Abstract

We present a new approach for combining holographic optical tweezers with confocal Raman spectroscopy. Multiple laser foci, generated using a liquid-crystal spatial light modulator, are individually used for both optical trapping and excitation of spontaneous Raman spectroscopy from trapped objects. Raman scattering from each laser focus is spatially filtered using reflective apertures on a digital micro-mirror device, which can be reconfigured with flexible patterns at video rate. We discuss operation of the instrument, and performance and viability considerations for biological measurements. We then demonstrate the capability of the instrument for fast, flexible, and interactive manipulation with molecular measurement of interacting live cell systems.

Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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References

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  1. D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: Techniques and applications in the life sciences,” Adv. Opt. Photonics 9, 315–428 (2017).
    [Crossref]
  2. B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
    [Crossref] [PubMed]
  3. K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
    [Crossref] [PubMed]
  4. J. W. Chan, A. Esposito, C. Talley, C. Hollars, S. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76, 599–603 (2004).
    [Crossref] [PubMed]
  5. Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
    [Crossref]
  6. G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
    [Crossref] [PubMed]
  7. A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
    [Crossref]
  8. M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
    [Crossref]
  9. M. D. Mannie, T. J. McConnell, C. Xie, and Y.-Q. Li, “Activation-dependent phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy,” J. Immunol. Methods 297, 53–60 (2005).
    [Crossref] [PubMed]
  10. A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
    [Crossref] [PubMed]
  11. A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
    [Crossref]
  12. A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
    [Crossref]
  13. I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
    [Crossref] [PubMed]
  14. R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
    [Crossref] [PubMed]
  15. J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, and T. Huser, “Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells,” Biophys. J. 90, 648–656 (2006).
    [Crossref]
  16. 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, 2180–2187 (2008).
    [Crossref] [PubMed]
  17. A. Ashkin, J. M. Dziedzic, J. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288–290 (1986).
    [Crossref] [PubMed]
  18. A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature 330, 769–771 (1987).
    [Crossref] [PubMed]
  19. D. G. Grier, “A revolution in optical manipulation,” Nature 424, 810–816 (2003).
    [Crossref] [PubMed]
  20. R. W. Bowman and M. J. Padgett, “Optical trapping and binding,” Reports on Prog. Phys. 76, 026401 (2013).
    [Crossref]
  21. R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
    [Crossref]
  22. C. Xie, M. A. Dinno, and Y.-Q. Li, “Near-infrared Raman spectroscopy of single optically trapped biological cells,” Opt. Lett. 27, 249–251 (2002).
    [Crossref]
  23. R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
    [Crossref] [PubMed]
  24. C. Xie, C. Goodman, M. A. Dinno, and Y.-Q. Li, “Real-time Raman spectroscopy of optically trapped living cells and organelles,” Opt. Express 12, 6208–6214 (2004).
    [Crossref] [PubMed]
  25. C. Xie, D. Chen, and Y.-q. Li, “Raman sorting and identification of single living micro-organisms with optical tweezers,” Opt. Lett. 30, 1800–1802 (2005).
    [Crossref] [PubMed]
  26. A. Y. Lau, L. P. Lee, and J. W. Chan, “An integrated optofluidic platform for Raman-activated cell sorting,” Lab on a Chip 8, 1116–1120 (2008).
    [Crossref] [PubMed]
  27. R. D. Snook, T. J. Harvey, E. C. Faria, and P. Gardner, “Raman tweezers and their application to the study of singly trapped eukaryotic cells,” Integr. Biol. 1, 43–52 (2009).
    [Crossref]
  28. P. Zhang, L. Kong, P. Setlow, and Y.-Q. Li, “Multiple-trap laser tweezers Raman spectroscopy for simultaneous monitoring of the biological dynamics of multiple individual cells,” Opt. Lett. 35, 3321–3323 (2010).
    [Crossref] [PubMed]
  29. L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
    [Crossref] [PubMed]
  30. J. W. Chan, “Recent advances in laser tweezers Raman spectroscopy (LTRS) for label-free analysis of single cells,” J. Biophotonics 6, 36–48 (2013).
    [Crossref]
  31. L. Kong and J. Chan, “A rapidly modulated multifocal detection scheme for parallel acquisition of Raman spectra from a 2-D focal array,” Anal. Chem. 86, 6604–6609 (2014).
    [Crossref] [PubMed]
  32. J. Qi and W.-C. Shih, “Parallel Raman microspectroscopy using programmable multipoint illumination,” Opt. Lett. 37, 1289–1291 (2012).
    [Crossref] [PubMed]
  33. P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
    [Crossref]
  34. G. Gibson, M. Dienerowitz, P. Kelleher, A. Harvey, and M. Padgett, “A multi-object spectral imaging instrument,” J. Opt. 15, 085302 (2013).
    [Crossref]
  35. F. Sinjab, K. Kong, G. Gibson, S. Varma, H. Williams, M. Padgett, and I. Notingher, “Tissue diagnosis using power-sharing multifocal Raman micro-spectroscopy and auto-fluorescence imaging,” Biomed. Opt. Express 7, 2993–3006 (2016).
    [Crossref] [PubMed]
  36. C. A. Lieber and A. Mahadevan-Jansen, “Automated method for subtraction of fluorescence from biological Raman spectra,” Appl. Spectrosc. 57, 1363–1367 (2003).
    [Crossref] [PubMed]
  37. B. D. Beier and A. J. Berger, “Method for automated background subtraction from Raman spectra containing known contaminants,” Analyst 134, 1198–1202 (2009).
    [Crossref] [PubMed]
  38. F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
    [Crossref]
  39. S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
    [Crossref] [PubMed]
  40. B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
    [Crossref]
  41. L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
    [Crossref] [PubMed]
  42. G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
    [Crossref]

