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Microfluidic Raman Spectroscopy for Bio-chemical Sensing and Analysis

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Part of the book series: Springer Series on Chemical Sensors and Biosensors ((SSSENSORS,volume 10))

Abstract

The detection and analysis of bio-chemical analytes are important in the fields of personal healthcare, drug development, and environmental science, among others. The field of microfluidics aims to realize portable devices which can perform fast and sensitive bioanalyte detection with minimal sample preparation. Raman spectroscopy is a powerful tool for analyte detection owing to its high specificity and its ability for multi-component detection in an analyte. Combining microfluidics with Raman spectroscopy would help achieve miniaturized analytical devices that may provide rich information about a given analyte. However, the low cross-section of Raman process demands special geometries to achieve such a convergence. The majority of the previous embodiments were restricted to free-space geometry, limiting portability. However, in recent studies, fiber-based Raman detection system incorporated in microfluidics offers the opportunity to develop portable optofluidic bioanalyte detection devices. Here, we review various approaches used for using Raman spectroscopy in microfluidics for analyte detection, and various analytical approaches that could be used to enhance the detection sensitivity of Raman spectroscopy-based detection. This is followed by a detailed discussion about the fiber-based optofluidic Raman detection systems.

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References

  1. Viskari PJ, Landers JP (2006) Unconventional detection methods for microfluidic devices. Electrophoresis 27(9):1797–1810. doi:10.1002/elps.200500565

    Article  CAS  Google Scholar 

  2. Mogensen KB, Klank H, Kutter JP (2004) Recent developments in detection for microfluidic systems. Electrophoresis 25(21–22):3498–3512. doi:10.1002/elps.200406108

    Article  CAS  Google Scholar 

  3. Hunt HC, Wilkinson JS (2008) Optofluidic integration for microanalysis. Microfluid Nanofluid 4(1–2):53–79. doi:10.1007/s10404-007-0223-y

    Article  CAS  Google Scholar 

  4. Raman CV, Krishnan KS (1928) A new type of secondary radiation. Nature 121:501–502. doi:10.1038/121501c0

    Article  CAS  Google Scholar 

  5. Lombardi JR, Birke RL (2008) A unified approach to surface-enhanced Raman spectroscopy. J Phys Chem C 112(14):5605–5617. doi:10.1021/Jp800167v

    Article  CAS  Google Scholar 

  6. Gotz S, Karst U (2007) Recent developments in optical detection methods for microchip separations. Anal Bioanal Chem 387(1):183–192. doi:10.1007/s00216-006-0820-8

    Article  Google Scholar 

  7. Chen CY, Morris MD (1988) Raman-spectroscopic detection system for capillary zone electrophoresis. Appl Spectrosc 42(3):515–518

    Article  CAS  Google Scholar 

  8. Chen C-Y, Morris MD (1991) On-line multichannel Raman spectroscopic detection system for capillary zone electrophoresis. J Chromatogr A 540:355–363

    Article  CAS  Google Scholar 

  9. Walker PA, Kowalchyk WK, Morris MD (1995) Online Raman spectroscopy of ribonucleotides preconcentrated by capillary isotachophoresis. Anal Chem 67(23):4255–4260. doi:10.1021/ac00119a009

    Article  CAS  Google Scholar 

  10. Walker PA, Morris MD, Burns MA, Johnson BN (1998) Isotachophoretic separations on a microchip. Normal Raman spectroscopy detection. Anal Chem 70(18):3766–3769

    Article  CAS  Google Scholar 

  11. Pan DH, Mathies RA (2001) Chromophore structure in lumirhodopsin and metarhodopsin I by time-resolved resonance Raman microchip spectroscopy. Biochemistry 40(26):7929–7936. doi:10.1021/Bi010670x

    Article  CAS  Google Scholar 

  12. Pan DH, Ganim Z, Kim JE, Verhoeven MA, Lugtenburg J, Mathies RA (2002) Time-resolved resonance Raman analysis of chromophore structural changes in the formation and decay of rhodopsin’s BSI intermediate. J Am Chem Soc 124(17):4857–4864. doi:10.1021/Ja012666e

    Article  CAS  Google Scholar 

  13. Keir R, Igata E, Arundell M, Smith WE, Graham D, McHugh C, Cooper JM (2002) SERRS. In situ substrate formation and improved detection using microfluidics. Anal Chem 74(7):1503–1508. doi:10.1021/Ac015625+

    Article  CAS  Google Scholar 

  14. Fortt R, Wootton RCR, de Mello AJ (2003) Continuous-flow generation of anhydrous diazonium species: monolithic microfluidic reactors for the chemistry of unstable intermediates. Org Process Res Dev 7(5):762–768. doi:10.1021/Op025586j

