Surface Plasmon Resonance: New Biointerface Designs and High-Throughput Affinity Screening

  • Matthew J. Linman
  • Quan Jason ChengEmail author
Part of the Springer Series on Chemical Sensors and Biosensors book series (SSSENSORS, volume 7)


Surface plasmon resonance (SPR) is a surface optical technique that measures minute changes in refractive index at a metal-coated surface. It has become increasingly popular in the study of biological and chemical analytes because of its label-free measurement feature. In addition, SPR allows for both quantitative and qualitative assessment of binding interactions in real time, making it ideally suited for probing weak interactions that are often difficult to study with other methods. This chapter presents the biosensor development in the last 3 years or so utilizing SPR as the principal analytical technique, along with a concise background of the technique itself. While SPR has demonstrated many advantages, it is a nonselective method and so, building reproducible and functional interfaces is vital to sensing applications. This chapter, therefore, focuses mainly on unique surface chemistries and assay approaches to examine biological interactions with SPR. In addition, SPR imaging for high-throughput screening based on microarrays and novel hyphenated techniques involving the coupling of SPR to other analytical methods is discussed. The chapter concludes with a commentary on the current state of SPR biosensing technology and the general direction of future biosensor research.


Surface plasmon resonance Microarray SPR imaging Protein-carbohydrate Protein-lipid Lectin 



Surface plasmon resonance


Association constant


Dissociation constant


Hexaethylene glycol spacer


Sambucus nigra agglutinin


High-mobility-group transcriptional factor


Soluble green fluorescent protein




Equilibrium dissociation constant


Equilibrium association constant


Systematic evolution of ligands by exponential enrichment


Enzyme-linked immunosorbent assay


Imaging ellipsometry


Carbohydrate-binding proteins


Tethered bilayer membrane




Gas chromatography


Vascular endothelial growth factor


Surface plasmon fluorescence spectroscopy


Peptide nucleic acids


Photon wave vector


Resonance units


Surface plasmon resonance imaging




Surface plasmons


Evanescent field


Estrogen receptor α


Mannosylerythritol lipid


Retinol binding protein 4


Single-stranded DNA


Gold nanoparticle




Lipid transfer protein


Human immunoglobulin G


Liquid chromatography


Mass spectrometry


Horseradish peroxidase






Surface plasmon wave vector



The authors acknowledge the financial support from National Science Foundation (CHE-0719224).