2018 (1)

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

2017 (1)

D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: Techniques and applications in the life sciences,” Adv. Opt. Photonics 9, 315–428 (2017).
[Crossref]

2016 (4)

A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
[Crossref]

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

F. Sinjab, K. Kong, G. Gibson, S. Varma, H. Williams, M. Padgett, and I. Notingher, “Tissue diagnosis using power-sharing multifocal Raman micro-spectroscopy and auto-fluorescence imaging,” Biomed. Opt. Express 7, 2993–3006 (2016).
[Crossref] [PubMed]

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

2015 (1)

B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
[Crossref] [PubMed]

2014 (3)

A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
[Crossref]

L. Kong and J. Chan, “A rapidly modulated multifocal detection scheme for parallel acquisition of Raman spectra from a 2-D focal array,” Anal. Chem. 86, 6604–6609 (2014).
[Crossref] [PubMed]

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

2013 (3)

R. W. Bowman and M. J. Padgett, “Optical trapping and binding,” Reports on Prog. Phys. 76, 026401 (2013).
[Crossref]

J. W. Chan, “Recent advances in laser tweezers Raman spectroscopy (LTRS) for label-free analysis of single cells,” J. Biophotonics 6, 36–48 (2013).
[Crossref]

G. Gibson, M. Dienerowitz, P. Kelleher, A. Harvey, and M. Padgett, “A multi-object spectral imaging instrument,” J. Opt. 15, 085302 (2013).
[Crossref]

2012 (3)

J. Qi and W.-C. Shih, “Parallel Raman microspectroscopy using programmable multipoint illumination,” Opt. Lett. 37, 1289–1291 (2012).
[Crossref] [PubMed]

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

2011 (1)

L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
[Crossref] [PubMed]

2010 (3)

P. Zhang, L. Kong, P. Setlow, and Y.-Q. Li, “Multiple-trap laser tweezers Raman spectroscopy for simultaneous monitoring of the biological dynamics of multiple individual cells,” Opt. Lett. 35, 3321–3323 (2010).
[Crossref] [PubMed]

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

2009 (2)

B. D. Beier and A. J. Berger, “Method for automated background subtraction from Raman spectra containing known contaminants,” Analyst 134, 1198–1202 (2009).
[Crossref] [PubMed]

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

2008 (2)

A. Y. Lau, L. P. Lee, and J. W. Chan, “An integrated optofluidic platform for Raman-activated cell sorting,” Lab on a Chip 8, 1116–1120 (2008).
[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, 2180–2187 (2008).
[Crossref] [PubMed]

