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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2006 (2)

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]

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]

2005 (6)

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. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li, and S. Akula, “Spectroscopic analysis of Kaposi’s sarcomaassociated 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]

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]

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)

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]

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

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 sarcomaassociated 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 sarcomaassociated 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 sarcomaassociated 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 sarcomaassociated 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.

K. Hamden, B. Bryan, P. Ford, C. Xie, Y. Li, and S. Akula, “Spectroscopic analysis of Kaposi’s sarcomaassociated 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]

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 sarcomaassociated 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. Phys. Lett. (1)

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

Appl. Spec. (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]

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 sarcomaassociated 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. Spec. (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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