    Article  CAS  Google Scholar 

  15. Fletcher PDI, Haswell SJ, Zhang XL (2003) Monitoring of chemical reactions within microreactors using an inverted Raman microscopic spectrometer. Electrophoresis 24(18):3239–3245. doi:10.1002/elps.200305532

    Article  CAS  Google Scholar 

  16. Lee M, Lee JP, Rhee H, Choo J, Chai YG, Lee EK (2003) Applicability of laser-induced Raman microscopy for in situ monitoring of imine formation in a glass microfluidic chip. J Raman Spectrosc 34(10):737–742. doi:10.1002/Jrs.1038

    Article  CAS  Google Scholar 

  17. Park T, Lee M, Choo J, Kim YS, Lee EK, Kim DJ, Lee SH (2004) Analysis of passive mixing behavior in a poly(dimethylsiloxane) microfluidic channel using confocal fluorescence and Raman microscopy. Appl Spectrosc 58(10):1172–1179

    Article  CAS  Google Scholar 

  18. Leung SA, Winkle RF, Wootton RCR, deMello AJ (2005) A method for rapid reaction optimisation in continuous-flow microfluidic reactors using online Raman spectroscopic detection. Analyst 130(1):46–51. doi:10.1039/B412069h

    Article  CAS  Google Scholar 

  19. Urakawa A, Trachsel F, von Rohr PR, Baiker A (2008) On-chip Raman analysis of heterogeneous catalytic reaction in supercritical co2: phase behaviour monitoring and activity profiling. Analyst 133(10):1352–1354. doi:10.1039/B808984c

    Article  CAS  Google Scholar 

  20. Salmon JB, Ajdari A, Tabeling P, Servant L, Talaga D, Joanicot M (2005) In situ Raman imaging of interdiffusion in a microchannel. Appl Phys Lett 86(9):094106. doi:10.1063/1.1873050; Artn 094106

    Article  Google Scholar 

  21. Connatser RM, Riddle LA, Sepaniak MJ (2004) Metal-polymer nanocomposites for integrated microfluidic separations and surface enhanced Raman spectroscopic detection. J Sep Sci 27(17–18):1545–1550. doi:10.1002/jssc.200401886

    Article  CAS  Google Scholar 

  22. Yea K, Lee S, Kyong JB, Choo J, Lee EK, Joo SW, Lee S (2005) Ultra-sensitive trace analysis of cyanide water pollutant in a PDMS microfluidic channel using surface-enhanced Raman spectroscopy. Analyst 130(7):1009–1011. doi:10.1039/B501980j

    Article  CAS  Google Scholar 

  23. Liu GL, Lee LP (2005) Nanowell surface enhanced Raman scattering arrays fabricated by soft-lithography for label-free biomolecular detections in integrated microfluidics. Appl Phy Lett 87(7):074101. doi:10.1063/1.2031935

    Article  Google Scholar 

  24. Docherty FT, Monaghan PB, Keir R, Graham D, Smith WE, Cooper JM (2004) The first SERRS multiplexing from labelled oligonucleotides in a microfluidics lab-on-a-chip. Chem Commun 1:118–119

    Article  Google Scholar 

  25. Park T, Lee S, Seong GH, Choo J, Lee EK, Kim YS, Ji WH, Hwang SY, Gweon D-G, Lee S (2005) Highly sensitive signal detection of duplex dye-labelled DNA oligonucleotides in a pdms microfluidic chip: confocal surface-enhanced Raman spectroscopic study. Lab Chip 5(4):437–442

    Article  CAS  Google Scholar 

  26. Lee D, Lee S, Seong GH, Choo J, Lee EK, Gweon DG, Lee S (2006) Quantitative analysis of methyl parathion pesticides in a polydimethylsiloxane microfluidic channel using confocal surface-enhanced Raman spectroscopy. Appl Spectrosc 60(4):373–377

    Article  Google Scholar 

  27. Jung JH, Choo J, Kim DJ, Lee S (2006) Quantitative determination of nicotine in a PDMS microfluidic channel using surface enhanced Raman spectroscopy. Bull Kor Chem Soc 27(2):277–280

    Article  CAS  Google Scholar 

  28. Jung J, Chen LX, Lee S, Kim S, Seong GH, Choo J, Lee EK, Oh CH, Lee S (2007) Fast and sensitive DNA analysis using changes in the fret signals of molecular beacons in a PDMS microfluidic channel. Anal Bioanal Chem 387(8):2609–2615. doi:10.1007/s00216-007-1158-6

