Exploring the Unique Characteristics of LSPR Biosensing

  • Julia M. Bingham
  • W. Paige Hall
  • Richard P. Van Duyne
Part of the Integrated Analytical Systems book series (ANASYS)


Plasmonic biosensors based on the localized surface plasmon resonance (LSPR) of metal nanoparticles have been developed using both nanoparticle arrays and single nanoparticles. We introduce LSPR biosensing by describing the initial experiments performed using both model systems and disease biomarkers. LSPR shift-enhancement methods, exploitation of the short electromagnetic field decay length, and single nanoparticle sensors are discussed as pathways to further exploit the strengths of LSPR biosensing. Coupling molecular identification to LSPR spectroscopy is a significant aspect of biosensing. Therefore, examples from surface-enhanced Raman spectroscopy and laser desorption ionization mass spectrometry are provided. This chapter highlights examples which emphasize the unique characteristics of LSPR biosensing.


Surface Plasmon Resonance Localize Surface Plasmon Resonance Surface Plasmon Resonance Sensor Ethylene Glycol Tetraacetic Acid Refractive Index Sensitivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by the National Science Foundation (Grants EEC-0647560, CHE-0911145, and BES-0507036), the NSF MRSEC (DMR-0520513) at the Materials Research Center of Northwestern University, the AFOSR/DARPA Project BAA07-61 (FA9550-08-1-0221), the NIH (5R56DK078691-02), the NCI (1 U54 CA119341-01), and a Ryan Fellowship to W.P.H.


  1. 1.
    Englebienne P. Use of colloidal gold surface plasmon resonance peak shift to infer affinity constants from the interactions between protein antigens and antibodies specific for single or multiple epitopes. Analyst. 1998;123:1599–603.CrossRefGoogle Scholar
  2. 2.
    Jeanmaire DL, Van Duyne RP. Surface Raman spectroelectrochemistry part I: heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode. J Electroanal Chem. 1977;84:1–20.CrossRefGoogle Scholar
  3. 3.
    Albrecht MG, Creighton JA. Anomalously intense Raman spectra of pyridine at a silver electrode. J Am Chem Soc. 1977;99:5215–9.CrossRefGoogle Scholar
  4. 4.
    Hulteen JC, Treichel DA, Van Duyne RP. Atomic force microscopy and surface-enhanced Raman spectroscopy. I. Ag island films and Ag film over polymer nanosphere surfaces supported on glass. J Chem Phys. 1993;99:2101–15.CrossRefGoogle Scholar
  5. 5.
    Hulteen JC, Van Duyne RP. Nanosphere lithography: a materials general fabrication process for periodic particle array surfaces. J Vac Sci Technol A. 1995;13:1553–8.CrossRefGoogle Scholar
  6. 6.
    Haes AJ, Zou S, Schatz GC, Van Duyne RP. A nanoscale optical biosensor: the long-range distance dependence of the localized surface plasmon resonance of noble metal nanoparticles. J Phys Chem B. 2004;108:109–16.CrossRefGoogle Scholar
  7. 7.
    Haes AJ, Zou S, Schatz GC, Van Duyne RP. A nanoscale optical biosensor: short range distance dependence of the localized surface plasmon resonance of noble metal nanoparticles. J Phys Chem B. 2004;108:6961–8.CrossRefGoogle Scholar
  8. 8.
    McFarland AD, Young MA, Dieringer JA, Van Duyne RP. Wavelength-scanned surface-enhanced Raman excitation spectroscopy. J Phys Chem B. 2005;109:11279–85.CrossRefGoogle Scholar
  9. 9.
    Leuvering JH, Thal PJ, van der Waart M, Schuurs AH. Sol particle immunoassay (SPIA). J Immunoassay. 1980;1:77–91.CrossRefGoogle Scholar
  10. 10.
    Elghanian R, Storhoff JJ, Mucic RC, Letsinger RL, Mirkin CA. Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science. 1997;277:1078–81.CrossRefGoogle Scholar
  11. 11.
    Haes AJ, Van Duyne RP. A nanoscale optical biosensor: sensitivity and selectivity of an approach based on the localized surface plasmon resonance spectroscopy of triangular silver nanoparticles. J Am Chem Soc. 2002;124:10596–604.CrossRefGoogle Scholar
  12. 12.
    Riboh JC, Haes AJ, McFarland AD, Yonzon CR, Van Duyne RP. A nanoscale optical biosensor: real-time immunoassay in physiological buffer enabled by improved nanoparticle adhesion. J Phys Chem B. 2003;107:1772–80.CrossRefGoogle Scholar
  13. 13.
