Plasmonic Exosome Biosensors for Medical Diagnostics

  • Agnes T. Reiner
  • Koji Toma
  • Alain R. Brisson
  • Dietmar Pils
  • Wolfgang Knoll
  • Jakub DostalekEmail author
Part of the Progress in Optical Science and Photonics book series (POSP, volume 3)


This chapter provides an overview of plasmonic biosensor technology for the analysis of extracellular lipid vesicles that hold potential to serve as new type of biomarkers. In particular, it discusses detection of exosomes that are secreted to bodily fluids and become of increasing interest in clinical research. Plasmonic biosensor technology is pushed forward to provide new means for their sensitive and specific detection without the need of specialized laboratories. It offers a versatile optical toolbox for probing various biological species by tightly confined electromagnetic field of surface plasmons. These optical waves originate from collective oscillations of electron charge density at metallic thin films and (nano)structures. This chapter gives an introduction to surface plasmon photonics and its use in direct surface plasmon resonance and in fluorescence spectroscopy-based biosensors. It provides a brief summary of current state-of-the-art in exosome biomarker research and discusses current advances in exosome plasmonic biosensors for medical diagnostics of diseases, in particular cancer.


Surface Plasmon Resonance Recipient Cell Lipid Vesicle Extracellular Vesicle Nanoparticle Tracking Analysis 
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 work was partially supported by Austrian Science Fund (FWF) through the project ACTIPLAS (P244920-N20) and by Austrian Federal Ministry for Transport, Innovation and Technology (GZ BMVIT-612.166/0001-III/I1/2010) via the International Graduate School Bio-Nano-Tech, a joint Ph.D. program of the University of Natural Resources and Life Sciences Vienna (BOKU), the Austrian Institute of Technology (AIT), and the Nanyang Technological University (NTU).


