Abstract

We have developed a novel multimodal microscopy system that incorporates confocal Raman, confocal reflectance, and quantitative phase microscopy (QPM) into a single imaging entity. Confocal Raman microscopy provides detailed chemical information from the sample, while confocal reflectance and quantitative phase microscopy show detailed morphology. Combining these intrinsic contrast imaging modalities makes it possible to obtain quantitative morphological and chemical information without exogenous staining. For validation and characterization, we have used this multi-modal system to investigate healthy and diseased blood samples. We first show that the thickness of a healthy red blood cell (RBC) shows good correlation with its hemoglobin distribution. Further, in malaria infected RBCs, we successfully image the distribution of hemozoin (malaria pigment) inside the cell. Our observations lead us to propose morphological screening by QPM and subsequent chemical imaging by Raman for investigating blood disorders. This new approach allows monitoring cell development and cell-drug interactions with minimal perturbation of the biological system of interest.

© 2011 OSA

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    [CrossRef] [PubMed]
  30. Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
    [CrossRef] [PubMed]
  31. B. R. Wood, S. J. Langford, B. M. Cooke, F. K. Glenister, J. Lim, and D. McNaughton, “Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites,” FEBS Lett. 554(3), 247–252 (2003).
    [CrossRef] [PubMed]
  32. T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
    [CrossRef] [PubMed]
  33. B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
    [CrossRef] [PubMed]
  34. W. B. Piekos, “Diffracted-light contrast enhancement: a re-examination of oblique illumination,” Microsc. Res. Tech. 46(4-5), 334–337 (1999).
    [CrossRef] [PubMed]
  35. S. Pagola, P. W. Stephens, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment β-haematin,” Nature 404(6775), 307–310 (2000).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2011 (1)

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. 16(3), 030506 (2011).
[CrossRef] [PubMed]

2010 (2)

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

2009 (3)

B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
[CrossRef] [PubMed]

A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[CrossRef] [PubMed]

2008 (4)

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73A(10), 895–903 (2008).
[CrossRef] [PubMed]

A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
[CrossRef] [PubMed]

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

2007 (4)

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[CrossRef] [PubMed]

J. W. Kang and C. K. Hong, “Phase-contrast microscopy by in-line phase-shifting digital holography: shape measurement of a titanium pattern with nanometer axial resolution,” Opt. Eng. 46(4), 040506–040508 (2007).
[CrossRef]

C. Matthäus, T. Chernenko, J. A. Newmark, C. M. Warner, and M. Diem, “Label-free detection of mitochondrial distribution in cells by nonresonant Raman microspectroscopy,” Biophys. J. 93(2), 668–673 (2007).
[CrossRef] [PubMed]

T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
[CrossRef] [PubMed]

2006 (2)

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, “Diffraction phase microscopy for quantifying cell structure and dynamics,” Opt. Lett. 31(6), 775–777 (2006).
[CrossRef] [PubMed]

J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006).
[CrossRef] [PubMed]

2005 (5)

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(35), 12371–12376 (2005).
[CrossRef] [PubMed]

T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, “Hilbert phase microscopy for investigating fast dynamics in transparent systems,” Opt. Lett. 30(10), 1165–1167 (2005).
[CrossRef] [PubMed]

P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
[CrossRef] [PubMed]

P. Marquet, B. Rappaz, P. J. Magistretti, E. Cuche, Y. Emery, T. Colomb, and C. Depeursinge, “Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy,” Opt. Lett. 30(5), 468–470 (2005).
[CrossRef] [PubMed]

C. Mann, L. Yu, C. M. Lo, and M. Kim, “High-resolution quantitative phase-contrast microscopy by digital holography,” Opt. Express 13(22), 8693–8698 (2005).
[CrossRef] [PubMed]

2003 (3)

N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
[CrossRef] [PubMed]

C. Krafft, T. Knetschke, A. Siegner, R. H. W. Funk, and R. Salzer, “Mapping of single cells by near infrared Raman microspectroscopy,” Vib. Spectrosc. 32(1), 75–83 (2003).
[CrossRef]

B. R. Wood, S. J. Langford, B. M. Cooke, F. K. Glenister, J. Lim, and D. McNaughton, “Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites,” FEBS Lett. 554(3), 247–252 (2003).
[CrossRef] [PubMed]

