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However, current laboratory workflows remain multistep, instrument-intensive, and difficult to scale up for high-throughput multiplex testing. Here we present an active-matrix digital microfluidic (AM-DMF) platform for high-throughput HPV genotyping, utilizing a tailing-actuated interfacial liquid mixing (TAIL-Mix) strategy to enable highly efficient nucleic acid extraction and robust downstream amplification. The AM-DMF chip features a 921,600-electrode array that uses programmable, time-sequenced electrode actuation to stretch and retract droplets. This mechanism generates TAIL-Mix, significantly enhancing mixing efficiency under low-Reynolds-number conditions. Through combined COMSOL simulations and OpenCV-based image analysis, we determined that optimal TAIL-Mix parameters (a tailing distance of 7\u20138 pixels; 1.5 steps s\u20131) achieve a homogeneous state (mixing index \u2265 0.9) within 2 s, superior to traditional schemes. This enhanced mixing proved to be critical for high-performance processing, enabling magnetic-bead DNA extraction with 75% DNA recovery while reducing the protocol time to 26 min and the sample input to 1.5 \u03bcL of sample (100-fold reduction compared with conventional protocols). By integrating TAIL-Mix-enhanced extraction, thermal cycling, and 21-plex end point fluorescence readout on a single chip, the platform successfully performs parallel 21-genotype PCR analysis for two samples. In a clinical cohort of 20 cervical samples, the AM-DMF assay shows 100% sensitivity and 100% specificity relative to qPCR. Ultimately, this TAIL-Mix-empowered AM-DMF system offers a robust solution for low-reagent consumption, high-throughput clinical diagnostics.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c01103","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:21:15Z","timestamp":1788438075000},"page":"26387-26396","source":"Crossref","is-referenced-by-count":0,"title":["Tailing-Actuated\nInterfacial Liquid Mixing (TAIL-Mix)\nEnables Efficient Nucleic Acid Extraction and Integrated HPV Genotyping\non a Digital Microfluidics Platform"],"prefix":"10.1021","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4058-2733","authenticated-orcid":true,"given":"Jiajian","family":"Ji","sequence":"first","affiliation":[{"name":"University of Science and Technology of China , , ,","place":["Hefei, China, 230026"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinpei","family":"Pang","sequence":"additional","affiliation":[{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Fu","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China , , ,","place":["Hefei, China, 230026"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maolin","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China , , ,","place":["Hefei, China, 230026"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6800-4871","authenticated-orcid":true,"given":"Kai","family":"Jin","sequence":"additional","affiliation":[{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-2287","authenticated-orcid":true,"given":"Hanbin","family":"Ma","sequence":"additional","affiliation":[{"name":"University of Electronic Science and Technology of China , , ,","place":["Chengdu, China, 610072"]},{"name":"Guangdong ACXEL Micro & Nano Tech Company, Ltd. , ,","place":["Foshan, China, 528000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhong","family":"Yan","sequence":"additional","affiliation":[{"name":"Nanjing University , , ,","place":["Suzhou, China, 215153"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0686-5182","authenticated-orcid":true,"given":"Siyi","family":"Hu","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China , , ,","place":["Hefei, China, 230026"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]},{"name":"Jiangsu Key Laboratory for Advanced Theranostics and Medical Instrumentation , ,","place":["Suzhou, China, 215163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Mei","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China , , ,","place":["Hefei, China, 230026"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , ,","place":["Suzhou, China, 215163"]},{"name":"Jiangsu Key Laboratory for Advanced Theranostics and Medical 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injection\nmolded slipchip with self-sampling for integrated point-of-care testing\nof human papilloma virus","volume":"11","author":"Zhang","year":"2024","journal-title":"Adv. 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In  2020 IEEE International Electron\nDevices Meeting (IEDM), 2020.","DOI":"10.1109\/IEDM13553.2020.9372110"},{"issue":"5","key":"2026091511075584700_cit25","doi-asserted-by":"publisher","first-page":"109324","DOI":"10.1016\/j.isci.2024.109324","article-title":"Active-matrix\ndigital microfluidics design for field programmable high-throughput\ndigitalized liquid handling","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"issue":"17","key":"2026091511075584700_cit26","doi-asserted-by":"publisher","first-page":"6905","DOI":"10.1021\/acs.analchem.3c00150","article-title":"Large-area electronics-enabled high-resolution\ndigital microfluidics for parallel single-cell manipulation","volume":"95","author":"Hu","year":"2023","journal-title":"Anal. 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