Nanometric probes based on surface-enhanced Raman scattering (SERS) are promising candidates for all-optical environmental, biological and technological sensing applications with intrinsic quantitative molecular specificity. However, the effectiveness of SERS probes depends on a delicate trade-off between particle size, stability and brightness that has so far hindered their wide application in SERS imaging methodologies. In this Article, we introduce holographic Raman microscopy, which allows single-shot three-dimensional single-particle localization. We validate our approach by simultaneously performing Fourier transform Raman spectroscopy of individual SERS nanoparticles and Raman holography, using shearing interferometry to extract both the phase and the amplitude of wide-field Raman images and ultimately localize and track single SERS nanoparticles inside living cells in three dimensions. Our results represent a step towards multiplexed single-shot three-dimensional concentration mapping in many different scenarios, including live cell and tissue interrogation and complex anti-counterfeiting applications.
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The materials and data that support the findings of this study are available from the corresponding authors on request.
The software used for data analysis is available from the corresponding authors on request.
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We thank M. Rivas for her support with the live-cell experiments. We acknowledge support by the Ministry of Science, Innovation and Universities (MCIU/AEI: RTI2018-099957-J-I00 and PGC2018-096875-B-I00), the Ministry of Economy (MINECO: CTQ2017-88648-R, RYC-2015-19107 and ‘Severo Ochoa’ programme for Centers of Excellence in R&D CEX2019-000910-S), the Catalan AGAUR (2017SGR1369 and 2017SGR883), Fundació Privada Cellex, Fundació Privada Mir-Puig, the Generalitat de Catalunya through the CERCA programme and the Universitat Rovira i Virgili (FR 2019-B2). N.F.v.H. acknowledges the financial support by the European Commission (ERC Advanced Grant 670949-LightNet).
The authors declare no competing interests.
Peer review information Nature Nanotechnology thanks Pasquale Memmolo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.
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Liebel, M., Pazos-Perez, N., van Hulst, N.F. et al. Surface-enhanced Raman scattering holography. Nat. Nanotechnol. 15, 1005–1011 (2020). https://doi.org/10.1038/s41565-020-0771-9
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