Functional drug screening of tumor organoids on an Active-Matrix Digital Microfluidic Chip for cancer precision medicine

Functional drug screening of tumor organoids on an Active-Matrix Digital Microfluidic Chip for cancer precision medicine | 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 Functional drug screening of tumor organoids on an Active-Matrix Digital Microfluidic Chip for cancer precision medicine Wenfei Dong, Ruimeng Sun, Zhengyang Feng, Tong Wu, Fang qiu Ding, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7772352/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Apr, 2026 Read the published version in Microsystems & Nanoengineering → Version 1 posted 11 You are reading this latest preprint version Abstract Cancer is a leading cause of morbidity and mortality worldwide, characterized by substantial inter-patient and intra-tumor heterogeneity that complicates treatment efficacy. While genomic profiling has advanced precision oncology, the prevalence of tumors lacking targetable mutations highlights the need for complementary functional assays. Here, we present a drug sensitivity testing platform based on active-matrix digital microfluidics (AM-DMF) integrated with patient-derived organoids (PDOs). We optimized protocols for sample loading, droplet generation and routing, and controlled drug exposure, achieving precise concentration gradients via iterative mix-split steps. By combining AM-DMF with PDOs, we enable automated liquid handling and high-content imaging to capture heterogeneous drug responses. This approach significantly enhances the efficiency, reproducibility, and sensitivity of drug testing-particularly for limited clinical samples and complex drug combinations. The platform provides an end-to-end workflow, from sample processing to quantitative response analysis, offering a systematic and scalable strategy for precision medicine. These findings establish an automatable, integrated pipeline for functional precision oncology, especially suited to scarce specimens and multi-drug regimens. Physical sciences/Nanoscience and technology/Nanobiotechnology/Microfluidics Physical sciences/Engineering/Electrical and electronic engineering Full Text Additional Declarations There is no conflict of interest Supplementary Files supplementary.docx Supplemental Drugdilutionpath.mp4 Drug dilution path Sortingandculture.mp4 Sorting and culture Cite Share Download PDF Status: Published Journal Publication published 15 Apr, 2026 Read the published version in Microsystems & Nanoengineering → Version 1 posted Editorial decision: revise 10 Nov, 2025 Review # 3 received at journal 30 Oct, 2025 Review # 1 received at journal 29 Oct, 2025 Review # 2 received at journal 21 Oct, 2025 Reviewer # 3 agreed at journal 08 Oct, 2025 Reviewer # 2 agreed at journal 08 Oct, 2025 Reviewer # 1 agreed at journal 08 Oct, 2025 Reviewers invited by journal 07 Oct, 2025 Submission checks completed at journal 07 Oct, 2025 Editor assigned by journal 03 Oct, 2025 First submitted to journal 03 Oct, 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. 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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-7772352","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":526251030,"identity":"c6f27c61-f015-49f1-aedc-9dca4b2f915f","order_by":0,"name":"Wenfei Dong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYJCCDwwGzECK+QBDYgNxOhhnQLSwJYC0SBCphQGkhceAgZEYLQbHew82fCiwljPnX/P5w8MdNnUM7IcfMPzcgUfLmXOJjTMM0o0tZ7zdJpF4Jk2CgSfNgLH3DG4tZjdyzB/zGBxO3HDj7DaGxLbDQIflMDAztuHRcv+NYfMfsJYzjz8ktv2XYOB/Q0DLDR7DZgaQlvM9DBKJbQckGCQI2GJ/JsewsQfoF4MbbGZAvyRLtkk8MzjYi0eLZPsZw4Yff6zlDM4ffvzx5w47fn7+5IcPfuLRggASCRCaDYgPEKOBgYGfSHWjYBSMglEw8gAAV8dV9kYd+foAAAAASUVORK5CYII=","orcid":"","institution":"Department of Biomaterials and Stem Cells, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, China.","correspondingAuthor":true,"prefix":"","firstName":"Wenfei","middleName":"","lastName":"Dong","suffix":""},{"id":526251031,"identity":"b380adf9-2ebc-41b3-acf4-54b5db347caf","order_by":1,"name":"Ruimeng Sun","email":"","orcid":"","institution":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.","correspondingAuthor":false,"prefix":"","firstName":"Ruimeng","middleName":"","lastName":"Sun","suffix":""},{"id":526251032,"identity":"77b6ddc5-ea17-441f-9497-e6cd48657947","order_by":2,"name":"Zhengyang Feng","email":"","orcid":"","institution":"Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China","correspondingAuthor":false,"prefix":"","firstName":"Zhengyang","middleName":"","lastName":"Feng","suffix":""},{"id":526251033,"identity":"ba7deee0-22df-4ed0-8f82-926fcf8cf8d1","order_by":3,"name":"Tong Wu","email":"","orcid":"","institution":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.","correspondingAuthor":false,"prefix":"","firstName":"Tong","middleName":"","lastName":"Wu","suffix":""},{"id":526251034,"identity":"6881438b-51c4-4877-8a7c-6224711ea42c","order_by":4,"name":"Fang qiu Ding","email":"","orcid":"","institution":"CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"qiu","lastName":"Ding","suffix":""},{"id":526251035,"identity":"e632a83f-d155-4fa2-9fe1-ebec49a4d980","order_by":5,"name":"Yong Wu","email":"","orcid":"","institution":"Guangdong ACXEL Micro \u0026 Nano Tech Co., Ltd., Foshan 528200, China","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Wu","suffix":""},{"id":526251036,"identity":"094c7913-3db5-43f6-927f-c9597a15f0c8","order_by":6,"name":"Kai Jin","email":"","orcid":"","institution":"CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Jin","suffix":""},{"id":526251037,"identity":"5e0a2045-0cc0-4eb7-b2cd-1a6d0b9b5296","order_by":7,"name":"Li Li","email":"","orcid":"","institution":"Suzhou Institute of Biomedical Engineering and Technology, CAS","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Li","suffix":""},{"id":526251038,"identity":"b44d0de6-db50-4981-ad3d-da53d6bc8464","order_by":8,"name":"Zhiqiang Jia","email":"","orcid":"","institution":"Department of Computer Science and Engineering, The Chinese University of Hong Kong, Hongkong, 999077, P. 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