Abstract

A microscope-based label-free microfluidic cytometer capable of acquiring two dimensional light scatter patterns from single cells, pattern analysis of which determines cellular information such as cell size, orientation and inner nanostructure, was developed. Finite-difference time-domain numerical simulations compared favorably with experimental scatter patterns from micrometer-sized beads and cells. The device was capable of obtaining light scattering patterns from the smallest mature blood cells (platelets) and cord blood hematopoietic stem/progenitor cells (CD34 + cells) and myeloid precursor cells. The potential for evaluation of cells using this label-free microfluidic cytometric technique was discussed.

© 2010 OSA

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2009

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

K. M. Jacobs, J. Q. Lu, and X. H. Hu, “Development of a diffraction imaging flow cytometer,” Opt. Lett. 34(19), 2985–2987 (2009).
[CrossRef] [PubMed]

2008

C. McGuckin, M. Jurga, H. Ali, M. Strbad, and N. Forraz, “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nat. Protoc. 3(6), 1046–1055 (2008).
[CrossRef] [PubMed]

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

2007

C. Monat, P. Domachuk, and B. J. Eggleton, “Integrated optofluidics: A new river of light,” Nat. Photonics 1(2), 106–114 (2007).
[CrossRef]

R. De, A. Zemel, and S. A. Safran, “Dynamics of cell orientation,” Nat. Phys. 3(9), 655–659 (2007).
[CrossRef]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[CrossRef] [PubMed]

2006

E. Maurer-Spurej, K. Brown, A. Labrie, A. Marziali, and O. Glatter, “Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions,” Phys. Med. Biol. 51(15), 3747–3758 (2006).
[CrossRef] [PubMed]

P. O. Krutzik and G. P. Nolan, “Fluorescent cell barcoding in flow cytometry allows high-throughput drug screening and signaling profiling,” Nat. Methods 3(5), 361–368 (2006).
[CrossRef] [PubMed]

D. Psaltis, S. R. Quake, and C. H. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[CrossRef] [PubMed]

H. Craighead, “Future lab-on-a-chip technologies for interrogating individual molecules,” Nature 442(7101), 387–393 (2006).
[CrossRef] [PubMed]

2005

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron. 11(4), 759–765 (2005).
[CrossRef]

C. G. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 014007 (2005).
[CrossRef]

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[CrossRef] [PubMed]

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J. 88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

2004

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

M. D. Abramoff, P. J. Magelhaes, and S. J. Ram, “Image Processing with ImageJ,” Biophoton. Int. 11, 36–42 (2004).

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
[CrossRef] [PubMed]

2001

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

2000

1996

A. Dunn and R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2(4), 898–905 (1996).
[CrossRef]

1993

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

1980

1979

G. C. Salzman, M. E. Wilder, and J. H. Jett, “Light scattering with stream-in-air flow systems,” J. Histochem. Cytochem. 27(1), 264–267 (1979).
[CrossRef] [PubMed]

Abramoff, M. D.

M. D. Abramoff, P. J. Magelhaes, and S. J. Ram, “Image Processing with ImageJ,” Biophoton. Int. 11, 36–42 (2004).

Ali, H.

C. McGuckin, M. Jurga, H. Ali, M. Strbad, and N. Forraz, “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nat. Protoc. 3(6), 1046–1055 (2008).
[CrossRef] [PubMed]

Backhouse, C.

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[CrossRef] [PubMed]

Backman, V.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron. 11(4), 759–765 (2005).
[CrossRef]

Bartholdi, M.

Bigelow, C. E.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J. 88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Brown, K.

E. Maurer-Spurej, K. Brown, A. Labrie, A. Marziali, and O. Glatter, “Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions,” Phys. Med. Biol. 51(15), 3747–3758 (2006).
[CrossRef] [PubMed]

Butler, W. F.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Calkins, D. J.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J. 88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Capjack, C.

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[CrossRef] [PubMed]

C. G. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 014007 (2005).
[CrossRef]

Capoglu, I. R.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Chachisvilis, M.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
[CrossRef] [PubMed]

Craighead, H.

H. Craighead, “Future lab-on-a-chip technologies for interrogating individual molecules,” Nature 442(7101), 387–393 (2006).
[CrossRef] [PubMed]

De, R.

