Abstract

Fast, label-free optical identification and quantification of biomolecules and other relevant biological materials in microfluidic devices and the vascular system will play a major role in liquid biopsy and related diagnoses. An optical microscope probing simultaneously non-linear coherent anti-Stokes Raman scattering (CARS) and linear scattering (LS) was used to probe microparticles in aqueous solutions flowed unconstrained in microfluidic channels. Despite the optical complexity of these systems, where out-of-focus microparticles randomly impede CARS and LS, and where water CARS generates a substantial background, we demonstrate that in-focus microparticles can be individually and unambiguously detected when CARS and LS are co-analyzed. The ability to chemically discriminate microscale features in optically realistic flows supports the relevance of multimodal CARS platforms for liquid biopsy.

© 2018 Optical Society of America

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References

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  1. I. A. Cree, “Liquid biopsy for cancer patients: principles and practice,” Pathogenesis 2, 1–4 (2015).
    [Crossref]
  2. N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
    [Crossref]
  3. A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
    [Crossref]
  4. D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006).
    [Crossref]
  5. M. I. Mohammed and M. P. Y. Desmulliez, “Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection,” Biosens. Bioelectron. 61, 478–484 (2014).
    [Crossref]
  6. E. B. Magnusson, S. Halldorsson, R. M. T. Fleming, and K. Leosson, “Real-time optical pH measurement in a standard microfluidic cell culture system,” Biomed. Opt. Express 4, 1749–1758 (2013).
    [Crossref]
  7. R. R. Anderson and J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
    [Crossref]
  8. M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
    [Crossref]
  9. S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
    [Crossref]
  10. A. J. deMello, “Control and detection of chemical reactions in microfluidic systems,” Nature 442, 394–402 (2006).
    [Crossref]
  11. X. Mao, J. R. Waldeisen, and T. J. Huang, ““Microfluidic drifting”—implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device,” Lab Chip 7, 1260–1262 (2007).
    [Crossref]
  12. A. Zumbusch, G. Holtom, and X. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82, 4142–4145 (1999).
    [Crossref]
  13. C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu. Rev. Anal. Chem. 1, 883–909 (2008).
    [Crossref]
  14. W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
    [Crossref]
  15. A. Barbara, F. Dubois, P. Quémerais, and L. Eng, “Non-resonant and non-enhanced Raman correlation spectroscopy,” Opt. Express 21, 15418–15429 (2013).
    [Crossref]
  16. F. Ganikhanov, C. L. Evans, B. G. Saar, and X. S. Xie, “High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy,” Opt. Lett. 31, 1872–1874 (2006).
    [Crossref]
  17. C. L. Evans, E. O. Potma, and X. S. Xie, “Coherent anti-Stokes Raman scattering spectral interferometry: determination of the real and imaginary components of nonlinear susceptibility χ^(3) for vibrational microscopy,” Opt. Lett. 29, 2923–2925 (2004).
    [Crossref]
  18. E. O. Potma, C. L. Evans, and X. S. Xie, “Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging,” Opt. Lett. 31, 241–243 (2006).
    [Crossref]
  19. T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
    [Crossref]
  20. J. Cheng, E. O. Potma, and S. X. Xie, “Coherent anti-stokes Raman scattering correlation spectroscopy: probing dynamical processes with chemical selectivity,” J. Phys. Chem. A 106, 8561–8568 (2002).
    [Crossref]
  21. K. A. Bailey and Z. D. Schultz, “Tracking bulk and interfacial diffusion using multiplex coherent anti-stokes Raman scattering correlation spectroscopy,” J. Phys. Chem. B 120, 6819–6828 (2016).
    [Crossref]
  22. M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
    [Crossref]
  23. C. H. Camp, S. Yegnanarayanan, A. A. Eftekhar, H. Sridhar, and A. Adibi, “Multiplex coherent anti-Stokes Raman scattering (MCARS) for chemically sensitive, label-free flow cytometry,” Opt. Express 17, 22879–22889 (2009).
    [Crossref]
  24. C. H. Camp, S. Yegnanarayanan, A. A. Eftekhar, and A. Adibi, “Label-free flow cytometry using multiplex coherent anti-Stokes Raman scattering (MCARS) for the analysis of biological specimens,” Opt. Lett. 36, 2309–2311 (2011).
    [Crossref]
  25. H.-W. Wang, N. Bao, T. L. Le, C. Lu, and J.-X. Cheng, “Microfluidic CARS cytometry,” Opt. Express 16, 5782–5789 (2008).
    [Crossref]
  26. G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
    [Crossref]

2017 (1)

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

2016 (2)

