Real-time Estimation of the Residual Moisture during Desorption with Temperature-based State Observers

Real-time Estimation of the Residual Moisture during Desorption with Temperature-based State Observers | 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 Real-time Estimation of the Residual Moisture during Desorption with Temperature-based State Observers Richard Braatz, Prakitr Srisuma, George Barbastathis This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4220099/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 Monitoring the residual moisture during desorption is vital to ensuring the final product quality in many chemical processes. One particular application is the lyophilization of biotherapeutics, e.g., mRNA vaccines, in which the bound water is removed via desorption during secondary drying. Successful liquid removal provides long-term stability for the vaccines, allowing for storage at higher temperature. This article proposes a novel technique for real-time estimation of the residual moisture during desorption, with application to lyophilization. A state observer is employed, which combines temperature measurement and mechanistic understanding of heat transfer and desorption kinetics, without requiring any online concentration measurement. Results from both simulations and experimental data show that the observer can accurately estimate the concentration of bound water in real time for all possible concentration levels, operating conditions, and measurement noise. This framework represents the first state observer for monitoring and control of the residual moisture in desorption-related processes. Physical sciences/Engineering/Chemical engineering Physical sciences/Mathematics and computing/Computational science State observer Desorption Bound water Lyophilization Freeze drying Secondary drying Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementary.pdf Supplementary Information 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-4220099","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":291997284,"identity":"7af0d531-008d-4b2c-bfac-a38312c1d098","order_by":0,"name":"Richard Braatz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqUlEQVRIiWNgGAWjYBACAwhlw8AGoniI1nKAIY2BjY1ELYcZGIjWYi59+OHnD3/OR/PJNzA+eNtGhBbLvjRjiQM8t3Pb2BiYDecSo8XgDIOBxAEJsBY2aV7itLB//nHA4BxIC/tvIrXwmEkcSDgAtoWZKC2WPTxlFmcOJAO1JDZLzjlHhBZzHvbNNyr+2OXObz588MObMiK0IAHGBtLUj4JRMApGwSjADQDMaTMFgKE4FwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-4304-3484","institution":"Massachusetts Institute of Technology","correspondingAuthor":true,"prefix":"","firstName":"Richard","middleName":"","lastName":"Braatz","suffix":""},{"id":291997285,"identity":"ae6b3fc3-559e-4fb4-b600-428b325921d0","order_by":1,"name":"Prakitr Srisuma","email":"","orcid":"https://orcid.org/0000-0002-6791-3942","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Prakitr","middleName":"","lastName":"Srisuma","suffix":""},{"id":291997286,"identity":"42069581-eb1d-4dc5-a68d-71ffb0da5607","order_by":2,"name":"George Barbastathis","email":"","orcid":"","institution":"Massachusetts Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"George","middleName":"","lastName":"Barbastathis","suffix":""}],"badges":[],"createdAt":"2024-04-05 00:35:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4220099/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4220099/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56823981,"identity":"58cfe190-1895-4d57-b260-0c38ae7079b4","added_by":"auto","created_at":"2024-05-21 02:34:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6908260,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptFile.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4220099/v1_covered_f4553815-fc1d-40b2-b146-ecf164981675.pdf"},{"id":54820652,"identity":"ca967e7a-cd75-4e49-bc8e-5988a99c666d","added_by":"auto","created_at":"2024-04-17 08:41:17","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":737827,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Information\u003c/p\u003e","description":"","filename":"Supplementary.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4220099/v1/dd4b607b69d05df3e68df291.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Real-time Estimation of the Residual Moisture during Desorption with Temperature-based State Observers","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"State observer, Desorption, Bound water, Lyophilization, Freeze drying, Secondary drying","lastPublishedDoi":"10.21203/rs.3.rs-4220099/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4220099/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Monitoring the residual moisture during desorption is vital to ensuring the final product quality in many chemical processes. 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