.

Engelhardt, R.

Engelke, D.

Erlinger, A.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Foerster, M.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

Frankowski, M.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

Fung, Y. C.

Y. C. Fung and P. Tong, “Theory of the sphering of red blood cells,” Biophys. J. 8(2), 175–198 (1968).
[Crossref] [PubMed]

Garstecki, P.

Godin, J.

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

Golan, L.

Goncharova, N. V.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Green, N. G.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[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]

Gwyer, J. D.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

Han, D.-C.

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

Harper, M.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Hart, S. J.

C. G. Hebert, A. Terray, and S. J. Hart, “Toward label-free optical fractionation of blood--optical force measurements of blood cells,” Anal. Chem. 83(14), 5666–5672 (2011).
[Crossref] [PubMed]

Hebert, C. G.

C. G. Hebert, A. Terray, and S. J. Hart, “Toward label-free optical fractionation of blood--optical force measurements of blood cells,” Anal. Chem. 83(14), 5666–5672 (2011).
[Crossref] [PubMed]

Hoekstra, A. G.

Hollis, V.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

Holloway, J.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

Holmes, D.

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

Isikman, S. O.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Justman, J.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Kapinos, L. E.

R. L. Schoch, L. E. Kapinos, and R. Y. Lim, “Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes,” Proc. Natl. Acad. Sci. U.S.A. 109(42), 16911–16916 (2012).
[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]

Kiehntopf, M.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

Knüttel, A.

Kosmacheva, S. M.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Kriezis, E. E.

Kummrow, A.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

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]

Lim, J.

Lim, R. Y.

R. L. Schoch, L. E. Kapinos, and R. Y. Lim, “Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes,” Proc. Natl. Acad. Sci. U.S.A. 109(42), 16911–16916 (2012).
[Crossref] [PubMed]

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]

Liu, Q. H.

Q. H. Liu, “The PSTD algorithm: A time‐domain method requiring only two cells per wavelength,” Microw. Opt. Technol. Lett. 15(3), 158–165 (1997).
[Crossref]

Lo, Y. H.

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

Lo, Y.-H.

T.-F. Wu, Z. Mei, and Y.-H. Lo, “Optofluidic device for label-free cell classification from whole blood,” Lab Chip 12(19), 3791–3797 (2012).
[Crossref] [PubMed]

Loiko, V. A.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Maltsev, V. P.

Marks, D. L.

Mei, Z.

T.-F. Wu, Z. Mei, and Y.-H. Lo, “Optofluidic device for label-free cell classification from whole blood,” Lab Chip 12(19), 3791–3797 (2012).
[Crossref] [PubMed]

Min, J.

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

Minai, L.

Mir, M.

Morgan, H.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

Mudanyali, O.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Munro, P.

Munro, P. R.

Nagashima, K.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

Neugebauer, U.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

Neukammer, J.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

Ossowski, P.

Ozcan, A.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Pan, Y.

Pettigrew, D.

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

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]

Popescu, G.

Popp, J.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[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]

Qiao, W.

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

Raiter-Smiljanic, A.

Ralston, T. S.

Ramoji, A.

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

Reccius, C. H.

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

Richards, B.

B. Richards and E. Wolf, “Electromagnetic diffraction in optical systems. II. Structure of the image field in an aplanatic system,” Proc. R. Soc. Lond. A Math. Phys. Sci. 253(1274), 358–379 (1959).
[Crossref]

Rosperich, J.

Ruban, G. I.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

Sampson, D. D.

Sarik, J.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Schmidt, M.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

Schmitt, J.

Schoch, R. L.

R. L. Schoch, L. E. Kapinos, and R. Y. Lim, “Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes,” Proc. Natl. Acad. Sci. U.S.A. 109(42), 16911–16916 (2012).
[Crossref] [PubMed]

Semyanov, K. A.

Sencan, I.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Seo, S.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[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]

Sia, S. K.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[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]

Su, T.-W.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

Szkulmowska, A.

Szkulmowski, M.

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]

Tangella, K.

Tarasov, P. A.

Terray, A.

C. G. Hebert, A. Terray, and S. J. Hart, “Toward label-free optical fractionation of blood--optical force measurements of blood cells,” Anal. Chem. 83(14), 5666–5672 (2011).
[Crossref] [PubMed]

Theisen, J.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

Tong, P.

Y. C. Fung and P. Tong, “Theory of the sphering of red blood cells,” Biophys. J. 8(2), 175–198 (1968).
[Crossref] [PubMed]

Török, P.

