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.

Extreme sensitivity biosensing platform based on hyperbolic metamaterials

Abstract

Optical sensor technology offers significant opportunities in the field of medical research and clinical diagnostics, particularly for the detection of small numbers of molecules in highly diluted solutions. Several methods have been developed for this purpose, including label-free plasmonic biosensors based on metamaterials. However, the detection of lower-molecular-weight (<500 Da) biomolecules in highly diluted solutions is still a challenging issue owing to their lower polarizability. In this context, we have developed a miniaturized plasmonic biosensor platform based on a hyperbolic metamaterial that can support highly confined bulk plasmon guided modes over a broad wavelength range from visible to near infrared. By exciting these modes using a grating-coupling technique, we achieved different extreme sensitivity modes with a maximum of 30,000 nm per refractive index unit (RIU) and a record figure of merit (FOM) of 590. We report the ability of the metamaterial platform to detect ultralow-molecular-weight (244 Da) biomolecules at picomolar concentrations using a standard affinity model streptavidin–biotin.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Fabrication and characterization of a metamaterial sensor device integrated with microfluidics.
Figure 2: Sensor calibration test results.
Figure 3: Evaluation of sensor performance using lower-molecular-weight biomolecules.
Figure 4: Evaluation of sensor performance without functionalization.

References

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

    CAS  Article  Google Scholar 

  2. De Angelis, F. et al. Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structures. Nature Photon. 5, 682–687 (2011).

    Article  Google Scholar 

  3. Zeng, S., Baillargeat, D., Hod, H. E. & Yong, K.-T. Nanomaterials enhanced surface plasmon resonance for biological and chemical sensing applications. Chem. Soc. Rev. 43, 3426–3452 (2014).

    CAS  Article  Google Scholar 

  4. Roy, R., Hohng, S. & Ha, T. A practical guide to single-molecule FRET. Nature Methods 5, 507–516 (2008).

    CAS  Article  Google Scholar 

  5. Poma, A. et al. Interactions between saporin, a ribosome-inactivating protein, and DNA: a study by atomic force microscopy. J. Microsc. 217, 69–74 (2005).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  7. Zijlstra, P., Paulo, P. M. R. & Orrit, M. Optical detection of single non-absorbing molecules using the surface plasmon resonance of a gold nanorod. Nature Nanotech. 7, 379–382 (2012).

    CAS  Article  Google Scholar 

  8. Ament, I. et al. Single unlabeled protein on individual plasmonic nanoparticles. Nano Lett. 12, 1092–1095 (2012).

    CAS  Article  Google Scholar 

  9. Acimovic, S. S. et al. LSPR chip for parallel, rapid, and sensitive detection of cancer markers in serum. Nano Lett. 14, 2636–2641 (2014).

    CAS  Article  Google Scholar 

  10. Im, H. et al. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nature Biotechnol. 32, 490–495 (2014).

    CAS  Article  Google Scholar 

  11. Svedendahl, M., Verre, R. & Kall, M. Refractometric biosensing based on optical phase filps in sparse and short-range-ordered nanoplasmonic layers. Light Sci. Appl. 3, e220 (2014).

    CAS  Article  Google Scholar 

  12. Wu, C. et al. Fano-resonant asymmetric metamaterials for ultrasensitive spectroscopy and identification of molecular manolayers. Nature Mater. 11, 69–75 (2012).

    CAS  Article  Google Scholar 

  13. Kravets, V. G. et al. Singular phase nano-optics in plasmonic metamaterials for label-free single-molecule detection. Nature Mater. 12, 304–309 (2013).

    CAS  Article  Google Scholar 

  14. Kabashin, A. V. et al. Plasmonic nanorod metamaterials for biosensing. Nature Mater. 8, 867–871 (2009).

    CAS  Article  Google Scholar 

  15. Rodrigo, D. et al. Mid-infrared plasmonic biosensing with graphene. Science 349, 165–168 (2015).

    CAS  Article  Google Scholar 

  16. Brolo, A. G. Plasmonics for future biosensors. Nature Photon. 6, 709–713 (2012).

    CAS  Article  Google Scholar 

  17. Raether, H. Surface Plasmons on Smooth and Rough Surfaces and on Gratings (Springer, 1988).

    Book  Google Scholar 

  18. Homola, J., Yee, S. S. & Gauglitz, G. Surface plasmon resonance sensors: review. Sensors Actuators B 54, 3–15 (1999).

    CAS  Article  Google Scholar 

  19. Chen, H. et al. Shape- and size-dependent refractive index sensitivity of gold nanoparticles. Langmuir 24, 5233–5237 (2008).

    CAS  Article  Google Scholar 

  20. Sannomiya, T. & Voros, J. Single plasmonic nanoparticles for biosensing. Trends Biotechnol. 29, 343–351 (2011).

    CAS  Article  Google Scholar 

  21. Mayer, K. M. et al. A single molecule immunoassay by localized surface plasmon resonance. Nanotechnology 21, 255503 (2010).

    Article  Google Scholar 

  22. Roper, D. K., Ahn, W., Taylor, B. & DallAsen, A. G. Enhanced spectral sensing by electromagnetic coupling with localized surface plasmons on subwavelength structures. IEEE Sensors J. 10, 531–540 (2010).

    CAS  Article  Google Scholar 

  23. Liu, N. et al. Planar metamaterial analogue of electromagnetically induced transparency for plasmonic sensing. Nano Lett. 10, 1103–1107 (2010).