    Haes AJ, Chang L, Klein WL, Van Duyne RP. Detection of a biomarker for Alzheimer’s disease from synthetic and clinical samples using a nanoscale optical biosensor. J Am Chem Soc. 2005;127:2264–71.CrossRefGoogle Scholar
  14. 14.
    Yonzon CR, Jeoung E, Zou S, Schatz GC, Mrksich M, Van Duyne RP. A comparative analysis of localized and propagating surface plasmon resonance sensors: the binding of concanavalin A to a monosaccharide functionalized self-assembled monolayer. J Am Chem Soc. 2004;126:12669–76.CrossRefGoogle Scholar
  15. 15.
    Whitney AV, Elam JW, Zou S, Zinovev AV, Stair PC, Schatz GC, et al. Localized surface plasmon resonance nanosensor: a high-resolution distance-dependence study using atomic layer deposition. J Phys Chem B. 2005;109:20522–8.CrossRefGoogle Scholar
  16. 16.
    Haes AJ, Zou S, Zhao J, Schatz GC, Van Duyne RP. Localized surface plasmon resonance spectroscopy near molecular resonances. J Am Chem Soc. 2006;128:10905–14.CrossRefGoogle Scholar
  17. 17.
    Zhao J, Das A, Zhang XY, Schatz GC, Sligar SG, Van Duyne RP. Resonance surface plasmon spectroscopy: low molecular weight substrate binding to cytochrome P450. J Am Chem Soc. 2006;128:11004–5.CrossRefGoogle Scholar
  18. 18.
    Zhao J, Jensen L, Sung J, Zou S, Schatz GC, Van Duyne RP. Interaction of plasmon and molecular resonances for rhodamine 6G adsorbed on silver nanoparticles. J Am Chem Soc. 2007;129:7647–56.CrossRefGoogle Scholar
  19. 19.
    Lipscomb JD, Gunsalus IC. Structural aspects of the active site of cytochrome P-450cam. Drug Metab Dispos. 1973;1:1–5.Google Scholar
  20. 20.
    Schlichting I, Berendzen J, Chu K, Stock AM, Maves SA, Benson DE, et al. The catalytic pathway of cytochrome P450cam at atomic resolution. Science. 2000;287:1615–22.CrossRefGoogle Scholar
  21. 21.
    Sligar SG. Coupling of spin, substrate, and redox equilibriums in cytochrome P450. Biochemistry. 1976;15:5399–406.CrossRefGoogle Scholar
  22. 22.
    He L, Musick MD, Nicewarner SR, Salinas FG, Benkovic SJ, Natan MJ, et al. Colloidal Au-enhanced surface plasmon resonance for ultrasensitive detection of DNA hybridization. J Am Chem Soc. 2000;122:9071–7.CrossRefGoogle Scholar
  23. 23.
    Lyon LA, Musick MD, Natan MJ. Colloidal Au-enhanced surface plasmon resonance immunosensing. Anal Chem. 1998;70:5177–83.CrossRefGoogle Scholar
  24. 24.
    Buckle PE, Davies RJ, Kinning T, Yeung D, Edwards PR, Pollard-Knight D. The resonant mirror: a novel optical sensor for direct sensing of biomolecular interactions part II: applications. Biosens Bioelectron. 1993;8:355–63.CrossRefGoogle Scholar
  25. 25.
    Hall WP, Ngatia SN, Van Duyne RP. LSPR biosensor signal enhancement using nanoparticle-antibody conjugates. J Phys Chem C. 2011;115:1410–4.CrossRefGoogle Scholar
  26. 26.
    Gunnarsson L, Rindzevicius T, Prikulis J, Kasemo B, Kall M, Zou SL, et al. Confined plasmons in nanofabricated single silver particle pairs: experimental observations of strong interparticle interactions. J Phys Chem B. 2005;109:1079–87.CrossRefGoogle Scholar
  27. 27.
    Su KH, Wei QH, Zhang X, Mock JJ, Smith DR, Schultz S. Interparticle coupling effects on plasmon resonances of nanogold particles. Nano Lett. 2003;3:1087–90.CrossRefGoogle Scholar
  28. 28.
    Jain PK, Huang WY, El-Sayed MA. On the universal scaling behavior of the distance decay of plasmon coupling in metal nanoparticle pairs: a plasmon ruler equation. Nano Lett. 2007;7:2080–8.CrossRefGoogle Scholar
  29. 29.
