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Adv."],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    The spatial confinement of electromagnetic hotspots (&lt;15 nanometers) in plasmonic nanostructures fundamentally restricts their utility for probing large, heterogeneous targets across diverse material and biological systems. We introduce a cascaded photonic-plasmonic strategy that bridges far-field illumination and near-field enhancement by integrating dielectric silicon dioxide microspheres that form subdiffraction nanojets on a plasmonic, gold-coated silicon dioxide nanoarray. This dual-layer architecture generates spatially extended electromagnetic \u201chotspaces\u201d exceeding 110 nanometers in lateral extent and sustaining analytical enhancement factors &gt; 10\n                    <jats:sup>6<\/jats:sup>\n                    , 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 (&lt;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.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec1846","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:00:56Z","timestamp":1778695256000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["From hotspots to hotspaces: Cascaded photonic-plasmonic coupling for SERS-based deep profiling of whole small extracellular vesicles"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-1431","authenticated-orcid":true,"given":"Haoming","family":"Bao","sequence":"first","affiliation":[{"name":"Key Lab of Materials Physics, Anhui Key Lab of Nanomaterials and Nanotechnology, Institute of Solid State Physics, HFIPS, Chinese Academy of Sciences, Hefei 230031, P.R. 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