  1. 1.
    Homola J (2008) Surface plasmon resonance sensors for detection of chemical and biological species. Chem Rev 108:462–493CrossRefGoogle Scholar
  2. 2.
    Liedberg B, Lundstrom I, Stenberg E (1993) Principles of biosensing with an extended coupling matrix and surface plasmon resonance. Sensors Actuators B Chem 11:63–72CrossRefGoogle Scholar
  3. 3.
    Smith EA, Corn RM (2003) Surface plasmon resonance imaging as a tool to monitor biomolecular interactions in an array based format. Appl Spectrosc 57:320A–332ACrossRefGoogle Scholar
  4. 4.
    Knoll W (1998) Interfaces and thin films as seen by bound electromagnetic waves. Annu Rev Phys Chem 49:569–638CrossRefGoogle Scholar
  5. 5.
    Raether H (1988) Surface plasmons on smooth and rough surfaces and on gratings springer tracts in modern physics. Springer, BerlinGoogle Scholar
  6. 6.
    Wiltschi B, Knoll W, Sinner E-K (2006) Binding assays with artificial tethered membranes using surface plasmon resonance. Methods 39:134–146CrossRefGoogle Scholar
  7. 7.
    Frutos AG, Corn RM (1998) SPR of ultrathin organic films. Anal Chem 70:449A–455AGoogle Scholar
  8. 8.
    Hashimoto S, Isobe T, Natsume T (2007) Biomolecular interaction analysis coupled with mass spectrometry to detect interacting proteins. In: Walker JM (ed) The proteomics protocols handbook. Humana Press, Totowa, NJGoogle Scholar
  9. 9.
    Redman JE (2007) Surface plasmon resonance for probing quadruplex folding and interactions with proteins and small molecules. Methods 43:302–312CrossRefGoogle Scholar
  10. 10.
    Jönsson U, Malmqvist M (1992) Real-time biospecific interaction analysis. Adv Biosensors 2:291–336Google Scholar
  11. 11.
    Edwards PR, Leatherbarrow RJ (1997) Determination of association rate constants by an optical biosensor using initial rate analysis. Anal Biochem 246:1–6CrossRefGoogle Scholar
  12. 12.
    Navratilova I, Myszka DG (2006) Investigating biomolecular interactions and binding properties using spr biosensors. Surface plasmon resonance based sensors. Springer, Berlin, pp 159–161Google Scholar
  13. 13.
    Li B, Che J, Long M (2008) Measuring binding kinetics of surface-bound molecules using the surface plasmon resonance technique. Anal Biochem 377:195–201CrossRefGoogle Scholar
  14. 14.
    Li Y-J, Zhang Y, Zhou F (2008) Sequential monitoring of film thickness variations with surface plasmon resonance imaging and imaging ellipsometry constructed with a single optical system. Anal Chem 80:891–897CrossRefGoogle Scholar
  15. 15.
    Steiner G (2004) Surface plasmon resonance imaging. Anal Bioanal Chem 379:328–331CrossRefGoogle Scholar
  16. 16.
    Hakomori S (2004) Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of cell recognition and membrane organization. Glyconjugate J 21:125–137CrossRefGoogle Scholar
  17. 17.
    Monsigny M, Mayer R, Roche AC (2000) Sugar–lectin interactions: sugar clusters, lectin multivalency and avidity. Carbohydr Lett 4:35–52Google Scholar
  18. 18.
    Linman MJ, Taylor JD, Yu H, Chen X, Cheng Q (2008) Surface plasmon resonance study of protein − carbohydrate interactions using biotinylated sialosides. Anal Chem 80:4007–4013CrossRefGoogle Scholar
  19. 19.
    Vornholt W, Hartmann M, Keusgen M (2007) SPR studies of carbohydrate–lectin interactions as useful tool for screening on lectin sources. Biosens Bioelectron 22:2983–2988CrossRefGoogle Scholar
  20. 20.
    de Boer AR, Hokke CH, Deelder AM, Wuhrer M (2008) Serum antibody screening by surface plasmon resonance using a natural glycan microarray. Glycoconj J 25:75–84CrossRefGoogle Scholar
  21. 21.
    Wang J, Lv R, Xu J, Xu D, Chen H (2008) Characterizing the interaction between aptamers and human IgE by use of surface plasmon resonance. Anal Bioanal Chem 390:1059–1065CrossRefGoogle Scholar
  22. 22.
    Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10:282–289CrossRefGoogle Scholar
  23. 23.
    Lee SJ, You B-S, Park JW, Niazi JH, Kim YS, Gu MB (2008) ssDNA aptamer-based surface plasmon resonance biosensor for the detection of retinol binding protein 4 for the early diagnosis of type 2 diabetes. Anal Chem 80:2867–2873CrossRefGoogle Scholar
  24. 24.
