Real-Time Optical Detection of Single Nanoparticles and Viruses Using Heterodyne Interferometry

  • Anirban Mitra
  • Lukas Novotny
Conference paper
Part of the NATO Science for Peace and Security Series B: Physics and Biophysics book series (NAPSB)


Nanoparticles play a significant role in various fields such as biomedical imaging and diagnostics [1–4], process control in semiconductor manufacturing [5], explosives [6], environmental monitoring and climate change [7, 8], and various other fields. Inhalation of ultrafine particulates in air has been shown to have adverse effects, such as inflammation of lungs or pulmonary and cardiovascular diseases [9, 10]. Nano-sized biological agents and pathogens such as viruses are known to be responsible for a wide variety of human diseases such as flu, AIDS and herpes, and have been used as biowarfare agents [11, 12].


Particle Trajectory Laser Focus Reference Field Sindbis Virus Heterodyne Detection 
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.


  1. 1.
    Yezhelyev M et al (2006) Emerging use of nanoparticles in diagnosis and treatment of breast cancer. Lancet Oncol 7:657–667CrossRefGoogle Scholar
  2. 2.
    Loo C et al (2004) Nanoshell-enabled photonics-based imaging and therapy of cancer. Technol Cancer Res Treat 3:33–40ADSGoogle Scholar
  3. 3.
    Choi M et al (2007) A cellular trojan horse for delivery of therapeutic nanoparticles into tumors. Nano Lett 7:3759–3765ADSCrossRefGoogle Scholar
  4. 4.
    Huang X, Jain PK, El-Sayed IH, El-Sayed MA (2007) Nanoparticles for cancer diagnosis and therapeutics. Nanomedicine 2:681–693CrossRefGoogle Scholar
  5. 5.
    Wali F, Knotter DM, Mud A, Kuper FG (2009) Impact of particles in ultra pure water on random yield loss in ic production. Microelectron Eng 86:140–144CrossRefGoogle Scholar
  6. 6.
    Brousseau L (2008) Enhanced nanocomposite combustion accelerant and methods for making the same. US Patent 7,338,711, 3 Apr 2008Google Scholar
  7. 7.
    Ramanathan V, Carmichael G (2008) Global and regional climate changes due to black carbon. Nat Geosci 1:221–227ADSCrossRefGoogle Scholar
  8. 8.
    Morawska L (2010) Airborne engineered nanoparticles: are they a health problem? Air Qual Clim Change 44:18–20Google Scholar
  9. 9.
    Oberdörster G (2000) Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 74:1–8CrossRefGoogle Scholar
  10. 10.
    Somers CM, McCarry BE, Malek F, Quinn JS (2004) Reduction of particulate air pollution lowers the risk of heritable mutations in mice. Science 304:1008–1010ADSCrossRefGoogle Scholar
  11. 11.
    Krug RM (2003) The potential use of influenza virus as an agent for bioterrorism. Antivir Res 57:147–150CrossRefGoogle Scholar
  12. 12.
    Anderson B, Friedman H, Bendinelli M (eds) (2006) Microorganisms and bioterrorism, 1st edn. Springer, New YorkGoogle Scholar
  13. 13.
    Hockett RD et al (1999) Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma hiv rna. J Exp Med 189:1545–1554CrossRefGoogle Scholar
  14. 14.
    Dulbecco R, Vogt M (1954) Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med 99:167–182CrossRefGoogle Scholar
  15. 15.
    Tsai W, Conley S, Kung H, Garrity R, Nara P (1996) Preliminaryin vitrogrowth cycle and transmission studies of hiv-1 in an autologous primary cell assay of blood-derived macrophages and peripheral blood mononuclear cells. Virology 226:205–216CrossRefGoogle Scholar
  16. 16.
    Dimitrov D et al (1993) Quantitation of human immunodeficiency virus type 1 infection kinetics. J Virol 67:2182–2190MathSciNetGoogle Scholar
