Abstract

Raman spectroscopy permits acquisition of molecular signatures from both cellular and sub-cellular samples. When combined with optical trapping we may interrogate an isolated cell reducing extraneous signals from the local environment. To date, experimental configurations have employed combinations of the single beam optical tweezers trap and Raman spectroscopy, using either the same beam or separate beams for Raman interrogation and trapping. A key problem in optical tweezers is the ability to hold and manoeuvre large cells. In this paper, we use a dual beam fibre trap to hold and manoeuvre cells combined with an orthogonally placed objective to record Raman spectra. The dual beam trap, due to its divergent light fields, offers an as yet unexploited ability to hold and move large cellular objects with reduced prospects of photodamage. We additionally show how this system permits us to move large primary human keratinocytes (approximately 30 microns in diameter), such that we may record Raman spectra from local parts of a trapped cell with ease. Finally, we develop a rudimentary microfluidic system used to generate a flow of cells. Using our dual beam trap, combined with this flow system, we hold and acquire Raman spectra from individual cells chosen from a sample of HL60 human promyelocytic leukemia cells.

© 2006 Optical Society of America

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    [CrossRef] [PubMed]
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  22. K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
    [CrossRef]
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    [CrossRef]
  24. M. P. MacDonald, G. C. Spalding and K. Dholakia, "Microfluidic sorting in an Optical Lattice," Nature 426, 421-424 (2003).
    [CrossRef] [PubMed]

2006 (2)

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

M. Wei, K. Yang, A. Karmenyan and A. Chiou, "Three-dimensional optical force field on a Chinese hamster ovary cell in a fiber-optical dual-beam trap," Opt. Express 14, 3056-3054 (2006).
[CrossRef] [PubMed]

2005 (6)

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

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

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

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

M. Mannie, T. McConnell, C. Xie and Y. Li, "Activation dependant phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy," J. Immunol. Methods 297,53-60 (2005)
[CrossRef] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

2004 (3)

S. A. Southern, M. H. Lewis and C. S. Herrington," Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation," Br J Cancer 90, 1949-1954 (2004).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

T. E. Bridges, M. P. Houlne and J. M. Harris, "Spatially resolved analysis of small particles by Confocal Raman Microspectroscopy: Depth profiling and optical trapping," Anal. Chem. 76,576-584 (2004).
[CrossRef] [PubMed]

2003 (2)

M. P. MacDonald, G. C. Spalding and K. Dholakia, "Microfluidic sorting in an Optical Lattice," Nature 426, 421-424 (2003).
[CrossRef] [PubMed]

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

2002 (3)

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

C. L. Kuyper and D. Chiu, "Optical trapping: A versatile technique for biomanipulation," Appl. Spec. 56,300-312 (2002).
[CrossRef]

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

2000 (1)

K. Ajito, M. Morita and K. Torimitsu, "Investigation of the molecular extraction process in single Subpicoliter Droplets using a near-infrared laser Raman trapping system," Anal. Chem. 72, 4721-4725 (2000).
[CrossRef] [PubMed]

1996 (1)

1993 (1)

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 (London) 347, 301-303 (1990).
[CrossRef]

1986 (1)

1977 (1)

S. J. Collins, R. C. Gallo and R. E. Gallagher, "Continuous growth & differentiation of human myeloid leukaemic cells in suspension culture," Nature 270,347-349 (1977).
[CrossRef] [PubMed]

1971 (1)

A. Ashkin, and J. M. Dziedzic, "Optical Levitation by Radiation Pressure," Appl. Phys. Lett. 19,283-285 (1971).
[CrossRef]

1970 (1)

F. Friedl, I. Kimura, T. Osato and Y. Ito, "Studies on a new human cell line (SiHa) derived from carcinoma of Uterus, I. Its establishment and morphology," Proc. Soc. Exp. Biol. Med. 135, 543-5 (1970).
[PubMed]

Ajito, K.

K. Ajito, M. Morita and K. Torimitsu, "Investigation of the molecular extraction process in single Subpicoliter Droplets using a near-infrared laser Raman trapping system," Anal. Chem. 72, 4721-4725 (2000).
[CrossRef] [PubMed]

Akula, S.

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

Ananthakrishnan, R.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[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 (London) 347, 301-303 (1990).
[CrossRef]

Ashkin, A.

Badizadegan, K

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Berns, M. W.

Bilby, C.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Bjorkholm, J. E.

Boone, C.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Bridges, T. E.

T. E. Bridges, M. P. Houlne and J. M. Harris, "Spatially resolved analysis of small particles by Confocal Raman Microspectroscopy: Depth profiling and optical trapping," Anal. Chem. 76,576-584 (2004).
[CrossRef] [PubMed]

Bryan, B.