Tsai, F.

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

Tseng, D.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

Tuchscheerer, A.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

van Berkel, C.

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

Van Bockstaele, D.

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[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]

Wang, Z.

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Wiese, M.

Wojtkowski, M.

Wolf, E.

B. Richards and E. Wolf, “Electromagnetic diffraction in optical systems. II. Structure of the image field in an aplanatic system,” Proc. R. Soc. Lond. A Math. Phys. Sci. 253(1274), 358–379 (1959).
[Crossref]

Wong, J.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

Wu, T.-F.

T.-F. Wu, Z. Mei, and Y.-H. Lo, “Optofluidic device for label-free cell classification from whole blood,” Lab Chip 12(19), 3791–3797 (2012).
[Crossref] [PubMed]

Yeheskely-Hayon, D.

Yelin, D.

Yildirim, H.

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

Yun, H.

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[Crossref] [PubMed]

Yurkin, M. A.

Zhu, H.

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

Zhu, R.

Anal. Chem. (4)

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T.-W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem. 82(11), 4621–4627 (2010).
[Crossref] [PubMed]

A. Ramoji, U. Neugebauer, T. Bocklitz, M. Foerster, M. Kiehntopf, M. Bauer, and J. Popp, “Toward a spectroscopic hemogram: Raman spectroscopic differentiation of the two most abundant leukocytes from peripheral blood,” Anal. Chem. 84(12), 5335–5342 (2012).
[Crossref] [PubMed]

C. G. Hebert, A. Terray, and S. J. Hart, “Toward label-free optical fractionation of blood--optical force measurements of blood cells,” Anal. Chem. 83(14), 5666–5672 (2011).
[Crossref] [PubMed]

Z. Wang, S. Y. Chin, C. D. Chin, J. Sarik, M. Harper, J. Justman, and S. K. Sia, “Microfluidic CD4+ T-cell counting device using chemiluminescence-based detection,” Anal. Chem. 82(1), 36–40 (2010).
[Crossref] [PubMed]

Appl. Opt. (2)

Biomed. Opt. Express (2)

Biophys. J. (1)

Y. C. Fung and P. Tong, “Theory of the sphering of red blood cells,” Biophys. J. 8(2), 175–198 (1968).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

G. I. Ruban, S. M. Kosmacheva, N. V. Goncharova, D. Van Bockstaele, and V. A. Loiko, “Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems,” J. Biomed. Opt. 12(4), 044017 (2007).
[Crossref] [PubMed]

J. Biophotonics (1)

J. Godin, C. H. Chen, S. H. Cho, W. Qiao, F. Tsai, and Y. H. Lo, “Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip,” J. Biophotonics 1(5), 355–376 (2008).
[Crossref] [PubMed]

J. Comput. Phys. (1)

J. P. Berenger, “A perfectly matched layer for the absorption of electromagnetic waves,” J. Comput. Phys. 114(2), 185–200 (1994).
[Crossref]

J. Opt. Soc. Am. A (2)

Lab Chip (8)

H. Yun, H. Bang, J. Min, C. Chung, J. K. Chang, and D.-C. Han, “Simultaneous counting of two subsets of leukocytes using fluorescent silica nanoparticles in a sheathless microchip flow cytometer,” Lab Chip 10(23), 3243–3254 (2010).
[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]

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]

T.-F. Wu, Z. Mei, and Y.-H. Lo, “Optofluidic device for label-free cell classification from whole blood,” Lab Chip 12(19), 3791–3797 (2012).
[Crossref] [PubMed]

A. Kummrow, J. Theisen, M. Frankowski, A. Tuchscheerer, H. Yildirim, K. Brattke, M. Schmidt, and J. Neukammer, “Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining,” Lab Chip 9(7), 972–981 (2009).
[Crossref] [PubMed]

H. Zhu, I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan, “Cost-effective and rapid blood analysis on a cell-phone,” Lab Chip 13(7), 1282–1288 (2013).
[Crossref] [PubMed]

C. van Berkel, J. D. Gwyer, S. Deane, N. G. Green, J. Holloway, V. Hollis, and H. Morgan, “Integrated systems for rapid point of care (PoC) blood cell analysis,” Lab Chip 11(7), 1249–1255 (2011).
[Crossref] [PubMed]

D. Holmes, D. Pettigrew, C. H. Reccius, J. D. Gwyer, C. van Berkel, J. Holloway, D. E. Davies, and H. Morgan, “Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry,” Lab Chip 9(20), 2881–2889 (2009).
[Crossref] [PubMed]

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Figures (16)

Fig. 1
Fig. 1

Schematic diagram of the image formation model composed of an OCT system and a microfluidic chip; a) a photo of the microfluidic chip and b) its depth resolved structure; c) the scattering volume design (TiO2 scatterers are not displayed); and d) an example OCT image showing the signals of interest.