    Article  CAS  Google Scholar 

  29. Chen L, Choo J (2008) Recent advances in surface-enhanced Raman scattering detection technology for microfluidic chips. Electrophoresis 29(9):1815–1828. doi:10.1002/elps.200700554

    Article  CAS  Google Scholar 

  30. Huebner A, Sharma S, Srisa-Art M, Hollfelder F, Edel JB, Demello AJ (2008) Microdroplets: a sea of applications? Lab Chip 8(8):1244–1254. doi:10.1039/B806405a

    Article  CAS  Google Scholar 

  31. Cristobal G, Arbouet L, Sarrazin F, Talaga D, Bruneel JL, Joanicot M, Servant L (2006) On-line laser Raman spectroscopic probing of droplets engineered in microfluidic devices. Lab Chip 6(9):1140–1146. doi:10.1039/B602702d

    Article  CAS  Google Scholar 

  32. Lau AY, Lee LP, Chan JW (2008) An integrated optofluidic platform for Raman-activated cell sorting. Lab Chip 8(7):1116–1120. doi:10.1039/b803598a

    Article  CAS  Google Scholar 

  33. Barnes SE, Cygan ZT, Yates JK, Beers KL, Amis EJ (2006) Raman spectroscopic monitoring of droplet polymerization in a microfluidic device. Analyst 131(9):1027–1033. doi:10.1039/B603693g

    Article  CAS  Google Scholar 

  34. Strehle KR, Cialla D, Rosch P, Henkel T, Kohler M, Popp J (2007) A reproducible surface-enhanced Raman spectroscopy approach. Online SERS measurements in a segmented microfluidic system. Anal Chem 79(4):1542–1547. doi:10.1021/Ac0615246

    Article  CAS  Google Scholar 

  35. Sarrazin F, Salmon JB, Talaga D, Servant L (2008) Chemical reaction imaging within microfluidic devices using confocal Raman spectroscopy: the case of water and deuterium oxide as a model system. Anal Chem 80(5):1689–1695. doi:10.1021/Ac7020147

    Article  CAS  Google Scholar 

  36. Salieb-Beugelaar GB, Simone G, Arora A, Philippi A, Manz A (2010) Latest developments in microfluidic cell biology and analysis systems. Anal Chem 82(12):4848–4864. doi:10.1021/ac1009707

    Article  CAS  Google Scholar 

  37. Stevenson DJ, Gunn-Moore F, Dholakia K (2010) Light forces the pace: optical manipulation for biophotonics. J Biomed Opt 15(4):041503

    Article  Google Scholar 

  38. Petrov DV (2007) Raman spectroscopy of optically trapped particles. J Opt A Pure Appl Opt 9(8):S139–S156. doi:10.1088/1464-4258/9/8/S06

    Article  CAS  Google Scholar 

  39. Ramser K, Enger J, Goksor M, Hanstorp D, Logg K, Kall M (2005) A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells. Lab Chip 5(4):431–436. doi:10.1039/b416749j

    Article  CAS  Google Scholar 

  40. Eriksson E, Scrimgeour J, Graneli A, Ramser K, Wellander R, Enger J, Hanstrop D, Goksor M (2007) Optical manipulation and microfluidics for studies of single cell dynamics. J Opt A Pure Appl Opt 9(8):S113–S121. doi:10.1088/1464-4258/9/8/S02

    Article  CAS  Google Scholar 

  41. Ramser K, Wenseleers W, Dewilde S, Van Doorslaer S, Moens L (2008) The combination of resonance Raman spectroscopy, optical tweezers and microfluidic systems applied to the study of various heme-containing single cells. Spectrosc-Int J 22(4):287–295. doi:10.3233/Spe-2008-0353

    Article  CAS  Google Scholar 

  42. Jess P, Garces-Chavez V, Smith D, Mazilu M, Riches A, Herrington CS, Sibbett W, Dholakia K (2006) A dual beam fibre trap for Raman micro-spectroscopy of single cells. J Pathol 210:28

    Google Scholar 

  43. Zhang XL, Yin HB, Cooper JM, Haswell SJ (2008) Characterization of cellular chemical dynamics using combined microfluidic and Raman techniques. Anal Bioanal Chem 390(3):833–840. doi:10.1007/s00216-007-1564-9

    Article  CAS  Google Scholar 

  44. Quang LX, Lim C, Seong GH, Choo J, Do KJ, Yoo SK (2008) A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis. Lab Chip 8(12):2214–2219. doi:10.1039/B808835g

