Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Nanoplasmonic optical antennas for life sciences and medicine

Abstract

Surface plasmons — light-induced oscillations of electrons at the surface of nanoplasmonic metallic nanoparticles or nanostructures — can be used in a wide range of applications. Such nanoplasmonic optical antennas can be interfaced with biological systems to answer diverse questions in life sciences and to solve problems in translational medicine. In particular, nanoplasmonics provide insight and solutions for intracellular exploration, gene delivery and regulation, and rapid precision molecular diagnostics. In this Review, we examine the development of nanoplasmonic optical antennas for in vitro and in vivo applications. We evaluate the use of optical nanoplasmonic antennas for the optical detection of mRNA in living cells and for in vivo molecular imaging. We also discuss nanoplasmonic optical antennas for in vivo gene delivery and the optical control of gene circuits. Finally, we highlight the use of nanoplasmonic-based molecular diagnostic systems for ultrafast precision medicine.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Cellular exploration.
Fig. 2: mRNA detection methods in living cells.
Fig. 3: In vivo molecular imaging.
Fig. 4: In vivo gene delivery and optical control of gene circuits.
Fig. 5: In vitro integrated molecular diagnostics.
Fig. 6: Plasmonic-based label-free molecular diagnostics.

Similar content being viewed by others

References

  1. Bergman, D. J. & Stockman, M. I. Surface plasmon amplification by stimulated emission of radiation: quantum generation of coherent surface plasmons in nanosystems. Phys. Rev. Lett. 90, 027402 (2003).

    Google Scholar 

  2. Kauranen, M. & Zayats, A. V. Nonlinear plasmonics. Nat. Photonics 6, 737–748 (2012).

    CAS  Google Scholar 

  3. Atwater, H. A. & Polman, A. Plasmonics for improved photovoltaic devices. Nat. Mater. 9, 205–213 (2010).

    CAS  Google Scholar 

  4. Garcia-Vidal, F. J., Martin-Moreno, L. & Pendry, J. B. Surfaces with holes in them: new plasmonic metamaterials. J. Opt. A. Pure Appl. Opt. 7, S97–S101 (2005).

    Google Scholar 

  5. Fang, N., Lee, H., Sun, C. & Zhang, X. Sub-diffraction-limited optical imaging with a silver superlens. Science 308, 534–537 (2005).

    CAS  Google Scholar 

  6. Ozbay, E. Plasmonics: merging photonics and electronics at nanoscale dimensions. Science 311, 189–193 (2006).

    CAS  Google Scholar 

  7. Haffner, C. et al. All-plasmonic Mach–Zehnder modulator enabling optical high-speed communication at the microscale. Nat. Photonics 9, 525–528 (2015).

    CAS  Google Scholar 

  8. Im, H. et al. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat. Biotechnol. 32, 490–495 (2014). Report on an excellent nanoplasmonic platform based on transmission SPR for molecular diagnostics through quantitative analysis of extracellular vesicles.

    CAS  Google Scholar 

  9. Son, J. H. et al. Ultrafast photonic PCR. Light Sci. Appl. 4, e280 (2015). Demonstration of ultrafast photonic PCR based on a plasmonic substrate for molecular diagnostics.

    CAS  Google Scholar 

  10. Kang, B., Austin, L. A. & El-Sayed, M. A. Real-time molecular imaging throughout the entire cell cycle by targeted plasmonic-enhanced Rayleigh/Raman spectroscopy. Nano Lett. 12, 5369–5375 (2012).

    CAS  Google Scholar 

  11. Kang, B., Austin, L. A. & El-Sayed, M. A. Observing real-time molecular event dynamics of apoptosis in living cancer cells using nuclear-targeted plasmonically enhanced Raman nanoprobes. ACS Nano 8, 4883–4892 (2014). References 10 and 11 are good examples of reports on the use of nanoplasmonic optical antennas in SERS-based real-time molecular imaging of native DNA and protein changes in living cells during different cellular activities.

    CAS  Google Scholar 

  12. Austin, L. A., Kang, B. & El-Sayed, M. A. Probing molecular cell event dynamics at the single-cell level with targeted plasmonic gold nanoparticles: a review. Nano Today 10, 542–558 (2015).

    CAS  Google Scholar 

  13. Bodelón, G., Costas, C., Pérez-Juste, J., Pastoriza-Santos, I. & Liz-Marzán, L. M. Gold nanoparticles for regulation of cell function and behavior. Nano Today 13, 46–60 (2017).

    Google Scholar 

  14. Yoo, S., Hong, S., Choi, Y., Park, J.-H. & Nam, Y. Photothermal inhibition of neural activity with near-infrared-sensitive nanotransducers. ACS Nano 8, 8040–8049 (2014).

