Surface-enhanced Raman scattering holography

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.

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.

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).

ICFO — Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain

Department of Physical and Inorganic Chemistry and EMaS, Universitat Rovira i Virgili, Tarragona, Spain

ICREA — Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

M.L. constructed the optical experiment, performed the measurements and analysed the data. M.L. conceived the experiment. N.P.P. and R.A.A.P. synthesized and characterized the nanoparticles.

M.L. wrote the manuscript. M.L., N.F.v.H. and R.A.A.P. contributed to the interpretation of the data, discussion and writing of the manuscript.

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.

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

Live-cell tracking video supporting Fig. 6, showing bright-field (grey) and SERS (pink) signals.

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