{"paper_id":"29bc4e84-0e17-442d-a910-74a9f581c17f","body_text":"A nanopore-gated sub-attoliter silicon nanocavity for non-invasive single molecule trapping and analysis | 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 A nanopore-gated sub-attoliter silicon nanocavity for non-invasive single molecule trapping and analysis Zhen Zhang, Funing Liu, Qitao Hu, Anton Sabantsev, Giovanni Muccio, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6355706/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Biomolecules exhibit dynamic conformations critical to their functions, yet observing these processes at the single-molecule level under native conditions remains a formidable challenge. While surface immobilization has been widely used to extend observation times, it can disrupt molecular dynamics and impede biological function. Recent advancements in single-molecule trapping techniques have addressed some limitations, but achieving precise, controllable, long-term trapping in a molecularly crowded environment without external forces remains difficult. Here, we introduce a nanopore-gated sub-attoliter silicon nanocavity that enables precise, non-invasive trapping of individual biomolecules for extended observation times, eliminating the need for surface immobilisation or external forces. Using nucleosomes as model systems, we demonstrate single-molecule Förster resonance energy transfer (smFRET) to monitor relative distances and directly observe dynamic unwrapping and rewrapping events induced by the chromatin remodelling enzyme Chd1. Our data further demonstrate that an applied electrical field can modulate the conformational properties of the macromolecules, emphasizing a key advantage of our device: it does not require an electrical field to retain trapped molecules. We envision this nanocavity platform as a powerful tool for the non-invasive interrogation of molecular dynamics in physiologically relevant environments, offering unperturbed access to weak and transient interactions that are central to biological regulation. Biological sciences/Biotechnology/Nanobiotechnology/Biosensors Biological sciences/Biotechnology/Nanobiotechnology/Nanopores Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supportinginformation.pdf Supplementary Information: A nanopore-gated sub-attoliter silicon nanocavity for non-invasive single molecule trapping and analysis Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6355706\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":440819414,\"identity\":\"0e2b4e31-c018-4205-8889-d8ea2b446030\",\"order_by\":0,\"name\":\"Zhen 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