  1. 1.
    R.L. Rich, D.G. Myszka, Survey of the year 2007 commercial optical biosensor literature. J. Mol. Recognit. 21, 355–400 (2008)CrossRefGoogle Scholar
  2. 2.
    J. Homola, Surface plasmon resonance sensors for detection of chemical and biological species. Chem. Rev. 108, 462–493 (2008)CrossRefGoogle Scholar
  3. 3.
    S. El Andaloussi, I. Maeger, X.O. Breakefield, M.J.A. Wood, Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug. Discov. 12, 348–358 (2013)CrossRefGoogle Scholar
  4. 4.
    L.S. Jung, J.S. Shumaker-Parry, C.T. Campbell, S.S. Yee, M.H. Gelb, Quantification of tight binding to surface-immobilized phospholipid vesicles using surface plasmon resonance: binding constant of phospholipase A(2). JACS 122, 4177–4184 (2000)CrossRefGoogle Scholar
  5. 5.
    M.A. Cooper, A. Hansson, S. Lofas, D.H. Williams, A vesicle capture sensor chip for kinetic analysis of interactions with membrane-bound receptors. Anal. Biochem. 277, 196–205 (2000)CrossRefGoogle Scholar
  6. 6.
    M. Bauch, K. Toma, M. Toma, Q. Zhang, J. Dostalek, Plasmon-enhanced fluorescence biosensors: a review. Plasmonics 1–19 (2013)Google Scholar
  7. 7.
    C. Hoppener, L. Novotny, Exploiting the light-metal interaction for biomolecular sensing and imaging. Q. Rev. Biophys. 45, 209–255 (2012)CrossRefGoogle Scholar
  8. 8.
    J.R. Lakowicz, K. Ray, M. Chowdhury, H. Szmacinski, Y. Fu, J. Zhang, K. Nowaczyk, Plasmon-controlled fluorescence: a new paradigm in fluorescence spectroscopy. Analyst 133, 1308–1346 (2008)CrossRefGoogle Scholar
  9. 9.
    S. Lal, N.K. Grady, J. Kundu, C.S. Levin, J.B. Lassiter, N.J. Halas, Tailoring plasmonic substrates for surface enhanced spectroscopies. Chem. Soc. Rev. 37, 898–911 (2008)CrossRefGoogle Scholar
  10. 10.
    B. Sharma, R.R. Frontiera, A.I. Henry, E. Ringe, R.P. Van Duyne, SERS: materials, applications, and the future. Mater. Today 15, 16–25 (2012)CrossRefGoogle Scholar
  11. 11.
    J. Dostalek, A. Kasry, W. Knoll, Long range surface plasmons for observation of biomolecular binding events at metallic surfaces. Plasmonics 2, 97–106 (2007)CrossRefGoogle Scholar
  12. 12.
    M.E. Stewart, C.R. Anderton, L.B. Thompson, J. Maria, S.K. Gray, J.A. Rogers, R.G. Nuzzo, Nanostructured plasmonic sensors. Chem. Rev. 108, 494–521 (2008)CrossRefGoogle Scholar
  13. 13.
    L. He, M.D. Musick, S.R. Nicewarner, F.G. Salinas, S.J. Benkovic, M.J. Natan, C.D. Keating, Colloidal Au-enhanced surface plasmon resonance for ultrasensitive detection of DNA hybridization. JACS 122, 9071–9077 (2000)CrossRefGoogle Scholar
  14. 14.
    M. Bauch, S. Hageneder, J. Dostalek, Plasmonic amplification for bioassays with epi-fluorescence readout. Opt. Express 22, 32026–32038 (2014)CrossRefGoogle Scholar
  15. 15.
    J. Dostalek, W. Knoll, Biosensors based on surface plasmon-enhanced fluorescence spectroscopy. Biointerphases 3, 12–22 (2008)CrossRefGoogle Scholar
  16. 16.
    P. Mitchell, E. Petfalski, A. Shevchenko, M. Mann, D. Tollervey, The exosome: a conserved eukaryotic RNA processing complex containing multiple 3′--> 5′ exoribonucleases. Cell 91, 457–466 (1997)CrossRefGoogle Scholar
  17. 17.
    C. Harding, J. Heuser, P. Stahl, Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 97, 329–339 (1983)CrossRefGoogle Scholar
  18. 18.
    G. Raposo, H.W. Nijman, W. Stoorvogel, R. Liejendekker, C.V. Harding, C.J. Melief, H.J. Geuze, B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183, 1161–1172 (1996)CrossRefGoogle Scholar
  19. 19.
    M. Colombo, G. Raposo, C. Thery, Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30, 255–289 (2014)CrossRefGoogle Scholar
  20. 20.
    M. Record, K. Carayon, M. Poirot, S. Silvente-Poirot, Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim. Biophys. Acta 1841, 108–120 (2014)CrossRefGoogle Scholar
  21. 21.
    C. Thery, L. Zitvogel, S. Amigorena, Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2, 569–579 (2002)Google Scholar
  22. 22.
    A. Beach, H.G. Zhang, M.Z. Ratajczak, S.S. Kakar, Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J. Ovarian Res. 7, 14 (2014)CrossRefGoogle Scholar
  23. 23.
