Abstract

Laser tweezers Raman spectroscopy (LTRS) was used to acquire the Raman spectra of leukemic T lymphocytes exposed to the chemotherapy drug doxorubicin at different time points over 72 hours. Changes observed in the Raman spectra were dependent on drug exposure time and concentration. The sequence of spectral changes includes an intensity increase in lipid Raman peaks, followed by an intensity increase in DNA Raman peaks, and finally changes in DNA and protein (phenylalanine) Raman vibrations. These Raman signatures are consistent with vesicle formation, cell membrane blebbing, chromatin condensation, and the cytoplasm of dead cells during the different stages of drug-induced apoptosis. These results suggest the potential of LTRS as a real-time single cell tool for monitoring apoptosis, evaluating the efficacy of chemotherapeutic treatments, or pharmaceutical testing.

© 2010 OSA

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    [PubMed]
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    [CrossRef] [PubMed]
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2009

T. G. Cotter, “Apoptosis and cancer: the genesis of a research field,” Nat. Rev. Cancer 9(7), 501–507 (2009).
[CrossRef] [PubMed]

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

C. S. Mulvey, C. A. Sherwood, and I. J. Bigio, “Wavelength-dependent backscattering measurements for quantitative real-time monitoring of apoptosis in living cells,” J. Biomed. Opt. 14(6), 064013 (2009).
[CrossRef] [PubMed]

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol. 13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

R. D. Snook, T. J. Harvey, E. Correia Faria, and P. Gardner, “Raman tweezers and their application to the study of singly trapped eukaryotic cells,” Integr Biol (Camb) 1(1), 43–52 (2009).
[CrossRef] [PubMed]

2008

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

J. Chan, S. Fore, S. Wachsmann-Hogiu, and T. Huser, “Raman spectroscopy and microscopy of individual cells and cellular components,” Laser Photonics Rev. 2(5), 325–349 (2008).
[CrossRef]

R. C. Taylor, S. P. Cullen, and S. J. Martin, “Apoptosis: controlled demolition at the cellular level,” Nat. Rev. Mol. Cell Biol. 9(3), 231–241 (2008).
[CrossRef] [PubMed]

A. Y. Lau, L. P. Lee, and J. W. Chan, “An integrated optofluidic platform for Raman-activated cell sorting,” Lab Chip 8(7), 1116–1120 (2008).
[CrossRef] [PubMed]

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, and L. Moens, “The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells,” Spectroscopy 22, 287–295 (2008).

2007

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

2006

P. R. T. Jess, V. Garcés-Chávez, 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(12), 5779–5791 (2006).
[CrossRef] [PubMed]

R. A. Nagourney, “Ex vivo programmed cell death and the prediction of response to chemotherapy,” Curr. Treat. Options Oncol. 7(2), 103–110 (2006).
[CrossRef] [PubMed]

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

2005

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

2004

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

2003

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

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

C. A. Lieber and A. Mahadevan-Jansen, “Automated method for subtraction of fluorescence from biological Raman spectra,” Appl. Spectrosc. 57(11), 1363–1367 (2003).
[CrossRef] [PubMed]

2002

C. G. Xie, M. A. Dinno, and Y. Q. Li, “Near-infrared Raman spectroscopy of single optically trapped biological cells,” Opt. Lett. 27(4), 249–251 (2002).
[CrossRef] [PubMed]

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

C. Ferraro-Peyret, L. Quemeneur, M. Flacher, J. P. Revillard, and L. Genestier, “Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes,” J. Immunol. 169(9), 4805–4810 (2002).
[PubMed]

2001

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

A. A. Sokolovskaya, T. N. Zabotina, D. Y. Blokhin, Z. G. Kadagidze, and A. Y. Baryshnikov, “Comparative analysis of apoptosis induced by various anticancer drugs in Jurkat cells,” Exp. Oncol. 23, 46–50 (2001).