    CAS  Google Scholar 

  15. Wang, X., Cui, Y. & Irudayaraj, J. Single-cell quantification of cytosine modifications by hyperspectral dark-field imaging. ACS Nano 9, 11924–11932 (2015).

    CAS  Google Scholar 

  16. Kang, J. W., So, P. T., Dasari, R. R. & Lim, D.-K. High resolution live cell Raman imaging using subcellular organelle-targeting SERS-sensitive gold nanoparticles with highly narrow intra-nanogap. Nano Lett. 15, 1766–1772 (2015).

    CAS  Google Scholar 

  17. Zhang, B., Kumar, R. B., Dai, H. & Feldman, B. J. A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes. Nat. Med. 20, 948–953 (2014).

    CAS  Google Scholar 

  18. Yang, K. S. et al. Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy. Sci. Transl Med. 9, eaal3226 (2017).

    Google Scholar 

  19. Zhang, B. et al. Diagnosis of Zika virus infection on a nanotechnology platform. Nat. Med. 23, 548–550 (2017).

    CAS  Google Scholar 

  20. Chen, C.-C. et al. DNA–gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. J. Am. Chem. Soc. 128, 3709–3715 (2006). Report on remote gene regulation in living cells with nanoplasmonic optical antennas.

    CAS  Google Scholar 

  21. Lee, S. E. et al. Photonic gene circuits by optically addressable siRNA-Au nanoantennas. ACS Nano 6, 7770–7780 (2012). Report on the use of nanoplasmonic optical antennas to reconfigure and regulate gene circuits in living cells.

    CAS  Google Scholar 

  22. Choi, Y., Kang, T. & Lee, L. P. Plasmon resonance energy transfer (PRET)-based molecular imaging of cytochrome c in living cells. Nano Lett. 9, 85–90 (2009). Report on PRET-based molecular imaging of a protein in a living cell.

    CAS  Google Scholar 

  23. Nakatsuji, H. et al. Thermosensitive ion channel activation in single neuronal cells by using surface-engineered plasmonic nanoparticles. Angew. Chem. Int. Ed. 54, 11725–11729 (2015).

    CAS  Google Scholar 

  24. Novotny, L. & Van Hulst, N. Antennas for light. Nat. Photonics 5, 83–90 (2011).

    CAS  Google Scholar 

  25. Rivnay, J., Wang, H., Fenno, L., Deisseroth, K. & Malliaras, G. G. Next-generation probes, particles, and proteins for neural interfacing. Sci. Adv. 3, e1601649 (2017).

    Google Scholar 

  26. Carvalho-de-Souza, J. L. et al. Photosensitivity of neurons enabled by cell-targeted gold nanoparticles. Neuron 86, 207–217 (2015).

    CAS  Google Scholar 

  27. Moskovits, M. Surface-enhanced spectroscopy. Rev. Mod. Phys. 57, 783–826 (1985).

    CAS  Google Scholar 

  28. Moskovits, M. Surface-enhanced Raman spectroscopy: a brief retrospective. J. Raman Spectrosc. 36, 485–496 (2005).

    CAS  Google Scholar 

  29. Kneipp, J., Kneipp, H. & Kneipp, K. SERS—a single-molecule and nanoscale tool for bioanalytics. Chem. Soc. Rev. 37, 1052–1060 (2008).

    CAS  Google Scholar 

  30. Lee, S. et al. Biological imaging of HEK293 cells expressing PLCγ1 using surface-enhanced Raman microscopy. Anal. Chem. 79, 916–922 (2007).

    CAS  Google Scholar 

  31. Wu, L. Y., Ross, B. M., Hong, S. & Lee, L. P. Bioinspired nanocorals with decoupled cellular targeting and sensing functionality. Small 6, 503–507 (2010).

    CAS  Google Scholar 

  32. Pallaoro, A., Hoonejani, M. R., Braun, G. B., Meinhart, C. D. & Moskovits, M. Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel. ACS Nano 9, 4328–4336 (2015).

    CAS  Google Scholar 

  33. Köker, T. et al. Cellular imaging by targeted assembly of hot-spot SERS and photoacoustic nanoprobes using split-fluorescent protein scaffolds. Nat. Commun. 9, 607 (2018).

    Google Scholar 

  34. Qian, X. et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 26, 83 (2008).

    CAS  Google Scholar 

  35. Khlebtsov, N. & Dykman, L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem. Soc. Rev. 40, 1647–1671 (2011).

    CAS  Google Scholar 

  36. Zhang, S., Gao, H. & Bao, G. Physical principles of nanoparticle cellular endocytosis. ACS Nano 9, 8655–8671 (2015).

    CAS  Google Scholar 

  37. Varkouhi, A. K., Scholte, M., Storm, G. & Haisma, H. J. Endosomal escape pathways for delivery of biologicals. J. Control. Release 151, 220–228 (2011).

