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Surface-enhanced Raman scattering: a new optical probe in molecular biophysics and biomedicine

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Abstract

Sensitive and detailed molecular structural information plays an increasing role in molecular biophysics and molecular medicine. Therefore, vibrational spectroscopic techniques, such as Raman scattering, which provide high structural information content are of growing interest in biophysical and biomedical research. Raman spectroscopy can be revolutionized when the inelastic scattering process takes place in the very close vicinity of metal nanostructures. Under these conditions, strongly increased Raman signals can be obtained due to resonances between optical fields and the collective oscillations of the free electrons in the metal. This effect of surface-enhanced Raman scattering (SERS) allows us to push vibrational spectroscopy to new limits in detection sensitivity, lateral resolution, and molecular structural selectivity. This opens up exciting perspectives also in molecular biospectroscopy. This article highlights three directions where SERS can offer interesting new capabilities. This includes SERS as a technique for detecting and tracking a single molecule, a SERS-based nanosensor for probing the chemical composition and the pH value in a live cell, and the effect of so-called surface-enhanced Raman optical activity, which provides information on the chiral organization of molecules on surfaces.

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References

  1. Gitai Z (2009) New fluorescence microscopy methods for microbiology: sharper, faster, and quantitative. Curr Opin Microbiol 12:341–346

    Article  CAS  Google Scholar 

  2. Xing Y, Xia ZY, Rao JH (2009) Semiconductor quantum dots for biosensing and in vivo imaging. IEEE Trans Nanobiosci 8:4–12

    Article  Google Scholar 

  3. Laserna JJ (1996) Modern techniques in Raman spectroscopy. Wiley, Chichester, New York, Brisbane, Toronto, Singapore

    Google Scholar 

  4. Puppels GJ, Mul FFMD, Otto C, Greve J, RobertNicoud M, Arndt-Jovin DJ, Jovin T (1990) Studying single living cells and chromosomes by confocal Raman microspectroscopy. Nature 347:301–303

    Article  CAS  Google Scholar 

  5. Hanlon EB, Manoharan R, Koo TW, Shafer KE, Motz JT, Fitzmaurice M, Kramer JR, Itzkan I, Dasari RR, Feld MS (2000) Prospects for in vivo Raman spectroscopy. Phys Med Biol 45:R1–R59

    Article  CAS  Google Scholar 

  6. Kneipp J, Bakker Schut TC, Kliffen M, Menke-Pluijmers M, Puppels GJ (2003) Characterization of breast duct epithelia: a Raman spectroscopic study. Vib Spectrosc 32:67–74

    Article  CAS  Google Scholar 

  7. Kneipp J, Miller LM, Joncic M, Kittel M, Lasch P, Beekes M, Naumann D (2003) In situ identification of protein structural changes in prion-infected tissue. Biochim Biophys Acta 1639:152–158

    CAS  Google Scholar 

  8. Scepanovic OR, Fitzmaurice M, Gardecki JA, Angheloiu GO, Awasthi S, Motz JT, Kramer JR, Dasari RR, Feld MS (2006) Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy. J Biomed Opt 11(2):021003

    Article  Google Scholar 

  9. Kneipp K (2007) Surface-enhanced Raman scattering. Phys Today 60:40–46

    Article  CAS  Google Scholar 

  10. Kneipp K, Kneipp H, Itzkan I, Dasari RR, Feld MS (2002) Surface-enhanced Raman scattering and biophysics. J Phys Condens Matter 14:R597–R624

    Article  CAS  Google Scholar 

  11. Kneipp K, Kneipp H (2006) Single molecule Raman scattering. Appl Spectrosc 60:322A–334A

    Article  CAS  Google Scholar 

  12. Stuart AD, Yuen JM, Shah NC, Lyandres O, Yonzon CR, Glucksberg MR, Walsh JT, Van Duyne RP (2006) In vivo glucose measurement by surface-enhanced Raman spectroscopy. Anal Chem 78:7211–7215

