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Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses

An Erratum to this article was published on 27 February 2013

This article has been updated

Abstract

The direct observation of nanoscale objects is a challenging task for optical microscopy because the scattering from an individual nanoparticle is typically weak at optical wavelengths. Electron microscopy therefore remains one of the gold standard visualization methods for nanoparticles, despite its high cost, limited throughput and restricted field-of-view. Here, we describe a high-throughput, on-chip detection scheme that uses biocompatible wetting films to self-assemble aspheric liquid nanolenses around individual nanoparticles to enhance the contrast between the scattered and background light. We model the effect of the nanolens as a spatial phase mask centred on the particle and show that the holographic diffraction pattern of this effective phase mask allows detection of sub-100 nm particles across a large field-of-view of >20 mm2. As a proof-of-concept demonstration, we report on-chip detection of individual polystyrene nanoparticles, adenoviruses and influenza A (H1N1) viral particles.

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Figure 1: Experimental setup, numerical model and sample preparation.
Figure 2: Large-FOV lensfree holographic microscopy of nanoparticles.
Figure 3: Lensfree holographic reconstructions of nanoparticles.
Figure 4: Lensfree holographic detection of 198 nm and 95 nm polystyrene beads with and without self-assembled nanolenses.
Figure 5: Simulated digital holographic reconstructions illustrating how liquid nanolenses enable the detection of otherwise undetectable 95 nm particles.
Figure 6: Detection of viruses.

Change history

  • 13 February 2013

    In the version of this Article originally published online, the particle contact angle θp in Fig. 1b,ii should have been labelled as 50°. This has now been corrected in the HTML and PDF versions of the Article.

References

  1. Betzig, E. & Chichester, R. J. Single molecules observed by near-field scanning optical microscopy. Science 262, 1422–1425 (1993).

    ADS  Article  Google Scholar 

  2. Lange, F. D. et al. Cell biology beyond the diffraction limit: near-field scanning optical microscopy. J. Cell Sci. 114, 4153–4160 (2001).

    Google Scholar 

  3. Kalkbrenner, T., Ramstein, M., Mlynek, J. & Sandoghdar, V. A single gold particle as a probe for apertureless scanning near-field optical microscopy. J. Microsc. 202, 72–76 (2001).

    MathSciNet  Article  Google Scholar 

  4. Ozcan, A. et al. Differential near-field scanning optical microscopy. Nano Lett. 6, 2609–2616 (2006).

    ADS  Article  Google Scholar 

  5. Huang, F. M. & Zheludev, N. I. Super-resolution without evanescent waves. Nano Lett. 9, 1249–1254 (2009).

    ADS  Article  Google Scholar 

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

    Article  Google Scholar 

  7. Kner, P., Chhun, B. B., Griffis, E. R., Winoto, L. & Gustafsson, M. G. L. Super-resolution video microscopy of live cells by structured illumination. Nature Methods 6, 339–342 (2009).

    Article  Google Scholar 

  8. Fitzgibbon, J., Bell, K., King, E. & Oparka, K. Super-resolution imaging of plasmodesmata using three-dimensional structured illumination microscopy. Plant Physiol. 153, 1453–1463 (2010).

    Article  Google Scholar 

  9. Binnig, G., Quate, C. F. & Gerber, C. Atomic force microscope. Phys. Rev. Lett. 56, 930–933 (1986).

    ADS  Article  Google Scholar 

  10. Ebenstein, Y., Nahum, E. & Banin, U. Tapping mode atomic force microscopy for nanoparticle sizing: tip–sample interaction effects. Nano Lett. 2, 945–950 (2002).

    ADS  Article  Google Scholar 

  11. Chithrani, B. D., Ghazani, A. A. & Chan, W. C. W. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 6, 662–668 (2006).

    ADS  Article  Google Scholar 

  12. Feinstone, S. M., Kapikian, A. Z. & Purcell, R. H. Hepatitis A: detection by immune electron microscopy of a virus-like antigen associated with acute illness. Science 182, 1026–1028 (1973).

    ADS  Article  Google Scholar 

  13. Hockley, D. J., Wood, R. D., Jacobs, J. P. & Garrett, A. J. Electron microscopy of human immunodeficiency virus. J. Gen. Virol. 69(10), 2455–2469 (1988).

    Article  Google Scholar 

  14. Pease, L. F. III et al. Quantitative characterization of virus-like particles by asymmetrical flow field flow fractionation, electrospray differential mobility analysis, and transmission electron microscopy. Biotechnol. Bioeng. 102, 845–855 (2009).