    Sonnichsen C, Reinhard BM, Liphardt J, Alivisatos AP. A molecular ruler based on plasmon coupling of single gold and silver nanoparticles. Nat Biotechnol. 2005;23:741–5.CrossRefGoogle Scholar
  30. 30.
    Reinhard BM, Sheikholeslami S, Mastroianni A, Alivisatos AP, Liphardt J. Use of plasmon coupling to reveal the dynamics of DNA bending and cleavage by single EcoRV restriction enzymes. Proc Natl Acad Sci U S A. 2007;104:2667–72.CrossRefGoogle Scholar
  31. 31.
    Schatz GC, Van Duyne Richard P. Electromagnetic mechanism of surface-enhance spectroscopy. In: Chalmers JM, Griffiths PR, editors. Handbook of vibrational spectroscopy. Chichester: Wiley; 2002.Google Scholar
  32. 32.
    Hall WP, Anker JN, Lin Y, Modica J, Mrksich M, Van Duyne RP. A calcium-modulated plasmonic switch. J Am Chem Soc. 2008;130:5836–7.CrossRefGoogle Scholar
  33. 33.
    Ishima R, Torchia DA. Protein dynamics from NMR. Nat Struct Biol. 2000;7:740–3.CrossRefGoogle Scholar
  34. 34.
    Heyduk T. Measuring protein conformational changes by FRET/LRET. Curr Opin Biotechnol. 2002;13:292–6.CrossRefGoogle Scholar
  35. 35.
    Lipfert J, Doniach S. Small-angle X-ray scattering from RNA, proteins, and protein complexes. Ann Rev Biophys Biomol Struct. 2007;36:307–27.CrossRefGoogle Scholar
  36. 36.
    Paynter S, Russell DA. Surface plasmon resonance measurement of pH-induced responses of immobilized biomolecules: conformational change or electrostatic interaction effects? Anal Biochem. 2002;309:85–95.CrossRefGoogle Scholar
  37. 37.
    Jonsson MP, Joensson P, Dahlin AB, Hoeoek F. Supported lipid bilayer formation and lipid-membrane-mediated biorecognition reactions studied with a new nanoplasmonic sensor template. Nano Lett. 2007;7:3462–8.CrossRefGoogle Scholar
  38. 38.
    Chah S, Hammond MR, Zare RN. Gold nanoparticles as a colorimetric sensor for protein conformational changes. Chem Biol. 2005;12:323–8.CrossRefGoogle Scholar
  39. 39.
    Dahlin AB, Tegenfeldt JO, Hook F. Improving the instrumental resolution of sensors based on localized surface plasmon resonance. Anal Chem. 2006;78:4416–23.CrossRefGoogle Scholar
  40. 40.
    Hodneland CD, Lee Y-S, Min D-H, Mrksich M. Selective immobilization of proteins to self-assembled monolayers presenting active site-directed capture ligands. Proc Natl Acad Sci U S A. 2002;99:5048–52.CrossRefGoogle Scholar
  41. 41.
    Deng C, Zhang X, Li N. Investigation of volatile biomarkers in lung cancer blood using solid-phase microextraction and capillary gas chromatography-mass spectrometry. J Chromatogr B. 2004;808:269–77.CrossRefGoogle Scholar
  42. 42.
    Nylander C, Liedberg B, Lind T. Gas detection by means of surface plasmon resonance. Sens Actuators. 1982;3:79–88.CrossRefGoogle Scholar
  43. 43.
    Liedberg B, Nylander C, Lunström I. Surface plasmon resonance for gas detection and biosensing. Sens Actuators. 1983;4:299–304.CrossRefGoogle Scholar
  44. 44.
    Bingham JM. PhD Dissertation, Fundamental and applied localized surface plasmon resonance spectroscopy studies from nanoparticle arrays to single nanoparticles. Northwestern University; 2010.Google Scholar
  45. 45.
    Bingham JM, Anker JN, Kreno LE, Van Duyne RP. Gas sensing with high-resolution localized surface plasmon resonance spectroscopy. J Am Chem Soc. 2010;132:17358–9.CrossRefGoogle Scholar
  46. 46.
    Kreno LE, Hupp JT, Van Duyne RP. Metal–organic framework thin film for enhanced localized surface plasmon resonance gas sensing. Anal Chem. 2010;82:8042–6.CrossRefGoogle Scholar
  47. 47.