    Article  CAS  Google Scholar 

  13. Qian XM, Nie SM (2008) Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. Chem Soc Rev 37:912–920

    Article  CAS  Google Scholar 

  14. Kneipp J, Kneipp H, Kneipp K (2008) SERS—a single-molecule and nanoscale tool for bioanalytics. Chem Soc Rev 37:1052–1060

    Article  CAS  Google Scholar 

  15. Hering K, Cialla D, Ackermann K, Dorfer T, Moller R, Schneidewind H, Mattheis R, Fritzsche W, Rosch P, Popp J (2008) SERS: a versatile tool in chemical and biochemical diagnostics. Anal Bioanal Chem 390:113–124

    Article  CAS  Google Scholar 

  16. Qian XM, Peng XH, Ansari DO, Yin-Goen Q, Chen GZ, Shin DM, Yang L, Young AN, Wang MD, Nie SM (2008) In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol 26:83–90

    Article  CAS  Google Scholar 

  17. Anker JN, Hall WP, Lyandres O, Shah NC, Zhao J, Van Duyne RP (2008) Biosensing with plasmonic nanosensors. Nat Mater 7:442–453

    Article  CAS  Google Scholar 

  18. Hudson SD, Chumanov G (2009) Bioanalytical applications of SERS (surface-enhanced Raman spectroscopy). Anal Bioanal Chem 394:679–686

    Article  CAS  Google Scholar 

  19. Scaffidi JP, Gregas MK, Seewaldt V, Vo-Dinh T (2009) SERS-based plasmonic nanobiosensing in single living cells. Anal Bioanal Chem 393:1135–1141

    Article  CAS  Google Scholar 

  20. Barron LD, Zhu FJ, Hecht L, Tranter GE, Isaacs NW (2007) Raman optical activity: an incisive probe of molecular chirality and biomolecular structure. J Mol Struct 834:7–16

    Article  Google Scholar 

  21. Nafie LA (1996) Vibrational optical activity in focus. Appl Spectrosc 50:A12–A12

    Article  Google Scholar 

  22. Haesler J, Schindelholz I, Riguet E, Bochet CG, Hug W (2007) Absolute configuration of chirally deuterated neopentane. Nature 446:526–529

    Article  CAS  Google Scholar 

  23. Otto A (1984) Surface-enhanced Raman scattering: ‘classical’ and ‘chemical’ origins. In: Cardona M, Guntherodt G (eds) Light scattering in solids IV. Electronic scattering, spin effects, SERS and morphic effects, vol 1984. Springer, Berlin, pp 289–418

    Google Scholar 

  24. Moskovits M (1985) Surface-enhanced spectroscopy. Rev Mod Phys 57:783–826

    Article  CAS  Google Scholar 

  25. Campion A, Kambhampati P (1998) Surface-enhanced Raman scattering. Chem Soc Rev 27:241–250

    Article  CAS  Google Scholar 

  26. Stockman MI, Shalaev VM, Moskovits M, Botet R, George TF (1992) Enhanced Raman scattering by fractal clusters: scale-invariant theory. Phys Rev B 46:2821–2830

    Article  Google Scholar 

  27. Li KR, Stockman MI, Bergman DJ (2003) Self-similar chain of metal nanospheres as an efficient nanolens. Phys Rev Lett 91:227402

    Article  Google Scholar 

  28. Schatz GC, Young MA, Van Duyne RP (2006) Electromagnetic mechanism of SERS. In: Surface-enhanced Raman scattering: physics and applications, vol 103. Springer, Berlin, pp 19–45

  29. Kneipp J, Kneipp H, Kneipp K (2006) Two-photon vibrational spectroscopy for biosciences based on surface-enhanced hyper-Raman scattering. Proc Natl Acad Sci USA 103:17149–17153

    Article  CAS  Google Scholar 

  30. So PTC, Dong CY, Masters BR, Berland KM (2000) Two-photon excitation fluorescence microscopy. Ann Rev Biomed Eng 2:399–429

    Article  CAS  Google Scholar 

  31. Kobat D, Durst ME, Nishimura N, Wong AW, Schaffer CB, Xu C (2009) Deep tissue multiphoton microscopy using longer wavelength excitation. Opt Express 17:13354–13364

