Skip to main content
SpringerLink
Log in

Whispering Gallery Mode Biomolecular Sensors

  • Chapter
Cavity-Enhanced Spectroscopy and Sensing

Part of the book series: Springer Series in Optical Sciences ((SSOS,volume 179))

Abstract

Optical resonator-based biosensors are emerging as one of the most sensitive microsystem biodetection technology that boasts all of the capabilities for a next-generation lab-on-chip device: label-free detection down to single molecules, multiplexed sensing capability, operation in aqueous environment as well as cost-effective integration on microchips. A scholarly introduction to the emerging field of whispering gallery mode resonator-based biosensors is given and their current applications are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. J.L. Arlett et al., Comparative advantages of mechanical biosensors. Nat. Nanotechnol. 6, 203–215 (2011)

    Article  ADS  Google Scholar 

  2. P.S. Waggoner, H.G. Craighead, Micro- and nanomechanical sensors for environmental, chemical, and biological detection. Lab Chip 7, 1238–1255 (2007)

    Article  Google Scholar 

  3. F. Patolsky et al., Nanowire sensors for medicine and the life sciences. Nanomedicine 1, 51–65 (2006)

    Article  Google Scholar 

  4. J. Li et al., Carbon nanotube sensors for gas and organic vapor detection. Nano Lett. 3, 929–933 (2003)

    Article  ADS  Google Scholar 

  5. F. Vollmer, S. Arnold, Whispering-gallery-mode biosensing: label-free detection down to single molecules. Nat. Methods 5, 591–596 (2008)

    Article  Google Scholar 

  6. P. Alivisatos, The use of nanocrystals in biological detection. Nat. Biotechnol. 22, 47–52 (2004)

    Article  Google Scholar 

  7. J.N. Anker et al., Biosensing with plasmonic nanosensors. Nat. Mater. 7, 442–453 (2008)

    Article  ADS  Google Scholar 

  8. K.K. Jain, Nanotechnology in clinical laboratory diagnostics. Clin. Chim. Acta 358, 37–54 (2005)

    Article  Google Scholar 

  9. G.M. Whitesides, The ‘right’ size in nanobiotechnology. Nat. Biotechnol. 21, 1161–1165 (2003)

    Article  Google Scholar 

  10. F. Vollmer et al., Single virus detection from the reactive shift of a whispering-gallery mode. Proc. Natl. Acad. Sci. USA 105, 20701–20704 (2008)

    Article  ADS  Google Scholar 

  11. A.K. Naik et al., Towards single-molecule nanomechanical mass spectrometry. Nat. Nanotechnol. 4, 445–450 (2009)

    Article  ADS  Google Scholar 

  12. M. Baaske, F. Vollmer, Optical resonator biosensors: molecular diagnostic and nanoparticle detection on an integrated platform. ChemPhysChem 13, 427–436 (2012)

    Article  Google Scholar 

  13. F. Patolsky et al., Electrical detection of single viruses. Proc. Natl. Acad. Sci. USA 101, 14017–14022 (2004)

    Article  ADS  Google Scholar 

  14. K. Wilson, F. Vollmer, Whispering Gallery Mode Resonator Biosensors, vol. 4 (Springer, Berlin, 2012)

    Google Scholar 

  15. F. Vollmer et al., Protein detection by optical shift of a resonant microcavity. Appl. Phys. Lett. 80, 4057–4059 (2002)

    Article  ADS  Google Scholar 

  16. S. Arnold et al., Shift of whispering-gallery modes in microspheres by protein adsorption. Opt. Lett. 28, 272–274 (2003)

    Article  ADS  Google Scholar 

  17. T.P. Burg et al., Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature 446, 1066–1069 (2007)

    Article  ADS  Google Scholar 

  18. F. Patolsky et al., Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species. Nat. Protoc. 1, 1711–1724 (2006)

    Article  Google Scholar 

  19. H.K. Hunt et al., Bioconjugation strategies for microtoroidal optical resonators. Sensors 10, 9317–9336 (2010)

    Article  Google Scholar 

  20. A.L. Washburn, R.C. Bailey, Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications. Analyst 136, 227–236 (2011)

    Article  ADS  Google Scholar 

  21. M. Curreli et al., Real-time, label-free detection of biological entities using nanowire-based FETs. IEEE Trans. Nanotechnol. 7, 651–667 (2008)

    Article  ADS  Google Scholar 

  22. B. Ilic et al., Virus detection using nanoelectromechanical devices. Appl. Phys. Lett. 85, 2604–2606 (2004)

    Article  ADS  Google Scholar 

  23. X.D. Fan, I.M. White, Optofluidic microsystems for chemical and biological analysis. Nat. Photonics 5, 591–597 (2011)

    Article  ADS  Google Scholar 

  24. A.J. Qavi et al., Label-free technologies for quantitative multiparameter biological analysis. Anal. Bioanal. Chem. 394, 121–135 (2009)

    Article  Google Scholar 

  25. M. Iqbal et al., Label-free biosensor arrays based on silicon ring resonators and high-speed optical scanning instrumentation. IEEE J. Sel. Top. Quantum Electron. 16, 654–661 (2010)

    Article  Google Scholar 

  26. K. Vahala (ed.), Optical Microcavities. Advanced Series in Applied Physics (World Scientific, Hackensack, 2004)

    Google Scholar 

  27. A.J. Qavi, R.C. Bailey, Multiplexed detection and label-free quantitation of MicroRNAs using arrays of silicon photonic microring resonators. Angew. Chem., Int. Ed. Engl. 49, 4608–4611 (2010)

    Article  Google Scholar 

  28. A. Ramachandran et al., A universal biosensing platform based on optical micro-ring resonators. Biosens. Bioelectron. 23, 939–944 (2008)

    Article  Google Scholar 

  29. Y.Z. Sun, X.D. Fan, Optical ring resonators for biochemical and chemical sensing. Anal. Bioanal. Chem. 399, 205–211 (2011)

    Article  Google Scholar 

  30. C.A. Barrios, Integrated microring resonator sensor arrays for labs-on-chips. Anal. Bioanal. Chem. 403, 1467–1475 (2012)

    Article  Google Scholar 

  31. L.N. He et al., Ultrasensitive detection of mode splitting in active optical microcavities. Phys. Rev. A 82 (2010)

    Google Scholar 

  32. T. Lu et al., High sensitivity nanoparticle detection using optical microcavities. Proc. Natl. Acad. Sci. USA 108, 5976–5979 (2011)

    Article  ADS  Google Scholar 

  33. Y. Lan et al., A self-reference sensing technique for ultra-sensitive chemical and biological detection using whispering gallery microresonators, Proc. SPIE Int. Soc. Opt. Eng. 7913, 791312 (2011)

    Article  Google Scholar 

  34. J.G. Zhu et al., Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities. Opt. Express 19, 16195–16206 (2011)

    Article  ADS  Google Scholar 

  35. C. Shi et al., Leveraging bimodal kinetics to improve detection specificity. Opt. Lett. 37, 1643–1645 (2012)

    Article  ADS  Google Scholar 

  36. I.M. White et al., Liquid-core optical ring-resonator sensors. Opt. Lett. 31, 1319–1321 (2006)

    Article  ADS  Google Scholar 

  37. S.M. Harazim et al., Lab-in-a-tube: on-chip integration of glass optofluidic ring resonators for label-free sensing applications. Lab Chip 12, 2649–2655 (2012)

    Article  Google Scholar 

  38. J.D. Suter et al., Label-free quantitative DNA detection using the liquid core optical ring resonator. Biosens. Bioelectron. 23, 1003–1009 (2008)

    Article  Google Scholar 

  39. H.Y. Zhu et al., Analysis of biomolecule detection with optofluidic ring resonator sensors. Opt. Express 15, 9139–9146 (2007)

    Article  ADS  Google Scholar 

  40. J. Lutti et al., A monolithic optical sensor based on whispering-gallery modes in polystyrene microspheres. Appl. Phys. Lett. 93 (2008)

    Google Scholar 

  41. F. Vollmer, Resonant detection of micro to nanoscopic OBjects using whispering gallery modes. PhD Thesis (2004)

    Google Scholar 

  42. K. De Vos et al., Silicon-on-insulator microring resonator for sensitive and label-free biosensing. Opt. Express 15, 7610–7615 (2007)

    Article  ADS  Google Scholar 

  43. L. Jin et al., Highly-sensitive silicon-on-insulator sensor based on two cascaded micro-ring resonators with vernier effect. Opt. Commun. 284, 156–159 (2011)