    McFarland AD, Van Duyne RP. Single silver nanoparticles as real-time optical sensors with zeptomole sensitivity. Nano Lett. 2003;3:1057–62.CrossRefGoogle Scholar
  48. 48.
    Raschke G, Kowarik S, Franzl T, Sonnichsen C, Klar TA, Feldmann J, et al. Biomolecular recognition based on single gold nanoparticle light scattering. Nano Lett. 2003;3:935–8.CrossRefGoogle Scholar
  49. 49.
    Van Duyne RP, Haes AJ, McFarland AD. Nanoparticle optics: sensing with nanoparticle arrays and single nanoparticles. Proc SPIE Int Soc Opt Eng. 2003;5223:197–207.Google Scholar
  50. 50.
    Bingham JM, Willets KA, Shah NC, Andrews DQ, Van Duyne Richard P. Localized surface plasmon resonance imaging: simultaneous single nanoparticle spectroscopy and diffusional dynamics. J Phys Chem C. 2009;113:16839–42.CrossRefGoogle Scholar
  51. 51.
    Mock JJ, Barbic M, Smith DR, Schultz DA, Schultz S. Shape effects in plasmon resonance of individual colloidal silver nanoparticles. J Chem Phys. 2002;116:6755–9.CrossRefGoogle Scholar
  52. 52.
    Sherry LJ, Chang S-H, Schatz GC, Van Duyne RP, Wiley BJ, Xia Y. Localized surface plasmon resonance spectroscopy of single silver nanocubes. Nano Lett. 2005;5:2034–8.CrossRefGoogle Scholar
  53. 53.
    Sherry LJ, Jin R, Mirkin CA, Schatz GC, Van Duyne RP. Localized surface plasmon resonance spectroscopy of single silver triangular nanoprisms. Nano Lett. 2006;6:2060–5.CrossRefGoogle Scholar
  54. 54.
    Nallathamby PD, Lee KJ, Xu X-H. Design of stable and uniform single nanoparticle photonics for in vivo dynamics imaging of nanoenvironments of zebrafish embryonic fluids. ACS Nano. 2008;2:1371–80.CrossRefGoogle Scholar
  55. 55.
    Qian H, Sheetz MP, Elson EL. Single particle tracking: analysis of diffusion and flow in two-dimensional systems. Biophys J. 1991;60:910–21.CrossRefGoogle Scholar
  56. 56.
    Saxton MJ. Single-particle tracking: the distribution of diffusion coefficients. Biophys J. 1997;72:1744–53.CrossRefGoogle Scholar
  57. 57.
    Saxton MJ, Jacobson K. Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct. 1997;26:373–99.CrossRefGoogle Scholar
  58. 58.
    Suzuki KGN, Fujiwara TK, Sanematsu F, Iino R, Edidin M, Kusumi A. GPI-anchored receptor clusters transiently recruit Lyn and Galpha for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1. J Cell Biol. 2007;177:717–30.CrossRefGoogle Scholar
  59. 59.
    Vrljic M, Nishimura SY, Brasselet S, Moerner WE, McConnell HM. Translational diffusion of individual class II MHC membrane proteins in cells. Biophys J. 2002;83:2681–92.CrossRefGoogle Scholar
  60. 60.
    Vrljic M, Nishimura SY, Moerner WE, McConnell HM. Cholesterol depletion suppresses the translational diffusion of class II major histocompatibility complex proteins in the plasma membrane. Biophys J. 2005;88:334–47.CrossRefGoogle Scholar
  61. 61.
    Jin RC, Cao YW, Mirkin CA, Kelly KL, Schatz GC, Zheng JG. Photoinduced conversion of silver nanospheres to nanoprisms. Science. 2001;294:1901–3.CrossRefGoogle Scholar
  62. 62.
    Dieringer JA, Lettan II RB, Scheidt KA, Van Duyne RP. A frequency domain existence proof of single-molecule surface-enhanced Raman spectroscopy. J Am Chem Soc. 2007;129:16249–56.CrossRefGoogle Scholar
  63. 63.
    Lyandres O, Shah NC, Yonzon CR, Walsh Jr JT, Glucksberg MR, Van Duyne RP. Real-time glucose sensing by surface-enhanced Raman spectroscopy in bovine plasma facilitated by a mixed decanethiol/mercaptohexanol partition layer. Anal Chem. 2005;77:6134–9.CrossRefGoogle Scholar
  64. 64.