R. De, A. Zemel, and S. A. Safran, “Dynamics of cell orientation,” Nat. Phys. 3(9), 655–659 (2007).
[CrossRef]

Dees, B.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Deiteren, K.

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

Diver, J.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
[CrossRef] [PubMed]

Domachuk, P.

C. Monat, P. Domachuk, and B. J. Eggleton, “Integrated optofluidics: A new river of light,” Nat. Photonics 1(2), 106–114 (2007).
[CrossRef]

Drezek, R.

Dunn, A.

Eggleton, B. J.

C. Monat, P. Domachuk, and B. J. Eggleton, “Integrated optofluidics: A new river of light,” Nat. Photonics 1(2), 106–114 (2007).
[CrossRef]

Ehrenman, K.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

El-Ali, J.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Emerson, S. G.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Engelund, M.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Forraz, N.

C. McGuckin, M. Jurga, H. Ali, M. Strbad, and N. Forraz, “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nat. Protoc. 3(6), 1046–1055 (2008).
[CrossRef] [PubMed]

Forster, A. H.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Foster, T. H.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J. 88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Furtado, M. R.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

Gewirtz, A. M.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Glatter, O.

E. Maurer-Spurej, K. Brown, A. Labrie, A. Marziali, and O. Glatter, “Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions,” Phys. Med. Biol. 51(15), 3747–3758 (2006).
[CrossRef] [PubMed]

Goolsby, C.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

Gotsaed, T.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Gul, H.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

Hagen, N.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
[CrossRef] [PubMed]

Heifetz, A.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Hiebert, R. D.

Hu, X. H.

K. M. Jacobs, J. Q. Lu, and X. H. Hu, “Development of a diffraction imaging flow cytometer,” Opt. Lett. 34(19), 2985–2987 (2009).
[CrossRef] [PubMed]

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[CrossRef] [PubMed]

Islam, M. Z.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

Jacobs, K. M.

Jalili, A.

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

Janowska-Wieczorek, A.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Jett, J. H.

G. C. Salzman, M. E. Wilder, and J. H. Jett, “Light scattering with stream-in-air flow systems,” J. Histochem. Cytochem. 27(1), 264–267 (1979).
[CrossRef] [PubMed]

Jurga, M.

C. McGuckin, M. Jurga, H. Ali, M. Strbad, and N. Forraz, “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nat. Protoc. 3(6), 1046–1055 (2008).
[CrossRef] [PubMed]

Kariv, I.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Kerker, M.

Kirkwood, S. E.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

Kowalska, M. A.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Krutzik, P. O.

P. O. Krutzik and G. P. Nolan, “Fluorescent cell barcoding in flow cytometry allows high-throughput drug screening and signaling profiling,” Nat. Methods 3(5), 361–368 (2006).
[CrossRef] [PubMed]

Kunte, D.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Kutter, J. P.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Labrie, A.

E. Maurer-Spurej, K. Brown, A. Labrie, A. Marziali, and O. Glatter, “Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions,” Phys. Med. Biol. 51(15), 3747–3758 (2006).
[CrossRef] [PubMed]

Lambeir, A. M.

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

Li, X.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron. 11(4), 759–765 (2005).
[CrossRef]

Liu, C. G.

C. G. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 014007 (2005).
[CrossRef]

Liu, Y.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Lu, J. Q.

K. M. Jacobs, J. Q. Lu, and X. H. Hu, “Development of a diffraction imaging flow cytometer,” Opt. Lett. 34(19), 2985–2987 (2009).
[CrossRef] [PubMed]

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[CrossRef] [PubMed]

Magelhaes, P. J.

M. D. Abramoff, P. J. Magelhaes, and S. J. Ram, “Image Processing with ImageJ,” Biophoton. Int. 11, 36–42 (2004).

Majka, M.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Marchand, P.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
[CrossRef] [PubMed]

Marchand, P. J.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Marquez-Curtis, L.

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

Marziali, A.

E. Maurer-Spurej, K. Brown, A. Labrie, A. Marziali, and O. Glatter, “Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions,” Phys. Med. Biol. 51(15), 3747–3758 (2006).
[CrossRef] [PubMed]

Maurer-Spurej, E.

