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In contrast to conventional single-use sensors that only offer a snapshot, here, we develop a regenerable plasmonic nanopore sensor that enables simultaneous optical fluorescence and electronic readouts for self-validating detection. The capability for regeneration allows continuous and repeated monitoring of H2S flux from single cells, enhancing the statistical reliability and precision of quantitative analysis in complex cellular environments. The confinement of a molecular probe within the plasmonic hotspot yields a drastic, order-of-magnitude enhancement in both fluorescence and electrical signals, achieving ultrahigh sensitivity with a record-low, subpicomolar detection limit for H2S (49 fM by fluorescence signal and 71 fM by electrical signal)\u2500surpassing all existing methods. The sensor also exhibits excellent selectivity against 14 biologically relevant interferents. We further demonstrate its practical utility by directly monitoring endogenous H2S release from individual living HeLa cells in real time under chemical stimulus. Benefiting from the mutually verifiable dual-signal outputs and a renewable sensing interface, the plasmonic nanopore sensor provides a robust and noninvasive platform for tracking signaling molecules in biological systems at the single-cell level.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c01945","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:14:04Z","timestamp":1785147244000},"page":"22827-22834","source":"Crossref","is-referenced-by-count":0,"title":["A Plasmon-Enhanced Self-Validating Optoelectronic\nNanopore for Ultrasensitive and Robust Hydrogen Sulfide Real-Time\nMonitoring in Single Living Cells"],"prefix":"10.1021","volume":"98","author":[{"given":"Zi-Hui","family":"Li","sequence":"first","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-1553","authenticated-orcid":true,"given":"Shuo-Hui","family":"Cao","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]},{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7815-6406","authenticated-orcid":true,"given":"Shenglin","family":"Cai","sequence":"additional","affiliation":[{"name":"University of Cambridge , , Lensfield Road , ,","place":["Cambridge, U.K., CB2 1EW"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5531-0167","authenticated-orcid":true,"given":"Gaofeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Peng","family":"Cai","sequence":"additional","affiliation":[{"name":"Xiamen Center for Disease Control and Prevention , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-1671","authenticated-orcid":true,"given":"Yao-Qun","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, P. R. China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026081109080304600_cit1","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nrd2425","article-title":"Hydrogen sulphide\nand its therapeutic potential","volume":"6","author":"Szabo\u0301","year":"2007","journal-title":"Nat. Rev. Drug\nDiscovery"},{"key":"2026081109080304600_cit2","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1089\/ars.2020.8211","article-title":"Hydrogen Sulfide\nin Inflammation: A Novel Mediator\nand Therapeutic Target","volume":"34","author":"Bhatia","year":"2021","journal-title":"Antioxid. 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