Abstract

In this work, the effects of thalassemia, a blood disease quite diffuse in the Mediterranean sea region, have been investigated at single cell level using a Raman Tweezers system. By resonant excitation of hemoglobin Raman bands, we have examined the oxygenation capability of β-thalassemic erythrocytes. A reduction of this fundamental erythrocyte function has been found. The measurements have been performed on a significant number of red blood cells; the relative statistical analysis is presented. Moreover, the response to photo-induced oxidative stress of diseased cells with respect to the normal ones has been analyzed. Finally, the deformability of thalassemic erythrocytes has been quantified by measuring the membrane shear modulus by using a double-trap system: the measurements have revealed an increase in membrane rigidity of more than 40%, giving evidence that the genetic defect associated to thalassemia, which manly relies on hemoglobin structure, also strongly affects the erythrocyte mechanical properties. Our results demonstrate that the developed set-up may have potential for the monitoring of blood diseases and their response to drug therapies.

© 2008 Optical Society of America

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    [CrossRef] [PubMed]
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2007 (4)

B. R. Wood, P. Caspers, G. J. Pupples, S. Pandiancherri, and D. McNaughton, "Resonance Raman Spectroscopy of red blood cell using near-infrared laser excitation," Anal. Bioanal. Chem. 387, 1691-1703 (2007).
[CrossRef]

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Enhancing Raman Tweezers by phase-sensitive detection," Anal. Chem. 79, 3708-3715 (2007).
[CrossRef] [PubMed]

O. Inya-Agha, N. Klauke, T. Davies, G. Smith, and J. M. Cooper, "Spectroscopic Probing of Dynamic Changes during Stimulation and Cell Remodeling in the Single Cardiac Myocyte," Anal. Chem. 79, 4581-4587 (2007).
[CrossRef] [PubMed]

K. Mohanty, S. Mohanty, S. Monajembashi, and K. O. O Greulich, "Orientation of erythrocytes in optical trap revealed by confocal fluorescence microscopy," J. Biomed. Opt. 12, 0605061-0605063 (2007).
[CrossRef]

2006 (5)

J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, "Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells," Biophys. J. 90, 648-656 (2006).
[CrossRef]

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Phase-sensitive detection in Raman tweezers," Appl. Phys. Lett. 89, 261116-261118 (2006).
[CrossRef]

P. J. Lambert, A. G. Whitman, O. F. Dyson, and S. M. Akula, "Raman spectroscopy: the gateway into tomorrow�??s virology," J. Virol. 3, 1-8 (2006).
[CrossRef]

P. R. T. Jess, V. Garcs-Chvez, D. Smith, M. Mazilu, L. Paterson, A. Riches, C. S. Herrington, W. Sibbett, and K. Dholakia, "Dual beam fibre trap for Raman micro-spectroscopy of single cells," Opt. Express 14, 5779-5791 (2006).
[CrossRef] [PubMed]

G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli, and D. Petrov, "The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy," J. Raman Spectrosc. 37, 858-864 (2006).
[CrossRef]

2005 (5)

C. Creely, G. Volpe, G. Singh, M. Soler, and D. Petrov, "Raman imaging of floating cells," Opt. Express 13, 6105-6110 (2005).
[CrossRef] [PubMed]

C. M. Creely, G. P. Singh, and D. V. Petrov, "Dual wavelength optical tweezers for confocal Raman spectroscopy," Opt. Commun. 245, 465-470 (2005).
[CrossRef]

C. Xie, D. Chen, and Y.-Q. Li, "Raman sorting and identification of single living micro-organisms with optical tweezers," Opt. Lett. 30, 1800-1802 (2005).
[CrossRef] [PubMed]

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

J. Li, M. Dao, C. T. Lim, and S. Suresh, "Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte," Biophys. J. 88, 3707-3719 (2005).
[CrossRef] [PubMed]

2004 (3)

I. P. Torres Filho, J. Terner, R. N. Pittman, L. G. Somera, and K. R. Ward, "Hemoglobin oxygen saturation measurements using resonance Raman intravital microscopy," Am. J. Physiol. Heart Circ. Physiol. 289, 488-495 (2004).
[CrossRef]

K. Ramser, K. Logg, M. Gokör, M. Käll, and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Opt. 9, 593-600 (2004).
[CrossRef] [PubMed]

C. Xie, C. Goodman, M. Dinno, and Y.-Q. Li, "Real-time Raman spectroscopy of optically trapped living cells and organelles," Opt. Express 12, 6208-6214 (2004).
[CrossRef] [PubMed]

2003 (2)

C. Xie and Y.-Q. Li, "Confocal micro-Raman spectroscopy of single biological cells using optical trapping and shifted excitation difference techniques," J. Appl. Phys. 93, 2982-2986 (2003).
[CrossRef]

R. Petry, M. Schmitt, and J. Popp, "Raman spectroscopy - a prospective tool in the life sciences," Chem. Phys. Chem. 4, 15-30 (2003).
[CrossRef]

2002 (4)

C. M. Harris, "Raman revisited," Anal Chem. 74, 433A-438A (2002).
[CrossRef] [PubMed]

M. P. Houlne, C. M. Sjostrom, R. H. Uibel, J. A. Kleimeyer, and J. M. Harris, "Confocal Raman Microscopy for Monitoring Chemical Reactions on Single Optically Trapped, Solid-Phase Support Particles," Anal. Chem. 74, 4311-4319 (2002).
[CrossRef] [PubMed]

C. Xie, M. A. Dinno, and Y.-Q. Li, "Near-infrared Raman spectroscopy of single optically trapped biological cells," Opt. Lett. 27, 249-251 (2002).
[CrossRef]

B. R. Wood and D. McNaughton, "Raman excitation wavelength investigation of single red blood cell in vivo," J. Raman Spectrosc. 33, 517-523 (2002).
[CrossRef]

2001 (3)

B. R. Wood, B. Tait, and D. McNaughton, "Micro-Raman characterization of the R to T state transition of haemoglobin within a single living erythrocyte," Biochem. Biophys. Acta 1539, 58-70 (2001).
[CrossRef] [PubMed]

K. Ajito and K. Torimitsu, "Near-infrared Raman spectroscopy of single particles," Trends Anal. Chem. 20, 255-262 (2001).
[CrossRef]

G. Lenormand, S. Hénon, A. Richert, and F. Gallet, "Direct measurement of the area expansion and shear moduli of the human red blood cell membrane skeleton," Biophys. J. 81, 43-56 (2001).
[CrossRef] [PubMed]

1999 (2)

S. Hénon, G. Lenormand, A. Richert, and F. Gallet, "A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers," Biophys. J. 76, 1145-1151 (1999).
[CrossRef]

G. J. Thomas, "Raman spectroscopy of protein and nucleic acid assemblies," Annu. Rev. Biophys. Biomol. Struct. 28, 1-27 (1999).
[CrossRef] [PubMed]

1998 (3)

K. Ajito, "Combined Near-Infrared Raman Microprobe and Laser Trapping System: Application to the Analysis of a Single Organic Microdroplet in Water," Appl. Spectrosc. 52, 339-342 (1998).
[CrossRef]

S. K. Boey, D. H. Boal, and D. E. Discher, "Simulations of the erythrocyte cytoskeleton at large deformation. I. Microscopic models," Biophys. J. 75, 1573-1583 (1998).
[CrossRef] [PubMed]

D. E. Discher, D. H. Boal, and S. K. Boey, "Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration," Biophys. J. 75, 1584-1597 (1998).
[CrossRef] [PubMed]

1996 (1)

S. Hu, K. M. Smith, and T. G. Spiro, "Assignment of Protoheme Resonance Raman Spectrum by Heme Labeling in Myoglobin" J. Am. Chem. Soc. 118, 12638-12646 (1996).
[CrossRef]

1995 (1)

1994 (1)

1992 (1)

K. Svoboda, C. F. Schmidt, D. Branton, and S. M. Block, "Conformation and elasticity of the isolated red blood cell membrane skeleton," Biophys. J. 63, 784-793 (1992).
[CrossRef] [PubMed]

1991 (1)

G. Athanasiou, N. Zoubos, and Y. Missirlis, "Erytrhrocyte membrane deformability in patients with thalassemia syndromes," Nouv. Rev. Fr. Hematol. 33, 15-20 (1991).
[PubMed]

1990 (1)

1989 (1)

E. Shinar, E. A. Rachmilewitz, and S. E. Lux, "Differing erythrocyte membrane skeletal protein defects in alpha and beta thalassemia," J. Clin. Invest. 83, 404-410 (1989).
[CrossRef] [PubMed]

1987 (2)

E. A. Evans and N. Mohandas, "Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity," Blood 70, 1443-1449 (1987).
[PubMed]

A. Ashkin and J. M. Dziedzic, "Optical trapping and manipulation of virus and bacteria," Science 235, 1517-1520 (1987).
[CrossRef] [PubMed]

1986 (1)

1982 (1)

D. J. Weatherall and J. B. Clegg, "Thalassemia revisited," Cell 29, 7-9 (1982).
[CrossRef] [PubMed]

1979 (1)

J. M. Salter, "The effect of radiation trapping of high intensity scattered radiation on multiphoton ionization rates and resonance fluorescence," J. Phys. B: Atom. Molec. Phys. 12, L763-L767 (1979).
[CrossRef]

1978 (2)

I. Kahane, A. Shifter, and E. A. Rachmilewitz, "Cross linking of red blood cells membrane proteins induced by oxidative stress in beta-thalassemia," FEBS Lett. 85, 267-270 (1978).
[CrossRef] [PubMed]

M. Abe, T. Kitagawa, and Y. Kyogoku, "Resonance Raman spectra of octaethylporphyrinato-Ni(II) and mesodeuterated and 15N substituted derivatives. II. A normal coordinate analysis," J. Chem. Phys. 69, 4526-4531 (1978).
[CrossRef]

1976 (1)

E. A. Rachmilewitz, B. M. Lubin, and S. B. Shohet, "Lipid membrane peroxidation in beta-thalassemia," Blood 47, 495-505 (1976).
[PubMed]

1973 (1)

E. A. Evans, "A new membrane concept applied to the analysis of fluid shear- and micropipette-deformed red blood cells," Biophys. J. 13, 941-954 (1973).
[CrossRef] [PubMed]

1972 (1)

H. Brunner, A. Mayer, and H. Sussner, "Resonance Raman Scattering on the heam group of the oxy- and deoxyhaemogloin," J. Mol. Biol. 70, 153-156 (1972).
[CrossRef] [PubMed]

Abe, M.

M. Abe, T. Kitagawa, and Y. Kyogoku, "Resonance Raman spectra of octaethylporphyrinato-Ni(II) and mesodeuterated and 15N substituted derivatives. II. A normal coordinate analysis," J. Chem. Phys. 69, 4526-4531 (1978).
[CrossRef]

Ajito, K.

Akula, S. M.

P. J. Lambert, A. G. Whitman, O. F. Dyson, and S. M. Akula, "Raman spectroscopy: the gateway into tomorrow�??s virology," J. Virol. 3, 1-8 (2006).
[CrossRef]

Ashkin, A.

Athanasiou, G.

G. Athanasiou, N. Zoubos, and Y. Missirlis, "Erytrhrocyte membrane deformability in patients with thalassemia syndromes," Nouv. Rev. Fr. Hematol. 33, 15-20 (1991).
[PubMed]

Berns, M. K.

Bjorkholm, J. E.

Block, S. M.

K. Svoboda, C. F. Schmidt, D. Branton, and S. M. Block, "Conformation and elasticity of the isolated red blood cell membrane skeleton," Biophys. J. 63, 784-793 (1992).
[CrossRef] [PubMed]

Boal, D. H.

S. K. Boey, D. H. Boal, and D. E. Discher, "Simulations of the erythrocyte cytoskeleton at large deformation. I. Microscopic models," Biophys. J. 75, 1573-1583 (1998).
[CrossRef] [PubMed]

D. E. Discher, D. H. Boal, and S. K. Boey, "Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration," Biophys. J. 75, 1584-1597 (1998).
[CrossRef] [PubMed]

Boey, S. K.

D. E. Discher, D. H. Boal, and S. K. Boey, "Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration," Biophys. J. 75, 1584-1597 (1998).
[CrossRef] [PubMed]

S. K. Boey, D. H. Boal, and D. E. Discher, "Simulations of the erythrocyte cytoskeleton at large deformation. I. Microscopic models," Biophys. J. 75, 1573-1583 (1998).
[CrossRef] [PubMed]

Branton, D.

K. Svoboda, C. F. Schmidt, D. Branton, and S. M. Block, "Conformation and elasticity of the isolated red blood cell membrane skeleton," Biophys. J. 63, 784-793 (1992).
[CrossRef] [PubMed]

Brock, B. J.

Brock, J. R.

Brunner, H.

H. Brunner, A. Mayer, and H. Sussner, "Resonance Raman Scattering on the heam group of the oxy- and deoxyhaemogloin," J. Mol. Biol. 70, 153-156 (1972).
[CrossRef] [PubMed]

Carls, J. C.

Caspers, P.

B. R. Wood, P. Caspers, G. J. Pupples, S. Pandiancherri, and D. McNaughton, "Resonance Raman Spectroscopy of red blood cell using near-infrared laser excitation," Anal. Bioanal. Chem. 387, 1691-1703 (2007).
[CrossRef]

Chan, J. W.

J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, "Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells," Biophys. J. 90, 648-656 (2006).
[CrossRef]

Chen, D.

Chu, S.

Clegg, J. B.

D. J. Weatherall and J. B. Clegg, "Thalassemia revisited," Cell 29, 7-9 (1982).
[CrossRef] [PubMed]

Cooper, J. M.

O. Inya-Agha, N. Klauke, T. Davies, G. Smith, and J. M. Cooper, "Spectroscopic Probing of Dynamic Changes during Stimulation and Cell Remodeling in the Single Cardiac Myocyte," Anal. Chem. 79, 4581-4587 (2007).
[CrossRef] [PubMed]

Creely, C.

Creely, C. M.