Fig. 2
Fig. 2

An illustration of the four key components of the three-dimensional full-wave model of OCT image formation.

Fig. 3
Fig. 3

Renders of the RBC and WBC refractive index models; a) a plot of the erythrocyte model topology; b) a three-dimensional rendering of the modeled erythrocyte surface, and c) a 3D rendering of the leukocyte (neutrophil) model.

Fig. 4
Fig. 4

a) The Fd-OCT system sample arm; MFD – mode field diameter, OB1 – objective lens of the collimator, L1, L2 – lenses, OB2 – objective lens; b) A zoomed-in, annotated, depiction of the objective lens shown in the boxed region of (a), illustrating the parameters used to calculate the focused illumination using Eq. (2).

Fig. 5
Fig. 5

Rendering of the staircase approximation to the TiO2 (a) and WBC granule (c), the result of simulations used to calculate the required value of Δ for modelling the TiO2 scatterers (b) and verification (d) that the granules are well represented by the shape in (c) for n3 ranging between nc and 1.6.

Fig. 6
Fig. 6

Rendering of the magnitude of electric field scattered by the discretized approximation to the TiO2 spheres using the PSTD method (a), and that of an ideal TiO2 sphere using Mie theory (b) for a plane wave polarized in the x-direction and propagating the z-direction. The field is normalized by the magnitude of the incident plane wave.

Fig. 7
Fig. 7

Plots of the phase-based differential parameter Slope; a) a horizontal profile through the experimentally acquired RBC signal; the blue line indicates a linear fit; b) a profile through the WBC signal plus linear fit; (c-d) simulated RBC and WBC profiles with linear fits. The black frame on the phase gradient ROI shown in (a) indicates the values used to calculate the first or last sample in the plot on the left. The label ‘Phase mean’ in the plots refers to the mean, taken over a rectangular frame, of phase gradient calculated for different positions of the frame.

Fig. 8
Fig. 8

Plots of the magnitude of the x-component of electric field, |Ex|; the plots shown in (a-d) are plotted in x-z plane containing the optical axis; a) the 3D homogeneous geometry for water only; b) a plot of |Ex| for the case presented in (a); c) the scattering geometry for the empty microchannel; d) a plot of |Ex| for the case presented in (c); e) plots of |Ex| in x-y planes spaced about the beam’s focus: the top row of images shows the plots associated with (a-b), and the lower shows those associated with (c-d).

Fig. 9
Fig. 9

Magnitude plots of the x-component of electric field, |Ex|, for the cases of an RBC and WBC present in the microchannel; the plots shown in (a-d) are plotted in x-z plane containing the optical axis; a) the scattering geometry for the RBC included in the microchannel; b) a plot of |Ex| for the case (a); (c-d) the plots corresponding to (a-b) but with a WBC in the microchannel; e) plots of |Ex| in x-y planes: the top row of images for the RBC case (i.e., a-b), and the lower row corresponds to the WBC case (i.e., c-d).

Fig. 10
Fig. 10

a) Simulated magnitude M-scans constructed from 407 A-scans; b) the M-scan from (a) with static background subtracted (differential magnitude M-scan); c) phase gradient M-scan based on complex M-scan shown as magnitude in (a). The left signal of interest in all M-scans refers to the RBC, while the right one to the WBC.

Fig. 11
Fig. 11

Comparison of simulated and experimental M-scans for data set 1; a) a simulated magnitude M-scan; b) the M-scan from (a) with background subtracted; c) an experimental M-scan created by fusing two independent M-scans (the top image shows a part of M-scan including a signal coming from the WBC and the lower image shows a signal derived from the RBC); d) the M-scans from (c) with background subtracted; e) the simulated M-scan from (a) divided by its dynamic range and with white noise, of standard deviation taken from (g), added; f) the simulated M-scan from (b) processed in the same way as (e) with noise derived from (h); g) the experimental M-scan from (c), divided by its dynamic range; h) the experimental M-scan from (d) processed in the same way as (g).

