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.

Plasmon-induced enhancement of ptychographic phase microscopy via sub-surface nanoaperture arrays

Nature Photonics volume 15, pages 222–229 (2021)Cite this article

Subjects

Abstract

The invention of phase contrast microscopy revolutionized optics, enabling the visualization of highly optically transparent samples without the need for staining. The technique utilizes phase shifts within the sample and is routinely employed in the characterization of biological material and other weakly interacting objects. However, the demand for increased contrast and quantification has continued to drive research into more advanced approaches to phase imaging. Here, we demonstrate that the combination of ptychographic coherent diffractive imaging with plasmonically active metamaterials yields a massive enhancement of both the reconstructed phase and amplitude by exploiting near-field interactions at the metamaterial surface. We present results from nanofabricated samples and tissue sections with thickness ranging from 4 nm to 4 μm. In addition to enabling quantitative phase imaging of metamaterials, this approach opens the way to imaging a wide range of extremely thin or highly transparent objects previously inaccessible to optical microscopy.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Fig. 1: Principles and experimental set-up for PE-ptychography.
Fig. 2: Comparison of conventional ptychography and PE-ptychography reconstructions.
Fig. 3: Simulated amplitude and phase contrast predicted for the nanofabricated chevrons.
Fig. 4: Reconstructions of ocular nerve tissue.
Fig. 5: Imaging of 4-μm-thick sections of breast tissue, comparing four different techniques.

Data availability

The data that support the plots and figures within this paper and other findings of this study are available from the corresponding author upon reasonable request.

Code availability

The code used to generate the figures within this paper and other findings of this study are available from the corresponding author upon reasonable request.

References

  1. Veselago, V. G. The electrodynamics of substances with simultaneously negative values of ε and μ. Sov. Phys. Usp. 10, 509–514 (1968).

    Article  ADS  Google Scholar 

  2. Kretschmann, E. & Raether, H. Notizen: radiative decay of non radiative surface plasmons excited by light. Zeitschrift für Naturforschung A 23, 2135–2136 (1968).

    Article  ADS  Google Scholar 

  3. Pendry, J. B. Negative refraction makes a perfect lens. Phys. Rev. Lett. 85, 3966–3969 (2000).

    Article  ADS  Google Scholar 

  4. Liedberg, B., Nylander, C. & Lunström, I. Surface plasmon resonance for gas detection and biosensing. Sens. Actuat. 4, 299–304 (1983).

    Article  Google Scholar 

  5. Smith, D. R., Schultz, S., Markoš, P. & Soukoulis, C. M. Determination of effective permittivity and permeability of metamaterials from reflection and transmission coefficients. Phys. Rev. B 65, 195104 (2002).

    Article  ADS  Google Scholar 

  6. Langley, D., Balaur, E., Sadatnajafi, C. & Abbey, B. Dual pitch plasmonic devices for polarization enhanced colour based sensing. Proc. SPIE 10013 (2016); https://doi.org/10.1117/12.2242975

  7. Langley, D. P. et al. Optical chemical barcoding based on polarization controlled plasmonic nanopixels. Adv. Funct. Mater. 28, 1704842 (2018).

    Article  Google Scholar 

  8. Sarid, D. et al. Optical field enhancement by long-range surface-plasma waves. Appl. Opt. 21, 3993–3995 (1982).

    Article  ADS  Google Scholar 

  9. Ebbesen, T. W. et al. Extraordinary optical transmission through sub-wavelength hole arrays. Nature 391, 667–669 (1998).

    Article  ADS  Google Scholar 

  10. Yang, Y. et al. Quantitative amplitude and phase imaging with interferometric plasmonic microscopy. ACS Nano 13, 13595–13601 (2019).

    Article  Google Scholar 

  11. Bouchal, P. et al. High-resolution quantitative phase imaging of plasmonic metasurfaces with sensitivity down to a single nanoantenna. Nano Lett. 19, 1242–1250 (2019).

    Article  ADS  Google Scholar 

  12. Kwon, H. et al. Single-shot quantitative phase gradient microscopy using a system of multifunctional metasurfaces. Nat. Photon. 14, 109–114 (2020).

    Article  ADS  Google Scholar 

  13. Yang, Y. et al. Label-free tracking of single organelle transportation in cells with nanometer precision using a plasmonic imaging technique. Small 11, 2878–2884 (2015).

    Article  Google Scholar 

  14. Anthony, N. et al. A direct approach to in-plane stress separation using photoelastic ptychography. Sci. Rep. 6, 30541 (2016).

    Article  ADS  Google Scholar 

  15. Maiden, A. M. & Rodenburg, J. M. An improved ptychographical phase retrieval algorithm for diffractive imaging. Ultramicroscopy 109, 1256–1262 (2009).

    Article  Google Scholar 

  16. Peterson, I. et al. Nanoscale Fresnel coherent diffraction imaging tomography using ptychography. Opt. Express 20, 24678–24685 (2012).