G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli, and D. Petrov, "The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy," J. Raman Spectrosc. 37, 858-864 (2006).
[CrossRef]

C. M. Creely, G. P. Singh, and D. V. Petrov, "Dual wavelength optical tweezers for confocal Raman spectroscopy," Opt. Commun. 245, 465-470 (2005).
[CrossRef]

Dao, M.

J. Li, M. Dao, C. T. Lim, and S. Suresh, "Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte," Biophys. J. 88, 3707-3719 (2005).
[CrossRef] [PubMed]

Davies, T.

O. Inya-Agha, N. Klauke, T. Davies, G. Smith, and J. M. Cooper, "Spectroscopic Probing of Dynamic Changes during Stimulation and Cell Remodeling in the Single Cardiac Myocyte," Anal. Chem. 79, 4581-4587 (2007).
[CrossRef] [PubMed]

De Luca, A. C.

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Enhancing Raman Tweezers by phase-sensitive detection," Anal. Chem. 79, 3708-3715 (2007).
[CrossRef] [PubMed]

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Phase-sensitive detection in Raman tweezers," Appl. Phys. Lett. 89, 261116-261118 (2006).
[CrossRef]

Dholakia, K.

Dinno, M.

Dinno, M. A.

Discher, D. E.

S. K. Boey, D. H. Boal, and D. E. Discher, "Simulations of the erythrocyte cytoskeleton at large deformation. I. Microscopic models," Biophys. J. 75, 1573-1583 (1998).
[CrossRef] [PubMed]

D. E. Discher, D. H. Boal, and S. K. Boey, "Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration," Biophys. J. 75, 1584-1597 (1998).
[CrossRef] [PubMed]

Dyson, O. F.

P. J. Lambert, A. G. Whitman, O. F. Dyson, and S. M. Akula, "Raman spectroscopy: the gateway into tomorrow�??s virology," J. Virol. 3, 1-8 (2006).
[CrossRef]

Dziedzic, J. M.

Enger, J.

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

Evans, E. A.

E. A. Evans and N. Mohandas, "Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity," Blood 70, 1443-1449 (1987).
[PubMed]

E. A. Evans, "A new membrane concept applied to the analysis of fluid shear- and micropipette-deformed red blood cells," Biophys. J. 13, 941-954 (1973).
[CrossRef] [PubMed]

Gallet, F.

G. Lenormand, S. Hénon, A. Richert, and F. Gallet, "Direct measurement of the area expansion and shear moduli of the human red blood cell membrane skeleton," Biophys. J. 81, 43-56 (2001).
[CrossRef] [PubMed]

S. Hénon, G. Lenormand, A. Richert, and F. Gallet, "A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers," Biophys. J. 76, 1145-1151 (1999).
[CrossRef]

Garcs-Chvez, V.

Geli, I. M.

G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli, and D. Petrov, "The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy," J. Raman Spectrosc. 37, 858-864 (2006).
[CrossRef]

Gokör, M.

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M. Gokör, M. Käll, and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Opt. 9, 593-600 (2004).
[CrossRef] [PubMed]

Goodman, C.

Greulich, K. O. O

K. Mohanty, S. Mohanty, S. Monajembashi, and K. O. O Greulich, "Orientation of erythrocytes in optical trap revealed by confocal fluorescence microscopy," J. Biomed. Opt. 12, 0605061-0605063 (2007).
[CrossRef]

Grötsch, H.

G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli, and D. Petrov, "The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy," J. Raman Spectrosc. 37, 858-864 (2006).
[CrossRef]

Hanstorp, D.

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M. Gokör, M. Käll, and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Opt. 9, 593-600 (2004).
[CrossRef] [PubMed]

Harris, C. M.

C. M. Harris, "Raman revisited," Anal Chem. 74, 433A-438A (2002).
[CrossRef] [PubMed]

Harris, J. M.

M. P. Houlne, C. M. Sjostrom, R. H. Uibel, J. A. Kleimeyer, and J. M. Harris, "Confocal Raman Microscopy for Monitoring Chemical Reactions on Single Optically Trapped, Solid-Phase Support Particles," Anal. Chem. 74, 4311-4319 (2002).
[CrossRef] [PubMed]

Hénon, S.

G. Lenormand, S. Hénon, A. Richert, and F. Gallet, "Direct measurement of the area expansion and shear moduli of the human red blood cell membrane skeleton," Biophys. J. 81, 43-56 (2001).
[CrossRef] [PubMed]

S. Hénon, G. Lenormand, A. Richert, and F. Gallet, "A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers," Biophys. J. 76, 1145-1151 (1999).
[CrossRef]

Herrington, C. S.

Houlne, M. P.

M. P. Houlne, C. M. Sjostrom, R. H. Uibel, J. A. Kleimeyer, and J. M. Harris, "Confocal Raman Microscopy for Monitoring Chemical Reactions on Single Optically Trapped, Solid-Phase Support Particles," Anal. Chem. 74, 4311-4319 (2002).
[CrossRef] [PubMed]

Hu, S.