2007 (1)

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

2006 (1)

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

2005 (2)

M. D. Mannie, T. J. McConnell, C. Xie, and Y.-Q. Li, “Activation-dependent 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, D. Chen, and Y.-q. Li, “Raman sorting and identification of single living micro-organisms with optical tweezers,” Opt. Lett. 30, 1800–1802 (2005).
[Crossref] [PubMed]

2004 (5)

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

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

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

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

2003 (2)

2002 (2)

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

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

1998 (1)

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

1993 (1)

G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
[Crossref]

1990 (1)

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

1987 (1)

A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature 330, 769–771 (1987).
[Crossref] [PubMed]

1986 (1)

Arndt-Jovin, D.

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Ashkin, A.

A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature 330, 769–771 (1987).
[Crossref] [PubMed]

A. Ashkin, J. M. Dziedzic, J. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288–290 (1986).
[Crossref] [PubMed]

Awuah, D.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

Beier, B. D.

B. D. Beier and A. J. Berger, “Method for automated background subtraction from Raman spectra containing known contaminants,” Analyst 134, 1198–1202 (2009).
[Crossref] [PubMed]

Berger, A. J.

B. D. Beier and A. J. Berger, “Method for automated background subtraction from Raman spectra containing known contaminants,” Analyst 134, 1198–1202 (2009).
[Crossref] [PubMed]

Bishop, A. E.

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

Bisson, I.

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

Bjorkholm, J.

Boitor, R.

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

Boitor, R. A.

A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
[Crossref]

Bowman, R. W.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

R. W. Bowman and M. J. Padgett, “Optical trapping and binding,” Reports on Prog. Phys. 76, 026401 (2013).
[Crossref]

Carberry, D. M.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Caspers, P.

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

Chan, J.

L. Kong and J. Chan, “A rapidly modulated multifocal detection scheme for parallel acquisition of Raman spectra from a 2-D focal array,” Anal. Chem. 86, 6604–6609 (2014).
[Crossref] [PubMed]

Chan, J. W.

J. W. Chan, “Recent advances in laser tweezers Raman spectroscopy (LTRS) for label-free analysis of single cells,” J. Biophotonics 6, 36–48 (2013).
[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, 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 on a Chip 8, 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, 648–656 (2006).
[Crossref]

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

Chau, D. Y.

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Chen, D.

Chiu, L.-D.

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

Choo-Smith, L.-P.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

Chu, S.

Demul, F.

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Dienerowitz, M.

G. Gibson, M. Dienerowitz, P. Kelleher, A. Harvey, and M. Padgett, “A multi-object spectral imaging instrument,” J. Opt. 15, 085302 (2013).
[Crossref]

Dinno, M. A.

Downes, A.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
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A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature 330, 769–771 (1987).
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A. Ashkin, J. M. Dziedzic, J. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288–290 (1986).
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Elfick, A.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

Elsheikha, H. M.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
[Crossref]

Emara, M.

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Endo, H.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Endtz, H. P.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

Esposito, A.

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

Faria, E. C.

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

Fujita, K.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Garcia-Nieto, S.

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

García-Nieto, S.

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Gardner, P.

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

Garritsen, H.

G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
[Crossref]

Gessner, R.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Ghaemmaghami, A. M.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Ghita, A.

A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
[Crossref]

Gibson, G.

Gibson, G. M.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Goodman, C.

Greve, J.

G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
[Crossref]

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Grier, D. G.

D. G. Grier, “A revolution in optical manipulation,” Nature 424, 810–816 (2003).
[Crossref] [PubMed]

Grieve, J. A.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Hall, L.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

Hamaguchi, H.-o.

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

Hanley, Q.

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Harvey, A.

G. Gibson, M. Dienerowitz, P. Kelleher, A. Harvey, and M. Padgett, “A multi-object spectral imaging instrument,” J. Opt. 15, 085302 (2013).
[Crossref]

Harvey, T. J.

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

Hench, L. L.

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

Hollars, C.

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

Huang, Y.-S.

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

Hullin-Matsuda, F.