    Article  ADS  Google Scholar 

  44. M.S. Luchansky, R.C. Bailey, Silicon photonic microring resonators for quantitative cytokine detection and T-cell secretion analysis. Anal. Chem. 82, 1975–1981 (2010)

    Article  Google Scholar 

  45. M.S. Luchansky, R.C. Bailey, Rapid, multiparameter profiling of cellular secretion using silicon photonic microring resonator arrays. J. Am. Chem. Soc. 133, 20500–20506 (2011)

    Article  Google Scholar 

  46. M.S. Luchansky et al., Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads. Lab Chip 11, 2042–2044 (2011)

    Article  Google Scholar 

  47. B.Q. Su et al., Compact silicon-on-insulator dual-microring resonator optimized for sensing. J. Lightwave Technol. 29, 1535–1541 (2011)

    Article  ADS  Google Scholar 

  48. H.Y. Zhu et al., Integrated refractive index optical ring resonator detector for capillary electrophoresis. Anal. Chem. 79, 930–937 (2007)

    Article  Google Scholar 

  49. I.M. White et al., SERS-based detection in an optofluidic ring resonator platform. Opt. Express 15, 17433–17442 (2007)

    Article  ADS  Google Scholar 

  50. J.T. Gohring et al., Detection of HER2 breast cancer biomarker using the opto-fluidic ring resonator biosensor. Sens. Actuators B, Chem. 146, 226–230 (2010)

    Article  Google Scholar 

  51. J.T. Gohring, X.D. Fan, Label free detection of CD4+ and CD8+T cells using the optofluidic ring resonator. Sensors 10, 5798–5808 (2010)

    Article  Google Scholar 

  52. J.D. Suter et al., Label-free DNA methylation analysis using opto-fluidic ring resonators. Biosens. Bioelectron. 26, 1016–1020 (2010)

    Article  Google Scholar 

  53. K.A. Wilson et al., Whispering gallery mode biosensor quantification of fibronectin adsorption kinetics onto alkylsilane monolayers and interpretation of resultant cellular response. Biomaterials 33, 225–236 (2012)

    Article  Google Scholar 

  54. C.E. Soteropulos et al., Determination of binding kinetics using whispering gallery mode microcavities. Appl. Phys. Lett. 99 (2011)

    Google Scholar 

  55. N.M. Hanumegowda et al., Refractometric sensors based on microsphere resonators. Appl. Phys. Lett. 87 (2005)

    Google Scholar 

  56. I. Teraoka, S. Arnold, Enhancing the sensitivity of a whispering-gallery mode microsphere sensor by a high-refractive-index surface layer. J. Opt. Soc. Am. B, Opt. Phys. 23, 1434–1441 (2006)

    Article  ADS  Google Scholar 

  57. H.C. Ren et al., High-Q microsphere biosensor—analysis for adsorption of rodlike bacteria. Opt. Express 15, 17410–17423 (2007)

    Article  ADS  Google Scholar 

  58. S. Arnold et al., Whispering gallery mode carousel—a photonic mechanism for enhanced nanoparticle detection in biosensing. Opt. Express 17, 6230–6238 (2009)

    Article  ADS  Google Scholar 

  59. V.S. Ilchenko et al., Pigtailing the high-Q microsphere cavity: a simple fiber coupler for optical whispering-gallery modes. Opt. Lett. 24, 723–725 (1999)

    Article  ADS  Google Scholar 

  60. V.S. Ilchenko, A.B. Matsko, Optical resonators with whispering-gallery modes, part II: applications. IEEE J. Sel. Top. Quantum Electron. 12, 15–32 (2006)

    Article  Google Scholar 

  61. L. He et al., Detecting single viruses and nanoparticles using whispering gallery microlasers. Nat. Nanotechnol. 6, 428–432 (2011)

    Article  ADS  Google Scholar 

  62. A. Yalcin et al., Optical sensing of biomolecules using microring resonators. IEEE J. Sel. Top. Quantum Electron. 12, 148–155 (2006)

    Article  Google Scholar 

  63. C.Y. Chao et al., Polymer microring resonators for biochemical sensing applications. IEEE J. Sel. Top. Quantum Electron. 12, 134–142 (2006)