2002 (1)

J. X. Cheng, Y. K. Jia, G. Zheng, and X. S. Xie, “Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology,” Biophys. J. 83(1), 502–509 (2002).
[CrossRef] [PubMed]

2000 (1)

S. Pagola, P. W. Stephens, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment β-haematin,” Nature 404(6775), 307–310 (2000).
[CrossRef] [PubMed]

1999 (3)

W. B. Piekos, “Diffracted-light contrast enhancement: a re-examination of oblique illumination,” Microsc. Res. Tech. 46(4-5), 334–337 (1999).
[CrossRef] [PubMed]

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

E. Cuche, F. Bevilacqua, and C. Depeursinge, “Digital holography for quantitative phase-contrast imaging,” Opt. Lett. 24(5), 291–293 (1999).
[CrossRef] [PubMed]

1998 (1)

1997 (1)

1994 (1)

1992 (1)

A. F. G. Slater and A. Cerami, “Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites,” Nature 355(6356), 167–169 (1992).
[CrossRef] [PubMed]

1990 (1)

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[CrossRef] [PubMed]

1928 (1)

C. V. Raman and K. S. Krishnan, “A new type of secondary radiation,” Nature 121(3048), 501–502 (1928).
[CrossRef]

Arndt-Jovin, D. J.

G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[CrossRef] [PubMed]

Auth, T.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Badizadegan, K.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[CrossRef] [PubMed]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[CrossRef] [PubMed]

Bambery, K. R.

B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
[CrossRef] [PubMed]

Barbul, A.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73A(10), 895–903 (2008).
[CrossRef] [PubMed]

Becker, K.

T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
[CrossRef] [PubMed]

Best, C. A.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Bevilacqua, F.

Bohle, D. S.

S. Pagola, P. W. Stephens, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment β-haematin,” Nature 404(6775), 307–310 (2000).
[CrossRef] [PubMed]

Brazhe, A. R.

A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
[CrossRef]

A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
[CrossRef] [PubMed]

Brazhe, N. A.

A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
[CrossRef]

A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
[CrossRef] [PubMed]

Brysgalova, N. Y.

A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
[CrossRef]

Burkhardt, H.

P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
[CrossRef] [PubMed]

Cerami, A.

A. F. G. Slater and A. Cerami, “Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites,” Nature 355(6356), 167–169 (1992).
[CrossRef] [PubMed]

Cheng, J. X.

J. X. Cheng, Y. K. Jia, G. Zheng, and X. S. Xie, “Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology,” Biophys. J. 83(1), 502–509 (2002).
[CrossRef] [PubMed]

Chernenko, T.

C. Matthäus, T. Chernenko, J. A. Newmark, C. M. Warner, and M. Diem, “Label-free detection of mitochondrial distribution in cells by nonresonant Raman microspectroscopy,” Biophys. J. 93(2), 668–673 (2007).
[CrossRef] [PubMed]

Choi, W.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
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A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(35), 12371–12376 (2005).
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Dasari, R. R.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
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[CrossRef] [PubMed]

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J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006).
[CrossRef] [PubMed]

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T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, “Hilbert phase microscopy for investigating fast dynamics in transparent systems,” Opt. Lett. 30(10), 1165–1167 (2005).
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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
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B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73A(10), 895–903 (2008).
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W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
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Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, “Diffraction phase microscopy for quantifying cell structure and dynamics,” Opt. Lett. 31(6), 775–777 (2006).
[CrossRef] [PubMed]

J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006).
[CrossRef] [PubMed]

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(35), 12371–12376 (2005).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006).
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C. Krafft, T. Knetschke, A. Siegner, R. H. W. Funk, and R. Salzer, “Mapping of single cells by near infrared Raman microspectroscopy,” Vib. Spectrosc. 32(1), 75–83 (2003).
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J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006).
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B. R. Wood, S. J. Langford, B. M. Cooke, F. K. Glenister, J. Lim, and D. McNaughton, “Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites,” FEBS Lett. 554(3), 247–252 (2003).
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Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
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N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
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C. Krafft, T. Knetschke, A. Siegner, R. H. W. Funk, and R. Salzer, “Mapping of single cells by near infrared Raman microspectroscopy,” Vib. Spectrosc. 32(1), 75–83 (2003).
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J. T. Motz, M. Fitzmaurice, A. Miller, S. J. Gandhi, A. S. Haka, L. H. Galindo, R. R. Dasari, J. R. Kramer, and M. S. Feld, “In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque,” J. Biomed. Opt. 11(2), 021003 (2006).
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[CrossRef] [PubMed]

