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Extreme sensitivity biosensing platform based on hyperbolic metamaterials

Nature Materials volume 15, pages 621–627 (2016)Cite this article

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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.

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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.

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References

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  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).

    Article  CAS  Google Scholar 

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

    Google Scholar 

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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.

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Authors and Affiliations

  1. Department of Physics, Case Western Reserve University, 10600 Euclid Avenue, Cleveland, Ohio 44106, USA

    Kandammathe Valiyaveedu Sreekanth, Mohamed ElKabbash, Efe Ilker, Michael Hinczewski & Giuseppe Strangi

  2. Mechanical and Aerospace Engineering Department, Case Biomanufacturing and Microfabrication Laboratory, Case Western Reserve University, Cleveland, Ohio 44106, USA

    Yunus Alapan & Umut A. Gurkan

  3. Biomedical Engineering Department, Case Western Reserve University, Cleveland, Ohio 44106, USA

    Umut A. Gurkan

  4. Department of Orthopedics, Case Western Reserve University, Cleveland, Ohio 44106, USA

    Umut A. Gurkan

  5. Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA

    Umut A. Gurkan

  6. CNR-NANOTEC Istituto di Nanotecnologia and Department of Physics, University of Calabria, 87036-Rende, Italy

    Antonio De Luca & Giuseppe Strangi

Authors
  1. Kandammathe Valiyaveedu Sreekanth
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  2. Yunus Alapan
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  7. Antonio De Luca
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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.

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The authors declare no competing financial interests.

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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

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