    CAS  Google Scholar 

  38. Lee, K., Cui, Y., Lee, L. P. & Irudayaraj, J. Quantitative imaging of single mRNA splice variants in living cells. Nat. Nanotechnol. 9, 474–480 (2014). Good example of a study showing mRNA detection in living cells using nanoplasmonic optical antennas.

    CAS  Google Scholar 

  39. Liu, G. L., Long, Y.-T., Choi, Y., Kang, T. & Lee, L. P. Quantized plasmon quenching dips nanospectroscopy via plasmon resonance energy transfer. Nat. Methods 4, 1015–2017 (2007).

    CAS  Google Scholar 

  40. Huang, X., Jain, P. K., El-Sayed, I. H. & El-Sayed, M. A. Plasmonic photothermal therapy (PPTT) using gold nanoparticles. Lasers Med. Sci. 23, 217–228 (2008).

    Google Scholar 

  41. Song, J., Zhou, J. & Duan, H. Self-assembled plasmonic vesicles of SERS-encoded amphiphilic gold nanoparticles for cancer cell targeting and traceable intracellular drug delivery. J. Am. Chem. Soc. 134, 13458–13469 (2012).

    CAS  Google Scholar 

  42. Bustin, S. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J. Mol. Endocrinol. 29, 23–39 (2002).

    CAS  Google Scholar 

  43. Brown, P. O. & Botstein, D. Exploring the new world of the genome with DNA microarrays. Nat. Genet. 21, 33–37 (1999).

    CAS  Google Scholar 

  44. Visvader, J. E. Cells of origin in cancer. Nature 469, 314–322 (2011).

    CAS  Google Scholar 

  45. Bao, G., Rhee, W. J. & Tsourkas, A. Fluorescent probes for live-cell RNA detection. Annu. Rev. Biomed. Eng. 11, 25–47 (2009).

    CAS  Google Scholar 

  46. Jayagopal, A., Halfpenny, K. C., Perez, J. W. & Wright, D. W. Hairpin DNA-functionalized gold colloids for the imaging of mRNA in live cells. J. Am. Chem. Soc. 132, 9789–9796 (2010).

    CAS  Google Scholar 

  47. Seferos, D. S., Giljohann, D. A., Hill, H. D., Prigodich, A. E. & Mirkin, C. A. Nano-flares: probes for transfection and mRNA detection in living cells. J. Am. Chem. Soc. 129, 15477–15479 (2007).

    CAS  Google Scholar 

  48. Halo, T. L. et al. NanoFlares for the detection, isolation, and culture of live tumor cells from human blood. Proc. Natl Acad. Sci. USA 111, 17104–17109 (2014).

    CAS  Google Scholar 

  49. Dulkeith, E. et al. Fluorescence quenching of dye molecules near gold nanoparticles: radiative and nonradiative effects. Phys. Rev. Lett. 89, 203002 (2002).

    CAS  Google Scholar 

  50. Pan, W. et al. Multiplexed detection and imaging of intracellular mRNAs using a four-color nanoprobe. Anal. Chem. 85, 10581–10588 (2013).

    CAS  Google Scholar 

  51. Yang, Y. et al. FRET nanoflares for intracellular mRNA detection: avoiding false positive signals and minimizing effects of system fluctuations. J. Am. Chem. Soc. 137, 8340–8343 (2015).

    CAS  Google Scholar 

  52. Cognet, L. et al. Single metallic nanoparticle imaging for protein detection in cells. Proc. Natl Acad. Sci. USA 100, 11350–11355 (2003).

    CAS  Google Scholar 

  53. Yguerabide, J. & Yguerabide, E. E. Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications: II. Experimental characterization. Anal. Biochem. 262, 157–176 (1998).

    CAS  Google Scholar 

  54. Raschke, G. et al. Biomolecular recognition based on single gold nanoparticle light scattering. Nano Lett. 3, 935–938 (2003).

    CAS  Google Scholar 

  55. Huang, B., Babcock, H. & Zhuang, X. Breaking the diffraction barrier: super-resolution imaging of cells. Cell 143, 1047–1058 (2010).

    CAS  Google Scholar 

  56. Ding, S.-Y. et al. Nanostructure-based plasmon-enhanced Raman spectroscopy for surface analysis of materials. Nat. Rev. Mater. 1, 16021 (2016).

    CAS  Google Scholar 

  57. Kleinman, S. L., Frontiera, R. R., Henry, A.-I., Dieringer, J. A. & Van Duyne, R. P. Creating, characterizing, and controlling chemistry with SERS hot spots. Phys. Chem. Chem. Phys. 15, 21–36 (2013).