    Article  CAS  Google Scholar 

  45. Mozharov S, Nordon A, Girkin JM, Littlejohn D (2010) Non-invasive analysis in micro-reactors using Raman spectrometry with a specially designed probe. Lab Chip 10(16):2101–2107. doi:10.1039/C004248j

    Article  CAS  Google Scholar 

  46. Connatser RM, Cochran M, Harrison RJ, Sepaniak MJ (2008) Analytical optimization of nanocomposite surface-enhanced Raman spectroscopy/scattering detection in microfluidic separation devices. Electrophoresis 29(7):1441–1450. doi:10.1002/elps.200700585

    Article  CAS  Google Scholar 

  47. Li HF, Lin JM, Su RG, Uchiyama K, Hobo T (2004) A compactly integrated laser-induced fluorescence detector for microchip electrophoresis. Electrophoresis 25(12):1907–1915. doi:10.1002/elps.200305867

    Article  CAS  Google Scholar 

  48. Ibarlucea B, Fernandez-Rosas E, Vila-Planas J, Demming S, Nogues C, Plaza JA, Büttgenbach S, Llobera A (2010) Cell screening using disposable photonic lab on a chip systems. Anal Chem 82(10):4246–4251. doi:10.1021/ac100590z

    Article  CAS  Google Scholar 

  49. Mahadevan-Jansen A, Mitchell MF, Ramanujam N, Utzinger U, Richards-Kortum R (1998) Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo. Photochem Photobiol 68(3):427–431

    Article  CAS  Google Scholar 

  50. Ashok PC, Singh GP, Tan KM, Dholakia K (2010) Fiber probe based microfluidic Raman spectroscopy. Opt Express 18(8):7642–7649

    Article  CAS  Google Scholar 

  51. McDonald JC, Duffy DC, Anderson JR, Chiu DT, Wu H, Schueller OJA, Whitesides GM (2000) Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21(1):27–40

    Article  CAS  Google Scholar 

  52. Utzinger U, Richards-Kortum RR (2003) Fiber optic probes for biomedical optical spectroscopy. J Biomed Opt 8(1):121–147

    Article  Google Scholar 

  53. Motz JT, Hunter M, Galindo LH, Gardecki JA, Kramer JR, Dasari RR, Feld MS (2004) Optical fiber probe for biomedical Raman spectroscopy. App Optics 43(3):542–554

    Article  Google Scholar 

  54. Ashok PC, Singh GP, Rendall HA, Krauss TF, Dholakia K (2011) Waveguide confined Raman spectroscopy for microfluidic interrogation. Lab Chip. doi:10.1039/c0lc00462f

  55. De Luca AC, Mazilu M, Riches A, Herrington CS, Dholakia K (2010) Online fluorescence suppression in modulated Raman spectroscopy. Anal Chem 82(2):738–745. doi:10.1021/Ac9026737

    Article  Google Scholar 

  56. Shreve AP, Cherepy NJ, Mathies RA (1992) Effective rejection of fluorescence interference in Raman spectroscopy using a shifted excitation difference technique. Appl Spectrosc 46(4):707–711

    Article  CAS  Google Scholar 

  57. Campani E et al (1981) A pulsed dye laser Raman spectrometer employing a new type of gated analogue detection. J Phys D Appl Phys 14(12):2189

    Article  CAS  Google Scholar 

  58. Ashok PC, Luca ACD, Mazilu M, Dholakia K (2011) Enhanced bioanalyte detection in waveguide confined Raman spectroscopy using modulation techniques. J Biophot. doi:10.1002/jbio.201000107

  59. Mazilu M, De Luca AC, Riches A, Herrington CS, Dholakia K (2010) Optimal algorithm for fluorescence suppression of modulated Raman spectroscopy. Opt Express 18(11):11382–11395

    Article  CAS  Google Scholar 

  60. Barman I, Singh GP, Dasari RR, Feld MS (2009) Turbidity-corrected Raman spectroscopy for blood analyte detection. Anal Chem 81(11):4233–4240. doi:10.1021/Ac8025509

    Article  CAS  Google Scholar 

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Acknowledgments

We thank the UK Engineering and Physical Sciences Research Council for funding. KD is a Royal Society-Wolfson Merit Award holder. The authors are grateful to Dr Andrew McKinley for critical reading of the manuscript and useful discussions.

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Correspondence to Praveen C. Ashok .

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Ashok, P.C., Dholakia, K. (2012). Microfluidic Raman Spectroscopy for Bio-chemical Sensing and Analysis. In: Fritzsche, W., Popp, J. (eds) Optical Nano- and Microsystems for Bioanalytics. Springer Series on Chemical Sensors and Biosensors, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25498-7_9

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