Bi-analyte demonstration of non-resonant, single-molecule SERS with isolated lithographic enhancement structures.

Bi-analyte demonstration of non-resonant, single-molecule SERS with isolated lithographic enhancement structures. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Bi-analyte demonstration of non-resonant, single-molecule SERS with isolated lithographic enhancement structures. Xin Jin, Hui Xia, S. R. J. Brueck This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8779954/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract Single molecule Raman spectroscopy using isolated, circular ~ 110 nm diameter, multilayer disk enhancement structures fabricated with 355 nm interferometric lithography in a 2D 400 nm period array is reported. Adenine and cytosine are selected as a bi-analyte pair, with comparable strength Raman lines arising from ring breathing modes in proximity (A: 743 cm -1 shift and C: 807 cm -1 shift). Samples are soaked in 1:2 A:C mixtures diluted in water to ~ 1x10 -3 to 5x10 -4 of a monolayer coverage. Raman spectra are obtained with 633 nm excitation. The spectra show Poisson statistics with individual spectra showing: only A; only C; and A & C features demonstrating single molecule sensitivity. Over 90% of the spectra are null spectra without either A or C features. Importantly, the enhancement structures are isolated from each other, no close approach is required as in the case of spherical nanoparticles where ~ 1 nm gap modes are responsible for the large enhancement required for non-resonant single molecule sensitivity. Physical sciences/Chemistry Physical sciences/Materials science Physical sciences/Optics and photonics Physical sciences/Physics SM-SERS – single molecule surface-enhanced Raman spectroscopy plasmonics magnetic dipole MIM – metal-insulator-metal bi-analyte adenine cytosine Full Text Additional Declarations No competing interests reported. Supplementary Files SISMSERSshortened.docx Cite Share Download PDF Status: Published Journal Publication published 21 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 10 Mar, 2026 Reviews received at journal 09 Mar, 2026 Reviews received at journal 26 Feb, 2026 Reviews received at journal 26 Feb, 2026 Reviewers agreed at journal 18 Feb, 2026 Reviewers agreed at journal 16 Feb, 2026 Reviews received at journal 14 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers invited by journal 10 Feb, 2026 Editor invited by journal 06 Feb, 2026 Editor assigned by journal 04 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 03 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8779954","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":591566755,"identity":"630071ee-6c02-4f18-912b-8c096bf82e75","order_by":0,"name":"Xin Jin","email":"","orcid":"","institution":"Daisy Genomics","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Jin","suffix":""},{"id":591566756,"identity":"28c82830-c2ef-43c7-8b1a-9daacb90c094","order_by":1,"name":"Hui Xia","email":"","orcid":"","institution":"Daisy Genomics","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Xia","suffix":""},{"id":591566757,"identity":"faf75993-8020-4ced-a629-6eb93483c97e","order_by":2,"name":"S. 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Adenine and cytosine are selected as a bi-analyte pair, with comparable strength Raman lines arising from ring breathing modes in proximity (A: 743 cm\u003csup\u003e-1\u003c/sup\u003e shift and C: 807 cm\u003csup\u003e-1\u003c/sup\u003e shift). Samples are soaked in 1:2 A:C mixtures diluted in water to ~ 1x10\u003csup\u003e-3\u003c/sup\u003e to 5x10\u003csup\u003e-4\u003c/sup\u003e of a monolayer coverage. Raman spectra are obtained with 633 nm excitation. The spectra show Poisson statistics with individual spectra showing: only A; only C; and A \u0026amp; C features demonstrating single molecule sensitivity. Over 90% of the spectra are null spectra without either A or C features. 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