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

Chan, J.

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

Chiou, A.

Chiu, D.

C. L. Kuyper and D. Chiu, "Optical trapping: A versatile technique for biomanipulation," Appl. Spec. 56,300-312 (2002).
[CrossRef]

Chu, S.

Collins, S. J.

S. J. Collins, R. C. Gallo and R. E. Gallagher, "Continuous growth & differentiation of human myeloid leukaemic cells in suspension culture," Nature 270,347-349 (1977).
[CrossRef] [PubMed]

Constable, A.

Creely, C.

Creely, C. M.

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

Dasari, R. R.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

de Mul, F. F. M.

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 (London) 347, 301-303 (1990).
[CrossRef]

Dholakia, K.

M. P. MacDonald, G. C. Spalding and K. Dholakia, "Microfluidic sorting in an Optical Lattice," Nature 426, 421-424 (2003).
[CrossRef] [PubMed]

Dinno, M. A.

Dziedzic, J. M.

Ebert, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Enger, J.

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

Enger, M.G.J.

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

Erickson, H.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Feld, M. S.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Ford, P.

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

Friedl, F.

F. Friedl, I. Kimura, T. Osato and Y. Ito, "Studies on a new human cell line (SiHa) derived from carcinoma of Uterus, I. Its establishment and morphology," Proc. Soc. Exp. Biol. Med. 135, 543-5 (1970).
[PubMed]

Funk, R.

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

Gallagher, R. E.

S. J. Collins, R. C. Gallo and R. E. Gallagher, "Continuous growth & differentiation of human myeloid leukaemic cells in suspension culture," Nature 270,347-349 (1977).
[CrossRef] [PubMed]

Gallo, R. C.

S. J. Collins, R. C. Gallo and R. E. Gallagher, "Continuous growth & differentiation of human myeloid leukaemic cells in suspension culture," Nature 270,347-349 (1977).
[CrossRef] [PubMed]

Goksor, M.

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

Greve, 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 (London) 347, 301-303 (1990).
[CrossRef]

Guck, J.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Haka, A. S.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Hamden, K.

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

Hanstorp, D.

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

Harris, J. M.

T. E. Bridges, M. P. Houlne and J. M. Harris, "Spatially resolved analysis of small particles by Confocal Raman Microspectroscopy: Depth profiling and optical trapping," Anal. Chem. 76,576-584 (2004).
[CrossRef] [PubMed]

Herrington, C. S.

S. A. Southern, M. H. Lewis and C. S. Herrington," Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation," Br J Cancer 90, 1949-1954 (2004).
[CrossRef] [PubMed]

Houlne, M. P.

T. E. Bridges, M. P. Houlne and J. M. Harris, "Spatially resolved analysis of small particles by Confocal Raman Microspectroscopy: Depth profiling and optical trapping," Anal. Chem. 76,576-584 (2004).
[CrossRef] [PubMed]

Huser, T.

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

Ihara, K.

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

Ito, Y.

F. Friedl, I. Kimura, T. Osato and Y. Ito, "Studies on a new human cell line (SiHa) derived from carcinoma of Uterus, I. Its establishment and morphology," Proc. Soc. Exp. Biol. Med. 135, 543-5 (1970).
[PubMed]

Jovin, T. M.

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 (London) 347, 301-303 (1990).
[CrossRef]

Kall, M.

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

Karmenyan, A.

Kas, J.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Kim, J.

Kimura, I.

F. Friedl, I. Kimura, T. Osato and Y. Ito, "Studies on a new human cell line (SiHa) derived from carcinoma of Uterus, I. Its establishment and morphology," Proc. Soc. Exp. Biol. Med. 135, 543-5 (1970).
[PubMed]

Kneipp, H.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Kneipp, K.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Knetschke, T.

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

Konig, K.

Krafft, C.

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

Kuyper, C. L.

C. L. Kuyper and D. Chiu, "Optical trapping: A versatile technique for biomanipulation," Appl. Spec. 56,300-312 (2002).
[CrossRef]

Lane, S.

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

Lenz, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Lewis, M. H.

S. A. Southern, M. H. Lewis and C. S. Herrington," Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation," Br J Cancer 90, 1949-1954 (2004).
[CrossRef] [PubMed]

Li, Y.

M. Mannie, T. McConnell, C. Xie and Y. Li, "Activation dependant phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy," J. Immunol. Methods 297,53-60 (2005)
[CrossRef] [PubMed]

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

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

Liang, H.

Lincoln, B.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Logg, K.

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

MacDonald, M. P.

M. P. MacDonald, G. C. Spalding and K. Dholakia, "Microfluidic sorting in an Optical Lattice," Nature 426, 421-424 (2003).
[CrossRef] [PubMed]

Mannie, M.