    CAS  Google Scholar 

  58. Alvarez-Puebla, R. A. & Liz-Marzán, L. M. SERS-based diagnosis and biodetection. Small 6, 604–610 (2010).

    CAS  Google Scholar 

  59. Braun, G. et al. Surface-enhanced Raman spectroscopy for DNA detection by nanoparticle assembly onto smooth metal films. J. Am. Chem. Soc. 129, 6378–6379 (2007).

    CAS  Google Scholar 

  60. Andreou, C., Hoonejani, M. R., Barmi, M. R., Moskovits, M. & Meinhart, C. D. Rapid detection of drugs of abuse in saliva using surface enhanced Raman spectroscopy and microfluidics. ACS Nano 7, 7157–7164 (2013).

    CAS  Google Scholar 

  61. Bantz, K. C. et al. Recent progress in SERS biosensing. Phys. Chem. Chem. Phys. 13, 11551–11567 (2011).

    Google Scholar 

  62. Kneipp, K. et al. Surface-enhanced Raman spectroscopy in single living cells using gold nanoparticles. Appl. Spectrosc. 56, 150–154 (2002). Report on SERS imaging of native chemical constituents within a single living cell using nanoplasmonic optical antennas.

    CAS  Google Scholar 

  63. Narayanan, N. et al. Investigation of apoptotic events at molecular level induced by SERS guided targeted theranostic nanoprobe. Nanoscale 8, 11392–11397 (2016).

    CAS  Google Scholar 

  64. Liang, L. et al. In situ surface-enhanced Raman scattering spectroscopy exploring molecular changes of drug-treated cancer cell nucleus. Anal. Chem. 87, 2504–2510 (2015).

    CAS  Google Scholar 

  65. Aioub, M. & El-Sayed, M. A. A real-time surface enhanced Raman spectroscopy study of plasmonic photothermal cell death using targeted gold nanoparticles. J. Am. Chem. Soc. 138, 1258–1264 (2016).

    CAS  Google Scholar 

  66. Kang, B. et al. Plasmon-enhanced Raman spectroscopic metrics for in situ quantitative and dynamic assays of cell apoptosis and necrosis. Chem. Sci. 8, 1243–1250 (2017).

    CAS  Google Scholar 

  67. Ali, M. R. et al. Simultaneous time-dependent surface-enhanced Raman spectroscopy, metabolomics, and proteomics reveal cancer cell death mechanisms associated with gold nanorod photothermal therapy. J. Am. Chem. Soc. 138, 15434–15442 (2016).

    CAS  Google Scholar 

  68. Huang, X., El-Sayed, I. H., Qian, W. & El-Sayed, M. A. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc. 128, 2115–2120 (2006).

    CAS  Google Scholar 

  69. Chatterjee, K., Sarkar, S., Rao, K. J. & Paria, S. Core/shell nanoparticles in biomedical applications. Adv. Colloid Interface Sci. 209, 8–39 (2014).

    CAS  Google Scholar 

  70. Li, J. F. et al. Shell-isolated nanoparticle-enhanced Raman spectroscopy. Nature 464, 392–395 (2010).

    CAS  Google Scholar 

  71. Zhang, H. et al. In situ dynamic tracking of heterogeneous nanocatalytic processes by shell-isolated nanoparticle-enhanced Raman spectroscopy. Nat. Commun. 8, 15447 (2017).

    CAS  Google Scholar 

  72. Lu, Y., Liu, G. L., Kim, J., Mejia, Y. X. & Lee, L. P. Nanophotonic crescent moon structures with sharp edge for ultrasensitive biomolecular detection by local electromagnetic field enhancement effect. Nano Lett. 5, 119–124 (2005).

    CAS  Google Scholar 

  73. Harmsen, S. et al. Surface-enhanced resonance Raman scattering nanostars for high-precision cancer imaging. Sci. Transl Med. 7, 271ra277 (2015).

    Google Scholar 

  74. Hong, S., Lee, M. Y., Jackson, A. O. & Lee, L. P. Bioinspired optical antennas: gold plant viruses. Light Sci. Appl. 4, e267 (2015).

    CAS  Google Scholar 

  75. Rodríguez-Lorenzo, L. et al. Zeptomol detection through controlled ultrasensitive surface-enhanced Raman scattering. J. Am. Chem. Soc. 131, 4616–4618 (2009).

    Google Scholar 

  76. Shi, C. et al. Intracellular surface-enhanced Raman scattering probes based on TAT peptide-conjugated Au nanostars for distinguishing the differentiation of lung resident mesenchymal stem cells. Biomaterials 58, 10–25 (2015).

    CAS  Google Scholar 

  77. Samanta, A. et al. Ultrasensitive near-infrared Raman reporters for SERS-based in vivo cancer detection. Angew. Chem. Int. Ed. 50, 6089–6092 (2011).