    Article  Google Scholar 

  15. Shevchuk, A. I. et al. Imaging single virus particles on the surface of cell membranes by high-resolution scanning surface confocal microscopy. Biophys. J. 94, 4089–4094 (2008).

    ADS  Article  Google Scholar 

  16. Ignatovich, F. V., Topham, D. & Novotny, L. Optical detection of single nanoparticles and viruses. IEEE J. Sel. Top. Quantum Electron. 12, 1292–1300 (2006).

    ADS  Article  Google Scholar 

  17. Daaboul, G. G. et al. High-throughput detection and sizing of individual low-index nanoparticles and viruses for pathogen identification. Nano Lett. 10, 4727–4731 (2010).

    ADS  Article  Google Scholar 

  18. Hong, X. et al. Background-free detection of single 5 nm nanoparticles through interferometric cross-polarization microscopy. Nano Lett. 11, 541–547 (2011).

    ADS  Article  Google Scholar 

  19. Stern, A. & Javidi, B. Improved-resolution digital holography using the generalized sampling theorem for locally band-limited fields. J. Opt. Soc. Am. A 23, 1227–1235 (2006).

    ADS  Article  Google Scholar 

  20. Rivenson, Y., Stern, A. & Javidi, B. Single exposure super-resolution compressive imaging by double phase encoding. Opt. Express 18, 15094–15103 (2010).

    ADS  Article  Google Scholar 

  21. Mudanyali, O., Bishara, W. & Ozcan, A. Lensfree super-resolution holographic microscopy using wetting films on a chip. Opt. Express 19, 17378–17389 (2011).

    ADS  Article  Google Scholar 

  22. Mudanyali, O. et al. Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications. Lab on a Chip 10, 1417–1428 (2010).

    Article  Google Scholar 

  23. Bishara, W. et al. Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array. Lab Chip 11, 1276–1279 (2011).

    Article  Google Scholar 

  24. Bishara, W., Su, T-W., Coskun, A. F. & Ozcan, A. Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution. Opt. Express 18, 11181–11191 (2010).

    ADS  Article  Google Scholar 

  25. Isikman, S. O. et al. Lens-free optical tomographic microscope with a large imaging volume on a chip. Proc. Natl Acad. Sci. USA doi:10.1073/pnas.1015638108 (2011).

  26. Greenbaum, A., Sikora, U. & Ozcan, A. Field-portable wide-field microscopy of dense samples using multi-height pixel super-resolution based lensfree imaging. Lab Chip 12, 1242–1245 (2012).

    Article  Google Scholar 

  27. Tseng, D. et al. Lensfree microscopy on a cellphone. Lab Chip 10, 1787–1792 (2010).

    Article  Google Scholar 

  28. Allier, C. P., Hiernard, G., Poher, V. & Dinten, J. M. Bacteria detection with thin wetting film lensless imaging. Biomed. Opt. Express 1, 762–770 (2010).

    Article  Google Scholar 

  29. Gopinathan, U., Pedrini, G., Javidi, B. & Osten, W. Lensless 3D digital holographic microscopic imaging at vacuum UV wavelength. J. Display Technol. 6, 479–483 (2010).

    ADS  Article  Google Scholar 

  30. Marquet, P. et al. Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy. Opt. Lett. 30, 468–470 (2005).

    ADS  Article  Google Scholar 

  31. Dubois, F., Joannes, L. & Legros, J-C. Improved three-dimensional imaging with a digital holography microscope with a source of partial spatial coherence. Appl. Opt. 38, 7085–7094 (1999).

    ADS  Article  Google Scholar 

  32. Moon, I. & Javidi, B. 3-D visualization and identification of biological microorganisms using partially temporal incoherent light in-line computational holographic imaging. IEEE Trans. Med. Imag. 27, 1782–1790 (2008).

    Article  Google Scholar 

  33. Xu, W., Jericho, M. H., Meinertzhagen, I. A. & Kreuzer, H. J. Digital in-line holography for biological applications. Proc. Natl Acad. Sci. USA 98, 11301–11305 (2001).

    ADS  Article  Google Scholar 

  34. Javidi, B., Yeom, S., Moon, I. & Daneshpanah, M. Real-time automated 3D sensing, detection, and recognition of dynamic biological micro-organic events. Opt. Express 14, 3806–3829 (2006).

    ADS  Article  Google Scholar 

  35. Javidi, B., Moon, I., Yeom, S. & Carapezza, E. Three-dimensional imaging and recognition of microorganism using single-exposure on-line (SEOL) digital holography. Opt. Express 13, 4492–4506 (2005).