M. Mannie, T. McConnell, C. Xie and Y. Li, "Activation dependant phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy," J. Immunol. Methods 297,53-60 (2005)
[CrossRef] [PubMed]

McConnell, T.

M. Mannie, T. McConnell, C. Xie and Y. Li, "Activation dependant phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy," J. Immunol. Methods 297,53-60 (2005)
[CrossRef] [PubMed]

Mervis, J.

Mitchell, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Morita, M.

K. Ajito, M. Morita and K. Torimitsu, "Investigation of the molecular extraction process in single Subpicoliter Droplets using a near-infrared laser Raman trapping system," Anal. Chem. 72, 4721-4725 (2000).
[CrossRef] [PubMed]

Motz, J. T.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Osato, T.

F. Friedl, I. Kimura, T. Osato and Y. Ito, "Studies on a new human cell line (SiHa) derived from carcinoma of Uterus, I. Its establishment and morphology," Proc. Soc. Exp. Biol. Med. 135, 543-5 (1970).
[PubMed]

Otto, C.

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 (London) 347, 301-303 (1990).
[CrossRef]

Petrov, D.

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

Prentiss, M.

Puppels, G. 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 (London) 347, 301-303 (1990).
[CrossRef]

Ramser, K.

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

Robert-Nicoud, M.

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 (London) 347, 301-303 (1990).
[CrossRef]

Romeyke, M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Salzer, R.

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

Schinkinger, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Shafer-Peltier, K. E.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Siegner, A.

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

Singh, G.

Singh, G. P.

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

Soler, M.

Southern, S. A.

S. A. Southern, M. H. Lewis and C. S. Herrington," Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation," Br J Cancer 90, 1949-1954 (2004).
[CrossRef] [PubMed]

Spalding, G. C.

M. P. MacDonald, G. C. Spalding and K. Dholakia, "Microfluidic sorting in an Optical Lattice," Nature 426, 421-424 (2003).
[CrossRef] [PubMed]

Taylor, D.

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

Torimitsu, K.

K. Ajito, M. Morita and K. Torimitsu, "Investigation of the molecular extraction process in single Subpicoliter Droplets using a near-infrared laser Raman trapping system," Anal. Chem. 72, 4721-4725 (2000).
[CrossRef] [PubMed]

Tromberg, B. J.

Ulvick, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Volpe, G.

Wei, M.

Wottowah, F.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Xie, C.

M. Mannie, T. McConnell, C. Xie and Y. Li, "Activation dependant phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy," J. Immunol. Methods 297,53-60 (2005)
[CrossRef] [PubMed]

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

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

Yang, K.

Yoshizawa, N.

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Zarinetchi, F.

Zwerdling, T.

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

Anal. Chem. (2)

K. Ajito, M. Morita and K. Torimitsu, "Investigation of the molecular extraction process in single Subpicoliter Droplets using a near-infrared laser Raman trapping system," Anal. Chem. 72, 4721-4725 (2000).
[CrossRef] [PubMed]

T. E. Bridges, M. P. Houlne and J. M. Harris, "Spatially resolved analysis of small particles by Confocal Raman Microspectroscopy: Depth profiling and optical trapping," Anal. Chem. 76,576-584 (2004).
[CrossRef] [PubMed]

Appl (2)

C. L. Kuyper and D. Chiu, "Optical trapping: A versatile technique for biomanipulation," Appl. Spec. 56,300-312 (2002).
[CrossRef]

K. Kneipp, A. S. Haka, H. Kneipp, K Badizadegan, N. Yoshizawa, C. Boone, K. E. Shafer-Peltier, J. T. Motz, R. R. Dasari and M. S. Feld, "Surface-enhanced Raman Spectroscopy in single living cells using Gold Nanoparticles," Appl. Spec. 56,150-154 (2002).
[CrossRef]

Appl. Phys. Lett. (1)

A. Ashkin, and J. M. Dziedzic, "Optical Levitation by Radiation Pressure," Appl. Phys. Lett. 19,283-285 (1971).
[CrossRef]

Biophys. J. (2)

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

J. Guck, S. Schinkinger, B. Lincoln, F. Wottowah, S. Ebert, M. Romeyke, D. Lenz, H. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick and C. Bilby, "Optical deformability as an inherant cell marker for malignant transformation and metastatic competence," Biophys. J. 88,3698 (2005).
[CrossRef]

Br J Cancer (1)

S. A. Southern, M. H. Lewis and C. S. Herrington," Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation," Br J Cancer 90, 1949-1954 (2004).
[CrossRef] [PubMed]

