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Surface\u2010enhanced Raman spectroscopy (SERS) integrated with aptamers, short single\u2010stranded DNA or RNA oligonucleotides, has attracted considerable attention by coupling programmable molecular recognition with ultrasensitive plasmon\u2010enhanced Raman detection. This review evaluates recent advances in aptamer\u2010based SERS biosensors for nucleic\u2010acid analysis, systematically examining sensing mechanisms, plasmonic substrate engineering, aptamer immobilization, signal\u2010transduction pathways, and amplification approaches, including catalytic hairpin assembly, hybridization chain reaction, rolling circle amplification, and CRISPR\u2010assisted systems. Recent developments in microfluidics, artificial intelligence\u2010assisted spectral analysis, portable Raman instrumentation, and point\u2010of\u2010care platforms are assessed while distinguishing true aptamer\u2010mediated sensing from conventional hybridization\u2010based DNA detection. Rational hotspot engineering, deterministic nanogap architectures, and advanced amplification strategies have enabled detection from femtomolar to attomolar levels with improved selectivity, multiplexing, and reproducibility. Challenges including substrate variability, quantitative standardization, aptamer stability, biosafety, and clinical translation are discussed. Future directions toward standardized, intelligent, clinically deployable SERS platforms for next\u2010generation molecular diagnostics and precision healthcare are proposed.<\/jats:p>","DOI":"10.1002\/tcr.70259","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:36:51Z","timestamp":1791776211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surface\u2010Enhanced Raman Spectroscopy Aptasensors for Nucleic\u2010Acid Detection: Advances, Challenges, and Future Perspectives"],"prefix":"10.1002","author":[{"given":"Md. Saiful","family":"Alam","sequence":"first","affiliation":[{"name":"Electrochemistry &amp; Catalysis Research Laboratory (ECRL) Department of Chemistry School of Physical Sciences Shahjalal University of Science and Technology  Sylhet Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5353-7979","authenticated-orcid":false,"given":"Kazi Mohammed Mehedi","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Physical Sciences Shahjalal University of Science and Technology  Sylhet Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Tarafdar","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Physical Sciences Shahjalal University of Science and Technology  Sylhet Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5375-3637","authenticated-orcid":false,"given":"Mohammad Imran","family":"Hossain","sequence":"additional","affiliation":[{"name":"Electrochemistry &amp; Catalysis Research Laboratory (ECRL) Department of Chemistry School of Physical Sciences Shahjalal University of Science and Technology  Sylhet Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6388-901X","authenticated-orcid":false,"given":"Mohammad Anwar","family":"Parvez","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering College of Engineering King Faisal University  Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-1771","authenticated-orcid":false,"given":"Mostafizur","family":"Rahaman","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9441-3986","authenticated-orcid":false,"given":"Mohammad A.","family":"Hasnat","sequence":"additional","affiliation":[{"name":"Electrochemistry &amp; Catalysis Research Laboratory (ECRL) Department of Chemistry School of Physical Sciences Shahjalal University of Science and Technology  Sylhet Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_15_2_1","first-page":"17","article-title":"Specific Enzymatic Amplification of DNA In Vitro: The Polymerase Chain Reaction. 1986","volume":"24","author":"Mullis K.","year":"1992","journal-title":"Biotechnology"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2014.07.001"},{"key":"e_1_2_15_4_1","first-page":"1","article-title":"Detection of 2019 \u2010nCoV by Real\u2010Time RT\u2010PCR","volume":"25","author":"Corman V. 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