    Article  ADS  Google Scholar 

  17. Thibault, P. et al. Probe retrieval in ptychographic coherent diffractive imaging. Ultramicroscopy 109, 338–343 (2009).

    Article  Google Scholar 

  18. Hoppe, W. Beugung im inhomogenen Primarstrahlwellenfeld. I. Prinzip einer Phasenmessung von Elektronenbeungungsinterferenzen. Acta Crystallogr. A 25, 495–501 (1969).

    Article  ADS  Google Scholar 

  19. Rodenburg, J. M. & Faulkner, H. M. L. A phase retrieval algorithm for shifting illumination. Appl. Phys. Lett. 85, 4795–4797 (2004).

    Article  ADS  Google Scholar 

  20. Rodenburg, J. et al. Hard-X-ray lensless imaging of extended objects. Phys. Rev. Lett. 98, 034801 (2007).

    Article  ADS  Google Scholar 

  21. Abbey, B. et al. Quantitative coherent diffractive imaging of an integrated circuit at a spatial resolution of 20 nm. Appl. Phys. Lett. 93, 214101 (2008).

    Article  ADS  Google Scholar 

  22. Chen, B. et al. Diffraction imaging: the limits of partial coherence. Phys. Rev. B 86, 235401 (2012).

    Article  ADS  Google Scholar 

  23. Miao, J., Charalambous, P., Kirz, J. & Sayre, D. Extending the methodology of X-ray crystallography to allow imaging of micrometre-sized non-crystalline specimens. Nature 400, 342–344 (1999).

    Article  ADS  Google Scholar 

  24. Zhang, F. et al. Phase retrieval by coherent modulation imaging. Nat. Commun. 7, 13367 (2016).

    Article  ADS  Google Scholar 

  25. Lan, T.-Y., Li, P.-N. & Lee, T.-K. Method to enhance the resolution of X-ray coherent diffraction imaging for non-crystalline bio-samples. New J. Phys. 16, 033016 (2014).

    Article  ADS  Google Scholar 

  26. Noh, D. Y., Kim, C., Kim, Y. & Song, C. Enhancing resolution in coherent X-ray diffraction imaging. J. Phys. Condens. Matter 28, 493001 (2016).

    Article  ADS  Google Scholar 

  27. Takayama, Y. et al. Signal enhancement and Patterson-search phasing for high-spatial-resolution coherent X-ray diffraction imaging of biological objects. Sci. Rep. 5, 8074 (2015).

    Article  Google Scholar 

  28. Lo, Y. H. et al. In situ coherent diffractive imaging. Nat. Commun. 9, 1826 (2018).

    Article  ADS  Google Scholar 

  29. Putkunz, C. T. et al. Phase-diverse coherent diffractive imaging: high sensitivity with low dose. Phys. Rev. Lett. 106, 013903 (2011).

    Article  ADS  Google Scholar 

  30. Putkunz, C. T. et al. Fresnel coherent diffraction tomography. Opt. Express 18, 11746–11753 (2010).

    Article  ADS  Google Scholar 

  31. Balaur, E. et al. Continuously tunable, polarization controlled, colour palette produced from nanoscale plasmonic pixels. Sci. Rep. 6, 28062 (2016).

    Article  ADS  Google Scholar 

  32. Fereidouni, F. et al. Microscopy with ultraviolet surface excitation for rapid slide-free histology. Nat. Biomed. Eng. 1, 957–966 (2017).

    Article  Google Scholar 

  33. Tu, H. et al. Stain-free histopathology by programmable supercontinuum pulses. Nat. Photon. 10, 534–540 (2016).

    Article  ADS  Google Scholar 

  34. Wong, T. T. W. et al. Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy. J. Sci. Adv. 3, e1602168 (2017).

    Article  ADS  Google Scholar 

  35. Neilson, K. A. et al. Less label, more free: approaches in label-free quantitative mass spectrometry. Proteomics 11, 535–553 (2011).

    Article  Google Scholar 

  36. Lu, F.-K. et al. Label-free DNA imaging in vivo with stimulated Raman scattering microscopy. Proc. Natl Acad. Sci. USA 112, 11624–11629 (2015).

    Article  ADS  Google Scholar 

  37. Ji, M. et al. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci. Transl. Med. 5, 201ra119 (2013).

    Article  Google Scholar 

  38. Lee, M. et al. Label-free optical quantification of structural alterations in Alzheimer’s disease. Sci. Rep. 6, 31034 (2016).

    Article  ADS  Google Scholar 

  39. Sompuram, S. R. et al. A novel microscope slide adhesive for poorly adherent tissue sections. J. Histotechnol. 26, 117–123 (2003).

    Article  Google Scholar 

  40. Matenaers, C. et al. Practicable methods for histological section thickness measurement in quantitative stereological analyses. PLoS ONE 13, e0192879 (2018).