    CAS  Google Scholar 

  78. Bohndiek, S. E. et al. A small animal Raman instrument for rapid, wide-area, spectroscopic imaging. Proc. Natl Acad. Sci. USA 110, 12408–12413 (2013).

    CAS  Google Scholar 

  79. Wang, H.-N. et al. Surface-enhanced Raman scattering nanosensors for in vivo detection of nucleic acid targets in a large animal model. Nano Res. https://doi.org/10.1007/s12274-018-1982-3 (2018).

    Article  Google Scholar 

  80. Cao, Y., Xie, T., Qian, R. C. & Long, Y. T. Plasmon resonance energy transfer: coupling between chromophore molecules and metallic nanoparticles. Small 13, 1601955 (2017).

    Google Scholar 

  81. Lee, J. Y. et al. Real-time investigation of cytochrome c release profiles in living neuronal cells undergoing amyloid beta oligomer-induced apoptosis. Nanoscale 7, 10340–10343 (2015).

    CAS  Google Scholar 

  82. Kim, J., Kim, J., Jeong, C. & Kim, W. J. Synergistic nanomedicine by combined gene and photothermal therapy. Adv. Drug Del. Rev. 98, 99–112 (2016).

    CAS  Google Scholar 

  83. Goodman, A. M. et al. Understanding resonant light-triggered DNA release from plasmonic nanoparticles. ACS Nano 11, 171–179 (2016).

    Google Scholar 

  84. Jones, M. R. et al. Plasmonically controlled nucleic acid dehybridization with gold nanoprisms. ChemPhysChem 10, 1461–1465 (2009).

    CAS  Google Scholar 

  85. Mintzer, M. A. & Simanek, E. E. Nonviral vectors for gene delivery. Chem. Rev. 109, 259–302 (2008).

    Google Scholar 

  86. Lee, S. E. et al. Biologically functional cationic phospholipid–gold nanoplasmonic carriers of RNA. J. Am. Chem. Soc. 131, 14066–14074 (2009).

    CAS  Google Scholar 

  87. Lee, S. E., Liu, G. L., Kim, F. & Lee, L. P. Remote optical switch for localized and selective control of gene interference. Nano Lett. 9, 562–570 (2009).

    CAS  Google Scholar 

  88. Deisseroth, K. Optogenetics. Nat. Methods 8, 26–29 (2011).

    CAS  Google Scholar 

  89. Link, S. & El-Sayed, M. A. Optical properties and ultrafast dynamics of metallic nanocrystals. Annu. Rev. Phys. Chem. 54, 331–366 (2003).

    CAS  Google Scholar 

  90. Jain, P. K., Qian, W. & El-Sayed, M. A. Ultrafast cooling of photoexcited electrons in gold nanoparticle-thiolated DNA conjugates involves the dissociation of the gold–thiol bond. J. Am. Chem. Soc. 128, 2426–2433 (2006).

    CAS  Google Scholar 

  91. Ramachandran, G. K. et al. A bond-fluctuation mechanism for stochastic switching in wired molecules. Science 300, 1413–1416 (2003).

    CAS  Google Scholar 

  92. Wang, Z. et al. Laser-triggered small interfering RNA releasing gold nanoshells against heat shock protein for sensitized photothermal therapy. Adv. Sci. 4, 1600327 (2017).

    Google Scholar 

  93. Wijaya, A., Schaffer, S. B., Pallares, I. G. & Hamad-Schifferli, K. Selective release of multiple DNA oligonucleotides from gold nanorods. ACS Nano 3, 80–86 (2009).

    CAS  Google Scholar 

  94. Huschka, R. et al. Gene silencing by gold nanoshell-mediated delivery and laser-triggered release of antisense oligonucleotide and siRNA. ACS Nano 6, 7681–7691 (2012).

    CAS  Google Scholar 

  95. Pecot, C. V., Calin, G. A., Coleman, R. L., Lopez-Berestein, G. & Sood, A. K. RNA interference in the clinic: challenges and future directions. Nat. Rev. Cancer 11, 59–67 (2011).

    CAS  Google Scholar 

  96. Hunter, A. C. & Moghimi, S. M. Cationic carriers of genetic material and cell death: a mitochondrial tale. Biochim. Biophys. Acta Bioenergetics 1797, 1203–1209 (2010).

    CAS  Google Scholar 

  97. Huang, X. et al. Light-activated RNA interference in human embryonic stem cells. Biomaterials 63, 70–79 (2015).

    CAS  Google Scholar 

  98. Zhang, P. et al. Near infrared-guided smart nanocarriers for microRNA-controlled release of doxorubicin/siRNA with intracellular ATP as fuel. ACS Nano 10, 3637–3647 (2016).

    CAS  Google Scholar 

  99. Anikeeva, P. & Deisseroth, K. Photothermal genetic engineering. ACS Nano 6, 7548–7552 (2012).

    CAS  Google Scholar 

  100. Nedaeinia, R. et al. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer Gene Ther. 24, 48–56 (2017).

    CAS  Google Scholar 

  101. Li, X. et al. Autoantibody profiling on a plasmonic nano-gold chip for the early detection of hypertensive heart disease. Proc. Natl Acad. Sci. USA 114, 7089–7094 (2017).

    CAS  Google Scholar 

  102. Wei, H., Abtahi, S. M. H. & Vikesland, P. J. Plasmonic colorimetric and SERS sensors for environmental analysis. Environ. Sci.: Nano 2, 120–135 (2015).

    CAS  Google Scholar 

  103. Piorek, B. D., Lee, S. J., Moskovits, M. & Meinhart, C. D. Free-surface microfluidics/surface-enhanced Raman spectroscopy for real-time trace vapor detection of explosives. Anal. Chem. 84, 9700–9705 (2012).

    CAS  Google Scholar 

  104. Tabakman, S. M. et al. Plasmonic substrates for multiplexed protein microarrays with femtomolar sensitivity and broad dynamic range. Nat. Commun. 2, 466 (2011). Demonstration of a plasmonic substrate with a large near-infrared fluorescence enhancement as a highly sensitive plasmonic ELISA platform for precision molecular diagnostics.

    Google Scholar 

  105. De La Rica, R. & Stevens, M. M. Plasmonic ELISA for the ultrasensitive detection of disease biomarkers with the naked eye. Nat. Nanotechnol. 7, 821–824 (2012).

    Google Scholar 

  106. Ambrosi, A., Airo, F. & Merkoci, A. Enhanced gold nanoparticle based ELISA for a breast cancer biomarker. Anal. Chem. 82, 1151–1156 (2010).

    CAS  Google Scholar 

  107. Zhan, L., Wu, W. B., Yang, X. X. & Huang, C. Z. Gold nanoparticle-based enhanced ELISA for respiratory syncytial virus. New J. Chem. 38, 2935–2940 (2014).

    CAS  Google Scholar 

  108. Tam, F., Goodrich, G. P., Johnson, B. R. & Halas, N. J. Plasmonic enhancement of molecular fluorescence. Nano Lett. 7, 496–501 (2007).

    CAS  Google Scholar 

  109. Song, S., Wang, L., Li, J., Fan, C. & Zhao, J. Aptamer-based biosensors. Trends Anal. Chem. 27, 108–117 (2008).

    CAS  Google Scholar 

  110. Toh, S. Y., Citartan, M., Gopinath, S. C. & Tang, T.-H. Aptamers as a replacement for antibodies in enzyme-linked immunosorbent assay. Biosens. Bioelectron. 64, 392–403 (2015).

    CAS  Google Scholar 

  111. Hu, R. et al. Novel electrochemical aptamer biosensor based on an enzyme–gold nanoparticle dual label for the ultrasensitive detection of epithelial tumour marker MUC1. Biosens. Bioelectron. 53, 384–389 (2014).

    CAS  Google Scholar 

  112. Zhou, Y. et al. Fabrication of an antibody-aptamer sandwich assay for electrochemical evaluation of levels of β-amyloid oligomers. Sci. Rep. 6, 35186 (2016).

    CAS  Google Scholar 

  113. Wan, H. et al. Proteoliposome-based full-length ZnT8 self-antigen for type 1 diabetes diagnosis on a plasmonic platform. Proc. Natl Acad. Sci. USA 114, 10196–10201 (2017).

    CAS  Google Scholar 

  114. Son, J. H. et al. Rapid optical cavity PCR. Adv. Health. Mater. 5, 167–174 (2016).

    CAS  Google Scholar 

  115. Roche, P. J. et al. Real time plasmonic qPCR: how fast is ultra-fast? 30 cycles in 54 seconds. Analyst 142, 1746–1755 (2017).

    CAS  Google Scholar 

  116. Liu, G. L. & Lee, L. P. Nanowell surface enhanced Raman scattering arrays fabricated by soft-lithography for label-free biomolecular detections in integrated microfluidics. Appl. Phys. Lett. 87, 074101 (2005).

    Google Scholar 

  117. Choi, C. J., Xu, Z., Wu, H.-Y., Liu, G. L. & Cunningham, B. T. Surface-enhanced Raman nanodomes. Nanotechnology 21, 415301 (2010).

    Google Scholar 

  118. Luo, S.-C., Sivashanmugan, K., Liao, J.-D., Yao, C.-K. & Peng, H.-C. Nanofabricated SERS-active substrates for single-molecule to virus detection in vitro: a review. Biosens. Bioelectron. 61, 232–240 (2014).