J. Donadieu and C. Hill, “Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review,” Br. J. Haematol. 115(1), 34–45 (2001).
[CrossRef] [PubMed]

2000

L. Möllgård, U. Tidefelt, B. Sundman-Engberg, C. Löfgren, and C. Paul, “In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay,” Leuk. Res. 24(5), 445–452 (2000).
[CrossRef] [PubMed]

S. W. Lowe and A. W. Lin, “Apoptosis in cancer,” Carcinogenesis 21(3), 485–495 (2000).
[CrossRef] [PubMed]

V. L. Johnson, S. C. W. Ko, T. H. Holmstrom, J. E. Eriksson, and S. C. Chow, “Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis,” J. Cell Sci. 113(Pt 17), 2941–2953 (2000).
[PubMed]

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

1999

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

J. C. Reed, “Dysregulation of apoptosis in cancer,” J. Clin. Oncol. 17(9), 2941–2953 (1999).
[PubMed]

1997

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Y. Takai, T. Masuko, and H. Takeuchi, “Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy,” Biochim. Biophys. Acta 1335(1-2), 199–208 (1997).
[PubMed]

1996

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

1994

J. F. Kerr, C. M. Winterford, and B. V. Harmon, “Apoptosis. Its significance in cancer and cancer therapy,” Cancer 73(8), 2013–2026 (1994).
[CrossRef] [PubMed]

1991

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

1989

J. M. Sargent and C. G. Taylor, “Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia,” Br. J. Cancer 60(2), 206–210 (1989).
[PubMed]

Ai, M.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Alava, M. A.

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Amadori, S.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Anel, A.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Arcese, W.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Asphahani, F.

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

Baryshnikov, A. Y.

A. A. Sokolovskaya, T. N. Zabotina, D. Y. Blokhin, Z. G. Kadagidze, and A. Y. Baryshnikov, “Comparative analysis of apoptosis induced by various anticancer drugs in Jurkat cells,” Exp. Oncol. 23, 46–50 (2001).

Bigio, I. J.

C. S. Mulvey, C. A. Sherwood, and I. J. Bigio, “Wavelength-dependent backscattering measurements for quantitative real-time monitoring of apoptosis in living cells,” J. Biomed. Opt. 14(6), 064013 (2009).
[CrossRef] [PubMed]

Bisson, I.

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Blokhin, D. Y.

A. A. Sokolovskaya, T. N. Zabotina, D. Y. Blokhin, Z. G. Kadagidze, and A. Y. Baryshnikov, “Comparative analysis of apoptosis induced by various anticancer drugs in Jurkat cells,” Exp. Oncol. 23, 46–50 (2001).

Boldt, S.

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

Bosch, M.

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

Buccisano, F.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Buckmaster, R.

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

Ceresoli, E.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Chan, J.

J. Chan, S. Fore, S. Wachsmann-Hogiu, and T. Huser, “Raman spectroscopy and microscopy of individual cells and cellular components,” Laser Photonics Rev. 2(5), 325–349 (2008).
[CrossRef]

Chan, J. W.

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

A. Y. Lau, L. P. Lee, and J. W. Chan, “An integrated optofluidic platform for Raman-activated cell sorting,” Lab Chip 8(7), 1116–1120 (2008).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

R. Liu, D. S. Taylor, D. L. Matthews, and J. W. Chan, “Parallel analysis of individual biological cells using multifocal laser tweezers Raman spectroscopy,” Appl. Spectrosc. (to be published).

Cheng, C.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Cheok, M. H.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Chow, S. C.

V. L. Johnson, S. C. W. Ko, T. H. Holmstrom, J. E. Eriksson, and S. C. Chow, “Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis,” J. Cell Sci. 113(Pt 17), 2941–2953 (2000).
[PubMed]

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

Coleman, M. L.

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

Correia Faria, E.

R. D. Snook, T. J. Harvey, E. Correia Faria, and P. Gardner, “Raman tweezers and their application to the study of singly trapped eukaryotic cells,” Integr Biol (Camb) 1(1), 43–52 (2009).
[CrossRef] [PubMed]

Cotter, T. G.

T. G. Cotter, “Apoptosis and cancer: the genesis of a research field,” Nat. Rev. Cancer 9(7), 501–507 (2009).
[CrossRef] [PubMed]

Cullen, S. P.

R. C. Taylor, S. P. Cullen, and S. J. Martin, “Apoptosis: controlled demolition at the cellular level,” Nat. Rev. Mol. Cell Biol. 9(3), 231–241 (2008).
[CrossRef] [PubMed]

D. Principe, M. I.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Dartsch, D. C.

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

de Mul, F. F. M.

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

Dewar, A.

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

Dewilde, S.

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, and L. Moens, “The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells,” Spectroscopy 22, 287–295 (2008).