S. Hu, K. M. Smith, and T. G. Spiro, "Assignment of Protoheme Resonance Raman Spectrum by Heme Labeling in Myoglobin" J. Am. Chem. Soc. 118, 12638-12646 (1996).
[CrossRef]

Huser, T.

J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, "Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells," Biophys. J. 90, 648-656 (2006).
[CrossRef]

Ihara, K.

J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, "Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells," Biophys. J. 90, 648-656 (2006).
[CrossRef]

Inya-Agha, O.

O. Inya-Agha, N. Klauke, T. Davies, G. Smith, and J. M. Cooper, "Spectroscopic Probing of Dynamic Changes during Stimulation and Cell Remodeling in the Single Cardiac Myocyte," Anal. Chem. 79, 4581-4587 (2007).
[CrossRef] [PubMed]

Jess, P. R. T.

Kahane, I.

I. Kahane, A. Shifter, and E. A. Rachmilewitz, "Cross linking of red blood cells membrane proteins induced by oxidative stress in beta-thalassemia," FEBS Lett. 85, 267-270 (1978).
[CrossRef] [PubMed]

Käll, M.

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M. Gokör, M. Käll, and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Opt. 9, 593-600 (2004).
[CrossRef] [PubMed]

Kitagawa, T.

M. Abe, T. Kitagawa, and Y. Kyogoku, "Resonance Raman spectra of octaethylporphyrinato-Ni(II) and mesodeuterated and 15N substituted derivatives. II. A normal coordinate analysis," J. Chem. Phys. 69, 4526-4531 (1978).
[CrossRef]

Klauke, N.

O. Inya-Agha, N. Klauke, T. Davies, G. Smith, and J. M. Cooper, "Spectroscopic Probing of Dynamic Changes during Stimulation and Cell Remodeling in the Single Cardiac Myocyte," Anal. Chem. 79, 4581-4587 (2007).
[CrossRef] [PubMed]

Kleimeyer, J. A.

M. P. Houlne, C. M. Sjostrom, R. H. Uibel, J. A. Kleimeyer, and J. M. Harris, "Confocal Raman Microscopy for Monitoring Chemical Reactions on Single Optically Trapped, Solid-Phase Support Particles," Anal. Chem. 74, 4311-4319 (2002).
[CrossRef] [PubMed]

Konig, K.

Kyogoku, Y.

M. Abe, T. Kitagawa, and Y. Kyogoku, "Resonance Raman spectra of octaethylporphyrinato-Ni(II) and mesodeuterated and 15N substituted derivatives. II. A normal coordinate analysis," J. Chem. Phys. 69, 4526-4531 (1978).
[CrossRef]

Lambert, P. J.

P. J. Lambert, A. G. Whitman, O. F. Dyson, and S. M. Akula, "Raman spectroscopy: the gateway into tomorrow�??s virology," J. Virol. 3, 1-8 (2006).
[CrossRef]

Lane, S. M.

J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, "Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells," Biophys. J. 90, 648-656 (2006).
[CrossRef]

Lankers, M.

Lenormand, G.

G. Lenormand, S. Hénon, A. Richert, and F. Gallet, "Direct measurement of the area expansion and shear moduli of the human red blood cell membrane skeleton," Biophys. J. 81, 43-56 (2001).
[CrossRef] [PubMed]

S. Hénon, G. Lenormand, A. Richert, and F. Gallet, "A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers," Biophys. J. 76, 1145-1151 (1999).
[CrossRef]

Li, J.

J. Li, M. Dao, C. T. Lim, and S. Suresh, "Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte," Biophys. J. 88, 3707-3719 (2005).
[CrossRef] [PubMed]

Li, Y.-Q.

Lim, C. T.

J. Li, M. Dao, C. T. Lim, and S. Suresh, "Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte," Biophys. J. 88, 3707-3719 (2005).
[CrossRef] [PubMed]

Liu, Y.

Logg, K.

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M. Gokör, M. Käll, and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Opt. 9, 593-600 (2004).
[CrossRef] [PubMed]

Lubin, B. M.

E. A. Rachmilewitz, B. M. Lubin, and S. B. Shohet, "Lipid membrane peroxidation in beta-thalassemia," Blood 47, 495-505 (1976).
[PubMed]

Lux, S. E.

E. Shinar, E. A. Rachmilewitz, and S. E. Lux, "Differing erythrocyte membrane skeletal protein defects in alpha and beta thalassemia," J. Clin. Invest. 83, 404-410 (1989).
[CrossRef] [PubMed]

Mayer, A.

H. Brunner, A. Mayer, and H. Sussner, "Resonance Raman Scattering on the heam group of the oxy- and deoxyhaemogloin," J. Mol. Biol. 70, 153-156 (1972).
[CrossRef] [PubMed]

Mazilu, M.