    K.W. Witwer, E.I. Buzas, L.T. Bemis, A. Bora, C. Lasser, J. Lotvall, E.N. Nolte-’t Hoen, M.G. Piper, S. Sivaraman, J. Skog, C. Thery, M.H. Wauben, F. Hochberg, Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell Vesicles, 2 (2013)Google Scholar
  24. 24.
    J.C. Akers, D. Gonda, R. Kim, B.S. Carter, C.C. Chen, Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol. 113, 1–11 (2013)CrossRefGoogle Scholar
  25. 25.
    E.L. Andaloussi, I. Mager, X.O. Breakefield, M.J. Wood, Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug. Discov. 12, 347–357 (2013)CrossRefGoogle Scholar
  26. 26.
    J.S. Schorey, S. Bhatnagar, Exosome function: from tumor immunology to pathogen biology. Traffic 9, 871–881 (2008)CrossRefGoogle Scholar
  27. 27.
    H. Valadi, K. Ekstrom, A. Bossios, M. Sjostrand, J.J. Lee, J.O. Lotvall, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–672 (2007)CrossRefGoogle Scholar
  28. 28.
    N. Chaput, C. Thery, Exosomes: immune properties and potential clinical implementations. Semin. Immunopathol. 33, 419–440 (2011)CrossRefGoogle Scholar
  29. 29.
    Y. Sun, J. Liu, Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances. Clin. Ther. 36, 863–872 (2014)CrossRefzbMATHGoogle Scholar
  30. 30.
    A.L. Revenfeld, R. Baek, M.H. Nielsen, A. Stensballe, K. Varming, M. Jorgensen, Diagnostic and prognostic potential of extracellular vesicles in peripheral blood. Clin. Ther. 36, 830–846 (2014)CrossRefGoogle Scholar
  31. 31.
    I. Kawikova, P.W. Askenase, Diagnostic and therapeutic potentials of exosomes in CNS diseases. Brain Res. S0006-8993(14)01343-2 (2014)Google Scholar
  32. 32.
    K. Hian Tan, S. Sim Tan, S.K. Sze, W.K. Ryan Lee, M. Jack Ng, S. Kiang Lim, Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. Am. J. Obstet. Gynecol. 211, 380 e1–e13 (2014)Google Scholar
  33. 33.
    N. Arraud, R. Linares, S. Tan, C. Gounou, J.M. Pasquet, S. Mornet, A.R. Brisson, Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J. Thromb. Haemost. 12, 614–627 (2014)CrossRefGoogle Scholar
  34. 34.
    E. van der Pol, F.A. Coumans, A.E. Grootemaat, C. Gardiner, I.L. Sargent, P. Harrison, A. Sturk, T.G. van Leeuwen, R. Nieuwland, Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J. Thromb. Haemost. 12, 1182–1192 (2014)CrossRefGoogle Scholar
  35. 35.
    N. Arraud, C. Gounou, R. Linares, A.R. Brisson, A simple flow cytometry method improves the detection of phosphatidylserine-exposing extracellular vesicles. J. Thromb. Haemost. 13, 237–247 (2015)CrossRefGoogle Scholar
  36. 36.
    D.L.M. Rupert, C. Lasser, M. Eldh, S. Block, V.P. Zhdanov, J.O. Lotvall, M. Bally, F. Hook, Determination of exosome concentration in solution using surface plasmon resonance spectroscopy. Anal. Chem. 86, 5929–5936 (2014)CrossRefGoogle Scholar
  37. 37.
    L. Zhu, K. Wang, J. Cui, H. Liu, X.L. Bu, H.L. Ma, W.Z. Wang, H. Gong, C. Lausted, L. Hood, G. Yang, Z.Y. Hu, Label-free quantitative detection of tumor-derived exosomes through surface plasmon resonance imaging. Anal. Chem. 86, 8857–8864 (2014)CrossRefGoogle Scholar
  38. 38.
    S. Scarano, M. Mascini, A.P.F. Turner, M. Minunni, Surface plasmon resonance imaging for affinity-based biosensors. Biosens. Bioelectron. 25, 957–966 (2010)CrossRefGoogle Scholar
  39. 39.
    H. Im, H.L. Shao, Y.I. Park, V.M. Peterson, C.M. Castro, R. Weissleder, H. Lee, Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat. Biotechnol. 32, 490–495 (2014)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  • Agnes T. Reiner
    • 1
    • 2
  • Koji Toma
    • 3
  • Alain R. Brisson
    • 4
  • Dietmar Pils
    • 5
  • Wolfgang Knoll
    • 1
    • 2
  • Jakub Dostalek
    • 1
    Email author
  1. 1.BioSensor TechnologiesAIT-Austrian Institute of Technology GmbHViennaAustria
  2. 2.Centre for Biomimetic Sensor Science, School of Materials Science and EngineeringNanyang Technological UniversitySingaporeSingapore
  3. 3.Institute of Biomaterials and BioengineeringTokyo Medical and Dental UniversityChiyoda-kuJapan
  4. 4.Molecular Imaging and NanoBioTechnologyUMR-5248-CBMN CNRS-University of Bordeaux-IPBPessacFrance
  5. 5.Department of Obstetrics and Gynecology, Molecular Oncology GroupMedical University of ViennaViennaAustria

Personalised recommendations