K. A. Bailey and Z. D. Schultz, “Tracking bulk and interfacial diffusion using multiplex coherent anti-stokes Raman scattering correlation spectroscopy,” J. Phys. Chem. B 120, 6819–6828 (2016).
[Crossref]

M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
[Crossref]

2015 (2)

I. A. Cree, “Liquid biopsy for cancer patients: principles and practice,” Pathogenesis 2, 1–4 (2015).
[Crossref]

N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
[Crossref]

2014 (1)

M. I. Mohammed and M. P. Y. Desmulliez, “Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection,” Biosens. Bioelectron. 61, 478–484 (2014).
[Crossref]

2013 (3)

E. B. Magnusson, S. Halldorsson, R. M. T. Fleming, and K. Leosson, “Real-time optical pH measurement in a standard microfluidic cell culture system,” Biomed. Opt. Express 4, 1749–1758 (2013).
[Crossref]

A. Barbara, F. Dubois, P. Quémerais, and L. Eng, “Non-resonant and non-enhanced Raman correlation spectroscopy,” Opt. Express 21, 15418–15429 (2013).
[Crossref]

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

2011 (1)

2009 (1)

2008 (2)

H.-W. Wang, N. Bao, T. L. Le, C. Lu, and J.-X. Cheng, “Microfluidic CARS cytometry,” Opt. Express 16, 5782–5789 (2008).
[Crossref]

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu. Rev. Anal. Chem. 1, 883–909 (2008).
[Crossref]

2007 (1)

X. Mao, J. R. Waldeisen, and T. J. Huang, ““Microfluidic drifting”—implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device,” Lab Chip 7, 1260–1262 (2007).
[Crossref]

2006 (4)

F. Ganikhanov, C. L. Evans, B. G. Saar, and X. S. Xie, “High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy,” Opt. Lett. 31, 1872–1874 (2006).
[Crossref]

E. O. Potma, C. L. Evans, and X. S. Xie, “Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging,” Opt. Lett. 31, 241–243 (2006).
[Crossref]

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006).
[Crossref]

A. J. deMello, “Control and detection of chemical reactions in microfluidic systems,” Nature 442, 394–402 (2006).
[Crossref]

2004 (1)

2002 (2)

T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
[Crossref]

J. Cheng, E. O. Potma, and S. X. Xie, “Coherent anti-stokes Raman scattering correlation spectroscopy: probing dynamical processes with chemical selectivity,” J. Phys. Chem. A 106, 8561–8568 (2002).
[Crossref]

1999 (1)

A. Zumbusch, G. Holtom, and X. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82, 4142–4145 (1999).
[Crossref]

1998 (1)

W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
[Crossref]

1995 (1)

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

1988 (1)

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

1981 (1)

R. R. Anderson and J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[Crossref]

Adibi, A.

Anderson, R. R.

R. R. Anderson and J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[Crossref]

Bailey, K. A.

K. A. Bailey and Z. D. Schultz, “Tracking bulk and interfacial diffusion using multiplex coherent anti-stokes Raman scattering correlation spectroscopy,” J. Phys. Chem. B 120, 6819–6828 (2016).
[Crossref]

Bao, N.

Barbara, A.

Bartlett, J.

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

Bonn, M.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Camp, C. H.

Cheng, J.

J. Cheng, E. O. Potma, and S. X. Xie, “Coherent anti-stokes Raman scattering correlation spectroscopy: probing dynamical processes with chemical selectivity,” J. Phys. Chem. A 106, 8561–8568 (2002).
[Crossref]

Cheng, J.-X.

Cheng, Y.

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

Ciancaleoni, G.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Cope, M.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

Cree, I. A.

I. A. Cree, “Liquid biopsy for cancer patients: principles and practice,” Pathogenesis 2, 1–4 (2015).
[Crossref]

Day, J. P. R.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Delpy, D. T.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

deMello, A. J.

A. J. deMello, “Control and detection of chemical reactions in microfluidic systems,” Nature 442, 394–402 (2006).
[Crossref]

Desmulliez, M. P. Y.

M. I. Mohammed and M. P. Y. Desmulliez, “Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection,” Biosens. Bioelectron. 61, 478–484 (2014).
[Crossref]

Di Meo, A.

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

Dubois, F.

Eftekhar, A. A.

Eng, L.

Esterowitz, D.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

Evans, C. L.

Fleming, R. M. T.

Ganikhanov, F.

Grossman, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

Halldorsson, S.

Hellerer, T.

T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
[Crossref]

Holtom, G.

A. Zumbusch, G. Holtom, and X. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82, 4142–4145 (1999).
[Crossref]

Horn, D.

W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
[Crossref]

Huang, T. J.

X. Mao, J. R. Waldeisen, and T. J. Huang, ““Microfluidic drifting”—implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device,” Lab Chip 7, 1260–1262 (2007).
[Crossref]

Jung, G.

T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
[Crossref]

Karachaliou, N.

N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
[Crossref]

Klingler, J. F.

W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
[Crossref]

Le, T. L.

Leosson, K.

Lu, C.

Magnusson, E. B.

Mao, X.

X. Mao, J. R. Waldeisen, and T. J. Huang, ““Microfluidic drifting”—implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device,” Lab Chip 7, 1260–1262 (2007).
[Crossref]

Mayo-de-Las-Casas, C.

N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
[Crossref]

Mohammed, M. I.

M. I. Mohammed and M. P. Y. Desmulliez, “Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection,” Biosens. Bioelectron. 61, 478–484 (2014).
[Crossref]

Molina-Vila, M. A.

N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
[Crossref]

Oshovsky, G. V.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Parekh, S. H.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Parrish, J. A.

R. R. Anderson and J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[Crossref]

Pasic, M. D.

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

Potma, E. O.

Psaltis, D.

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006).
[Crossref]

Quake, S. R.

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006).
[Crossref]

Quémerais, P.

Rabasovic, M. D.

M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
[Crossref]

Rago, G.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Rajadhyaksha, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

Reek, J. N. H.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Reynolds, E. O. R.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

Rock, W.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Rosell, R.

N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
[Crossref]

Rox Anderson, R.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

Rozouvan, S.

W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
[Crossref]

Saar, B. G.

Schiller, A.

T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
[Crossref]

Schrof, W.

W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
[Crossref]

Schultz, Z. D.

K. A. Bailey and Z. D. Schultz, “Tracking bulk and interfacial diffusion using multiplex coherent anti-stokes Raman scattering correlation spectroscopy,” J. Phys. Chem. B 120, 6819–6828 (2016).
[Crossref]

Sisamakis, E.

M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
[Crossref]

Soudijn, M. L.

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Sridhar, H.

Waldeisen, J. R.

X. Mao, J. R. Waldeisen, and T. J. Huang, ““Microfluidic drifting”—implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device,” Lab Chip 7, 1260–1262 (2007).
[Crossref]

Wang, H.-W.

Webb, R. H.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

Wennmalm, S.

M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
[Crossref]

Widengren, J.

M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
[Crossref]

Wray, S.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

Wyatt, J. S.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

Xie, S. X.

J. Cheng, E. O. Potma, and S. X. Xie, “Coherent anti-stokes Raman scattering correlation spectroscopy: probing dynamical processes with chemical selectivity,” J. Phys. Chem. A 106, 8561–8568 (2002).
[Crossref]

Xie, X.

A. Zumbusch, G. Holtom, and X. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82, 4142–4145 (1999).
[Crossref]

Xie, X. S.

Yang, C.

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006).
[Crossref]

Yegnanarayanan, S.

Yousef, G. M.

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

Zumbusch, A.

T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
[Crossref]

A. Zumbusch, G. Holtom, and X. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82, 4142–4145 (1999).
[Crossref]

Anal. Chem. (1)

G. V. Oshovsky, G. Rago, J. P. R. Day, M. L. Soudijn, W. Rock, S. H. Parekh, G. Ciancaleoni, J. N. H. Reek, and M. Bonn, “Coherent anti-stokes Raman scattering microspectroscopic kinetic study of fast hydrogen bond formation in microfluidic devices,” Anal. Chem. 85, 8923–8927 (2013).
[Crossref]

Ann. Transl. Med. (1)

N. Karachaliou, C. Mayo-de-Las-Casas, M. A. Molina-Vila, and R. Rosell, “Real-time liquid biopsies become a reality in cancer treatment,” Ann. Transl. Med. 3, 36 (2015).
[Crossref]

Annu. Rev. Anal. Chem. (1)

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu. Rev. Anal. Chem. 1, 883–909 (2008).
[Crossref]

Biochim. Biophys. Acta (1)

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta 933, 184–192 (1988).
[Crossref]

Biomed. Opt. Express (1)

Biosens. Bioelectron. (1)

M. I. Mohammed and M. P. Y. Desmulliez, “Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection,” Biosens. Bioelectron. 61, 478–484 (2014).
[Crossref]

Chem. Phys. Chem. (2)

T. Hellerer, A. Schiller, G. Jung, and A. Zumbusch, “Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy,” Chem. Phys. Chem. 3, 630–633 (2002).
[Crossref]

