{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:43:41Z","timestamp":1774691021060,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T00:00:00Z","timestamp":1576108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["No. 2016YFC0800703"],"award-info":[{"award-number":["No. 2016YFC0800703"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here, a \u201c3D extensible\u201d microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures\u2014check valve (in), check valve (out), double-check valve (in and out), and on\u2013off valve\u2014were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a \u201c3D extensible\u201d architecture to fulfill the needs of the function integration, the adaptive \u201cworld-to-chip\u201d interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.<\/jats:p>","DOI":"10.3390\/mi10120873","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T11:06:41Z","timestamp":1576148801000},"page":"873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Fully Integrated In Vitro Diagnostic Microsystem for Pathogen Detection Developed Using a \u201c3D Extensible\u201d Microfluidic Design Paradigm"],"prefix":"10.3390","volume":"10","author":[{"given":"Zhi","family":"Geng","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China"},{"name":"FengteBio Corporation, Beijing 100079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China"},{"name":"FengteBio Corporation, Beijing 100079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baobao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3000-3168","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature05058","article-title":"The origins and the future of microfluidics","volume":"442","author":"Whitesides","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nature13118","article-title":"The present and future role of microfluidics in biomedical research","volume":"507","author":"Sackmann","year":"2014","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/smll.201000946","article-title":"Microfluidic devices for bioapplications","volume":"7","author":"Yeo","year":"2011","journal-title":"Small"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1021\/acs.analchem.6b04630","article-title":"Point-of-care diagnostics: Recent developments in a connected age","volume":"89","author":"Nayak","year":"2017","journal-title":"Anal. 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