E. Maurer-Spurej, K. Brown, A. Labrie, A. Marziali, and O. Glatter, “Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions,” Phys. Med. Biol. 51(15), 3747–3758 (2006).
[CrossRef] [PubMed]

McBride, L. J.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

McGuckin, C.

C. McGuckin, M. Jurga, H. Ali, M. Strbad, and N. Forraz, “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nat. Protoc. 3(6), 1046–1055 (2008).
[CrossRef] [PubMed]

Mercer, E. M.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Mogensen, K. B.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Monat, C.

C. Monat, P. Domachuk, and B. J. Eggleton, “Integrated optofluidics: A new river of light,” Nat. Photonics 1(2), 106–114 (2007).
[CrossRef]

Nolan, G. P.

P. O. Krutzik and G. P. Nolan, “Fluorescent cell barcoding in flow cytometry allows high-throughput drug screening and signaling profiling,” Nat. Methods 3(5), 361–368 (2006).
[CrossRef] [PubMed]

Otto, P.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

Patterson, B. K.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

Perch-Nielsen, I. R.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Petrácek, J.

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

Pietrzkowski, Z.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Pradhan, P.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Psaltis, D.

D. Psaltis, S. R. Quake, and C. H. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[CrossRef] [PubMed]

Quake, S. R.

D. Psaltis, S. R. Quake, and C. H. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[CrossRef] [PubMed]

Ram, S. J.

M. D. Abramoff, P. J. Magelhaes, and S. J. Ram, “Image Processing with ImageJ,” Biophoton. Int. 11, 36–42 (2004).

Ratajczak, J.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Ratajczak, M. Z.

M. Majka, A. Janowska-Wieczorek, J. Ratajczak, K. Ehrenman, Z. Pietrzkowski, M. A. Kowalska, A. M. Gewirtz, S. G. Emerson, and M. Z. Ratajczak, “Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner,” Blood 97(10), 3075–3085 (2001).
[CrossRef] [PubMed]

Raymond, D. E.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Richards-Kortum, R.

Rogers, J. D.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Roy, H. K.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Rozmus, W.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[CrossRef] [PubMed]

C. G. Liu, C. Capjack, and W. Rozmus, “3-D simulation of light scattering from biological cells and cell differentiation,” J. Biomed. Opt. 10(1), 014007 (2005).
[CrossRef]

Safran, S. A.

R. De, A. Zemel, and S. A. Safran, “Dynamics of cell orientation,” Nat. Phys. 3(9), 655–659 (2007).
[CrossRef]

Salzman, G. C.

Shirvaikar, N.

L. Marquez-Curtis, A. Jalili, K. Deiteren, N. Shirvaikar, A. M. Lambeir, and A. Janowska-Wieczorek, “Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization?” Stem Cells 26(5), 1211–1220 (2008).
[CrossRef] [PubMed]

Singh, K.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

Snakenborg, D.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Strbad, M.

C. McGuckin, M. Jurga, H. Ali, M. Strbad, and N. Forraz, “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nat. Protoc. 3(6), 1046–1055 (2008).
[CrossRef] [PubMed]

Su, X. T.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[CrossRef] [PubMed]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[CrossRef] [PubMed]

Subramanian, H.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Taflove, A.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A. 105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron. 11(4), 759–765 (2005).
[CrossRef]

Till, M.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

Tsui, Y. Y.

X. T. Su, S. E. Kirkwood, H. Gul, K. Singh, M. Z. Islam, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Light scattering characterization of single biological cells in a microfluidic cytometer,” Proc. SPIE 7386, 738602, 738602-8 (2009).
[CrossRef]

Tu, E.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Wang, M. M.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Wang, Z.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Watson, D.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
[CrossRef] [PubMed]

Wilder, M. E.

G. C. Salzman, M. E. Wilder, and J. H. Jett, “Light scattering with stream-in-air flow systems,” J. Histochem. Cytochem. 27(1), 264–267 (1979).
[CrossRef] [PubMed]

Wilson, J. D.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J. 88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Wolff, A.

Z. Wang, J. El-Ali, M. Engelund, T. Gotsaed, I. R. Perch-Nielsen, K. B. Mogensen, D. Snakenborg, J. P. Kutter, and A. Wolff, “Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements,” Lab Chip 4(4), 372–377 (2004).
[CrossRef] [PubMed]

Wolinsky, S. M.