    Lyandres O, Yuen JM, Shah NC, VanDuyne RP, Walsh Jr JT, Glucksberg MR. Progress toward an in vivo surface-enhanced Raman spectroscopy glucose sensor. Diabetes Technol Ther. 2008;10:257–65.CrossRefGoogle Scholar
  65. 65.
    Zhang X, Young MA, Lyandres O, Van Duyne RP. Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy. J Am Chem Soc. 2005;127:4484–9.CrossRefGoogle Scholar
  66. 66.
    Zhang X, Zhao J, Whitney AV, Elam JW, Van Duyne RP. Ultrastable substrates for surface-enhanced Raman spectroscopy: Al2O3 overlayers fabricated by atomic layer deposition yield improved anthrax biomarker detection. J Am Chem Soc. 2006;128:10304–9.CrossRefGoogle Scholar
  67. 67.
    Burlingame AL, Boyd RK, Gaskell SJ. Mass spectrometry. Anal Chem. 1996;68:599R–651.CrossRefGoogle Scholar
  68. 68.
    Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature. 2003;422:198–207.CrossRefGoogle Scholar
  69. 69.
    Anker JN, Hall WP, Lambert MP, Velasco PT, Mrksich M, Klein WL, et al. Detection and identification of bioanalytes with high-resolution LSPR spectroscopy and MALDI mass spectrometry. J Phys Chem C. 2009;113:5891–4.CrossRefGoogle Scholar
  70. 70.
    Wustholz KL, Henry A-I, Bingham JM, Kleinman SL, Natan MJ, Freeman RG, et al. Exploring single-molecule SERS and single-nanoparticle plasmon microscopy. Proc SPIE Int Soc Opt Eng. 2009;7394.Google Scholar
  71. 71.
    Qian X, Peng X-H, Ansari DO, Yin-Goen Q, Chen GZ, Shin DM, et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol. 2008;26:83–90.CrossRefGoogle Scholar
  72. 72.
    Zavaleta CL, Smith BR, Walton I, Doering W, Davis G, Shojaei B, et al. Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy. Proc Natl Acad Sci U S A. 2009;106:13511–6.CrossRefGoogle Scholar
  73. 73.
    Porter MD, Lipert RJ, Siperko LM, Wang G, Narayanan R. SERS as a bioassay platform: fundamentals, design, and applications. Chem Soc Rev. 2008;37:1001–11.CrossRefGoogle Scholar
  74. 74.
    McMahon JA, Wang YM, Sherry LJ, Van Duyne RP, Marks LD, Gray SK, et al. Correlating the structure, optical spectra, and electrodynamics of single silver nanocubes. J Phys Chem C. 2009;113:2731–5.CrossRefGoogle Scholar
  75. 75.
    Munechika K, Smith JM, Chen Y, Ginger DS. Plasmon line widths of single silver nanoprisms as a function of particle size and plasmon peak position. J Phys Chem C. 2007;111:18906–11.CrossRefGoogle Scholar
  76. 76.
    Stiles RL, Willets KA, Sherry LJ, Roden JM, Van Duyne RP. Investigating tip-nanoparticle interactions in spatially correlated total internal reflection plasmon spectroscopy and atomic force microscopy. J Phys Chem C. 2008;112:11696–701.CrossRefGoogle Scholar
  77. 77.
    Piner RD, Zhu J, Xu F, Hong S, Mirkin CA. Dip Pen nanolithography. Science. 1999;283:661–3.CrossRefGoogle Scholar
  78. 78.
    Gates BD, Xu Q, Stewart M, Ryan D, Willson CG, Whitesides GM. New approaches to nanofabrication: molding, printing, and other techniques. Chem Rev. 2005;105:1171–96.CrossRefGoogle Scholar
  79. 79.
    Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 2002;54:631–51.CrossRefGoogle Scholar
  80. 80.
    Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5:161–71.CrossRefGoogle Scholar
  81. 81.
    Nie S, Xing Y, Kim GJ, Simons JW. Nanotechnology applications in cancer. Annu Rev Biomed Eng. 2007;9:257–88.CrossRefGoogle Scholar
  82. 82.
    Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7:771–82.CrossRefGoogle Scholar
  83. 83.
    Cognet L, Berciaud S, Lasne D, Lounis B. Photothermal methods for single nonluminescent nano-objects. Anal Chem. 2008;80:2288–94.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Julia M. Bingham
    • 1
  • W. Paige Hall
    • 2
  • Richard P. Van Duyne
    • 2
  1. 1.Department of ChemistrySaint Xavier UniversityChicagoUSA
  2. 2.Department of ChemistryNorthwestern UniversityEvanstonUSA

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