    CAS  Article  Google Scholar 

  24. Shen, Y. et al. Plasmonic gold mushroom arrays with refractive index sensing figures of merit approaching the theoretical limit. Nature Commun. 4, 2381 (2013).

    Article  Google Scholar 

  25. Cao, C. et al. Metamaterials-based label-free nanosensor for conformation and affinity biosensing. ACS Nano 7, 7583–7591 (2013).

    CAS  Article  Google Scholar 

  26. Zeng, S. et al. Graphene-gold metasurface architectures for ultrasensitive plasmonic biosensing. Adv. Mater. 27, 6163–6169 (2015).

    CAS  Article  Google Scholar 

  27. Poddubny, A., Iorsh, I., Belov, P. & Kivshar, Y. Hyperbolic metamaterials. Nature Photon. 7, 948–957 (2013).

    CAS  Article  Google Scholar 

  28. Lu, D., Kan, J. J., Fullerton, E. E. & Liu, Z. Enhancing spontaneous emission rates of molecules using nanopatterned multilayer hyperbolic metamaterials. Nature Nanotech. 9, 48–53 (2014).

    CAS  Article  Google Scholar 

  29. Krishnamoorthy, H. N. S. et al. Topological transitions in metamaterials. Science 336, 205–209 (2012).

    CAS  Article  Google Scholar 

  30. Jacob, Z., Smolyaninov, I. I. & Narimanov, E. E. Broadband Purcell effect: radiative decay engineering with metamaterials. Appl. Phys. Lett. 100, 181105 (2012).

    Article  Google Scholar 

  31. Hoffman, A. J. et al. Negative refraction in semiconductor metamaterials. Nature Mater. 6, 946–950 (2007).

    CAS  Article  Google Scholar 

  32. Sreekanth, K. V., De Luca, A. & Strangi, G. Negative refraction in graphene-based hyperbolic metamaterials. Appl. Phys. Lett. 103, 023107 (2013).

    Article  Google Scholar 

  33. Ono, A., Kato, J. I. & Kawat, S. Subwavelength optical imaging through a metallic nanorod array. Phys. Rev. Lett. 95, 267407 (2005).

    Article  Google Scholar 

  34. Zhukovsky, S. V., Kidwai, O. & Sipe, J. E. Physical nature of volume plasmon polaritons in hyperbolic metamaterials. Opt. Exp. 21, 14982–14987 (2013).

    Article  Google Scholar 

  35. Avrutsky, I., Salakhutdinov, I., Elser, J. & Podolskiy, V. Highly confined optical modes in nanoscale metal-dielectric multilayers. Phys. Rev. B 75, 241402 (2007).

    Article  Google Scholar 

  36. Sreekanth, K. V., De Luca, A. & Strangi, G. Experimental demonstration of surface and bulk plasmon polaritons in hypergratings. Sci. Rep. 3, 3291 (2013).

    Article  Google Scholar 

  37. Sreekanth, K. V., De Luca, A. & Strangi, G. Excitation of volume plasmon polaritons in metal-dielectric metamaterials using 1D and 2D diffraction gratings. J. Opt. 16, 105103 (2014).

    Google Scholar 

  38. Sreekanth, K. V., Hari Krishna, K., De Luca, A. & Strangi, G. Large spontaneous emission rate enhancement in grating coupled hyperbolic metamaterials. Sci. Rep. 4, 6340 (2014).

    CAS  Article  Google Scholar 

  39. Cortes, C. L., Newman, W., Molesky, S. & Jacob, Z. Quantum nanophotonics using hyperbolic metamaterials. J. Opt. 14, 063001 (2012).

    Article  Google Scholar 

  40. Yan, W., Shen, L., Ran, L. & Kong, J. A. Surface modes at the interfaces between isotropic media and indefinite media. J. Opt. Soc. Am. A 24, 530–535 (2007).

    Article  Google Scholar 

  41. Baptista, P. et al. Gold nanoparticles for the development of clinical diagnosis methods. Anal. Bioanal. Chem. 391, 943–50 (2008).

    CAS  Article  Google Scholar 

  42. Weast, R. C. CRC Handbook of Chemistry and Physics (CRC Press, 1987).

    Google Scholar 

Download references

Acknowledgements

We acknowledge support from the Ohio Third Frontier Project ‘Research Cluster on Surfaces in Advanced Materials (RC-SAM) at Case Western Reserve University’. This work was also supported in part by Grant # 2013126 from the Doris Duke Charitable Foundation and by the Italian Project ‘NanoLase’-PRIN 2012, protocol number 2012JHFYMC. In addition, we acknowledge the support of the MORE Center at Case Western Reserve University and the GU Malignancies Program of the Case Comprehensive Cancer Center.

Author information

Authors and Affiliations

Authors

Contributions

K.V.S. and G.S. conceived the idea. K.V.S., Y.A., M.E., U.A.G., A.D.L. and G.S. designed the research. K.V.S. fabricated and characterized the sensor device, performed experiments and carried out numerical simulations. Y.A. fabricated the microfluidic channels, performed surface chemistry and prepared biologically relevant samples. M.E. performed experiments. E.I. and M.H. developed the theoretical models. K.V.S. and G.S. wrote the manuscript. All authors analysed the data, discussed the results, and edited the manuscript.

Corresponding authors

Correspondence to Kandammathe Valiyaveedu Sreekanth or Giuseppe Strangi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 2992 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sreekanth, K., Alapan, Y., ElKabbash, M. et al. Extreme sensitivity biosensing platform based on hyperbolic metamaterials. Nature Mater 15, 621–627 (2016). https://doi.org/10.1038/nmat4609

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat4609

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing