Abstract

We report a novel fiber probe based Raman detection system on a microfluidic platform where a split Raman probe is directly embedded into a polydimethylsiloxane (PDMS) chip. In contrast to previous Raman detection schemes in microfluidics, probe based detection offers reduced background and portability. Compared to conventional backscattering probe designs, the split fiber probe we used in this system, results in a reduced size and offers flexibility to modify the collection geometry to minimize the background generated by the fibers. Also our microfluidic chip design enables us to obtain an alignment free system. As a proof of concept we demonstrate the sensitivity of the device for urea detection at relevant human physiological levels with a low acquisition time. The development of this system on a microfluidic platform means portable, lab on a chip devices for biological analyte detection and environmental sensing using Raman spectroscopy are now within reach.

© 2010 OSA

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  1. K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
    [CrossRef]
  2. R. Daw and J. Finkelstein, “Lab on a chip,” Nature 442(7101), 367–367 (2006).
    [CrossRef]
  3. P. J. Viskari and J. P. Landers, “Unconventional detection methods for microfluidic devices,” Electrophoresis 27(9), 1797–1810 (2006).
    [CrossRef] [PubMed]
  4. R. M. Connatser, L. A. Riddle, and M. J. Sepaniak, “Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection,” J. Sep. Sci. 27(17-18), 1545–1550 (2004).
    [CrossRef]
  5. L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
    [CrossRef] [PubMed]
  6. K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
    [CrossRef] [PubMed]
  7. S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
    [CrossRef]
  8. J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43(3), 542–554 (2004).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  10. H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
    [CrossRef] [PubMed]
  11. U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8(1), 121–147 (2003).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  13. J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
    [CrossRef] [PubMed]
  14. B. X. Yang and L. Bankir, ““Urea and urine concentrating ability: new insights from studies in mice,” Am,” J. Physiol-Renal 288(5), F881–F896 (2005).
    [CrossRef]
  15. I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
    [CrossRef] [PubMed]
  16. J. W. McMurdy and A. J. Berger, “Raman spectroscopy-based creatinine measurement in urine samples from a multipatient population,” Appl. Spectrosc. 57(5), 522–525 (2003).
    [CrossRef] [PubMed]
  17. A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
    [CrossRef]

2010 (1)

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

2009 (2)

Y. Komachi, T. Katagiri, H. Sato, and H. Tashiro, “Improvement and analysis of a micro Raman probe,” Appl. Opt. 48(9), 1683–1696 (2009).
[CrossRef] [PubMed]

I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
[CrossRef] [PubMed]

2008 (1)

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

2006 (2)

R. Daw and J. Finkelstein, “Lab on a chip,” Nature 442(7101), 367–367 (2006).
[CrossRef]

P. J. Viskari and J. P. Landers, “Unconventional detection methods for microfluidic devices,” Electrophoresis 27(9), 1797–1810 (2006).
[CrossRef] [PubMed]

2005 (3)

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
[CrossRef]

B. X. Yang and L. Bankir, ““Urea and urine concentrating ability: new insights from studies in mice,” Am,” J. Physiol-Renal 288(5), F881–F896 (2005).
[CrossRef]

2004 (2)

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43(3), 542–554 (2004).
[CrossRef] [PubMed]

R. M. Connatser, L. A. Riddle, and M. J. Sepaniak, “Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection,” J. Sep. Sci. 27(17-18), 1545–1550 (2004).
[CrossRef]

2003 (2)

2000 (2)

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

1999 (1)

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

1998 (1)

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

Anderson, J. R.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

Bankir, L.

B. X. Yang and L. Bankir, ““Urea and urine concentrating ability: new insights from studies in mice,” Am,” J. Physiol-Renal 288(5), F881–F896 (2005).
[CrossRef]

Barman, I.

I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
[CrossRef] [PubMed]

Bennett, B.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Berger, A. J.

Bruining, H. A.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Bruschke, A. V.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Buschman, H. P.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Chiu, D. T.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

Choo, J.

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

Connatser, R. M.

R. M. Connatser, L. A. Riddle, and M. J. Sepaniak, “Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection,” J. Sep. Sci. 27(17-18), 1545–1550 (2004).
[CrossRef]

Dasari, R. R.

I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
[CrossRef] [PubMed]

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43(3), 542–554 (2004).
[CrossRef] [PubMed]

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

Daw, R.

R. Daw and J. Finkelstein, “Lab on a chip,” Nature 442(7101), 367–367 (2006).
[CrossRef]

De Luca, A. C.

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

deMello, A. J.

S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
[CrossRef]

Dholakia, K.

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

Do, K. J.

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

Duffy, D. C.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

Enger, J.

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Feld, M. S.

I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
[CrossRef] [PubMed]

J. T. Motz, M. Hunter, L. H. Galindo, J. A. Gardecki, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Optical fiber probe for biomedical Raman spectroscopy,” Appl. Opt. 43(3), 542–554 (2004).
[CrossRef] [PubMed]

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

Finkelstein, J.

R. Daw and J. Finkelstein, “Lab on a chip,” Nature 442(7101), 367–367 (2006).
[CrossRef]

Galindo, L. H.

Gardecki, J. A.

Goksör, M.

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Hanstorp, D.

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Herrington, C. S.

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

Hunter, M.

Itzkan, I.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

Käll, M.

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Katagiri, T.

Kneipp, H.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

Kneipp, K.

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

Komachi, Y.

Kramer, J. R.

Landers, J. P.

P. J. Viskari and J. P. Landers, “Unconventional detection methods for microfluidic devices,” Electrophoresis 27(9), 1797–1810 (2006).
[CrossRef] [PubMed]

Leung, S. A.

S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
[CrossRef]

Lim, C.

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

Logg, K.

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Mahadevan-Jansen, A.

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

Marple, E. T.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Mazilu, M.

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

McDonald, J. C.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

McMurdy, J. W.

Mitchell, M. F.

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

Motz, J. T.

Puppels, G. J.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Quang, L. X.

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

Ramanujam, N.

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

Ramser, K.

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Richards-Kortum, R.

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

Richards-Kortum, R. R.

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8(1), 121–147 (2003).
[CrossRef] [PubMed]

Riches, A.

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

Riddle, L. A.

R. M. Connatser, L. A. Riddle, and M. J. Sepaniak, “Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection,” J. Sep. Sci. 27(17-18), 1545–1550 (2004).
[CrossRef]

Sato, H.

Schueller, O. J. A.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

Schut, T. C.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Seong, G. H.

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

Sepaniak, M. J.

R. M. Connatser, L. A. Riddle, and M. J. Sepaniak, “Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection,” J. Sep. Sci. 27(17-18), 1545–1550 (2004).
[CrossRef]

Singh, G. P.

I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
[CrossRef] [PubMed]

Tashiro, H.

Utzinger, U.

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8(1), 121–147 (2003).
[CrossRef] [PubMed]

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

van der Laarse, A.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Viskari, P. J.

P. J. Viskari and J. P. Landers, “Unconventional detection methods for microfluidic devices,” Electrophoresis 27(9), 1797–1810 (2006).
[CrossRef] [PubMed]

Wach, M. L.

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

Whitesides, G. M.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

Winkle, R. F.

S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
[CrossRef]

Wootton, R. C. R.

S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
[CrossRef]

Wu, H.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

Yang, B. X.

B. X. Yang and L. Bankir, ““Urea and urine concentrating ability: new insights from studies in mice,” Am,” J. Physiol-Renal 288(5), F881–F896 (2005).
[CrossRef]

Yoo, S. K.