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

Huser, 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, 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, 648–656 (2006).
[Crossref]

J. W. Chan, A. Esposito, C. Talley, C. Hollars, S. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76, 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, 648–656 (2006).
[Crossref]

Johal, R. K.

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

Jovin, T.

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Jovin, W.

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Kann, B.

B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
[Crossref] [PubMed]

Karashima, T.

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

Kawata, S.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Kelleher, P.

G. Gibson, M. Dienerowitz, P. Kelleher, A. Harvey, and M. Padgett, “A multi-object spectral imaging instrument,” J. Opt. 15, 085302 (2013).
[Crossref]

Kiefer, W.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Kirschner, C.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

Kobayashi, T.

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

Kong, K.

Kong, L.

L. Kong and J. Chan, “A rapidly modulated multifocal detection scheme for parallel acquisition of Raman spectra from a 2-D focal array,” Anal. Chem. 86, 6604–6609 (2014).
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L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
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P. Zhang, L. Kong, P. Setlow, and Y.-Q. Li, “Multiple-trap laser tweezers Raman spectroscopy for simultaneous monitoring of the biological dynamics of multiple individual cells,” Opt. Lett. 35, 3321–3323 (2010).
[Crossref] [PubMed]

Kummer, J.

G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
[Crossref]

Lane, S.

J. W. Chan, A. Esposito, C. Talley, C. Hollars, S. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76, 599–603 (2004).
[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, 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, 648–656 (2006).
[Crossref]

Lankers, M.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[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 on a Chip 8, 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 on a Chip 8, 1116–1120 (2008).
[Crossref] [PubMed]

Li, Y.-q.

Lieber, C. A.

Linnenberger, A.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Mahadevan-Jansen, A.

Mannie, M. D.

M. D. Mannie, T. J. McConnell, C. Xie, and Y.-Q. Li, “Activation-dependent phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy,” J. Immunol. Methods 297, 53–60 (2005).
[Crossref] [PubMed]

Maquelin, K.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

McConnell, T. J.

M. D. Mannie, T. J. McConnell, C. Xie, and Y.-Q. Li, “Activation-dependent phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy,” J. Immunol. Methods 297, 53–60 (2005).
[Crossref] [PubMed]

McDonald, A.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

McNaughton, D.

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

Miles, M. J.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Naemat, A.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
[Crossref]

Naumann, D.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

Negm, O. H.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

Notingher, I.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: Techniques and applications in the life sciences,” Adv. Opt. Photonics 9, 315–428 (2017).
[Crossref]

A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
[Crossref]

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

F. Sinjab, K. Kong, G. Gibson, S. Varma, H. Williams, M. Padgett, and I. Notingher, “Tissue diagnosis using power-sharing multifocal Raman micro-spectroscopy and auto-fluorescence imaging,” Biomed. Opt. Express 7, 2993–3006 (2016).
[Crossref] [PubMed]

A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
[Crossref]

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

Offerhaus, H. L.

B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
[Crossref] [PubMed]

Ogura, T.

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

Okada, M.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Otto, C.

B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
[Crossref] [PubMed]

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Padgett, M.

Padgett, M. J.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

R. W. Bowman and M. J. Padgett, “Optical trapping and binding,” Reports on Prog. Phys. 76, 026401 (2013).
[Crossref]

Palonpon, A. F.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Pandiancherri, S.

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

Pascut, F.

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

Pascut, F. C.

A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
[Crossref]

Petry, R.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Phillips, D. B.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Polak, J. M.

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

Popp, J.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Puppels, G.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
[Crossref]

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Puppels, G. J.

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

Qi, J.

Randle, W. L.

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (2004).
[Crossref] [PubMed]

Robertnicoud, M.

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Rösch, P.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Royer, P.-J.

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Salazar, F.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

Schmitt, M.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Serati, S.

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Setlow, P.

L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
[Crossref] [PubMed]

P. Zhang, L. Kong, P. Setlow, and Y.-Q. Li, “Multiple-trap laser tweezers Raman spectroscopy for simultaneous monitoring of the biological dynamics of multiple individual cells,” Opt. Lett. 35, 3321–3323 (2010).
[Crossref] [PubMed]

Shakesheff, K. M.

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

Shakib, F.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Shih, W.-C.