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

Dholakia, K.

Dinno, M. A.

Donadieu, J.

J. Donadieu and C. Hill, “Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review,” Br. J. Haematol. 115(1), 34–45 (2001).
[CrossRef] [PubMed]

Downing, J. R.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Engels, I. H.

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

Enger, J.

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

Eriksson, J. E.

V. L. Johnson, S. C. W. Ko, T. H. Holmstrom, J. E. Eriksson, and S. C. Chow, “Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis,” J. Cell Sci. 113(Pt 17), 2941–2953 (2000).
[PubMed]

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

Esposito, A. P.

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

Evans, W. E.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Ferraro-Peyret, C.

C. Ferraro-Peyret, L. Quemeneur, M. Flacher, J. P. Revillard, and L. Genestier, “Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes,” J. Immunol. 169(9), 4805–4810 (2002).
[PubMed]

Flacher, M.

C. Ferraro-Peyret, L. Quemeneur, M. Flacher, J. P. Revillard, and L. Genestier, “Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes,” J. Immunol. 169(9), 4805–4810 (2002).
[PubMed]

Fore, S.

J. Chan, S. Fore, S. Wachsmann-Hogiu, and T. Huser, “Raman spectroscopy and microscopy of individual cells and cellular components,” Laser Photonics Rev. 2(5), 325–349 (2008).
[CrossRef]

Gamen, S.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Garcés-Chávez, V.

Gardner, P.

R. D. Snook, T. J. Harvey, E. Correia Faria, and P. Gardner, “Raman tweezers and their application to the study of singly trapped eukaryotic cells,” Integr Biol (Camb) 1(1), 43–52 (2009).
[CrossRef] [PubMed]

Genestier, L.

C. Ferraro-Peyret, L. Quemeneur, M. Flacher, J. P. Revillard, and L. Genestier, “Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes,” J. Immunol. 169(9), 4805–4810 (2002).
[PubMed]

Goksör, M.

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

Greve, J.

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

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

Hanstorp, D.

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

Harmon, B. V.

J. F. Kerr, C. M. Winterford, and B. V. Harmon, “Apoptosis. Its significance in cancer and cancer therapy,” Cancer 73(8), 2013–2026 (1994).
[CrossRef] [PubMed]

Harvey, T. J.

R. D. Snook, T. J. Harvey, E. Correia Faria, and P. Gardner, “Raman tweezers and their application to the study of singly trapped eukaryotic cells,” Integr Biol (Camb) 1(1), 43–52 (2009).
[CrossRef] [PubMed]

He, B.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Hench, L. L.

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Herrington, C. S.

Hill, C.

J. Donadieu and C. Hill, “Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review,” Br. J. Haematol. 115(1), 34–45 (2001).
[CrossRef] [PubMed]

Hollars, C. W.

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

Holmstrom, T. H.

V. L. Johnson, S. C. W. Ko, T. H. Holmstrom, J. E. Eriksson, and S. C. Chow, “Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis,” J. Cell Sci. 113(Pt 17), 2941–2953 (2000).
[PubMed]

Huser, T.

J. Chan, S. Fore, S. Wachsmann-Hogiu, and T. Huser, “Raman spectroscopy and microscopy of individual cells and cellular components,” Laser Photonics Rev. 2(5), 325–349 (2008).
[CrossRef]

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

Jell, G.

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Jess, P. R. T.

Johnson, D.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

Johnson, V. L.

V. L. Johnson, S. C. W. Ko, T. H. Holmstrom, J. E. Eriksson, and S. C. Chow, “Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis,” J. Cell Sci. 113(Pt 17), 2941–2953 (2000).
[PubMed]

Kadagidze, Z. G.

A. A. Sokolovskaya, T. N. Zabotina, D. Y. Blokhin, Z. G. Kadagidze, and A. Y. Baryshnikov, “Comparative analysis of apoptosis induced by various anticancer drugs in Jurkat cells,” Exp. Oncol. 23, 46–50 (2001).

Käll, M.

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

Kass, G. E. N.

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

Kerr, J. F.

J. F. Kerr, C. M. Winterford, and B. V. Harmon, “Apoptosis. Its significance in cancer and cancer therapy,” Cancer 73(8), 2013–2026 (1994).
[CrossRef] [PubMed]

Ko, S. C. W.