B. K. Patterson, M. Till, P. Otto, C. Goolsby, M. R. Furtado, L. J. McBride, and S. M. Wolinsky, “Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry,” Science 260(5110), 976–979 (1993).
[CrossRef] [PubMed]

Yang, C. H.

D. Psaltis, S. R. Quake, and C. H. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442(7101), 381–386 (2006).
[CrossRef] [PubMed]

Yang, J. M.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Yang, P.

J. Q. Lu, P. Yang, and X. H. Hu, “Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method,” J. Biomed. Opt. 10(2), 024022 (2005).
[CrossRef] [PubMed]

Zemel, A.

R. De, A. Zemel, and S. A. Safran, “Dynamics of cell orientation,” Nat. Phys. 3(9), 655–659 (2007).
[CrossRef]

Zhang, H. C.

M. M. Wang, E. Tu, D. E. Raymond, J. M. Yang, H. C. Zhang, N. Hagen, B. Dees, E. M. Mercer, A. H. Forster, I. Kariv, P. J. Marchand, and W. F. Butler, “Microfluidic sorting of mammalian cells by optical force switching,” Nat. Biotechnol. 23(1), 83–87 (2005).
[CrossRef]

Appl. Opt.

Biophoton. Int.

M. D. Abramoff, P. J. Magelhaes, and S. J. Ram, “Image Processing with ImageJ,” Biophoton. Int. 11, 36–42 (2004).

Biophys. J.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J. 88(4), 2929–2938 (2005).
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D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J. 87(2), 1298–1306 (2004).
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Figures (8)

Fig. 1
Fig. 1

A schematic diagram for the microscope-based label-free microfluidic light scattering cytometer. Laser light is coupled into the microfluidic channel via an optical fiber. The 2D scatter pattern from a single scatterer is obtained by the CCD detector via an optical lens.

Fig. 2
Fig. 2

Illustration for obtaining 2D scatter patterns via defocusing. (a) Image of a 4 µm bead in the microfluidic channel when the optical system was in focus. (b) Scatter pattern of the 4 µm bead when the optical system was defocused.

Fig. 3
Fig. 3

A schematic diagram illustrating the scattered light path in the microscope-based LFMC. The light scattered from a single scatterer propagates through multi-layer of medium onto the CCD detector. The scattered light angular range that can be detected is determined by the medium that the light propagates and by the numerical aperture of the objective lens. The microfluidic chip is with a width of approximately 2.54 cm and the distance from the bottom of the chip to the CCD screen surface is about 15 cm (Note the illustration is not to scale).

Fig. 4
Fig. 4

Validation of the scattered light angular range of the microscope-based LFMC using standard polystyrene beads. Experimental scatter patterns obtained from (a) a 4 µm bead, and (b) a 9.6 µm bead. Simulated scatter patterns for (c) a 4 µm bead, and (d) a 9.6 µm bead. The collection angles for the scatter pattern are from 79 to 101 degrees.

Fig. 5
Fig. 5

Determination of cell orientation by using the microscope-based LFMC. (a), (b) and (c) are the representative experimental 2D scatter patterns from platelets. (d), (e) and (f) are the cell models for platelets at different orientations. (g), (h) and (i) are the AETHER 2D scatter patterns. The platelet scatter patterns have fringe structures ((a), (c), (g) and (i)) from the cell microstructures or no fringes ((b) and (h)) when the effective cell microstructure is small.

Fig. 6
Fig. 6

Representative 2D scatter patterns from myeloid precursor cells and CD34 + cells. (a) Representative experimental scatter pattern from a myeloid precursor cell. (b) CD34 + cell scatter pattern. (c) and (d) are the cell models for the myeloid precursor cell and CD34 + cells, respectively. (e) and (f) are AETHER 2D scatter patterns of the cell models (c) and (d), respectively.

Fig. 8
Fig. 8

Real space analysis of the intensity maxima in the 2D scatter patterns for potential cell discrimination. The immature cord blood CD34 + cells may be discriminated from the more mature myeloid precursor cells.

Fig. 7
Fig. 7

Distribution of mitochondria in a representative CD34 + cell as observed by confocal fluorescence microscopy.

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