Shipp, D. W.

D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: Techniques and applications in the life sciences,” Adv. Opt. Photonics 9, 315–428 (2017).
[Crossref]

Sinjab, F.

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: Techniques and applications in the life sciences,” Adv. Opt. Photonics 9, 315–428 (2017).
[Crossref]

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

F. Sinjab, K. Kong, G. Gibson, S. Varma, H. Williams, M. Padgett, and I. Notingher, “Tissue diagnosis using power-sharing multifocal Raman micro-spectroscopy and auto-fluorescence imaging,” Biomed. Opt. Express 7, 2993–3006 (2016).
[Crossref] [PubMed]

Smith, N. I.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Snook, R. D.

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

Sodeoka, M.

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Sottile, V.

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
[Crossref]

Strohbuecker, S.

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

Talley, C.

J. W. Chan, A. Esposito, C. Talley, C. Hollars, S. Lane, and T. Huser, “Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy,” Anal. Chem. 76, 599–603 (2004).
[Crossref] [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, 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, 648–656 (2006).
[Crossref]

Tighe, P. J.

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

Torii, H.

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

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, 2180–2187 (2008).
[Crossref] [PubMed]

van den Braak, N.

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

Van Vliet, L.

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Varma, S.

Verbeek, P.

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Verveer, P.

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

Wang, G.

L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
[Crossref] [PubMed]

Williams, H.

Windbergs, M.

B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
[Crossref] [PubMed]

Winter, C.

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Wood, B. R.

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

Xie, C.

Yamamoto, M.

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

Yamane, T.

A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature 330, 769–771 (1987).
[Crossref] [PubMed]

Yu, J.

L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
[Crossref] [PubMed]

Zhang, P.

L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
[Crossref] [PubMed]

P. Zhang, L. Kong, P. Setlow, and Y.-Q. Li, “Multiple-trap laser tweezers Raman spectroscopy for simultaneous monitoring of the biological dynamics of multiple individual cells,” Opt. Lett. 35, 3321–3323 (2010).
[Crossref] [PubMed]

Zoladek, A. B.

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[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, 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, 648–656 (2006).
[Crossref]

Adv. Drug Deliv. Rev. (1)

B. Kann, H. L. Offerhaus, M. Windbergs, and C. Otto, “Raman microscopy for cellular investigations-from single cell imaging to drug carrier uptake visualization,” Adv. Drug Deliv. Rev. 89, 71–90 (2015).
[Crossref] [PubMed]

Adv. Opt. Photonics (1)

D. W. Shipp, F. Sinjab, and I. Notingher, “Raman spectroscopy: Techniques and applications in the life sciences,” Adv. Opt. Photonics 9, 315–428 (2017).
[Crossref]

Anal. Bioanal. Chem. (1)

B. R. Wood, P. Caspers, G. J. Puppels, S. Pandiancherri, and D. McNaughton, “Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation,” Anal. Bioanal. Chem. 387, 1691–1703 (2007).
[Crossref]

Anal. Chem. (4)

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

I. Notingher, I. Bisson, A. E. Bishop, W. L. Randle, J. M. Polak, and L. L. Hench, “In situ spectral monitoring of mRNA translation in embryonic stem cells during differentiation in vitro,” Anal. Chem. 76, 3185–3193 (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, 2180–2187 (2008).
[Crossref] [PubMed]

L. Kong and J. Chan, “A rapidly modulated multifocal detection scheme for parallel acquisition of Raman spectra from a 2-D focal array,” Anal. Chem. 86, 6604–6609 (2014).
[Crossref] [PubMed]

Analyst (3)

A. B. Zoladek, R. K. Johal, S. Garcia-Nieto, F. Pascut, K. M. Shakesheff, A. M. Ghaemmaghami, and I. Notingher, “Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy,” Analyst 135, 3205–3212 (2010).
[Crossref] [PubMed]

A. Ghita, F. C. Pascut, V. Sottile, and I. Notingher, “Monitoring the mineralisation of bone nodules in vitro by space-and time-resolved Raman micro-spectroscopy,” Analyst 139, 55–58 (2014).
[Crossref]