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

Anal. Chem. (3)

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, “In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy,” Anal. Chem. 72(16), 3771–3775 (2000).
[CrossRef] [PubMed]

I. Barman, G. P. Singh, R. R. Dasari, and M. S. Feld, “Turbidity-corrected Raman spectroscopy for blood analyte detection,” Anal. Chem. 81(11), 4233–4240 (2009).
[CrossRef] [PubMed]

A. C. De Luca, M. Mazilu, A. Riches, C. S. Herrington, and K. Dholakia, “Online fluorescence suppression in modulated Raman spectroscopy,” Anal. Chem. 82(2), 738–745 (2010).
[CrossRef]

Analyst (Lond.) (1)

S. A. Leung, R. F. Winkle, R. C. R. Wootton, and A. J. deMello, “A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection,” Analyst (Lond.) 130(1), 46–51 (2005).
[CrossRef]

Appl. Opt. (2)

Appl. Spectrosc. (1)

Chem. Rev. (1)

K. Kneipp, H. Kneipp, I. Itzkan, R. R. Dasari, and M. S. Feld, “Ultrasensitive chemical analysis by Raman spectroscopy,” Chem. Rev. 99(10), 2957–2976 (1999).
[CrossRef]

Electrophoresis (2)

P. J. Viskari and J. P. Landers, “Unconventional detection methods for microfluidic devices,” Electrophoresis 27(9), 1797–1810 (2006).
[CrossRef] [PubMed]

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. A. Schueller, and G. M. Whitesides, “Fabrication of microfluidic systems in poly(dimethylsiloxane),” Electrophoresis 21(1), 27–40 (2000).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8(1), 121–147 (2003).
[CrossRef] [PubMed]

J. Physiol-Renal (1)

B. X. Yang and L. Bankir, ““Urea and urine concentrating ability: new insights from studies in mice,” Am,” J. Physiol-Renal 288(5), F881–F896 (2005).
[CrossRef]

J. Sep. Sci. (1)

R. M. Connatser, L. A. Riddle, and M. J. Sepaniak, “Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection,” J. Sep. Sci. 27(17-18), 1545–1550 (2004).
[CrossRef]

Lab Chip (2)

L. X. Quang, C. Lim, G. H. Seong, J. Choo, K. J. Do, and S. K. Yoo, “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8(12), 2214–2219 (2008).
[CrossRef] [PubMed]

K. Ramser, J. Enger, M. Goksör, D. Hanstorp, K. Logg, and M. Käll, “A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells,” Lab Chip 5(4), 431–436 (2005).
[CrossRef] [PubMed]

Nature (1)

R. Daw and J. Finkelstein, “Lab on a chip,” Nature 442(7101), 367–367 (2006).
[CrossRef]

Photochem. Photobiol. (1)

A. Mahadevan-Jansen, M. F. Mitchell, N. Ramanujam, U. Utzinger, and R. Richards-Kortum, “Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo,” Photochem. Photobiol. 68(3), 427–431 (1998).
[CrossRef] [PubMed]

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Figures (5)

Fig. 1
Fig. 1

[a] Design of the microfluidic chip. The head of the fiber probe is inserted to the chip and the analyte to be detected is injected to the chip through inlet and goes out through outlet [b] Photograph of the PDMS based chip where collection and excitation probes are inserted

Fig. 2
Fig. 2

Photograph of the probe based microfluidic Raman detection system

Fig. 3
Fig. 3

Raman spectra of ethanol recorded for an acquisition time of 5s for probes at 90° and 180° orientations

Fig. 4
Fig. 4

Plot of concentration vs. SNR for Raman spectra of Urea. The ‘ + ’ symbol represents the SNR measured at a particular concentration from 10 spectra recorded with 5s acquisition time each. The solid line represents the linear fit for the evaluated SNR data. The dotted line represent the limit of detection where SNR = 1. The Noise Equivalent Concentration (NEC) is evaluated as 0.144 from the plot.

Fig. 5
Fig. 5

Plot of ethanol Raman peak intensity at 884 cm−1vs. flow speed for an acquisition time of 5s

Equations (3)

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Θ = Ω ' × A
Ω ' = π × ( N A ) 2
Δ c = σ s o l f

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