McNaughton, D.

B. R. Wood, P. Caspers, G. J. Pupples, S. Pandiancherri, and D. McNaughton, "Resonance Raman Spectroscopy of red blood cell using near-infrared laser excitation," Anal. Bioanal. Chem. 387, 1691-1703 (2007).
[CrossRef]

B. R. Wood and D. McNaughton, "Raman excitation wavelength investigation of single red blood cell in vivo," J. Raman Spectrosc. 33, 517-523 (2002).
[CrossRef]

B. R. Wood, B. Tait, and D. McNaughton, "Micro-Raman characterization of the R to T state transition of haemoglobin within a single living erythrocyte," Biochem. Biophys. Acta 1539, 58-70 (2001).
[CrossRef] [PubMed]

Missirlis, Y.

G. Athanasiou, N. Zoubos, and Y. Missirlis, "Erytrhrocyte membrane deformability in patients with thalassemia syndromes," Nouv. Rev. Fr. Hematol. 33, 15-20 (1991).
[PubMed]

Mohandas, N.

E. A. Evans and N. Mohandas, "Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity," Blood 70, 1443-1449 (1987).
[PubMed]

Mohanty, K.

K. Mohanty, S. Mohanty, S. Monajembashi, and K. O. O Greulich, "Orientation of erythrocytes in optical trap revealed by confocal fluorescence microscopy," J. Biomed. Opt. 12, 0605061-0605063 (2007).
[CrossRef]

Mohanty, S.

K. Mohanty, S. Mohanty, S. Monajembashi, and K. O. O Greulich, "Orientation of erythrocytes in optical trap revealed by confocal fluorescence microscopy," J. Biomed. Opt. 12, 0605061-0605063 (2007).
[CrossRef]

Monaivais, G.

Monajembashi, S.

K. Mohanty, S. Mohanty, S. Monajembashi, and K. O. O Greulich, "Orientation of erythrocytes in optical trap revealed by confocal fluorescence microscopy," J. Biomed. Opt. 12, 0605061-0605063 (2007).
[CrossRef]

Pandiancherri, S.

B. R. Wood, P. Caspers, G. J. Pupples, S. Pandiancherri, and D. McNaughton, "Resonance Raman Spectroscopy of red blood cell using near-infrared laser excitation," Anal. Bioanal. Chem. 387, 1691-1703 (2007).
[CrossRef]

Paterson, L.

Pesce, G.

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Enhancing Raman Tweezers by phase-sensitive detection," Anal. Chem. 79, 3708-3715 (2007).
[CrossRef] [PubMed]

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Phase-sensitive detection in Raman tweezers," Appl. Phys. Lett. 89, 261116-261118 (2006).
[CrossRef]

Petrov, D.

G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli, and D. Petrov, "The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy," J. Raman Spectrosc. 37, 858-864 (2006).
[CrossRef]

C. Creely, G. Volpe, G. Singh, M. Soler, and D. Petrov, "Raman imaging of floating cells," Opt. Express 13, 6105-6110 (2005).
[CrossRef] [PubMed]

Petrov, D. V.

C. M. Creely, G. P. Singh, and D. V. Petrov, "Dual wavelength optical tweezers for confocal Raman spectroscopy," Opt. Commun. 245, 465-470 (2005).
[CrossRef]

Petry, R.

R. Petry, M. Schmitt, and J. Popp, "Raman spectroscopy - a prospective tool in the life sciences," Chem. Phys. Chem. 4, 15-30 (2003).
[CrossRef]

Pittman, R. N.

I. P. Torres Filho, J. Terner, R. N. Pittman, L. G. Somera, and K. R. Ward, "Hemoglobin oxygen saturation measurements using resonance Raman intravital microscopy," Am. J. Physiol. Heart Circ. Physiol. 289, 488-495 (2004).
[CrossRef]

Popp, J.

R. Petry, M. Schmitt, and J. Popp, "Raman spectroscopy - a prospective tool in the life sciences," Chem. Phys. Chem. 4, 15-30 (2003).
[CrossRef]

Pupples, G. J.

B. R. Wood, P. Caspers, G. J. Pupples, S. Pandiancherri, and D. McNaughton, "Resonance Raman Spectroscopy of red blood cell using near-infrared laser excitation," Anal. Bioanal. Chem. 387, 1691-1703 (2007).
[CrossRef]

Rachmilewitz, E. A.

E. Shinar, E. A. Rachmilewitz, and S. E. Lux, "Differing erythrocyte membrane skeletal protein defects in alpha and beta thalassemia," J. Clin. Invest. 83, 404-410 (1989).
[CrossRef] [PubMed]

I. Kahane, A. Shifter, and E. A. Rachmilewitz, "Cross linking of red blood cells membrane proteins induced by oxidative stress in beta-thalassemia," FEBS Lett. 85, 267-270 (1978).
[CrossRef] [PubMed]

E. A. Rachmilewitz, B. M. Lubin, and S. B. Shohet, "Lipid membrane peroxidation in beta-thalassemia," Blood 47, 495-505 (1976).
[PubMed]

Ramser, K.