M. D. Rabasovic, E. Sisamakis, S. Wennmalm, and J. Widengren, “Label-free fluctuation spectroscopy based on coherent anti-stokes Raman scattering from bulk water molecules,” Chem. Phys. Chem. 17, 1025–1033 (2016).
[Crossref]

J. Invest. Dermatol. (2)

R. R. Anderson and J. A. Parrish, “The optics of human skin,” J. Invest. Dermatol. 77, 13–19 (1981).
[Crossref]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. Rox Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[Crossref]

J. Phys. Chem. A (1)

J. Cheng, E. O. Potma, and S. X. Xie, “Coherent anti-stokes Raman scattering correlation spectroscopy: probing dynamical processes with chemical selectivity,” J. Phys. Chem. A 106, 8561–8568 (2002).
[Crossref]

J. Phys. Chem. B (1)

K. A. Bailey and Z. D. Schultz, “Tracking bulk and interfacial diffusion using multiplex coherent anti-stokes Raman scattering correlation spectroscopy,” J. Phys. Chem. B 120, 6819–6828 (2016).
[Crossref]

Lab Chip (1)

X. Mao, J. R. Waldeisen, and T. J. Huang, ““Microfluidic drifting”—implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device,” Lab Chip 7, 1260–1262 (2007).
[Crossref]

Mol. Cancer (1)

A. Di Meo, J. Bartlett, Y. Cheng, M. D. Pasic, and G. M. Yousef, “Liquid biopsy: a step forward towards precision medicine in urologic malignancies,” Mol. Cancer 16, 80 (2017).
[Crossref]

Nature (2)

D. Psaltis, S. R. Quake, and C. Yang, “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006).
[Crossref]

A. J. deMello, “Control and detection of chemical reactions in microfluidic systems,” Nature 442, 394–402 (2006).
[Crossref]

Opt. Express (3)

Opt. Lett. (4)

Pathogenesis (1)

I. A. Cree, “Liquid biopsy for cancer patients: principles and practice,” Pathogenesis 2, 1–4 (2015).
[Crossref]

Phys. Rev. E (1)

W. Schrof, J. F. Klingler, S. Rozouvan, and D. Horn, “Raman correlation spectroscopy: a method for studying chemical composition and dynamics of disperse systems,” Phys. Rev. E 57, R2523–R2526 (1998).
[Crossref]

Phys. Rev. Lett. (1)

A. Zumbusch, G. Holtom, and X. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82, 4142–4145 (1999).
[Crossref]

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Figures (5)

Fig. 1.
Fig. 1. Multimodal CARS microscope with microfluidics, also including a charged-coupled device (CCD) camera for alignment. The pump and Stokes input beams are combined with a beam splitter (Thorlabs BSW29), and CARS and LS outputs are separated with a dichroic mirror (Thorlabs DMLP605). M, mirror; BS, beam splitter; DL, delay line; DM, dichroic mirror; OBJ, objective; MF, microfluidics; L, lens; PH, pinhole; PD, photodiode; SF, spectral filter; PM, photomultiplier.
Fig. 2.
Fig. 2. CARS (orange) and spontaneous Raman (red) spectra of PS microparticles dried on glass. A CARS spectrum reconstructed from microfluidic time traces is also shown (blue). Inset: CARS image of PS microparticles with the Raman shift changed from 3050  cm1 to 2820  cm1 halfway through.
Fig. 3.
Fig. 3. (a) LS pump transmission image showing four clustered PS microparticles on glass (scale bar 5 µm). (b) CARS image (Raman shift 3050  cm1) of the same area as in (a). (c) Line profiles extracted from (a) and (b) normalized so that the maximum signal is 1. (d) LS versus CARS scatter plot constructed from the data in (c). The plot exhibits a U-shape with the C branch marking positions in the line profiles where the microparticle crosses the optical focus and thus where the PS resonant CARS signal is measured. The S branch marks those positions where there is no microparticle and where the LS is decreased from scattering at the microparticle edges.
Fig. 4.
Fig. 4. (a)–(i) LS versus CARS 2D histograms with the Raman shift set from 2800  cm1 to 3200  cm1. The histograms are presented in logarithmic scale to emphasize the C branches, clearly visible where CARS resonance occurs. The counts were normalized so that for all plots the sum of all bins is 1.
Fig. 5.
Fig. 5. (a) 2D histogram at 3050  cm1; also shown is the boundary between C and S branches (dashed line) used to extract the events shown in (d). The whole histogram count is normalized to 1. (b) LS and (c) CARS 1D histograms at 2800  cm1 (orange) and 3050  cm1 (blue), offset for clarity. S branch dominates over C branch. (d) 1D CARS histograms of the extracted C branches at 2800  cm1 and 3050  cm1 (linear norm. count scale).

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