    CAS  Google Scholar 

  119. Kanipe, K. N., Chidester, P. P., Stucky, G. D. & Moskovits, M. Large format surface-enhanced Raman spectroscopy substrate optimized for enhancement and uniformity. ACS Nano 10, 7566–7571 (2016).

    CAS  Google Scholar 

  120. Im, H. et al. Self-assembled plasmonic nanoring cavity arrays for SERS and LSPR biosensing. Adv. Mater. 25, 2678–2685 (2013).

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  122. Ebbesen, T. W., Lezec, H. J., Ghaemi, H., Thio, T. & Wolff, P. Extraordinary optical transmission through sub-wavelength hole arrays. Nature 391, 667–669 (1998).

    CAS  Google Scholar 

  123. Escobedo, C. On-chip nanohole array based sensing: a review. Lab Chip 13, 2445–2463 (2013).

    CAS  Google Scholar 

  124. Gartia, M. R. et al. Colorimetric plasmon resonance imaging using nano lycurgus cup arrays. Adv. Opt. Mater. 1, 68–76 (2013). Report on a nanoplasmonic platform for molecular diagnostics based on a large spectral shift and direct colour change upon molecular binding.

    Google Scholar 

  125. Seo, S., Zhou, X. & Liu, G. L. Sensitivity tuning through additive heterogeneous plasmon coupling between 3D assembled plasmonic nanoparticle and nanocup arrays. Small 12, 3453–3462 (2016).

    CAS  Google Scholar 

  126. Wang, X., Chang, T.-W., Lin, G., Gartia, M. R. & Liu, G. L. Self-referenced smartphone-based nanoplasmonic imaging platform for colorimetric biochemical sensing. Anal. Chem. 89, 611–615 (2016).

    Google Scholar 

  127. Xin, H., Li, Y., Liu, X. & Li, B. Escherichia coli-based biophotonic waveguides. Nano Lett. 13, 3408–3413 (2013).

    CAS  Google Scholar 

  128. Lambert, N. et al. Quantum biology. Nat. Phys. 9, 10–18 (2013).

    CAS  Google Scholar 

  129. Tame, M. S. et al. Quantum plasmonics. Nat. Phys. 9, 329–340 (2013).

    CAS  Google Scholar 

  130. Yeh, E.-C. et al. Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip. Sci. Adv. 3, e1501645 (2017).

    Google Scholar 

  131. Kim, B. N., Diaz, J. A., Hong, S. G., Lee, S. H. & Lee, L. P. in Proc. 18th Int. Conf. Miniaturized Systems for Chemistry and Life Sciences 2247–2249 (CBMS, 2014).

  132. Wei, Q. et al. Plasmonics enhanced smartphone fluorescence microscopy. Sci. Rep. 7, 2124 (2017).

    Google Scholar 

  133. Pantelopoulos, A. & Bourbakis, N. G. A survey on wearable sensor-based systems for health monitoring and prognosis. IEEE Trans. Syst. Man. Cybern. C. 40, 1–12 (2010).

    Google Scholar 

  134. Turkevich, J., Stevenson, P. C. & Hillier, J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc. 11, 55–75 (1951).

    Google Scholar 

  135. Kimling, J. et al. Turkevich method for gold nanoparticle synthesis revisited. J. Phys. Chem. B 110, 15700–15707 (2006).

    CAS  Google Scholar 

  136. Xia, Y., Xiong, Y., Lim, B. & Skrabalak, S. E. Shape-controlled synthesis of metal nanocrystals: simple chemistry meets complex physics? Angew. Chem. Int. Ed. 48, 60–103 (2009).

    CAS  Google Scholar 

  137. Reetz, M. T. & Helbig, W. Size-selective synthesis of nanostructured transition metal clusters. J. Am. Chem. Soc. 116, 7401–7402 (1994).

    CAS  Google Scholar 

  138. Yu, Y.-Y., Chang, S.-S., Lee, C.-L. & Wang, C. C. Gold nanorods: electrochemical synthesis and optical properties. J. Phys. Chem. B 101, 6661–6664 (1997).

    CAS  Google Scholar 

  139. Decher, G. Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277, 1232–1237 (1997).

    CAS  Google Scholar 

  140. Sun, S. et al. Fabrication of gold micro- and nanostructures by photolithographic exposure of thiol-stabilized gold nanoparticles. Nano Lett. 6, 345–350 (2006).

    CAS  Google Scholar 

  141. Hicks, E. M. et al. Controlling plasmon line shapes through diffractive coupling in linear arrays of cylindrical nanoparticles fabricated by electron beam lithography. Nano Lett. 5, 1065–1070 (2005).