    Article  Google Scholar 

  41. Elmore, J. G. et al. Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA 313, 1122–1132 (2015).

    Article  Google Scholar 

  42. Kumari, G., Kandula, J. & Narayana, C. How far can we probe by SERS? J. Phys. Chem. C 119, 20057–20064 (2015).

    Article  Google Scholar 

  43. Holzwarth, C. W., Barwicz, T. & Smith, H. I. Optimization of hydrogen silsesquioxane for photonic applications. J. Vac. Sci. Technol. B 25, 2658–2661 (2007).

    Article  Google Scholar 

  44. Namatsu, H. et al. Three-dimensional siloxane resist for the formation of nanopatterns with minimum linewidth fluctuations. J. Vac. Sci. Technol. B 16, 69–76 (1998).

    Article  Google Scholar 

  45. Giannuzzi, L. A. & Stevie, F. A. Introduction to Focused Ion Beams: Instrumentation, Theory, Techniques and Practice (Springer Science & Business Media, 2006).

  46. COMSOL Multiphysics v. 5.2a (COMSOL AB); www.comsol.com

  47. Babar, S. & Weaver, J. H. Optical constants of Cu, Ag and Au revisited. Appl. Opt. 54, 477–481 (2015).

    Article  ADS  Google Scholar 

  48. Davie, S. A. et al. Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice. Transgenic Res. 16, 193–201 (2007).

    Article  ADS  Google Scholar 

  49. Orian, J. M. et al. Insertional mutagenesis inducing hypomyelination in transgenic mice. J. Neurosci. Res. 39, 604–612 (1994).

    Article  Google Scholar 

  50. Sandberg, R. L. et al. Studies of materials at the nanometer scale using coherent X-ray diffraction imaging. JOM 65, 1208–1220 (2013).

    Article  Google Scholar 

  51. Abbey, B. et al. Keyhole coherent diffractive imaging. Nat. Phys. 4, 394–398 (2008).

    Article  Google Scholar 

  52. Williams, G. J. et al. Fresnel coherent diffractive imaging. Phys. Rev. Lett. 97, 025506 (2006).

    Article  ADS  Google Scholar 

  53. Huang, X. et al. Optimization of overlap uniformness for ptychography. Opt. Express 22, 12634–12644 (2014).

    Article  ADS  Google Scholar 

  54. Quiney, H. M. et al. Diffractive imaging of highly focused X-ray fields. Nat. Phys. 2, 101–104 (2006).

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge support from the Australian Research Council through the ARC Centre of Excellence in Advanced Molecular Imaging and fellowship funding from the Victorian Cancer Agency (B.S.P.). B.A. acknowledges support from the La Trobe Biomedical and Environmental Sensor Technology (BEST) Research Centre. This work was performed in part at the Melbourne Centre for Nanofabrication (MCN) in the Victorian Node of the Australian National Fabrication Facility (ANFF).

Author information

Author notes

  1. These authors contributed equally: E. Balaur, G. A. Cadenazzi.

Authors and Affiliations

  1. The ARC Centre of Excellence for Advanced Molecular Imaging, La Trobe University, Melbourne, Victoria, Australia

    Eugeniu Balaur, Guido A. Cadenazzi & Brian Abbey

  2. Nanophysics & NIC@IIT, Istituto Italiano Di Tecnologia, Genoa, Italy

    Nicholas Anthony

  3. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia

    Alex Spurling & Belinda S. Parker

  4. Ian Holmes Imaging Center, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia

    Eric Hanssen

  5. Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia

    Eric Hanssen

  6. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia

    Jacqueline Orian & Belinda S. Parker

  7. Research School of Physics, The Australian National University, Acton, Australian Capital Territory, Australia

    Keith A. Nugent

  8. Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    Belinda S. Parker

Authors
  1. Eugeniu Balaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guido A. Cadenazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicholas Anthony
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alex Spurling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric Hanssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacqueline Orian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Keith A. Nugent
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Belinda S. Parker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Brian Abbey
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.A. conceived the initial idea. B.A., G.A.C. and E.B. are responsible for the conceptual design. B.S.P. was responsible for the design and management of cancer histological studies. G.A.C. undertook the experimental demonstration. E.B. produced the fabricated samples and performed the FEM simulations. N.A. assisted with experiments. E.H. prepared the biological samples and microtome slices. J.O. and A.S. prepared the biological samples. B.A. directed the project. K.A.N. discussed the results. B.A., G.A.C., E.B., B.S.P., N.A., E.H., J.O., A.S. and K.A.N. discussed the results and contributed to the manuscript.

Corresponding author

Correspondence to Brian Abbey.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Photonics thanks Karsten Holldack, Jianwei Miao and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Supplementary information

Supplementary Information

Supplementary Figs. 1–5 and Table 1.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Balaur, E., Cadenazzi, G.A., Anthony, N. et al. Plasmon-induced enhancement of ptychographic phase microscopy via sub-surface nanoaperture arrays. Nat. Photonics 15, 222–229 (2021). https://doi.org/10.1038/s41566-020-00752-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41566-020-00752-0

This article is cited by

Search

Advanced 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