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B. R. Wood, S. J. Langford, B. M. Cooke, F. K. Glenister, J. Lim, and D. McNaughton, “Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites,” FEBS Lett. 554(3), 247–252 (2003).
[CrossRef] [PubMed]

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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
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Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
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[CrossRef] [PubMed]

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C. Matthäus, T. Chernenko, J. A. Newmark, C. M. Warner, and M. Diem, “Label-free detection of mitochondrial distribution in cells by nonresonant Raman microspectroscopy,” Biophys. J. 93(2), 668–673 (2007).
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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
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C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
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A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
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P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
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C. Matthäus, T. Chernenko, J. A. Newmark, C. M. Warner, and M. Diem, “Label-free detection of mitochondrial distribution in cells by nonresonant Raman microspectroscopy,” Biophys. J. 93(2), 668–673 (2007).
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W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
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N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
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Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
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Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
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A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
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P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
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Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
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Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
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N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
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T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, “Hilbert phase microscopy for investigating fast dynamics in transparent systems,” Opt. Lett. 30(10), 1165–1167 (2005).
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T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
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P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
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B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73A(10), 895–903 (2008).
[CrossRef] [PubMed]

P. Marquet, B. Rappaz, P. J. Magistretti, E. Cuche, Y. Emery, T. Colomb, and C. Depeursinge, “Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy,” Opt. Lett. 30(5), 468–470 (2005).
[CrossRef] [PubMed]

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G. J. Puppels, F. F. M. de Mul, C. Otto, J. Greve, M. Robert-Nicoud, D. J. Arndt-Jovin, and T. M. Jovin, “Studying single living cells and chromosomes by confocal Raman microspectroscopy,” Nature 347(6290), 301–303 (1990).
[CrossRef] [PubMed]

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P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
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P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
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A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
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C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
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Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
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N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. 16(3), 030506 (2011).
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T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
[CrossRef] [PubMed]

Schmitt, M.

T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
[CrossRef] [PubMed]

P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
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A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A. 102(35), 12371–12376 (2005).
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N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. 16(3), 030506 (2011).
[CrossRef] [PubMed]

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C. Krafft, T. Knetschke, A. Siegner, R. H. W. Funk, and R. Salzer, “Mapping of single cells by near infrared Raman microspectroscopy,” Vib. Spectrosc. 32(1), 75–83 (2003).
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A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
[CrossRef] [PubMed]

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S. Pagola, P. W. Stephens, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment β-haematin,” Nature 404(6775), 307–310 (2000).
[CrossRef] [PubMed]

Suresh, S.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

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N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. 16(3), 030506 (2011).
[CrossRef] [PubMed]

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P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
[CrossRef] [PubMed]

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N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. 16(3), 030506 (2011).
[CrossRef] [PubMed]

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C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

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N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
[CrossRef] [PubMed]

Volokhina, E.

N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
[CrossRef] [PubMed]

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N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
[CrossRef] [PubMed]

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C. Matthäus, T. Chernenko, J. A. Newmark, C. M. Warner, and M. Diem, “Label-free detection of mitochondrial distribution in cells by nonresonant Raman microspectroscopy,” Biophys. J. 93(2), 668–673 (2007).
[CrossRef] [PubMed]

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N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt. 16(3), 030506 (2011).
[CrossRef] [PubMed]

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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
[CrossRef] [PubMed]

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B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
[CrossRef] [PubMed]

B. R. Wood, S. J. Langford, B. M. Cooke, F. K. Glenister, J. Lim, and D. McNaughton, “Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites,” FEBS Lett. 554(3), 247–252 (2003).
[CrossRef] [PubMed]

Xie, X. S.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[CrossRef] [PubMed]

J. X. Cheng, Y. K. Jia, G. Zheng, and X. S. Xie, “Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology,” Biophys. J. 83(1), 502–509 (2002).
[CrossRef] [PubMed]

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

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Yaqoob, Z.

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009).
[CrossRef] [PubMed]

Yu, L.

Yusipovich, A. I.