B. D. Beier and A. J. Berger, “Method for automated background subtraction from Raman spectra containing known contaminants,” Analyst 134, 1198–1202 (2009).
[Crossref] [PubMed]

Appl. Spectrosc. (1)

Biomed. Opt. Express (1)

Biophys. J. (1)

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

Chem Phys Chem (1)

R. Gessner, C. Winter, P. Rösch, M. Schmitt, R. Petry, W. Kiefer, M. Lankers, and J. Popp, “Identification of biotic and abiotic particles by using a combination of optical tweezers and in situ Raman spectroscopy,” Chem Phys Chem 5, 1159–1170 (2004).
[Crossref] [PubMed]

Comput. Phys. Commun. (1)

R. W. Bowman, G. M. Gibson, A. Linnenberger, D. B. Phillips, J. A. Grieve, D. M. Carberry, S. Serati, M. J. Miles, and M. J. Padgett, ““Red Tweezers”: Fast, customisable hologram generation for optical tweezers,” Comput. Phys. Commun. 185, 268–273 (2014).
[Crossref]

Cytom. Part A (1)

G. Puppels, H. Garritsen, J. Kummer, and J. Greve, “Carotenoids located in human lymphocyte subpopulations and natural killer cells by Raman microspectroscopy,” Cytom. Part A 14, 251–256 (1993).
[Crossref]

Faraday Discuss. (1)

R. Boitor, F. Sinjab, S. Strohbuecker, V. Sottile, and I. Notingher, “Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography,” Faraday Discuss. 187, 199–212 (2016).
[Crossref] [PubMed]

Integr. Biol. (1)

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

J. Allergy Clin. Immunol. (1)

F. Salazar, L. Hall, O. H. Negm, D. Awuah, P. J. Tighe, F. Shakib, and A. M. Ghaemmaghami, “The mannose receptor negatively modulates the toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2, 3-dioxygenase axis in dendritic cells affecting t helper cell polarization,” J. Allergy Clin. Immunol. 137, 1841–1851 (2016).
[Crossref]

J. Biophotonics (2)

L.-D. Chiu, F. Hullin-Matsuda, T. Kobayashi, H. Torii, and H.-o. Hamaguchi, “On the origin of the 1602 cm–1 Raman band of yeasts; contribution of ergosterol,” J. Biophotonics 5, 724–728 (2012).
[Crossref] [PubMed]

J. W. Chan, “Recent advances in laser tweezers Raman spectroscopy (LTRS) for label-free analysis of single cells,” J. Biophotonics 6, 36–48 (2013).
[Crossref]

J. Immunol. Methods (1)

M. D. Mannie, T. J. McConnell, C. Xie, and Y.-Q. Li, “Activation-dependent 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. Microbiol. Methods (1)

K. Maquelin, C. Kirschner, L.-P. Choo-Smith, N. van den Braak, H. P. Endtz, D. Naumann, and G. Puppels, “Identification of medically relevant microorganisms by vibrational spectroscopy,” J. Microbiol. Methods 51, 255–271 (2002).
[Crossref] [PubMed]

J. Microsc. (1)

P. Verveer, Q. Hanley, P. Verbeek, L. Van Vliet, and W. Jovin, “Theory of confocal fluorescence imaging in the programmable array microscope (PAM),” J. Microsc. 189, 192–198 (1998).
[Crossref]

J. Opt. (1)

G. Gibson, M. Dienerowitz, P. Kelleher, A. Harvey, and M. Padgett, “A multi-object spectral imaging instrument,” J. Opt. 15, 085302 (2013).
[Crossref]

J. Raman Spectrosc. (2)

Y.-S. Huang, T. Karashima, M. Yamamoto, T. Ogura, and H.-o. Hamaguchi, “Raman spectroscopic signature of life in a living yeast cell,” J. Raman Spectrosc. 35, 525–526 (2004).
[Crossref]

A. Naemat, F. Sinjab, A. McDonald, A. Downes, A. Elfick, H. M. Elsheikha, and I. Notingher, “Visualizing the interaction of acanthamoeba castellanii with human retinal epithelial cells by spontaneous raman and CARS imaging,” J. Raman Spectrosc. 49, 412–423 (2018).
[Crossref]

