Raman identification of single nucleotides flowing through permeable plasmonic films
Surface-Enhanced Raman Scattering has been studied for decades as a recognition technique due to its high sensitivity and discriminative power, particularly in biological applications. Inspired by nanopore sequencing technology, we developed a plasmonic device capable of operating in a flow-through configuration to detect individual molecules passing through plasmonic hotspots. This device is a permeable plasmonic film, through which single molecules are sequentially delivered via electrophoresis, while Raman spectra are recorded in real-time. A very effective light-matter coupling, combined with the ultrasmall size of plasmonic spots, enabled access to angstrom spatial and microsecond temporal scales compatible with polymer sequencing. We successfully slowed the translocation process and captured Raman spectra of the four nucleotides at a time resolution down to 20 μs under our experimental conditions. We achieved a discrimination accuracy of 89% at the single-molecule level. Also, we demonstrated a spatial resolution on the order of a few nucleotides, suggesting the potential for sequencing applications.
Authors
- Paolo Canepa (ORCID: https://orcid.org/0000-0002-2205-286X)
- Kirill Khabarov (ORCID: https://orcid.org/0000-0002-8710-7040)
- Federica Villa (ORCID: https://orcid.org/0000-0002-9840-0269)
- Francesco Tantussi (ORCID: https://orcid.org/0000-0002-0812-082X)
- Nick Goldman (ORCID: https://orcid.org/0000-0001-8486-2211)
- Francesco Gentile (ORCID: https://orcid.org/0000-0002-1724-6301)
- Foroogh Khozeymeh (ORCID: https://orcid.org/0000-0002-8417-7350)
- Giulia Bruno (ORCID: https://orcid.org/0009-0004-4931-1958)
- Bikash Kumar Bhandari (ORCID: https://orcid.org/0000-0001-8698-5258)
- I. Baldi
- Riccardo Marongiu
- Michele Dipalo (ORCID: https://orcid.org/0000-0002-1823-8231)
- Maria Blanco Formoso
- Veronica Storari
- Henri Haka (ORCID: https://orcid.org/0009-0008-6159-8559)
- Francesco De Angelis (ORCID: https://orcid.org/0000-0001-6053-2488)
Institutions
- European Bioinformatics Institute (GB)
- Italian Institute of Technology (IT)
- Magna Graecia University (IT)
- University of Genoa (IT)
- Politecnico di Milano (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-14
- DOI
- https://doi.org/10.1038/s41467-025-64165-9
- Citations
- 2
- Primary Topic
- Gold and Silver Nanoparticles Synthesis and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.85
Funders
- European Molecular Biology Laboratory
- Dipartimenti di Eccellenza
- European Commission
- Horizon 2020 Framework Programme