    CAS  Google Scholar 

  142. Haynes, C. & Van Duyne, R. Nanosphere lithography: a versatile nanofabrication tool for studies of size-dependent nanoparticle optics. J. Phys. Chem. B 105, 5599–5611 (2001).

    CAS  Google Scholar 

  143. Narayanan, K. B. & Sakthivel, N. Biological synthesis of metal nanoparticles by microbes. Adv. Colloid Interface Sci. 156, 1–13 (2010).

    CAS  Google Scholar 

  144. Kharissova, O. V., Dias, H. R., Kharisov, B. I., Pérez, B. O. & Pérez, V. M. J. The greener synthesis of nanoparticles. Trends Biotechnol. 31, 240–248 (2013).

    CAS  Google Scholar 

  145. Singh, P., Kim, Y.-J., Zhang, D. & Yang, D.-C. Biological synthesis of nanoparticles from plants and microorganisms. Trends Biotechnol. 34, 588–599 (2016).

    CAS  Google Scholar 

  146. Wen, A. M. & Steinmetz, N. F. Design of virus-based nanomaterials for medicine, biotechnology, and energy. Chem. Soc. Rev. 45, 4074–4126 (2016).

    CAS  Google Scholar 

  147. Kostiainen, M. A. et al. Electrostatic assembly of binary nanoparticle superlattices using protein cages. Nat. Nanotechnol. 8, 52–56 (2013).

    CAS  Google Scholar 

  148. Sun, J. et al. Core-controlled polymorphism in virus-like particles. Proc. Natl Acad. Sci. USA 104, 1354–1359 (2007).

    CAS  Google Scholar 

  149. Wen, A. M., Podgornik, R., Strangi, G. & Steinmetz, N. F. Photonics and plasmonics go viral: self-assembly of hierarchical metamaterials. Rend. Lincei Sci. Fis. Nat. 26, 129–141 (2015).

    Google Scholar 

  150. Agnihotri, S., Mukherji, S. & Mukherji, S. Size-controlled silver nanoparticles synthesized over the range 5–100 nm using the same protocol and their antibacterial efficacy. RSC Adv. 4, 3974–3983 (2014).

    CAS  Google Scholar 

  151. Link, S. & El-Sayed, M. A. Size and temperature dependence of the plasmon absorption of colloidal gold nanoparticles. J. Phys. Chem. B 103, 4212–4217 (1999).

    CAS  Google Scholar 

  152. Ristig, S. et al. Nanostructure of wet-chemically prepared, polymer-stabilized silver–gold nanoalloys (6 nm) over the entire composition range. J. Mater. Chem. B 3, 4654–4662 (2015).

    CAS  Google Scholar 

  153. Wiley, B. J. et al. Maneuvering the surface plasmon resonance of silver nanostructures through shape-controlled synthesis. J. Phys. Chem. B 110, 15666–15675 (2006).

    CAS  Google Scholar 

  154. Jain, P. K., Lee, K. S., El-Sayed, I. H. & El-Sayed, M. A. Calculated absorption and scattering properties of gold nanoparticles of different size, shape & composition: applications in biological imaging & biomedicine. J. Phys. Chem. B 110, 7238–7248 (2006).

    CAS  Google Scholar 

  155. Loo, C. et al. Nanoshell-enabled photonics-based imaging and therapy of cancer. Technol. Cancer Res. Treat. 3, 33–40 (2004).

    CAS  Google Scholar 

  156. Skrabalak, S. E., Au, L., Li, X. & Xia, Y. Facile synthesis of Ag nanocubes and Au nanocages. Nat. Protoc. 2, 2182–2190 (2007).

    CAS  Google Scholar 

  157. Yuan, H. et al. Gold nanostars: surfactant-free synthesis, 3D modelling, and two-photon photoluminescence imaging. Nanotechnology 23, 075102 (2012).

    Google Scholar 

  158. Chen, J. et al. Gold nanocages as photothermal transducers for cancer treatment. Small 6, 811–817 (2010).

    CAS  Google Scholar 

  159. Hrelescu, C., Sau, T. K., Rogach, A. L., Jäckel, F. & Feldmann, J. Single gold nanostars enhance Raman scattering. Appl. Phys. Lett. 94, 153113 (2009).

    Google Scholar 

Download references

Acknowledgements

The authors thank S.J. Taylor for help with revising the manuscript before submission.

Author information

Authors and Affiliations

Authors

Contributions

H.X. researched data for the article. H.X. and L.P.L. contributed to the discussion of content and wrote the article. All authors edited the manuscript before submission.

Corresponding author

Correspondence to Luke P. Lee.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xin, H., Namgung, B. & Lee, L.P. Nanoplasmonic optical antennas for life sciences and medicine. Nat Rev Mater 3, 228–243 (2018). https://doi.org/10.1038/s41578-018-0033-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41578-018-0033-8

This article is cited by

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research