  17. 17.
    Clark NA, Lunacek JH, Benedek GB (1970) A study of brownian motion using light scattering. Am J Phys 38:575–585ADSCrossRefGoogle Scholar
  18. 18.
    Blom MT, Chmela E, Oosterbroek R, Tijssen R, van den Berg A (2003) On-chip hydrodynamic chromatography separation and detection of nanoparticles and biomolecules. Anal Chem 75:6761CrossRefGoogle Scholar
  19. 19.
    Prikulis J et al (2004) Optical spectroscopy of single trapped metal nanoparticles in solution. Nano Lett 4:115–118ADSCrossRefGoogle Scholar
  20. 20.
    Bouhelier A, Beversluis MR, Novotny L (2003) Characterization of nanoplasmonic structures by locally excited photoluminescence. Appl Phys Lett 83:5041–5043ADSCrossRefGoogle Scholar
  21. 21.
    Yguerabide J, Yguerabide EE (1998) Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications. Anal Biochem 262:157–176CrossRefGoogle Scholar
  22. 22.
    Sönnichsen C, Geier S, Hecker NE, von Plessen G, Feldmann J (2000) Spectroscopy of single metallic nanoparticles using total internal reflection microscopy. Appl Phys Lett 77:2949–2951ADSCrossRefGoogle Scholar
  23. 23.
    Schultz S, Smith D, Mock J, Schultz D (2000) Single-target molecule detection with nonbleaching multicolor optical immunolabels. Proc Natl Acad Sci USA 97:996–1001ADSCrossRefGoogle Scholar
  24. 24.
    Lindfors K, Kalkbrenner T, Stoller P, Sandoghdar V (2004) Detection and spectroscopy of gold nanoparticles using supercontinum white light confocal microscopy. Phys Rev Lett 93:037401ADSCrossRefGoogle Scholar
  25. 25.
    Arnold S, Khoshsima M, Teraoka I (2003) Shift of whispering-gallery modes in microspheres by protein adsorption. Opt Lett 28:272–274ADSCrossRefGoogle Scholar
  26. 26.
    Arnold S, Ramjit R, Keng D, Kolchenko V, Teraoka I (2008) Microparticle photophysics illuminates viral bio-sensing. Faraday Discuss 137:65–83ADSCrossRefGoogle Scholar
  27. 27.
    Vollmer F, Arnold S (2008) Whispering-gallery-mode biosensing: label-free detection down to single molecules. Nat Methods 5:591–596CrossRefGoogle Scholar
  28. 28.
    Vollmer F, Arnold S, Keng D (2008) Single virus detection from the reactive shift of a whispering-gallery mode. Proc Natl Acad Sci USA 105:20701–20704ADSCrossRefGoogle Scholar
  29. 29.
    Zhu J et al (2009) On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-q microresonator. Nat Photon 4:46–49ADSCrossRefGoogle Scholar
  30. 30.
    Yanik AA et al (2010) An optofluidic nanoplasmonic biosensor for direct detection of live viruses from biological media. Nano Lett 10:4962–4969MathSciNetADSCrossRefGoogle Scholar
  31. 31.
    Ymeti A et al (2007) Fast, ultrasensitive virus detection using a young interferometer sensor. Nano Lett 7:394–397ADSCrossRefGoogle Scholar
  32. 32.
    Daaboul GG et al (2010) High-throughput detection and sizing of individual low-index nanoparticles and viruses for pathogen identification. Nano Lett 10:4727–4731ADSCrossRefGoogle Scholar
  33. 33.
    Patolsky F et al (2004) Electrical detection of single viruses. Proc Natl Acad Sci USA 101:14017–14022ADSCrossRefGoogle Scholar
  34. 34.
    Fraikin J-L, Teesalu T, McKenney CM, Ruoslahti E, Cleland AN (2011) A high-throughput label-free nanoparticle analyser. Nat Nanotechnol 6:308–313. doi:10.1038/nnano.2011.24ADSCrossRefGoogle Scholar
  35. 35.
    Stern E et al (2007) Importance of the debye screening length on nanowire field effect transistor sensors. Nano Lett 7:3405–3409ADSCrossRefGoogle Scholar
  36. 36.