Lab on a Chip (1)

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

Nat. Protoc. (1)

L. Kong, P. Zhang, G. Wang, J. Yu, P. Setlow, and Y.-q. Li, “Characterization of bacterial spore germination using phase-contrast and fluorescence microscopy, Raman spectroscopy and optical tweezers,” Nat. Protoc. 6, 625–639 (2011).
[Crossref] [PubMed]

Nature (3)

A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature 330, 769–771 (1987).
[Crossref] [PubMed]

D. G. Grier, “A revolution in optical manipulation,” Nature 424, 810–816 (2003).
[Crossref] [PubMed]

G. Puppels, F. Demul, C. Otto, J. Greve, M. Robertnicoud, D. Arndt-Jovin, and T. Jovin, “Studying single living cells and chromosomes by confocal Raman spectroscopy,” Nature 347, 301–303 (1990).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (5)

PLoS one (1)

S. García-Nieto, R. K. Johal, K. M. Shakesheff, M. Emara, P.-J. Royer, D. Y. Chau, F. Shakib, and A. M. Ghaemmaghami, “Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity,” PLoS one 5, e10123 (2010).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. (1)

M. Okada, N. I. Smith, A. F. Palonpon, H. Endo, S. Kawata, M. Sodeoka, and K. Fujita, “Label-free Raman observation of cytochrome c dynamics during apoptosis,” Proc. Natl. Acad. Sci. 109, 28–32 (2012).
[Crossref]

Reports on Prog. Phys. (1)

R. W. Bowman and M. J. Padgett, “Optical trapping and binding,” Reports on Prog. Phys. 76, 026401 (2013).
[Crossref]

Sci. Reports (1)

A. Naemat, H. M. Elsheikha, R. A. Boitor, and I. Notingher, “Tracing amino acid exchange during host-pathogen interaction by combined stable-isotope time-resolved Raman spectral imaging,” Sci. Reports 6, 20811 (2016).
[Crossref]

Supplementary Material (1)

NameDescription
» Visualization 1       Optically trapped 5 micron diameter polystyrene beads in water with simultaneous Raman spectra acquired from each location at 4x10 frame readouts per second (40 spectra per second total).

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Figures (7)