K. Ramser, J. Enger, M. Gokör, D. Hanstorp, K. Logg, and M. Käll, "A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells," Lab Chip 5, 431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M. Gokör, M. Käll, and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Opt. 9, 593-600 (2004).
[CrossRef] [PubMed]

Richert, A.

G. Lenormand, S. Hénon, A. Richert, and F. Gallet, "Direct measurement of the area expansion and shear moduli of the human red blood cell membrane skeleton," Biophys. J. 81, 43-56 (2001).
[CrossRef] [PubMed]

S. Hénon, G. Lenormand, A. Richert, and F. Gallet, "A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers," Biophys. J. 76, 1145-1151 (1999).
[CrossRef]

Riches, A.

Rusciano, G.

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Enhancing Raman Tweezers by phase-sensitive detection," Anal. Chem. 79, 3708-3715 (2007).
[CrossRef] [PubMed]

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Phase-sensitive detection in Raman tweezers," Appl. Phys. Lett. 89, 261116-261118 (2006).
[CrossRef]

Salter, J. M.

J. M. Salter, "The effect of radiation trapping of high intensity scattered radiation on multiphoton ionization rates and resonance fluorescence," J. Phys. B: Atom. Molec. Phys. 12, L763-L767 (1979).
[CrossRef]

Sasso, A.

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Enhancing Raman Tweezers by phase-sensitive detection," Anal. Chem. 79, 3708-3715 (2007).
[CrossRef] [PubMed]

G. Rusciano, A. C. De Luca, G. Pesce, and A. Sasso, "Phase-sensitive detection in Raman tweezers," Appl. Phys. Lett. 89, 261116-261118 (2006).
[CrossRef]

Schmidt, C. F.

K. Svoboda, C. F. Schmidt, D. Branton, and S. M. Block, "Conformation and elasticity of the isolated red blood cell membrane skeleton," Biophys. J. 63, 784-793 (1992).
[CrossRef] [PubMed]

Schmitt, M.

R. Petry, M. Schmitt, and J. Popp, "Raman spectroscopy - a prospective tool in the life sciences," Chem. Phys. Chem. 4, 15-30 (2003).
[CrossRef]

Shifter, A.

I. Kahane, A. Shifter, and E. A. Rachmilewitz, "Cross linking of red blood cells membrane proteins induced by oxidative stress in beta-thalassemia," FEBS Lett. 85, 267-270 (1978).
[CrossRef] [PubMed]

Shinar, E.

E. Shinar, E. A. Rachmilewitz, and S. E. Lux, "Differing erythrocyte membrane skeletal protein defects in alpha and beta thalassemia," J. Clin. Invest. 83, 404-410 (1989).
[CrossRef] [PubMed]

Shohet, S. B.

E. A. Rachmilewitz, B. M. Lubin, and S. B. Shohet, "Lipid membrane peroxidation in beta-thalassemia," Blood 47, 495-505 (1976).
[PubMed]

Sibbett, W.

Singh, G.

Singh, G. P.

G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli, and D. Petrov, "The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy," J. Raman Spectrosc. 37, 858-864 (2006).
[CrossRef]

C. M. Creely, G. P. Singh, and D. V. Petrov, "Dual wavelength optical tweezers for confocal Raman spectroscopy," Opt. Commun. 245, 465-470 (2005).
[CrossRef]

Sjostrom, C. M.

M. P. Houlne, C. M. Sjostrom, R. H. Uibel, J. A. Kleimeyer, and J. M. Harris, "Confocal Raman Microscopy for Monitoring Chemical Reactions on Single Optically Trapped, Solid-Phase Support Particles," Anal. Chem. 74, 4311-4319 (2002).
[CrossRef] [PubMed]

Smith, D.

Smith, G.

O. Inya-Agha, N. Klauke, T. Davies, G. Smith, and J. M. Cooper, "Spectroscopic Probing of Dynamic Changes during Stimulation and Cell Remodeling in the Single Cardiac Myocyte," Anal. Chem. 79, 4581-4587 (2007).
[CrossRef] [PubMed]

Smith, K. M.

S. Hu, K. M. Smith, and T. G. Spiro, "Assignment of Protoheme Resonance Raman Spectrum by Heme Labeling in Myoglobin" J. Am. Chem. Soc. 118, 12638-12646 (1996).
[CrossRef]

Soler, M.

Somera, L. G.

I. P. Torres Filho, J. Terner, R. N. Pittman, L. G. Somera, and K. R. Ward, "Hemoglobin oxygen saturation measurements using resonance Raman intravital microscopy," Am. J. Physiol. Heart Circ. Physiol. 289, 488-495 (2004).
[CrossRef]

Sonek, G. J.