    Bohren CF, Huffmann DR (1983) Absorption and scattering of light by small particles. Wiley, New YorkGoogle Scholar
  37. 37.
    Givan AL (2001) Flow cytometry: first principles, 2nd edn. Wiley-Liss, New YorkCrossRefGoogle Scholar
  38. 38.
    Berne BJ, Pecora R (2000) Dynamic light scattering: with applications to chemistry, biology, and physics, 1st edn. Dover Publications, New YorkGoogle Scholar
  39. 39.
    Mie G (1908) Beiträge zur optik trüber medien, speziell kolloidaler metallösungen. Ann d Phys 330:376–445ADSCrossRefGoogle Scholar
  40. 40.
    Batchelder JS, Taubenblatt MA (1991) Measurement of size and refractive index of particles using the complex forward-scattered electromagnetic field. US Patent 5,037,202Google Scholar
  41. 41.
    Batchelder JS, DeCain DM, Taubenblatt MA, Wickramasinghe HK, Williams CC (1991) Particulate inspection of fluids using interferometric light measurements. US Patent 5,061,070Google Scholar
  42. 42.
    Plakhotnik T, Palm V (2001) Interferometric signatures of single molecules. Phys Rev Lett 87:183602ADSCrossRefGoogle Scholar
  43. 43.
    Ignatovich FV, Novotny L (2006) Real-time and background-free detection of nanoscale particles. Phys Rev Lett 96:013901ADSCrossRefGoogle Scholar
  44. 44.
    Mitra A, Deutsch B, Ignatovich F, Dykes C, Novotny L (2010) Nano-optofluidic detection of single viruses and nanoparticles. ACS Nano 4:1305–1312CrossRefGoogle Scholar
  45. 45.
    Person S, Deutsch B, Mitra A, Novotny L (2011) Material-specific detection and classification of single nanoparticles. Nano Lett 11:257–261ADSCrossRefGoogle Scholar
  46. 46.
    Deutsch B, Beams R, Novotny L (2010) Nanoparticle detection using dual-phase interferometry. Appl Opt 49:4921–4925ADSCrossRefGoogle Scholar
  47. 47.
    Ignatovich FV, Topham D, Novotny L (2006) Optical detection of single nanoparticles and viruses. IEEE J Sel Top Quantum Electron 12:1292–1300CrossRefGoogle Scholar
  48. 48.
    Ignatovich FV, Novotny L (2003) Experimental study of nanoparticle detection by optical gradient forces. Rev Sci Instrum 74:5231–5235ADSCrossRefGoogle Scholar
  49. 49.
    Novotny L, Hecht B (2006) Principles of nano-optics. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  50. 50.
    Keshner M (1982) 1/f noise. Proc IEEE 70:212–218ADSCrossRefGoogle Scholar
  51. 51.
    Strauss EG (2001) Viruses and human disease, 1st edn. Academic, New YorkGoogle Scholar
  52. 52.
    Oster G (1950) Two-phase formation in solutions of tobacco mosaic virus and the problem of long-range forces. J Gen Physiol 33:445–473CrossRefGoogle Scholar
  53. 53.
    Tang G et al (2006) Assessment of joule heating and its effects on electroosmotic flow and electrophoretic transport of solutes in microfluidic channels. Electrophoresis 27:628–639CrossRefGoogle Scholar
  54. 54.
    Knox JH, McCormack KA (1994) Enhanced dielectric contrast in scattering-type scanning near-field optical microscopy. Chromatographia 38:207–214CrossRefGoogle Scholar
  55. 55.
    Takasaki T, Kurane I, Aihara H, Ohkawa N, Yamaguchi J (1997) Electron microscopic study of human immunodeficiency virus type 1 (hiv-1) core structure: two rna strands in the core of mature and budding particles. Arch Virol 142:375–382CrossRefGoogle Scholar
  56. 56.
    Zhang W et al (2002) Placement of the structural proteins in sindbis virus. J Virol 76:11645–11658CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Physics and AstronomyUniversity of RochesterRochesterUSA
  2. 2.Institute of OpticsUniversity of RochesterRochesterUSA

Personalised recommendations