    Article  Google Scholar 

  32. Schade R, Weiss T, Liefeith K (2009) Two-photon techniques in tissue engineering. Int J Artif Organs 32:394

    Google Scholar 

  33. Stepanenko I, Kompanetz V, Makhneva Z, Chekalin S, Moskalenko A, Razjivin A (2009) Two-photon excitation spectroscopy of carotenoid-containing and carotenoid-depleted LH2 complexes from purple bacteria. J Phys Chem B 113:11720–11723

    Article  CAS  Google Scholar 

  34. Kneipp K, Kneipp H, Kartha VB, Manoharan R, Deinum G, Itzkan I, Dasari RR, Feld MS (1998) Detection and identification of a single DNA base molecule using surface-enhanced Raman scattering (SERS). Phys Rev E 57:R6281–R6284

    Article  CAS  Google Scholar 

  35. Kneipp K, Kneipp H, Abdali S, Berg RW, Bohr H (2004) Single molecule Raman detection of enkephalin on silver colloidal particles. Spectrosc Int J 18:433–440

    CAS  Google Scholar 

  36. Kneipp J (2006) Nanosensors based on SERS for applications in living cells. In: Surface-enhanced Raman scattering: physics and applications, vol 103. Springer, Berlin, pp 335–349

  37. Chourpa I, Lei FH, Dubois P, Manfait M, Sockalingum GD (2008) Intracellular applications of analytical SERS spectroscopy and multispectral imaging. Chem Soc Rev 37:993–1000

    Article  CAS  Google Scholar 

  38. Kneipp J, Kneipp H, Rice WL, Kneipp K (2005) Optical probes for biological applications based on surface-enhanced Raman scattering from indocyanine green on gold nanoparticles. Anal Chem 77:2381–2385

    Article  CAS  Google Scholar 

  39. Kneipp J, Kneipp H, McLaughlin M, Brown D, Kneipp K (2006) In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates. Nano Lett 6:2225–2231

    Article  CAS  Google Scholar 

  40. Dijkstra RJ, Scheenen W, Dam N, Roubos EW, ter Meulen JJ (2007) Monitoring neurotransmitter release using surface-enhanced Raman spectroscopy. J Neurosci Methods 159:43–50

    Article  CAS  Google Scholar 

  41. Michota A, Bukowska J (2003) Surface-enhanced Raman scattering (SERS) of 4-mercaptobenzoic acid on silver and gold substrates. J Raman Spectrosc 34:21–25

    Article  CAS  Google Scholar 

  42. Bishnoi SW, Rozell CJ, Levin CS, Gheith MK, Johnson BR, Johnson DH, Halas NJ (2006) All-optical nanoscale pH meter. Nano Lett 6:1687–1692

    Article  CAS  Google Scholar 

  43. Talley CE, Jusinski L, Hollars CW, Lane SM, Huser T (2004) Intracellular pH sensors based on surface-enhanced Raman scattering. Anal Chem 76:7064–7068

    Article  CAS  Google Scholar 

  44. Kneipp J, Kneipp H, Wittig B, Kneipp K (2007) One- and two-photon excited optical pH probing for cells using surface-enhanced Raman and hyper-Raman nanosensors. Nano Lett 7:2819–2823

    Article  CAS  Google Scholar 

  45. Muller N, Payan E, Lapicque F, Bannwarth B, Netter P (1990) Pharmacological aspects of chiral nonsteroidal antiinflammatory drugs. Fundam Clin Pharmacol 4:617–634

    Article  CAS  Google Scholar 

  46. Skelley AM, Scherer JR, Aubrey AD, Grover WH, Ivester RHC, Ehrenfreund P, Grunthaner FJ, Bada JL, Mathies RA (2005) Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars. Proc Natl Acad Sci USA 102:1041–1046

    Article  CAS  Google Scholar 

  47. Kumar AP, Jin D, Lee YI (2009) Recent development on spectroscopic methods for chiral analysis of enantiomeric compounds. Appl Spectrosc Rev 44:267–316