Spiro, T. G.

S. Hu, K. M. Smith, and T. G. Spiro, "Assignment of Protoheme Resonance Raman Spectrum by Heme Labeling in Myoglobin" J. Am. Chem. Soc. 118, 12638-12646 (1996).
[CrossRef]

Suresh, S.

J. Li, M. Dao, C. T. Lim, and S. Suresh, "Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte," Biophys. J. 88, 3707-3719 (2005).
[CrossRef] [PubMed]

Sussner, H.

H. Brunner, A. Mayer, and H. Sussner, "Resonance Raman Scattering on the heam group of the oxy- and deoxyhaemogloin," J. Mol. Biol. 70, 153-156 (1972).
[CrossRef] [PubMed]

Svoboda, K.

K. Svoboda, C. F. Schmidt, D. Branton, and S. M. Block, "Conformation and elasticity of the isolated red blood cell membrane skeleton," Biophys. J. 63, 784-793 (1992).
[CrossRef] [PubMed]

Tait, B.

B. R. Wood, B. Tait, and D. McNaughton, "Micro-Raman characterization of the R to T state transition of haemoglobin within a single living erythrocyte," Biochem. Biophys. Acta 1539, 58-70 (2001).
[CrossRef] [PubMed]

Taylor, D. S.

J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, "Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells," Biophys. J. 90, 648-656 (2006).
[CrossRef]

Terner, J.

I. P. Torres Filho, J. Terner, R. N. Pittman, L. G. Somera, and K. R. Ward, "Hemoglobin oxygen saturation measurements using resonance Raman intravital microscopy," Am. J. Physiol. Heart Circ. Physiol. 289, 488-495 (2004).
[CrossRef]

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I. P. Torres Filho, J. Terner, R. N. Pittman, L. G. Somera, and K. R. Ward, "Hemoglobin oxygen saturation measurements using resonance Raman intravital microscopy," Am. J. Physiol. Heart Circ. Physiol. 289, 488-495 (2004).
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Figures (10)

Fig. 1.
Fig. 1.

Experimental set-up of the combined Optical Tweezers and Raman Spectrometer: L, lens; M, mirror; DM, dichroic mirror; GM, galvomirror; NF, notch filter.

Fig. 2.
Fig. 2.

A: Sketch of the stretching procedure used for the present investigation. B: Same frames of a video recorded during the stretching of a normal RBC.

Fig. 3.
Fig. 3.

Upper part: Typical Raman spectrum of an healthy RBC, obtained with an integration time of 10 s. The solid line corresponds to a fitting with 14 Lorentzian profiles, while the dashed lines indicate the deconvoluted curves. Lower part: Residual obtained as the difference between the experimental and the best-fit spectrum.

Fig. 4.
Fig. 4.

Comparison between the Raman spectra of normal and β-thalassemic RBC. The arrows indicate the spectral features affected by intensity changes, while the dashed lines highlight the observed energy shift.

Fig. 5.
Fig. 5.

Trends of the relative intensity for selected Raman peaks (ν37, ν10 and ν13) corresponding to the two types of cells (see text for details).

Fig. 6.
Fig. 6.

A: Statistical distributions of the ratio R=I ν37/I ν11 obtained by analyzing 300 RBCs from a single normal (pink histogram) and thalassemic (blue histogram) donor. The fitting of these distributions with Gaussian profile is also shown. B: Gaussian profiles obtained by fitting the experimental distributions relative to 6 normal (Hi) and 6 thalassemic (Ti) volunteers. The weighted-mean and the standard deviation for the two kinds of cells are evidenced by horizontal bars.

Fig. 7.
Fig. 7.

Intensity of the Raman ν11 band, as function of the exposure-time to the trapping radiation for normal (∙) and β-thalassemic (∘) RBCs. The intensity values are normalized to the value at t=20 s.

Fig. 8.
Fig. 8.

Intensity of the Raman ν11 band, as function of the exposure-time to the Raman probe for normal (∙) and β-thalassemic (∘) RBCs. The intensity values are normalized to the value at t=3 s.

Fig. 9.
Fig. 9.

The Raman spectra of a normal RBC exposed to 532 nm radiation for 10 and 150 s. Solid lines are the best fit lineshape convolutions.

Fig. 10.
Fig. 10.

Response to applied stretching for normal and abnormal RBCs.

Tables (2)

Tables Icon

Table 1. Assignment and spectral position (cm-1) of the Hb Raman bands observed in this work. For comparison, we also report the bands observed by Wood et al. [32] for both oxyand deoxy-Hb with excitation at 514 nm.

Tables Icon

Table 2. Observed wavenumber (cm-1) relative to 4 Raman peaks for normal and β-thalassemic RBCs.

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