A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
[CrossRef]

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T. Frosch, S. Koncarevic, L. Zedler, M. Schmitt, K. Schenzel, K. Becker, and J. Popp, “In situ localization and structural analysis of the malaria pigment hemozoin,” J. Phys. Chem. B 111(37), 11047–11056 (2007).
[CrossRef] [PubMed]

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Zheng, G.

J. X. Cheng, Y. K. Jia, G. Zheng, and X. S. Xie, “Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology,” Biophys. J. 83(1), 502–509 (2002).
[CrossRef] [PubMed]

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A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[CrossRef]

Analyst (Lond.) (1)

B. R. Wood, A. Hermelink, P. Lasch, K. R. Bambery, G. T. Webster, M. A. Khiavi, B. M. Cooke, S. Deed, D. Naumann, and D. McNaughton, “Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics,” Analyst (Lond.) 134(6), 1119–1125 (2009).
[CrossRef] [PubMed]

Appl. Environ. Microbiol. (1)

P. Rösch, M. Harz, M. Schmitt, K. D. Peschke, O. Ronneberger, H. Burkhardt, H. W. Motzkus, M. Lankers, S. Hofer, H. Thiele, and J. Popp, “Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations,” Appl. Environ. Microbiol. 71(3), 1626–1637 (2005).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biophys. J. (3)

N. Uzunbajakava, A. Lenferink, Y. Kraan, E. Volokhina, G. Vrensen, J. Greve, and C. Otto, “Nonresonant confocal Raman imaging of DNA and protein distribution in apoptotic cells,” Biophys. J. 84(6), 3968–3981 (2003).
[CrossRef] [PubMed]

J. X. Cheng, Y. K. Jia, G. Zheng, and X. S. Xie, “Laser-scanning coherent anti-Stokes Raman scattering microscopy and applications to cell biology,” Biophys. J. 83(1), 502–509 (2002).
[CrossRef] [PubMed]

C. Matthäus, T. Chernenko, J. A. Newmark, C. M. Warner, and M. Diem, “Label-free detection of mitochondrial distribution in cells by nonresonant Raman microspectroscopy,” Biophys. J. 93(2), 668–673 (2007).
[CrossRef] [PubMed]

Cytometry A (1)

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73A(10), 895–903 (2008).
[CrossRef] [PubMed]

FEBS Lett. (1)

B. R. Wood, S. J. Langford, B. M. Cooke, F. K. Glenister, J. Lim, and D. McNaughton, “Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites,” FEBS Lett. 554(3), 247–252 (2003).
[CrossRef] [PubMed]

J. Appl. Phys. (1)

A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, A. R. Brazhe, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys. 105(10), 102037 (2009).
[CrossRef]

J. Biomed. Opt. (3)

A. R. Brazhe, N. A. Brazhe, G. V. Maksimov, P. S. Ignatyev, A. B. Rubin, E. Mosekilde, and O. V. Sosnovtseva, “Phase-modulation laser interference microscopy: an advance in cell imaging and dynamics study,” J. Biomed. Opt. 13(3), 034004 (2008).
[CrossRef] [PubMed]

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Opt. Express (1)

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Proc. Natl. Acad. Sci. U.S.A. (4)

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Figures (3)

Fig. 1
Fig. 1

Home-built multimodal microscopy system. The system incorporates confocal Raman, quantitative phase contrast, confocal reflectance and bright field microscopes. By combining four intrinsic imaging modalities, quantitative morphological and chemical information can be acquired from unstained live cells. The high-throughput stage (in the dashed line) is for characterizing liquid or powder samples that do not require spatial resolution.

Fig. 2
Fig. 2

(a) Bright field, (b) confocal reflectance, and (c) quantitative phase contrast images of a healthy blood smear. The color bar indicates phase variation in radians. (d) Hemoglobin distribution from Raman mapping for the boxed RBC in (a).

Fig. 3
Fig. 3

(a) Bright field image for blood smear. (b) QPM image for the boxed RBC in (a). (c) Raman image reconstructed from the first principal component. Scale bar represents 2µm. (d) Spectrum of the first principal component. (e) Raman image reconstructed from the second principal component. Scale bar represents 2µm. (f) Spectrum of the second principal component. The characteristic hemozoin peak at 1374 cm−1 is clearly shown.

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