{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:42:40Z","timestamp":1791477760306,"version":"4.3.4"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172370"],"award-info":[{"award-number":["82172370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82172370"],"award-info":[{"award-number":["82172370"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Contract System Project of Chongqing Talent Plan","award":["cstc2022ycjh-bgzxm0257"],"award-info":[{"award-number":["cstc2022ycjh-bgzxm0257"]}]},{"name":"the Key Program of Technology Innovation and Application Development of Chongqing","award":["CSTB2022TIAD-KPX0190"],"award-info":[{"award-number":["CSTB2022TIAD-KPX0190"]}]},{"name":"Clinical Medical Innovation Capacity Cultivation Program of the Army Characteristic Medical Center","award":["ZXZYTSLC11"],"award-info":[{"award-number":["ZXZYTSLC11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>Circulating tumor cells (CTCs) are valuable liquid-biopsy biomarkers, yet their extreme rarity makes high-purity, high-throughput enrichment challenging. In spiral inertial microfluidics, high cell loading induces long-range hydrodynamic interactions that broaden the focused blood-cell stream; consequently, a subpopulation completes the ~0.5 and ~1.0 Dean-cycle migrations with a phase delay, compressing the CTC\u2013blood cell gap and degrading purity. Here we propose a Dean-cycle phase-regulated double-spiral design informed by this phenomenon. This design aims to mitigate the stream-broadening effect by boosting the Dean number during the first half-cycle to promote synchronized blood-cell migration and shifting the CTC equilibrium position near one full cycle to further widen the CTC\u2013blood cell separation. We implement this strategy in a second-generation double-spiral microfluidic chip (SDMC) and scale it to a four-channel parallel array (ASDMC). Under optimized conditions, ASDMC processes diluted whole blood (hematocrit = 4%) without the need for red blood cell (RBC) lysis or antibody labeling, achieving a sample throughput of 1200 \u03bcL\u00b7min\u22121. Specifically, it exhibits a mean recovery rate of 98.8% across three spiked tumor cell lines (MCF-7, PC-9, and Mahlavu) and a mean white blood cell (WBC) depletion efficiency of 93.3%. In a pilot clinical testing of 20 patients (NSCLC and HCC), enriched fractions enabled immunofluorescence identification of CK+CD45\u2212DAPI+ CTCs, with an exploratory trend of increasing CTC counts with advanced disease stage (4\u201334 cells\u00b7mL\u22121). These results describe a scalable, label-free platform, and the observed purification performance aligns with our proposed mechanism: Dean-cycle phase regulation to mitigate blood-cell migration lag. Our findings support further technical validation and clinical assessment in larger cohorts.<\/jats:p>","DOI":"10.3390\/mi17040446","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:11:28Z","timestamp":1775445088000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Suppressing Blood-Cell Migration Lag via Dean-Cycle Phase Regulation Enables High-Purity CTC Enrichment in an Inertial Microfluidic Array"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9769-9095","authenticated-orcid":false,"given":"Taihang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China"},{"name":"Department of Biomedical Materials Science, Army Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haozheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiange","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-8978","authenticated-orcid":false,"given":"Qing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China"},{"name":"Department of Biomedical Materials Science, Army Medical University, Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41392-021-00817-8","article-title":"Circulating Tumor Cells: Biology and Clinical Significance","volume":"6","author":"Lin","year":"2021","journal-title":"Signal Transduct. 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