DNA-Encapsulating Lipid Nanoparticles: an alcohol-sensitive surrogate tracer to investigate microbial transmission in healthcare settings with and without hand hygiene | 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 DNA-Encapsulating Lipid Nanoparticles: an alcohol-sensitive surrogate tracer to investigate microbial transmission in healthcare settings with and without hand hygiene Lara Pfuderer, Hugo Sax, Robert Grass This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6563403/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Understanding the transmission routes of microbial pathogens is essential for infection prevention and control in healthcare settings. However, using infectious microorganisms to this end is challenging and poses potential risks. We explored alcohol-sensitive DNA-encapsulating lipid nanoparticles (LNP) as surrogate tracers to investigate microbial transmission, including the effect of hand hygiene. LNPs embedded in various synthetic matrices were evaluated under controlled laboratory conditions to identify the optimal formulation. The chosen LNP glycerine and sucrose formulation was subsequently tested in patient care experiments, both with and without hand hygiene conducted according to established standards using ABHR. Predefined contact surfaces and body sites were sampled and analysed for LNP integrity through quantitative polymerase chain reaction. The study revealed that the LNP formulation remained stable when dried on a surface. Hand hygiene using ABHR reduced LNP integrity to ≤ 1%. Without hand hygiene, LNPs transferred between surfaces maintained nearly 100% integrity. However, stability decreased during skin-to-skin transfer. In a typical patient care interaction, the study LNP formulation demonstrated a rapid, low-risk, and reliable approach for evaluating short pathogen transmission pathways, including the impact of hand hygiene. It shows promise as a diagnostic tool for assessing the effectiveness of transmission prevention measures in real-life clinical settings. Health sciences/Diseases/Infectious diseases Biological sciences/Biochemistry/Lipids/Membrane lipids Biological sciences/Microbiology/Policy and public health in microbiology Pathogen transmission surrogate markers nanoparticles hand hygiene disinfectants simulation Full Text Additional Declarations Competing interest reported. LP and RG filed a patent application registered by ETH Zurich. HS owns and heads a company dedicated to research and consulting in IPC and patient safety (Hugo Sax Health Design AG). Supplementary Files SupplementaryMaterialScientificReports.docx Cite Share Download PDF Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 01 Jul, 2025 Reviews received at journal 09 Jun, 2025 Reviewers agreed at journal 06 Jun, 2025 Reviews received at journal 05 Jun, 2025 Reviewers agreed at journal 05 Jun, 2025 Reviewers invited by journal 05 Jun, 2025 Editor invited by journal 15 May, 2025 Editor assigned by journal 15 May, 2025 Submission checks completed at journal 13 May, 2025 First submitted to journal 13 May, 2025 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. 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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-6563403","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":468079737,"identity":"93135f57-fb02-4f6c-a31c-fb3e3c56e51c","order_by":0,"name":"Lara Pfuderer","email":"","orcid":"","institution":"ETH Zurich","correspondingAuthor":false,"prefix":"","firstName":"Lara","middleName":"","lastName":"Pfuderer","suffix":""},{"id":468079738,"identity":"54b3787c-22da-4af7-82fa-42f044bb5d14","order_by":1,"name":"Hugo Sax","email":"","orcid":"","institution":"University of Bern","correspondingAuthor":false,"prefix":"","firstName":"Hugo","middleName":"","lastName":"Sax","suffix":""},{"id":468079739,"identity":"e68249dd-945f-4b62-99f0-34399c46dd79","order_by":2,"name":"Robert Grass","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYFACHiT2B4YDYJoZRBjg1ZIAYTLOgGhhbCZaCzMPMVrM23sPPq78wWC3vf344882NXfkdBuYjz8u+MMgb45Di8yZc8mGZxIYkuecyTGTzjn2zNjsAFti8wweBsOdDdi1SEjkmEk2ALVIMOSwMec2HE7cdoDHsJlHgiHB4ABOLeY/wVr4nz/+bNlwuH7bAf6PzTwGeLWYMQK12ElIJBhIMzYcTjA7wMPYzJOARwvPuWTJhjSJBAmJN2aSPccOG247zGY4m+eAhOEGXFrYew9+bLCxsZfgT3/84UfNYXmz480PPvP8sZHHZQtMZ2IDnM0MEcGrHgTsCaoYBaNgFIyCkQsA+4RYA/SrA4sAAAAASUVORK5CYII=","orcid":"","institution":"ETH Zurich","correspondingAuthor":true,"prefix":"","firstName":"Robert","middleName":"","lastName":"Grass","suffix":""}],"badges":[],"createdAt":"2025-04-30 09:23:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6563403/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6563403/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-12040-4","type":"published","date":"2025-07-31T16:05:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88268272,"identity":"6ccc4f49-c8bc-474c-91d6-24610b574dd4","added_by":"auto","created_at":"2025-08-04 16:50:35","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":738103,"visible":true,"origin":"","legend":"","description":"","filename":"PfudererScientificReportsManuskriptV10.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6563403/v1_covered_03fb0bdc-79ec-4af1-9337-7563a31fe981.pdf"},{"id":84193728,"identity":"6b6d3d8e-bdee-4e35-8ba9-ad73c56cf64a","added_by":"auto","created_at":"2025-06-09 07:13:57","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":286261,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialScientificReports.docx","url":"https://assets-eu.researchsquare.com/files/rs-6563403/v1/b9399d144b0a8f862b754a1b.docx"}],"financialInterests":"Competing interest reported. 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