V. L. Johnson, S. C. W. Ko, T. H. Holmstrom, J. E. Eriksson, and S. C. Chow, “Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis,” J. Cell Sci. 113(Pt 17), 2941–2953 (2000).
[PubMed]

Kolch, W.

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

Kraan, Y.

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

L. Coco, F.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Lane, S. M.

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

Lasierra, P.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Lau, A. Y.

A. Y. Lau, L. P. Lee, and J. W. Chan, “An integrated optofluidic platform for Raman-activated cell sorting,” Lab Chip 8(7), 1116–1120 (2008).
[CrossRef] [PubMed]

Lee, L. P.

A. Y. Lau, L. P. Lee, and J. W. Chan, “An integrated optofluidic platform for Raman-activated cell sorting,” Lab Chip 8(7), 1116–1120 (2008).
[CrossRef] [PubMed]

Lenferink, A.

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

Li, Y.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Li, Y. Q.

Lieber, C. A.

Lin, A. W.

S. W. Lowe and A. W. Lin, “Apoptosis in cancer,” Carcinogenesis 21(3), 485–495 (2000).
[CrossRef] [PubMed]

Liu, R.

R. Liu, D. S. Taylor, D. L. Matthews, and J. W. Chan, “Parallel analysis of individual biological cells using multifocal laser tweezers Raman spectroscopy,” Appl. Spectrosc. (to be published).

Löfgren, C.

L. Möllgård, U. Tidefelt, B. Sundman-Engberg, C. Löfgren, and C. Paul, “In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay,” Leuk. Res. 24(5), 445–452 (2000).
[CrossRef] [PubMed]

Logg, K.

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

Los, M.

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

Lowe, S. W.

S. W. Lowe and A. W. Lin, “Apoptosis in cancer,” Carcinogenesis 21(3), 485–495 (2000).
[CrossRef] [PubMed]

Mahadevan-Jansen, A.

Marquardt, H.

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

Martin, S. J.

R. C. Taylor, S. P. Cullen, and S. J. Martin, “Apoptosis: controlled demolition at the cellular level,” Nat. Rev. Mol. Cell Biol. 9(3), 231–241 (2008).
[CrossRef] [PubMed]

Martinez-Lorenzo, M. J.

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Masuko, T.

Y. Takai, T. Masuko, and H. Takeuchi, “Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy,” Biochim. Biophys. Acta 1335(1-2), 199–208 (1997).
[PubMed]

Matthews, D. L.

R. Liu, D. S. Taylor, D. L. Matthews, and J. W. Chan, “Parallel analysis of individual biological cells using multifocal laser tweezers Raman spectroscopy,” Appl. Spectrosc. (to be published).

Maurillo, L.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Mazilu, M.

Moens, L.

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, and L. Moens, “The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells,” Spectroscopy 22, 287–295 (2008).

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

Möllgård, L.

L. Möllgård, U. Tidefelt, B. Sundman-Engberg, C. Löfgren, and C. Paul, “In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay,” Leuk. Res. 24(5), 445–452 (2000).
[CrossRef] [PubMed]

Mulvey, C. S.

C. S. Mulvey, C. A. Sherwood, and I. J. Bigio, “Wavelength-dependent backscattering measurements for quantitative real-time monitoring of apoptosis in living cells,” J. Biomed. Opt. 14(6), 064013 (2009).
[CrossRef] [PubMed]

Naeve, C. W.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Nagourney, R. A.

R. A. Nagourney, “Ex vivo programmed cell death and the prediction of response to chemotherapy,” Curr. Treat. Options Oncol. 7(2), 103–110 (2006).
[CrossRef] [PubMed]

Naval, J.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Niepel, M.

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol. 13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

Notingher, I.

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Notingher, P. L.

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Olminkhof, J. H. F.

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

Olson, M. F.

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

Orrenius, S.

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

Otto, C.

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

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

Owen, C. A.

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

Paterson, L.

Paul, C.

L. Möllgård, U. Tidefelt, B. Sundman-Engberg, C. Löfgren, and C. Paul, “In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay,” Leuk. Res. 24(5), 445–452 (2000).
[CrossRef] [PubMed]

Peng, L.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Pérez-Galán, P.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

Piñeiro, A.