    Article  Google Scholar 

  64. A. Ksendzov, Y. Lin, Integrated optics ring-resonator sensors for protein detection. Opt. Lett. 30, 3344–3346 (2005)

    Article  ADS  Google Scholar 

  65. C. Delezoide et al., Vertically coupled polymer microracetrack resonators for label-free biochemical sensors. IEEE Photonics Technol. Lett. 24, 270–272 (2012)

    Article  ADS  Google Scholar 

  66. J.T. Kirk et al., Multiplexed inkjet functionalization of silicon photonic biosensors. Lab Chip 11, 1372–1377 (2011)

    Article  Google Scholar 

  67. A. Francois, M. Himmelhaus, Whispering gallery mode biosensor operated in the stimulated emission regime. Appl. Phys. Lett. 94 (2009)

    Google Scholar 

  68. M. Himmelhaus et al., Optical sensors based on whispering gallery modes in fluorescent microbeads: response to specific interactions. Sensors 10, 6257–6274 (2010)

    Article  Google Scholar 

  69. M. Himmelhaus, A. Francois, In-vitro sensing of biomechanical forces in live cells by a whispering gallery mode biosensor. Biosens. Bioelectron. 25, 418–427 (2009)

    Article  Google Scholar 

  70. J. Yang, L.J. Guo, Optical sensors based on active microcavities. IEEE J. Sel. Top. Quantum Electron. 12, 143–147 (2006)

    Article  Google Scholar 

  71. A. Weller et al., Whispering gallery mode biosensors in the low-Q limit. Appl. Phys. B, Lasers Opt. 90, 561–567 (2008)

    Article  ADS  Google Scholar 

  72. E. Nuhiji, P. Mulvaney, Detection of unlabeled oligonucleotide targets using whispering gallery modes in single, fluorescent microspheres. Small 3, 1408–1414 (2007)

    Article  Google Scholar 

  73. A. Schweinsberg et al., An environmental sensor based on an integrated optical whispering gallery mode disk resonator. Sens. Actuators B, Chem. 123, 727–732 (2007)

    Article  Google Scholar 

  74. R.W. Boyd, J.E. Heebner, Sensitive disk resonator photonic biosensor. Appl. Opt. 40, 5742–5747 (2001)

    Article  ADS  Google Scholar 

  75. M. Pollinger et al., Ultrahigh-Q tunable whispering-gallery-mode microresonator. Phys. Rev. Lett. 103 (2009)

    Google Scholar 

  76. E.J. Smith et al., Lab-in-a-tube: detection of individual mouse cells for analysis in flexible split-wall microtube resonator sensors. Nano Lett. 11, 4037–4042 (2011)

    Article  ADS  Google Scholar 

  77. J.D. Swaim et al., Detection limits in whispering gallery biosensors with plasmonic enhancement. Appl. Phys. Lett. 99 (2011)

    Google Scholar 

  78. M.A. Santiago-Cordoba et al., Nanoparticle-based protein detection by optical shift of a resonant microcavity. Appl. Phys. Lett. 99 (2011)

    Google Scholar 

  79. S.I. Shopova et al., Plasmonic enhancement of a whispering-gallery-mode biosensor for single nanoparticle detection. Appl. Phys. Lett. 98 (2011)

    Google Scholar 

  80. M.A. Santiago-Cordoba et al., Ultrasensitive detection of a protein by optical trapping in a photonic-plasmonic microcavity. J. Biophotonics 5, 629–638 (2012)

    Article  Google Scholar 

  81. M.L. Gorodetsky et al., Ultimate Q of optical microsphere resonators. Opt. Lett. 21, 453–455 (1996)

    Article  ADS  Google Scholar 

  82. J. Topolancik, F. Vollmer, Photoinduced transformations in bacteriorhodopsin membrane monitored with optical microcavities. Biophys. J. 92, 2223–2229 (2007)

    Article  ADS  Google Scholar 

  83. F. Vollmer et al., Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities. Biophys. J. 85, 1974–1979 (2003)

    Article  ADS  Google Scholar 

  84. A.J. Qavi et al., Anti-DNA:RNA antibodies and silicon photonic microring resonators: increased sensitivity for multiplexed microRNA detection. Anal. Chem. 83, 5949–5956 (2011)