    ADS  Article  Google Scholar 

  36. Zalevsky, Z., Gur, E., Garcia, J., Micó, V. & Javidi, B. Superresolved and field-of-view extended digital holography with particle encoding. Opt. Lett. 37, 2766–2768 (2012).

    ADS  Article  Google Scholar 

  37. Borkowski, A., Zalevsky, Z. & Javidi, B. Geometrical superresolved imaging using nonperiodic spatial masking. J. Opt. Soc. Am. A 26, 589–601 (2009).

    ADS  Article  Google Scholar 

  38. Mendlovic, D. & Zalevsky, Z. Optical Super Resolution (Erich Schmidt, 2003).

    Google Scholar 

  39. Young, T. An essay on the cohesion of fluids. Phil. Trans. R. Soc. Lond. 95, 65–87 (1805).

    ADS  Article  Google Scholar 

  40. Gennes, P-G. D., Brochard-Wyart, F. & Quéré, D. Capillarity and Wetting Phenomena: Drops, Bubbles, Pearls, Waves (Springer, 2004).

    Book  Google Scholar 

  41. Yeh, E. K., Newman, J. & Radke, C. J. Equilibrium configurations of liquid droplets on solid surfaces under the influence of thin-film forces: Part II. Shape calculations. Colloids Surf. 156, 525–546 (1999).

    Article  Google Scholar 

  42. Israelachvili, J. N. Intermolecular and Surface Forces (Academic Press, 2011).

    Google Scholar 

  43. Compostizo, A., Cancho, S. M., Rubio, R. G. & Crespo Colin, A. Experimental study of the equation of state and the surface tension of water-soluble polymers: poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol) + water at 298.15 K. Phys. Chem. Chem. Phys. 3, 1861–1866 (2001).

    Article  Google Scholar 

  44. Nadkarni, G. D. & Garoff, S. An investigation of microscopic aspects of contact angle hysteresis: pinning of the contact line on a single defect. Europhys. Lett. 20, 523–528 (1992).

    ADS  Article  Google Scholar 

  45. Marsh, J. A. & Cazabat, A. M. Dynamics of contact line depinning from a single defect. Phys. Rev. Lett. 71, 2433–2436 (1993).

    ADS  Article  Google Scholar 

  46. Born, P., Blum, S., Munoz, A. & Kraus, T. Role of the meniscus shape in large-area convective particle assembly. Langmuir 27, 8621–8633 (2011).

    Article  Google Scholar 

  47. Bonn, D., Eggers, J., Indekeu, J., Meunier, J. & Rolley, E. Wetting and spreading. Rev. Mod. Phys. 81, 739–805 (2009).

    ADS  Article  Google Scholar 

  48. Beltrame, P., Knobloch, E., Hänggi, P. & Thiele, U. Rayleigh and depinning instabilities of forced liquid ridges on heterogeneous substrates. Phys. Rev. E 83, 016305 (2011).

    ADS  MathSciNet  Article  Google Scholar 

  49. Kasarova, S. N., Sultanova, N. G., Ivanov, C. D. & Nikolov, I. D. Analysis of the dispersion of optical plastic materials. Opt. Mater. 29, 1481–1490 (2007).

    ADS  Article  Google Scholar 

  50. Mohsen-Nia, M., Modarress, H. & Rasa, H. Measurement and modeling of density, kinematic viscosity, and refractive index for poly(ethylene glycol) aqueous solution at different temperatures. J. Chem. Eng. Data 50, 1662–1666 (2005).

    Article  Google Scholar 

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Acknowledgements

Ozcan Research Lab acknowledges the support of the Army Research Office Young Investigator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), an NSF CAREER Award, an Office of Naval Research Young Investigator Award and the National Institutes of Health (NIH) Director's New Innovator Award (DP2OD006427) from the Office of The Director, NIH. The work at CEA-Leti was supported by the Carnot Institutes Network. The authors thank Hangfei Qi and Ren Sun of UCLA for H1N1 and adenovirus specimens.

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Contributions

O.M. performed the experiments and processed the resulting data. E.M. developed the theory and conducted numerical simulations and the related analysis. E.M., W.L., A.G and A.F.C. assisted in conducting the experiments and data analysis. O.M., E.M., Y.H., C.P.A. and A.O. planned the research and O.M., E.M. and A.O. wrote the manuscript. A.O. supervised the project.

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Correspondence to Aydogan Ozcan.

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Mudanyali, O., McLeod, E., Luo, W. et al. Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses. Nature Photon 7, 247–254 (2013). https://doi.org/10.1038/nphoton.2012.337

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