S. Gamen, A. Anel, P. Pérez-Galán, P. Lasierra, D. Johnson, A. Piñeiro, and J. Naval, “Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells,” Exp. Cell Res. 258(1), 223–235 (2000).
[CrossRef] [PubMed]

S. Gamen, A. Anel, P. Lasierra, M. A. Alava, M. J. Martinez-Lorenzo, A. Piñeiro, and J. Naval, “Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way,” FEBS Lett. 417(3), 360–364 (1997).
[CrossRef] [PubMed]

Polak, J. M.

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Pui, C. H.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Puppels, G. J.

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

Quemeneur, L.

C. Ferraro-Peyret, L. Quemeneur, M. Flacher, J. P. Revillard, and L. Genestier, “Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes,” J. Immunol. 169(9), 4805–4810 (2002).
[PubMed]

Ramser, K.

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, and L. Moens, “The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells,” Spectroscopy 22, 287–295 (2008).

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

K. Ramser, J. Enger, M. Goksör, 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(4), 431–436 (2005).
[CrossRef] [PubMed]

Reed, J. C.

J. C. Reed, “Dysregulation of apoptosis in cancer,” J. Clin. Oncol. 17(9), 2941–2953 (1999).
[PubMed]

Relling, M. V.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Revillard, J. P.

C. Ferraro-Peyret, L. Quemeneur, M. Flacher, J. P. Revillard, and L. Genestier, “Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes,” J. Immunol. 169(9), 4805–4810 (2002).
[PubMed]

Riches, A.

Rossmann, E.

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

Sahai, E. A.

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

Sargent, J. M.

J. M. Sargent and C. G. Taylor, “Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia,” Br. J. Cancer 60(2), 206–210 (1989).
[PubMed]

Schaefer, A.

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

Schulze-Osthoff, K.

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

Segers-Nolten, G. M. J.

G. J. Puppels, J. H. F. Olminkhof, G. M. J. Segers-Nolten, C. Otto, F. F. M. de Mul, and J. Greve, “Laser irradiation and Raman spectroscopy of single living cells and chromosomes: sample degradation occurs with 514.5 nm but not with 660 nm laser light,” Exp. Cell Res. 195(2), 361–367 (1991).
[CrossRef] [PubMed]

Selvakumaran, J.

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

Sherwood, C. A.

C. S. Mulvey, C. A. Sherwood, and I. J. Bigio, “Wavelength-dependent backscattering measurements for quantitative real-time monitoring of apoptosis in living cells,” J. Biomed. Opt. 14(6), 064013 (2009).
[CrossRef] [PubMed]

Sibbett, W.

Smith, D.

Snook, R. D.

R. D. Snook, T. J. Harvey, E. Correia Faria, and P. Gardner, “Raman tweezers and their application to the study of singly trapped eukaryotic cells,” Integr Biol (Camb) 1(1), 43–52 (2009).
[CrossRef] [PubMed]

Sokolovskaya, A. A.

A. A. Sokolovskaya, T. N. Zabotina, D. Y. Blokhin, Z. G. Kadagidze, and A. Y. Baryshnikov, “Comparative analysis of apoptosis induced by various anticancer drugs in Jurkat cells,” Exp. Oncol. 23, 46–50 (2001).

Sorger, P. K.

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol. 13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

Spagnoli, A.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Spencer, S. L.

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol. 13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

Stevens, M. M.

C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, and M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006).
[CrossRef] [PubMed]

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Sundman-Engberg, B.

L. Möllgård, U. Tidefelt, B. Sundman-Engberg, C. Löfgren, and C. Paul, “In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay,” Leuk. Res. 24(5), 445–452 (2000).
[CrossRef] [PubMed]

Takai, Y.

Y. Takai, T. Masuko, and H. Takeuchi, “Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy,” Biochim. Biophys. Acta 1335(1-2), 199–208 (1997).
[PubMed]

Takeuchi, H.

Y. Takai, T. Masuko, and H. Takeuchi, “Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy,” Biochim. Biophys. Acta 1335(1-2), 199–208 (1997).
[PubMed]

Talley, C. E.

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

Tao, Z.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Taylor, C. G.

J. M. Sargent and C. G. Taylor, “Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia,” Br. J. Cancer 60(2), 206–210 (1989).
[PubMed]

Taylor, D. S.

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

R. Liu, D. S. Taylor, D. L. Matthews, and J. W. Chan, “Parallel analysis of individual biological cells using multifocal laser tweezers Raman spectroscopy,” Appl. Spectrosc. (to be published).

Taylor, R. C.

R. C. Taylor, S. P. Cullen, and S. J. Martin, “Apoptosis: controlled demolition at the cellular level,” Nat. Rev. Mol. Cell Biol. 9(3), 231–241 (2008).
[CrossRef] [PubMed]

Thein, M.

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

Tidefelt, U.

L. Möllgård, U. Tidefelt, B. Sundman-Engberg, C. Löfgren, and C. Paul, “In vitro chemosensitivity testing in acute non lymphocytic leukemia using the bioluminescence ATP assay,” Leuk. Res. 24(5), 445–452 (2000).
[CrossRef] [PubMed]

Tsigkou, O.

I. Notingher, G. Jell, P. L. Notingher, I. Bisson, O. Tsigkou, J. M. Polak, M. M. Stevens, and L. L. Hench, “Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells,” J. Mol. Struct. 744-747, 179–185 (2005).
[CrossRef]

Tuscano, J.

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

Uzunbajakava, N.

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

Van Doorslaer, S.

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, and L. Moens, “The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells,” Spectroscopy 22, 287–295 (2008).

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

Venditti, A.

F. Buccisano, L. Maurillo, A. Spagnoli, M. I. D. Principe, E. Ceresoli, F. L. Coco, W. Arcese, S. Amadori, and A. Venditti, “Monitoring of minimal residual disease in acute myeloid leukemia,” Curr. Opin. Oncol. 21(6), 582–588 (2009).
[CrossRef] [PubMed]

Volokhina, E.

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

Vrensen, G.

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

Wachsmann-Hogiu, S.

J. Chan, S. Fore, S. Wachsmann-Hogiu, and T. Huser, “Raman spectroscopy and microscopy of individual cells and cellular components,” Laser Photonics Rev. 2(5), 325–349 (2008).
[CrossRef]

Wang, G.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Weis, M.

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

Wenseleers, W.

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, and L. Moens, “The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells,” Spectroscopy 22, 287–295 (2008).

K. Ramser, W. Wenseleers, S. Dewilde, S. Van Doorslaer, L. Moens, and D. Hanstorp, “Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin,” J. Biomed. Opt. 12(4), 044009 (2007).
[CrossRef] [PubMed]

Wesselborg, S.

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

Winterford, C. M.

J. F. Kerr, C. M. Winterford, and B. V. Harmon, “Apoptosis. Its significance in cancer and cancer therapy,” Cancer 73(8), 2013–2026 (1994).
[CrossRef] [PubMed]

Xie, C. G.

Xu, J.

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

Yang, W.

M. H. Cheok, W. Yang, C. H. Pui, J. R. Downing, C. Cheng, C. W. Naeve, M. V. Relling, and W. E. Evans, “Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells,” Nat. Genet. 34(1), 85–90 (2003).
[CrossRef] [PubMed]

Yao, H.

H. Yao, Z. Tao, M. Ai, L. Peng, G. Wang, B. He, and Y. Li, “Raman spectroscopic analysis of apoptosis of single human gastric cancer cells,” Vib. Spectrosc. 50(2), 193–197 (2009).
[CrossRef]

Yeo, M.

M. L. Coleman, E. A. Sahai, M. Yeo, M. Bosch, A. Dewar, and M. F. Olson, “Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I,” Nat. Cell Biol. 3(4), 339–345 (2001).
[CrossRef] [PubMed]

Zabotina, T. N.

A. A. Sokolovskaya, T. N. Zabotina, D. Y. Blokhin, Z. G. Kadagidze, and A. Y. Baryshnikov, “Comparative analysis of apoptosis induced by various anticancer drugs in Jurkat cells,” Exp. Oncol. 23, 46–50 (2001).

Zhang, M.

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

Zwerdling, T.

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

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(2), 648–656 (2006).
[CrossRef] [PubMed]

Anal. Chem.

J. W. Chan, A. P. Esposito, C. E. Talley, C. W. Hollars, S. M. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76(3), 599–603 (2004).
[CrossRef] [PubMed]

J. W. Chan, D. S. Taylor, S. M. Lane, T. Zwerdling, J. Tuscano, and T. Huser, “Nondestructive identification of individual leukemia cells by laser trapping Raman spectroscopy,” Anal. Chem. 80(6), 2180–2187 (2008).
[CrossRef] [PubMed]

Analyst (Lond.)

R. Buckmaster, F. Asphahani, M. Thein, J. Xu, and M. Zhang, “Detection of drug-induced cellular changes using confocal Raman spectroscopy on patterned single-cell biosensors,” Analyst (Lond.) 134(7), 1440–1446 (2009).
[CrossRef] [PubMed]

Apoptosis

D. C. Dartsch, A. Schaefer, S. Boldt, W. Kolch, and H. Marquardt, “Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis,” Apoptosis 7(6), 537–548 (2002).
[CrossRef] [PubMed]

Appl. Spectrosc.

R. Liu, D. S. Taylor, D. L. Matthews, and J. W. Chan, “Parallel analysis of individual biological cells using multifocal laser tweezers Raman spectroscopy,” Appl. Spectrosc. (to be published).

C. A. Lieber and A. Mahadevan-Jansen, “Automated method for subtraction of fluorescence from biological Raman spectra,” Appl. Spectrosc. 57(11), 1363–1367 (2003).
[CrossRef] [PubMed]

Biochem. J.

G. E. N. Kass, J. E. Eriksson, M. Weis, S. Orrenius, and S. C. Chow, “Chromatin condensation during apoptosis requires ATP,” Biochem. J. 318(Pt 3), 749–752 (1996).
[PubMed]

Biochim. Biophys. Acta

Y. Takai, T. Masuko, and H. Takeuchi, “Lipid structure of cytotoxic granules in living human killer T lymphocytes studied by Raman microspectroscopy,” Biochim. Biophys. Acta 1335(1-2), 199–208 (1997).
[PubMed]

Biophys. J.

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(2), 648–656 (2006).
[CrossRef] [PubMed]

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

Blood

S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff, “Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction,” Blood 93(9), 3053–3063 (1999).
[PubMed]

Br. J. Cancer

J. M. Sargent and C. G. Taylor, “Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia,” Br. J. Cancer 60(2), 206–210 (1989).
[PubMed]

Br. J. Haematol.

J. Donadieu and C. Hill, “Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review,” Br. J. Haematol. 115(1), 34–45 (2001).
[CrossRef] [PubMed]

Cancer

J. F. Kerr, C. M. Winterford, and B. V. Harmon, “Apoptosis. Its significance in cancer and cancer therapy,” Cancer 73(8), 2013–2026 (1994).
[CrossRef] [PubMed]

Carcinogenesis

S. W. Lowe and A. W. Lin, “Apoptosis in cancer,” Carcinogenesis 21(3), 485–495 (2000).
[CrossRef] [PubMed]

Curr. Opin. Chem. Biol.

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol. 13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

Curr. Opin. Oncol.

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Integr Biol (Camb)

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Figures (5)

Fig. 1
Fig. 1

Raman spectra of individual Jurkat cells after different times of drug exposure. Spectral data are shown (only 4 out of 30 per data point) for continuous doxorubicin exposure after 24h, 48h, and 72h for drug concentrations of 0.1 μM and 0.5 μM.

Fig. 2
Fig. 2

PCA scatter plot of Raman spectra of control (no drug exposure) and drug exposed (0.5 μM doxorubicin) Jurkat cells over 72 h. Three groups are visible (circled in black) that are located apart from the control cell group (circled in blue).

Fig. 4
Fig. 4

Mean Raman spectra of the cells in (A) Group 1, (B) Group 2, and (C) Group 3.

Fig. 3
Fig. 3

PCA scatter plot of 0.1 and 0.5 μM drug exposed and control (no drug exposure) cells at 24, 48, and 72 h. Groups 1, 2, and 3 indicate the sequence in which these clusters are formed. A dependence between the temporal evolution of the spectral changes and drug concentration is also observed based on the distribution of data points in each of the groups.

Fig. 5
Fig. 5

Comparison of mean Raman spectra from (A) Group 1 (B) Group 2 and (C) Group 3 with the mean Raman spectra of control cells to visualize major spectral changes over time during drug cell interaction. An arrow pointing up or down indicates an increase or decrease in the peak, respectively, and peak assignments are provided: lipid (L), DNA (D), and protein (P). White light images of cells representative of each group and control cells are also shown.

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