    Article  Google Scholar 

  85. A.L. Washburn et al., DNA-encoding to improve performance and allow parallel evaluation of the binding characteristics of multiple antibodies in a surface-bound immunoassay format. Anal. Chem. 83, 3572–3580 (2011)

    Article  Google Scholar 

  86. J.G. Zhu et al., On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator. Nat. Photonics 4, 46–49 (2010)

    Article  ADS  Google Scholar 

  87. W. Kim et al., Observation and characterization of mode splitting in microsphere resonators in aquatic environment. Appl. Phys. Lett. 98 (2011)

    Google Scholar 

  88. D.S. Weiss et al., Splitting of high-Q mie modes induced by light backscattering in silica microspheres. Opt. Lett. 20, 1835–1837 (1995)

    Article  ADS  Google Scholar 

  89. M.L. Gorodetsky et al., Rayleigh scattering in high-Q microspheres. J. Opt. Soc. Am. B, Opt. Phys. 17, 1051–1057 (2000)

    Article  ADS  Google Scholar 

  90. A. Mazzei et al., Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light. Phys. Rev. Lett. 99 (2007)

    Google Scholar 

  91. M. Borselli et al., Beyond the Rayleigh scattering limit in high-Q silicon microdisks: theory and experiment. Opt. Express 13, 1515–1530 (2005)

    Article  ADS  Google Scholar 

  92. T.J. Kippenberg et al., Purcell-factor-enhanced scattering from Si nanocrystals in an optical microcavity. Phys. Rev. Lett. 103 (2009)

    Google Scholar 

  93. K. De Vos et al., Multiplexed antibody detection with an array of silicon-on-insulator microring resonators. IEEE Photonics J. 1, 225–235 (2009)

    Article  ADS  Google Scholar 

  94. H.A. Huckabay, R.C. Dunn, Whispering gallery mode imaging for the multiplexed detection of biomarkers. Sens. Actuators B, Chem. 160, 1262–1267 (2011)

    Article  Google Scholar 

  95. S.Y. Lin, K.B. Crozier, Planar silicon microrings as wavelength-multiplexed optical traps for storing and sensing particles. Lab Chip 11, 4047–4051 (2011)

    Article  Google Scholar 

  96. A.L. Washburn et al., Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators. Anal. Chem. 82, 69–72 (2010)

    Article  Google Scholar 

  97. O. Scheler et al., Label-free, multiplexed detection of bacterial tmRNA using silicon photonic microring resonators. Biosens. Bioelectron. 36, 56–61 (2012)

    Article  Google Scholar 

  98. M.S. McClellan et al., Label-free virus detection using silicon photonic microring resonators. Biosens. Bioelectron. 31, 388–392 (2012)

    Article  Google Scholar 

  99. V.R. Dantham et al., Taking whispering gallery-mode single virus detection and sizing to the limit. Appl. Phys. Lett. 101 (2012)

    Google Scholar 

  100. F. Vollmer, L. Yang, Label-free detection with high-Q microcavities: a review of biosensing mechanisms for integrated devices, in Nanophotonics (de Gruyter, Berlin, 2012). doi:10.1515/nanoph-2012-0021

    Google Scholar 

  101. M.R. Foreman, F. Vollmer, Level repulsion in hybrid photonic-plasmonic microresonators for enhanced biodetection. Phys. Rev. A 88 (2013)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Nanophotonics & Biosensing, Max Planck Institute for the Science of Light, G. Scharowksy Str. 1 / Bau 24, 91058, Erlangen, Germany

    Yuqiang Wu & Frank Vollmer

Authors
  1. Yuqiang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank Vollmer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuqiang Wu .

Editor information

Editors and Affiliations

  1. CNR-Istituto Nazionale di Ottica (INO), Pozzuoli, Italy

    Gianluca Gagliardi

  2. Dept. of Chemistry, Queen's University, Kingston, Ontario, Canada

    Hans-Peter Loock

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Wu, Y., Vollmer, F. (2014). Whispering Gallery Mode Biomolecular Sensors. In: Gagliardi, G., Loock, HP. (eds) Cavity-Enhanced Spectroscopy and Sensing. Springer Series in Optical Sciences, vol 179. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40003-2_9

Download citation

Publish with us

Policies and ethics

Search

Navigation