J. Biomed. Optics (1)

K. Ramser, K. Logg, M.G.J. Enger, M. Kall and D. Hanstorp, "Resonance Raman spectroscopy of optically trapped functional erythrocytes," J. Biomed. Optics 9,593-600 (2004).
[CrossRef]

J. Immunol. Methods (1)

M. Mannie, T. McConnell, C. Xie and Y. Li, "Activation dependant phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy," J. Immunol. Methods 297,53-60 (2005)
[CrossRef] [PubMed]

J. Viro. Meth. (1)

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li and S. Akula, "Spectroscopic analysis of Kaposi’s sarcoma-associated herpesvirus infected cells by Raman tweezers," J. Viro. Meth. 129,145-151 (2005).
[CrossRef]

Lab on a Chip (1)

K. Ramser, J. Enger, M. Goksor, D. Hanstorp, K. Logg and M. Kall, "A Microfluidic System enabling Raman Measurements of the Oxygenation cycle in single optically trapped red blood cells," Lab on a Chip 5,431-436 (2005).
[CrossRef] [PubMed]

Nature (2)

M. P. MacDonald, G. C. Spalding and K. Dholakia, "Microfluidic sorting in an Optical Lattice," Nature 426, 421-424 (2003).
[CrossRef] [PubMed]

S. J. Collins, R. C. Gallo and R. E. Gallagher, "Continuous growth & differentiation of human myeloid leukaemic cells in suspension culture," Nature 270,347-349 (1977).
[CrossRef] [PubMed]

Nature (London) (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 (London) 347, 301-303 (1990).
[CrossRef]

Opt. Commun. (1)

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

Opt. Express (2)

Opt. Lett. (4)

Proc. Soc. Exp. Biol. Med. (1)

F. Friedl, I. Kimura, T. Osato and Y. Ito, "Studies on a new human cell line (SiHa) derived from carcinoma of Uterus, I. Its establishment and morphology," Proc. Soc. Exp. Biol. Med. 135, 543-5 (1970).
[PubMed]

Vib (1)

C. Krafft, T. Knetschke, A. Siegner, R. Funk and R. Salzer, "Mapping of single cells by near infrared Raman Microspectroscopy," Vib. Spec. 32,75-83 (2003).
[CrossRef]

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Figures (8)

Fig. 1.
Fig. 1.

Schematic of the Experimental arrangement. PBSC: Polarising Beam Splitting Cube; HWP: Half Wave Plate; F1, F2: Fibre one and two; HNF: Holographic Notch Filter; DM: Dichroic Mirror; CA: Confocal Aperture and BEF: Band Edge Filter.

Fig. 2.
Fig. 2.

A 100 micron polymer sphere trapped in a fibre optical light force trap, viewed from below. The fibre trap uses 62.5/125µm (core size/cladding size) multimode fibre, a trapping power of 800mW in each fibre arm and a fibre separation of 240µm.

Fig. 3.
Fig. 3.

Left Chart showing the variation in Raman intensity, of the 1000cm-1 benzene ring breathing mode of polystyrene, as the microsphere is scanned across the Raman excitation laser. Right hand chart shows a fit of the data obeying a Lorentian relationship.

Fig. 4.
Fig. 4.

A conglomerate of spheres in the fibre trap created from two 7µm EDMA spheres and two 5µm polymer spheres. They are shown with their measured Raman spectra demonstrating the ability of this technique to gain localized sensitive chemical information.

Fig. 5.
Fig. 5.

Raman Spectra obtained from 3 different positions within a PHK cell: Nucleus (A), Cytoplasm (B) and Membrane (C). The actual laser position during the excitation is also shown by the letters in the top left diagram. The top right hand diagram shows spectra taken from the nucleus of a cell in the fibre optical trap (1) and absorbed onto a glass coverslip (2). The use of the fibre optical trap reduces the background allowing us to discern the Raman features in more detail.

Fig. 6.
Fig. 6.

Band Assignment for Raman Spectra of PHK. Abbreviations:P-Protein, Tyr-Tyrosine, T-Thymine, G-Guanine, A-Adenine, C-Cytosine, bk-DNA sugar-phosphate Back Bone, Trp-Tryptophan, CY-Cytoplasm, NC-Nucleus, M-Membrane.

Fig. 7.
Fig. 7.

Chart displaying the results of the principle component analysis for 5 spectra taken at each of the 3 different locations within the cell. This demonstrates further how we may gain an insight into the intra cellular makeup.

Fig. 8.
Fig. 8.

Fibre optical trapping and Raman examination of a 10 micron sphere and a HL60 cell in a microfluidic flow constructed from a square capillary tube, the horizontal object in the figure, with two fibers placed orthogonally against the capillary walls forming a dual beam trap with the laser, exciting the Raman transitions, introduced from below the trap.

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