Fig. 12
Fig. 12

An identical analysis to that presented in Fig. 11, but for data set 2. All images (a-h) directly correspond to that presented in Fig. 11. The SNR for data set 2 is 34dB.

Fig. 13
Fig. 13

Simulated and experimental phase gradient M-scans; a) a simulated phase gradient M-scan corresponding with the M-scans depicted in Fig. 11(a) and Fig. 12(a); b) an experimental phase gradient M-scan corresponding with the M-scan of Fig. 11(c) (data set 1); c) a simulated phase gradient M-scan with noise added, derived directly from data shown as magnitude in Fig. 11(e) and Fig. 12(e); d) an experimental phase gradient M-scan corresponding with the M-scan of Fig. 12(g) (data set 2).

Fig. 14
Fig. 14

Illustration of the attenuation of the OCT signal (magnitude); all plots and images are presented in decibel scale; a) profiles (A-scans) through the signals of interest for: experimental RBC (red line, depicted as an image in (e), data set 2), experimental WBC (black line, data set 2), simulated RBC (green line, also depicted in (f)) and simulated WBC (blue line). The dashed lines (magenta) indicate the SNR level for data set 2 (34dB); b) the corresponding profiles for data set 1 (SNR 38dB); (c-d) the profiles through the TiO2-PDMS layer in the absence of cells: experimental (orange lines, shown as the images in (g-h)), for experimental data set 2 (c) and data set 1 (d), and simulated profiles (brown lines) also depicted in (i). The vertical lines in images (e-f) indicate the origin of the associated profile plots.

Fig. 15
Fig. 15

Two-dimensional scatter plots of differential parameter values for RBC (red dots) and WBC (black dots) signals of interest combined with simulated differential parameter values (green dot: RBC, dark blue dot: WBC). Experimental values shown in (b) and (d) were calculated for experimental data set 1, while the remainder of the plots were calculated using data set 2; a) Speckle contrast [‒] (not scaled) vs. Standard deviations (magnitude) [a.u.] (×235); b) Speckle contrast [‒] (not scaled) vs. Standard deviations (magnitude) [a.u.] (×247); (c-d) Speckle contrast [‒] vs. Slope [‒] (both not scaled); e) Speckle contrast [‒] (not scaled) vs. Phase 2DFT [a.u.] (×2.2); f) Axial (vertical) speckle size [μm] vs. Standard deviations (phase) [rad] (both not scaled). The scaling factors are provided in parentheses.

Fig. 16
Fig. 16

Plots illustrating the sensitivity of the differential parameters to axial position of the ROI, calculated for simulated (the left column in each frame) and exemplar experimental data (the right columns), which consists of 130 RBC signals and 130 WBC signals, derived from experimental data set 2. The parameter values shown in row (b) in the left frame are presented in logarithmic scale. The red line in each plot indicates differential parameters obtained for the RBC signals, while the black line corresponds to the WBCs.

Tables (2)

Tables Icon

Table 1 Parameters of the numerical simulation. Most of symbols are defined in Fig. 4; ΔλMAX stands for maximum spectral width (wavelength width) and NAOB2 indicates numerical aperture of the objective lens OB2.

Tables Icon

Table 2 Differential parameters.

Equations (7)

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f( x )=0.26d 1 ( 2x/d ) 2 ( 0.1583+1.5262 ( 2x/d ) 2 0.8579 ( 2x/d ) 4 ),
e i ( r b ,k )= ik f OB2 2π | r ˜ f |<N A OB2 e ^ ( r ˜ f ) exp( ( F| r ˜ f | N A OB2 ) 2 )exp( ik r b s ) d 2 r ˜ f 1 | r ˜ f | 2 ,
J * ( t )={ k ^ × e i ( r b , k 0 )exp( i ω 0 ( t t 0 ) )exp( π ( ( t t 0 )/W ) 2 ) },
α sc ( k )= 2 ( T e sc ( r b ,k ) )( T e i ( r b ,k ) )d r bx d r by ,
I( z z ref )= 0 S( k ) | α sc ( k )+ α ref ( k ) | 2 exp( ik2( z z ref ) )d( 1/λ ),
( N thresh N v /2 N thresh +1 )( j=1 N h /2+1 i= N thresh +1 N v /2 | a ij | )/( j=1 N h /2+1 i=1 N thresh | a ij | ),
C ROI = σ s m ¯ s ,

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