Fig. 1
Fig. 1 HOT-RMS instrument. (a) Multiple laser foci are used to trap and excite Raman scattering from microscopic cells/particles. (b) Raman spectra from each trap can be read-out simultaneously at the CCD spectrograph, after spatial filtering at a DMD with reflective confocal pinhole patterns shown in (c). Glossary: LC-SLM: liquid-crystal spatial light modulator, INC: microscope incubator enclosure, TEL: 4f telescope relay, DCB: dichroic beamsplitter, OBJ: microscope objective, DMD: digital micro-mirror device, ImSp: imaging spectrometer, DMD Cam: CMOS inspection camera for DMD, SPF: short-pass filter, NF: notch filter, M: near infra-red mirror, Mic Cam: microscope camera. Dashed pink lines represent planes perpendicular to the optical axis which are sample-conjugate. Dashed black lines show rays reflected from the DMD plane away from the spectrometer direction.
Fig. 2
Fig. 2 Optimization of HOT-RMS signal collection. (a) RMS spectra acquired from bulk polystyrene for different DMD pinhole configurations with parameters outlined in (b). (c) RMS spectra acquired for a single 3 µm polystyrene microparticle manipulated axially through the objective focus (z-position) using RedTweezers software (raw data, 1s acquisition per spectrum). (d) Intensity of the prominent 1001cm−1 band vs. z-position from the data in (c). The red line is a fit to the data using the sum of two Gaussians.
Fig. 3
Fig. 3 HOT-RMS calibration and power consistency. (a) Four RMS spectra acquired simultaneously from bulk polystyrene at the extremes of the FOV (inset: DMD camera image co-ordinates in µm). Note: while points A and D share an overlapping co-ordinate on the CCD height axis, their spectra do not overlap as there is a slight rotation between the co-ordinate axes. (b) shows the corresponding calibration curves for each spectrum in (a) fitted to 5 bands using a 5th order polynomial. (c) Intensity variation between HOT-RMS laser spots (10 patterns, N = 6). Laser power was attenuated so as not to saturate the camera in order to provide a reliable intensity estimation. (d) Distribution of the 60 image-based intensity measurements as a fraction of ηP0, with Gaussian fit (mean: 16.7% ηP0, standard error: ±2.4% ηP0). (e) RMS spectra corresponding to 60 measurements in (c), with corresponding distribution in (f) of area of the 1001cm−1 band, with Gaussian fit (mean: 16.7% ηP0, standard error: ±2.5% ηP0).
Fig. 4
Fig. 4 Demonstration of real-time interactive optical manipulation and RMS acquisition. The numbered regions marked by colored rectangles in the movie frames (from DMD camera) correspond to four CCD binning regions used to acquire Raman spectra (see Visualization 1). These frames show manipulation of four polystyrene beads (5µm) within the different regions. During optical manipulation, binned CCD acquisitions are obtained at 10Hz (rate limited by mechanical shutter speed, exposure time 10ms indicating 100Hz readout is achievable with a faster shutter), with each readout producing four Raman spectra, one from each region. The time-resolved spectra are shown in the four colormap images (color limits adjusted for clarity). For the first 90 seconds, measurements were carried out with the microscope halogen light illumination for bright-field imaging. Co-ordinate axes labels relative to the spectrograph CCD plane are shown for the movie frames and time-course Raman spectra to aid clarity.
Fig. 5
Fig. 5 Examples of HOT-RMS multi-beam trapping measurements of various cell types, with DMD camera images (scale bars 10µm) showing the fixed pinhole locations for measurement of the trapped cells (a,c,e) and Raman spectra from each trapping location (b,d,f; spectra shifted for clarity). (a,b) Mammalian red blood cells (Pi = 3mW, 60s acquisition, 5th order polynomial baseline and quartz background subtraction). (c,d) S. Cerevisiae yeast (Pi = 50mW, 2s acquisition, 1st order polynomial baseline subtracted). (e,f) P. Aeruginosa bacteria (Pi = 50mW, 10s acquisition, 1st order polynomial baseline subtraction)
Fig. 6
Fig. 6 Control of laser power for HOT-RMS measurements. (a): Time-course Raman spectra (raw data) of red blood cells (RBCs) trapped at various laser power Pi. (i) Rapid changes in the Raman spectra of a RBC trapped at Pi = 27mW can be seen (0.5s per spectrum). (ii) Two RBCs trapped with Pi = 13mW also show some change over time, though at a reduced rate (2.5s acquisition per spectrum). (iii) Ten RBCs trapped with Pi = 3mW, with the mean of the first and last 60s of a 180s time-course Raman spectra acquisition shown. (b): Time-course Raman spectra of S. Cerevisiae yeast trapped at various laser power Pi. (i) Raman spectra from selected time-points of a time-course measurement of a yeast cell trapped with Pi = 800mW (raw data). Time-course baseline-subtracted Raman spectra of trapped yeast, focusing on the 1550–1700cm−1 region are shown for (ii) Pi = 800mW, (iii) Pi = 400mW, and (iv) Pi = 200mW.
Fig. 7
Fig. 7 Formation of an immunological synapse (IS) between an adherent dendritic cell (DC) and optically trapped T cells monitored by RMS. (a) Raman spectra and microscope images at t=0 when a DC with one T cell already interacting has another T cell brought into contact using the HOT-RMS instrument. The schematic shows the locations from which Raman spectra were acquired (20s acquisition). (b) Raman spectra and microscope images showing further induced interactions with two more trapped T cells brought into contact with the same DC in (a) at t=+1hr, with a second schematic showing estimated sampling locations. (c) and (d) show Raman difference spectra between the oldest IS junction (J1) and the new junctions J3 and J4 (measured at t=+1hr shortly after their formation). Raman spectra in (a) and (b) have a linear baseline and quartz background subtracted, wheras (c) and (d) show raw Raman spectral data. (e) Time-course Raman spectra for a trapped T cell (raw data), with carotenoid Raman band locations at 1157cm−1 and 1525cm−1 highlighted. All scale bars 10µm.

Equations (1)

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P i = η P 0 N ± ϵ

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