    Article  CAS  Google Scholar 

  48. Barron LD, Buckingham AD (1971) Raman optical activity. Mol Phys 20:1111

    Article  CAS  Google Scholar 

  49. Deplazes E, van Bronswijk W, Zhu F, Barron LD, Ma S, Nafie LA, Jalkanen KJ (2008) A combined theoretical and experimental study of the structure and vibrational absorption, vibrational circular dichroism, Raman and Raman optical activity spectra of the L-histidine zwitterion. Theor Chem Acc 119:155–176

    Article  CAS  Google Scholar 

  50. Jalkanen KJ, Degtyarenko IM, Nieminen XC, Nafie LA, Zhu F, Barron LD (2008) Role of hydration in determining the structure and vibrational spectra of L-alanine and N-acetyl L-alanine N′-methylamide in aqueous solution: a combined theoretical and experimental study. Theor Chem Acc 119:191–210

    Article  CAS  Google Scholar 

  51. Jensen L (2009) Surface-enhanced vibrational Raman optical activity: a time-dependent density functional theory approach. J Phys Chem A 113:4437–4444

    Article  CAS  Google Scholar 

  52. Kneipp H, Kneipp J, Kneipp K (2006) Surface enhanced Raman optical activity (SEROA) on adenine in silver colloidal solution. Anal Chem 78:1363

    Article  CAS  Google Scholar 

  53. Chen Q, Frankel DJ, Richardson NV (2002) Self-assembly of adenine on Cu(110) surfaces. Langmuir 2002:3219–3225

    Article  Google Scholar 

  54. Barron LD, Hecht L, McColl IH, Blanch EW (2004) Raman optical activity comes of age. Mol Phys 102:731–744

    Article  CAS  Google Scholar 

  55. Sass JK, Neff H, Moskovits M, Holloway S (1981) Electric field gradient effects on the spectroscopy of adsorbed molecules. J Phys Chem 85:621–623

    Article  CAS  Google Scholar 

  56. Efrima S (1983) The effect of large electric-field gradients on the Raman optical-activity of molecules adsorbed on metal-surfaces. Chem Phys Lett 102:79–82

    Article  CAS  Google Scholar 

  57. Efrima S (1985) Raman optical-activity of molecules adsorbed on metal-surfaces—theory. J Chem Phys 83:1356–1362

    Article  CAS  Google Scholar 

  58. Humblot V, Barlow SM, Raval R (2004) Two-dimensional organisational chirality through supramolecular assembly of molecules at metal surfaces. Prog Surf Sci 76:1–19

    Article  CAS  Google Scholar 

  59. Humblot V, Raval R (2005) Chiral metal surfaces from the adsorption of chiral and achiral molecules. Appl Surf Sci 241:150–156

    Article  CAS  Google Scholar 

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Acknowledgments

We would like to thank the reviewers and the editor for useful comments and suggestions for improving our manuscript.

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Authors and Affiliations

  1. Federal Institute for Materials Research and Testing, Berlin, Germany

    Janina Kneipp

  2. Chemistry Department, Humboldt University Berlin, Berlin, Germany

    Janina Kneipp

  3. Institute of Molecular Biology and Bioinformatics, Charité University Medicine, Berlin, Germany

    Burghardt Wittig & Katrin Kneipp

  4. Physics Department, Danish Technical University, Lyngby, Denmark

    Henrik Bohr & Katrin Kneipp

Authors
  1. Janina Kneipp
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  2. Burghardt Wittig
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  3. Henrik Bohr
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  4. Katrin Kneipp
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Correspondence to Janina Kneipp.

Additional information

Dedicated to Professor Sandor Suhai on the occasion of his 65th birthday and published as part of the Suhai Festschrift Issue.

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Kneipp, J., Wittig, B., Bohr, H. et al. Surface-enhanced Raman scattering: a new optical probe in molecular biophysics and biomedicine. Theor Chem Acc 125, 319–327 (2010). https://doi.org/10.1007/s00214-009-0665-2

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  • DOI: https://doi.org/10.1007/s00214-009-0665-2

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