From hotspots to hotspaces: Cascaded photonic-plasmonic coupling for SERS-based deep profiling of whole small extracellular vesicles
, a regime inaccessible to conventional surface-enhanced Raman scattering (SERS) platforms. In silico simulations and experiments reveal ~20-fold enhancements in signal intensity and spatial reach compared to conventional nanoarrays. As a proof of concept, we demonstrate ultrasensitive, label-free classification of extracellular vesicles, 80 to 200 nm in diameter, derived from patients with colorectal cancer with 99.8% accuracy, surpassing traditional SERS (<87.5%). More broadly, this cascaded excitation strategy shifts the emphasis from nanogap optimization to the engineering of spatially extended fields through hybrid light-focusing architectures, enabling advances in spectroscopy, biosensing, nanophotonics, and diagnostics.
Authors
- L Li
- Jaslyn Ru Ting Chen (ORCID: https://orcid.org/0009-0007-0425-0495)
- Xing Yi Ling (ORCID: https://orcid.org/0000-0001-5495-6428)
- Sheng Yuan Leong (ORCID: https://orcid.org/0009-0003-9952-1067)
- Emily Xi Tan (ORCID: https://orcid.org/0000-0001-5643-974X)
- Haoming Bao (ORCID: https://orcid.org/0000-0003-1071-1431)
- Lam Bang Thanh Nguyen (ORCID: https://orcid.org/0000-0002-2036-3808)
- Chang Hoong Chek (ORCID: https://orcid.org/0009-0007-1862-067X)
- Hailong Zhang (ORCID: https://orcid.org/0000-0002-8951-7094)
- Xiang Zhao (ORCID: https://orcid.org/0009-0009-3260-7986)
- In Yee Phang
- Jie Zhou
- Guo Kang Leon
- Han Wei Hou (ORCID: https://orcid.org/0000-0001-6631-6321)
Institutions
- Jiangnan University (CN)
- Army Medical University (CN)
- Nanyang Technological University (SG)
- Hefei Institutes of Physical Science (CN)
- Southwest Hospital (CN)
- Institute of Solid State Physics (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2026-05-13
- DOI
- https://doi.org/10.1126/sciadv.aec1846
- Primary Topic
- Near-Field Optical Microscopy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- ASCRS Research Foundation
- National Natural Science Foundation of China
- Natural Science Foundation of Anhui Province
- Digital Technology Supercluster