    Su X, Neo SJ, Pek W, Thomsen JS (2008) A two-step antibody strategy for surface plasmon resonance spectroscopy detection of protein–DNA interactions in nuclear extracts. Anal Biochem 376:137–143CrossRefGoogle Scholar
  25. 25.
    Miao Y, Cui T, Leng F, Wilson WD (2008) Inhibition of high-mobility-group A2 protein binding to DNA by netropsin: a biosensor-surface plasmon resonance assay. Anal Biochem 374:7–15CrossRefGoogle Scholar
  26. 26.
    Berggård T, Linse S, James P (2007) Methods for the detection and analysis of protein-protein interactions. Proteomics 7:2833–2842CrossRefGoogle Scholar
  27. 27.
    Murphy AJ, Kemp F, Love J (2008) Surface plasmon resonance characterization of calspermin–calmodulin binding kinetics. Anal Biochem 376:61–72CrossRefGoogle Scholar
  28. 28.
    Feng L, Ferguson C, Nielsen PO, Chakravarty L, Rzepecki PW, Prestwich GD (2006) Methods of probing phosphoinositides-protein interactions. In: Feng LP, Prestwich GD (eds) Functional lipidomics. Taylor & Francis, Boca Raton, FL, pp 215–274Google Scholar
  29. 29.
    Ito S, Imura T, Fukuoka T, Morita T, Sakai H, Abe M, Kitamoto D (2007) Kinetic studies on the interactions between glycolipid biosurfactant-assembled monolayers and various classes of immunoglobulins using surface plasmon resonance. Colloids Surf Biointerfaces 58:165–171CrossRefGoogle Scholar
  30. 30.
    Kernstock RM, Girotti AW (2007) Lipid transfer protein binding of unmodified natural lipids as assessed by surface plasmon resonance methodology. Anal Biochem 365:111–121CrossRefGoogle Scholar
  31. 31.
    Phillips KS, Han J-H, Martinez M, Wang Z, Carter D, Cheng Q (2006) Nanoscale classifciation of gold substrates for surface plasmon resonance analysis of protein toxins with supported lipid membranes. Anal Chem 78:596–603CrossRefGoogle Scholar
  32. 32.
    Phillips KS, Wilkop T, Han J-H, Wu J-J, Al-Kaysi RO, Cheng Q (2006) Surface plasmon resonance imaging analysis of protein-receptor binding in supported membrane arrays on gold substrates with calcinated silicate films. J Am Chem Soc 128:9590–9591CrossRefGoogle Scholar
  33. 33.
    Taylor JD, Phillips KS, Cheng Q (2007) Microfluidic fabrication of addressable tethered lipid bilayer arrays and optimization using SPR with silane-derivatized nanoglassy substrates. Lab Chip 7:927–930CrossRefGoogle Scholar
  34. 34.
    Verducci JS, Melfi VF, Lin S, Wang Z, Roy S, Sen CK (2006) Microarray analysis of gene expression: considerations in data mining and statistical treatment. Physiol Genomics 25:355–363CrossRefGoogle Scholar
  35. 35.
    Dong Y, Wilkop T, Xu D, Wang Z, Cheng Q (2008) Microchannel chips for the multiplexed analysis of human immunoglobulin G–antibody interactions by surface plasmon resonance imaging. Anal Bioanal Chem 390:1575–1583CrossRefGoogle Scholar
  36. 36.
    Wang Z, Wilkop T, Xu D, Dong Y, Ma G, Cheng Q (2007) Surface plasmon resonance imaging for affinity analysis of aptamer–protein interactions with PDMS microfluidic chips. Anal Bioanal Chem 389:819–825CrossRefGoogle Scholar
  37. 37.
    Luo Y, Yu F, Zare RN (2008) Microfluidic device for immunoassays based on surface plasmon resonance imaging. Lab Chip 8:694–700CrossRefGoogle Scholar
  38. 38.
    Ladd J, Taylor AD, Pilarik M, Homola J, Jiang S (2008) Hybrid surface platform for the simultaneous detection of proteins and DNAs using a surface plasmon resonance imaging sensor. Anal Chem 80:4231–4236CrossRefGoogle Scholar
  39. 39.
    Sato Y, Hosokawa K, Maeda M (2008) Detection of non-cross-linking interaction between DNA-modified gold nanoparticles and a DNA-modified flat gold surface using surface plasmon resonance imaging on a microchip. Colloids Surf Biointerfaces 62:71–76CrossRefGoogle Scholar
  40. 40.
    Manera MG, Spadavecchia J, Leone A, Quaranta F, Rella R, Dell'atti D, Minunni M, Mascini M, Siciliano P (2008) Surface plasmon resonance imaging technique for nucleic acid detection. Sensors Actuators B Chem 130:82–87CrossRefGoogle Scholar
  41. 41.
    Garcia BH II, Goodman RM (2008) Use of surface plasmon resonance imaging to study viral rna: protein interactions. J Virol Methods 147:18–25CrossRefGoogle Scholar
  42. 42.
    Singh BK, Hillier AC (2007) Multicolor surface plasmon resonance imaging of ink jet-printed protein microarrays. Anal Chem 79:5124–5132CrossRefGoogle Scholar
  43. 43.
