{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:01:34Z","timestamp":1790146894031,"version":"4.0.1"},"reference-count":116,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22474030"],"award-info":[{"award-number":["22474030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22274034"],"award-info":[{"award-number":["22274034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small Methods"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Surface\u2010enhanced Raman scattering (SERS) has emerged as a powerful platform for nucleic acids analyses due to its ultrahigh sensitivity and intrinsic molecular specificity. However, unlike small\u2010molecule systems, SERS responses of nucleic acids remain highly variable and strongly dependent on experimental conditions, limiting structural interpretability and reproducibility. In this Review, we provide a unified perspective that reframes SERS of nucleic acids as an interface\u2010defined physicochemical process rather than a direct molecular fingerprinting technique. We systematically analyze how interfacial accessibility, adsorption configuration, conformational reorganization, and electromagnetic (EM) selection collectively govern spectral formation through a hierarchical selection mechanism. On this basis, we propose that SERS spectra predominantly encode ensembles of interface\u2010selected conformations, which generally diverge from intrinsic solution\u2010phase structures, thereby explaining the widespread inconsistencies observed across different studies. This framework establishes a conceptual foundation for transforming SERS of nucleic acids from an empirical sensing approach into a controllable and predictive platform for structural analysis and biosensing applications.<\/jats:p>","DOI":"10.1002\/smtd.71055","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:18:03Z","timestamp":1790144283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["What Does SERS Measure in Nucleic Acids? An Interface\u2010Defined Perspective"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1984-6160","authenticated-orcid":false,"given":"Guangping","family":"Li","sequence":"first","affiliation":[{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio\u2212processProcess of Ministry of Education Hefei University of Technology  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Usman","sequence":"additional","affiliation":[{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio\u2212processProcess of Ministry of Education Hefei University of Technology  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio\u2212processProcess of Ministry of Education Hefei University of Technology  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Wu","sequence":"additional","affiliation":[{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio\u2212processProcess of Ministry of Education Hefei University of Technology  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio\u2212processProcess of Ministry of Education Hefei University of Technology  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0910-2444","authenticated-orcid":false,"given":"Honglin","family":"Liu","sequence":"additional","affiliation":[{"name":"Joint Research Center for Food Derived Functional Factors and Synthetic Biology of IHM, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, China Light Industry Key Laboratory of Meat Microbial Control and Utilization, School of Food and Biological Engineering, Engineering Research Center of Bio\u2212processProcess of Ministry of Education Hefei University of Technology  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010024\u201001860\u2010w"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202506426"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010024\u201002342\u20109"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5cs01522g"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007218\u20101"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010023\u201000263\u20106"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrs.1355"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C001054P"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5cs00124b"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010021\u201000083\u20106"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29143338"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/chemosensors11070399"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2025.11840"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00668"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/c7cs00809k"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/bios11070230"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2025.117519"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010025\u201000828\u20105"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CS00090K"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2015.09.008"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB00427B"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b04224"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2cp04566d"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013242\u2010x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202307091"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.242000"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcc.4c06042"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja066263w"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c02143"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2022.123941"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c12393"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja105678z"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja800023j"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04277"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.4c01060"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1515\/nanoph\u20102024\u20100230"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1515\/nanoph\u20102024\u20100230"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.4c02611"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b01426"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00604\u2010024\u201006336\u2010x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b01045"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b04183"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2025.127869"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.8b01353"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5TB02751A"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0288224"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcc.6b02753"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11671\u2010017\u20102121\u2010x"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjnano.2.66"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201014774\u20103"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366\u20106999.211874"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201004118\u20107"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c19208"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201703165"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/bios10050053"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.4172\/2161\u20101009.100028"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2019.00030"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2004.11.001"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202503257"},{"issue":"21","key":"e_1_2_11_61_1","doi-asserted-by":"crossref","DOI":"10.3390\/molecules24213921","article-title":"SERS Studies of Adsorption on Gold Surfaces of Mononucleotides With Attached Hexanethiol Moiety: Comparison With Selected Single\u2010Stranded Thiolated DNA Fragments","volume":"24","author":"Pyrak E.","year":"2019","journal-title":"Molecules"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2011.05.049"},{"issue":"15","key":"e_1_2_11_63_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202208250","article-title":"Plasmonic Dual\u2010Gap Nanodumbbells for Label\u2010Free On\u2010Particle Raman DNA Assays","volume":"35","author":"Kim J.\u2010M.","year":"2023","journal-title":"Advanced Materials"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201005920\u2010z"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1cs15155j"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202400976"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/la205036p"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202317463"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.5c03708"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b04885"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja3014055"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr100313v"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0325539"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CS00238F"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2021.112064"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00604\u2010018\u20102775\u20109"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144246"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja304118z"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5sc04459f"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1cc13705k"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1cc00628b"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphc.201701223"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201704460"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570\u2010017\u20100041"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557\u2010018\u20100046\u20103"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr030067f"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.6b01276"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh8362"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010021\u201000083\u20106"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar800249y"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrs.5400"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1515\/nanoph\u20102013\u20100024"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano8090730"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.21"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5303.1102"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c04052"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr030698"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac0613582"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.anchem.1.031207.112814"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp800167v"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi034621r"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.3390\/s22134889"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201205748"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1039\/d4cs01242a"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202523381"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr2001178"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.75804"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200904359"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja209351u"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b00891"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.5c00775"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.optmat.2021.111779"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.21"},{"key":"e_1_2_11_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2025.139070"},{"key":"e_1_2_11_115_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202310941"},{"key":"e_1_2_11_116_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202100087"},{"key":"e_1_2_11_117_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6c02165"}],"container-title":["Small Methods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smtd.71055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smtd.71055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smtd.71055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:18:05Z","timestamp":1790144285000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smtd.71055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":116,"alternative-id":["10.1002\/smtd.71055"],"URL":"https:\/\/doi.org\/10.1002\/smtd.71055","archive":["Portico"],"relation":{},"ISSN":["2366-9608","2366-9608"],"issn-type":[{"value":"2366-9608","type":"print"},{"value":"2366-9608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"assertion":[{"value":"2026-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71055"}}