    Beusink JB, Lokate AMC, Besselink GAJ, Pruijn GJM, Schasfoort RBM (2008) Angle-scanning SPR imaging for detection of biomolecular interactions on microarrays. Biosens Bioelectron 23:839–844CrossRefGoogle Scholar
  44. 44.
    Li Y, Lee HJ, Corn RM (2007) Detection of protein biomarkers using RNA aptamer microarrays and enzymatically amplified surface plasmon resonance imaging. Anal Chem 79:1082–1088CrossRefGoogle Scholar
  45. 45.
    Inoue Y, Mori T, Yamanouchi G, Han X, Sonoda T, Niidome T, Katayama Y (2008) Surface plasmon resonance imaging measurements of caspase reactions on peptide microarrays. Anal Biochem 375:147–149CrossRefGoogle Scholar
  46. 46.
    Malic L, Cui B, Veres T, Tabrizian M (2007) Enhanced surface plasmon resonance imaging detection of DNA hybridization on periodic gold nanoposts. Opt Lett 32:3092–3094CrossRefGoogle Scholar
  47. 47.
    Linman MJ, Yu H, Chen X, Cheng Q (2009) Fabrication and characterization of a sialoside-based carbohydrate microarray biointerface for protein binding analysis with surface plasmon resonance imaging. ACS Appl Mater Interfaces 1:1755–1762CrossRefGoogle Scholar
  48. 48.
    Mercey E, Sadir R, Maillart E, Roget A, Baleux F, Lortat-Jacob H, Livache T (2008) Polypyrrole oligosaccharide array and surface plasmon resonance imaging for the measurement of glycosaminoglycan binding interactions. Anal Chem 80:3476–3482CrossRefGoogle Scholar
  49. 49.
    Karamanska R, Clarke J, Blixt O, MacRae JI, Zhang JQ, Crocker PR, Laurent N, Wright A, Flitsch SL, Russell DA, Field RA (2008) Surface plasmon resonance imaging for real-time, label-free analysis of protein interactions with carbohydrate microarrays. Glycoconj J 25:69–74CrossRefGoogle Scholar
  50. 50.
    Marchesini GR, Buijs J, Haasnoot W, Hooijerink D, Jansson O, Nielen MWF (2008) Nanoscale affinity chip interface for coupling inhibition SPR immunosensor screening with nano-LC TOF MS. Anal Chem 80:1159–1168CrossRefGoogle Scholar
  51. 51.
    Visser NFC, Scholten A, van den Heuvel RHH, Heck AJR (2007) Surface-plasmon-resonance-based chemical proteomics: efficient specific extraction and semiquantitative identification of cyclic nucleotide-binding proteins from cellular lysates by using a combination of surface plasmon resonance, sequential elution and liquid chromatography–tandem mass spectrometry. Chem Bio Chem 7:298–305Google Scholar
  52. 52.
    Nedelkov D, Nelson RW (2006) Surface plasmon resonance mass spectrometry for protein analysis. In: Nedelkov DN, Nelson RW (eds) Methods in molecular biology: new and emerging proteomic techniques. Humana Press, Totowa, NJ, pp 131–139CrossRefGoogle Scholar
  53. 53.
    Nedelkov D, Tubb KA, Nelson RW (2006) Surface plasmon resonance-enabled mass spectrometry arrays. Electrophoresis 27:3671–3675CrossRefGoogle Scholar
  54. 54.
    Nedelkov D (2007) Development of surface plasmon resonance mass spectrometry array platform. Anal Chem 79:5987–5990CrossRefGoogle Scholar
  55. 55.
    Borch J, Roepstorff P (2006) Combinations of SPR and MS for characterization of native and recombinant proteins in cell lysates. Mol Biotechnol 33:179–190CrossRefGoogle Scholar
  56. 56.
    Bouffartigues E, Leh H, Anger-Leroy M, Rimsky S, Buckle M (2007) Rapid coupling of surface plasmon resonance (SPR and SPRi) and proteinchip based mass spectrometry for the identification of proteins in nucleoprotein interactions. Nucl Acids Res 35:e39CrossRefGoogle Scholar
  57. 57.
    Du M, Zhou F (2008) Postcolumn renewal of sensor surfaces for high-performance liquid chromatography − surface plasmon resonance detection. Anal Chem 80:4225–4230CrossRefGoogle Scholar
  58. 58.
    Neumann T, Johansson M-L, Kambhampati D, Knoll W (2002) Surface-plasmon fluorescence spectroscopy. Adv Funct Mater 12:575–586CrossRefGoogle Scholar
  59. 59.
    Mitamura K, Imae T, Tian S, Knoll W (2008) Surface plasmon fluorescence investigation of energy-transfer-controllable organic thin films. Langmuir 24:2266–2270CrossRefGoogle Scholar
  60. 60.
    Chu L-Q, Forch R, Knoll W (2007) Surface-plasmon-enhanced fluorescence spectroscopy for DNA detection using fluorescently labeled PNA as “DNA Indicator”. Angew Chem Int Ed 46:4944–4947CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of CaliforniaRiversideUSA

Personalised recommendations