{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:57:45Z","timestamp":1791291465328,"version":"4.3.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/na","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21827812"],"award-info":[{"award-number":["21827812"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071408"],"award-info":[{"award-number":["32071408"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Microfluidic chip-based drug screening has attracted increasing attention owing to its miniaturization, automation, high throughput, simple operation, and excellent biocompatibility. Efficient release of target cells after co-culture with different drug concentrations is critical for investigating drug-induced alterations in cellular gene expression and enhancing microfluidic screening performance. In this study, a direction-sensitive microstructure with adaptive flow resistance regulation was constructed based on a fluidic-circuit-equivalent resistance model. This structure generated distinct distributions under forward and reverse flow directions, achieving efficient cell capture and release. Guided by theoretical analysis and simulation optimization, a microfluidic device integrating a concentration gradient generator, trap array, and flow resistance-regulating microchannels was fabricated. By simply switching the driving direction, the device can conveniently switch between forward capture and reverse release modes with high stability. In forward capture mode, the main channel exhibits the lowest flow resistance, and cells flow along the main channel and are captured in the traps. In reverse release mode, the main channel switches to the highest flow resistance, and cells in the traps are efficiently released backward along bypass channels to the collection outlet without recapture. Using K562 cells, the effects of channel width on cell capture and release efficiencies were investigated to determine the optimal design parameters. Finally, the device achieved a capture efficiency of 92.0 \u00b1 4.4% and a release efficiency of 70.0 \u00b1 8.6%, with maximum values of 97.2% and 87.8%, respectively. To further verify the device\u2019s applicability for drug screening, four concentrations of nilotinib were generated using the device. After K562 cells were cultured under the four concentrations for 48 h, the on-chip IC50 of nilotinib against K562 cells was determined to be approximately 10.79 \u03bcM, close to the result of 14.10 \u03bcM measured in the off-chip microplate. Subsequently, the treated cells were collected after reverse release and subjected to RNA-seq. The results showed that 20 \u03bcM nilotinib treatment significantly downregulated the expression of MYC, LYN, and BCL2L12, which are related to BCR-ABL signaling, by 18.3-fold, 3.6-fold, and 4.7-fold, respectively. Meanwhile, the treatment inhibited the viability of K562 cells to 23.9 \u00b1 3.5%.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c03273","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:02:08Z","timestamp":1790024528000},"page":"28905-28916","source":"Crossref","is-referenced-by-count":0,"title":["Hydrodynamic\nCell Capture and Release Microfluidic\nChip for Cancer Drug Screening"],"prefix":"10.1021","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9474-0388","authenticated-orcid":true,"given":"Xuefeng","family":"Wang","sequence":"first","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-2540","authenticated-orcid":true,"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing Polytechnic University of Electronic Technology , , ,","place":["Chongqing, China, 401331"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6877-8677","authenticated-orcid":true,"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-3302","authenticated-orcid":true,"given":"Ning","family":"Hu","sequence":"additional","affiliation":[{"name":"Chongqing University , , ,","place":["Chongqing, China, 400044"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026100608082799600_cit1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/s41556-018-0256-3","article-title":"Chemotherapy\nelicits pro-metastatic extracellular vesicles in breast cancer models","volume":"21","author":"Keklikoglou","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"2026100608082799600_cit2","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.gendis.2023.04.005","article-title":"Chemotherapy\ninduces breast cancer stem cell enrichment through repression of glutathione\nS-transferase Mu","volume":"11","author":"He","year":"2024","journal-title":"Genes Dis."},{"key":"2026100608082799600_cit3","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.ccell.2023.03.008","article-title":"Neutrophil extracellular traps formed\nduring chemotherapy confer treatment resistance via TGF-\u03b2 activation","volume":"41","author":"Mousset","year":"2023","journal-title":"Cancer Cell"},{"key":"2026100608082799600_cit4","doi-asserted-by":"publisher","first-page":"365ra159","DOI":"10.1126\/scitranslmed.aag1093","article-title":"The synthetic\ndiazonamide DZ-2384 has distinct effects on microtubule curvature\nand dynamics without neurotoxicity","volume":"8","author":"Wieczorek","year":"2016","journal-title":"Sci. Transl.\nMed."},{"key":"2026100608082799600_cit5","doi-asserted-by":"publisher","first-page":"4363","DOI":"10.1038\/s41467-024-48616-3","article-title":"Drug screening on digital microfluidics\nfor cancer precision medicine","volume":"15","author":"Zhai","year":"2024","journal-title":"Nat. Commun."},{"key":"2026100608082799600_cit6","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3390\/bios13020274","article-title":"Construction\nand Manipulation of Serial Gradient Dilution Array on a Microfluidic\nSlipchip for Screening and Characterizing Inhibitors against Human\nPancreatic Lipase","volume":"13","author":"Yang","year":"2023","journal-title":"Biosensors"},{"key":"2026100608082799600_cit7","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s13206-024-00154-2","article-title":"Multi-layered\nMicrofluidic Drug Screening Platform Enabling Simultaneous Generation\nof Linear and Logarithmic Concentration Gradients","volume":"18","author":"Yoon","year":"2024","journal-title":"BioChip J."},{"key":"2026100608082799600_cit8","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1126\/science.aax6234","article-title":"Massively\nmultiplex chemical transcriptomics at single-cell\nresolution","volume":"367","author":"Srivatsan","year":"2020","journal-title":"Science"},{"key":"2026100608082799600_cit9","doi-asserted-by":"publisher","first-page":"2400454","DOI":"10.1002\/smtd.202400454","article-title":"Atmospheric Pressure Enhanced Self-Sealing\nRotation-SlipChip with Programmable Concentration","volume":"8","author":"Wan","year":"2024","journal-title":"Small Methods"},{"key":"2026100608082799600_cit10","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2023.133939","article-title":"All-in-one\nmicrofluidic chip for 30-min quantitative point-of-care-testing of\nnucleic acids","volume":"390","author":"Zhang","year":"2023","journal-title":"Sens. Actuators, B"},{"key":"2026100608082799600_cit11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41551-025-01441-5","article-title":"Self-powered rapid antigen-specific\nT-cell response assay for Mycobacterium tuberculosis infections","volume":"10","author":"Ning","year":"2026","journal-title":"Nat. Biomed. Eng."},{"key":"2026100608082799600_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2024.125884","article-title":"A hydrodynamic-based\ndual-function microfluidic chip for high throughput\ndiscriminating tumor cells","volume":"273","author":"Wei","year":"2024","journal-title":"Talanta"},{"key":"2026100608082799600_cit13","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1039\/D4LC00290C","article-title":"Microfluidic\nSynthesis of Hemin@ZIF-8 Nanozyme with Applications in Cellular Reactive\nOxygen Species Detection and Anticancer Drug Screening","volume":"24","author":"Wang","year":"2024","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit14","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.1021\/acsptsci.4c00565","article-title":"A High-Throughput and Logarithm-Serial-Dilution Microfluidic Chip\nfor Combinational Drug Screening on Tumor Organoids","volume":"7","author":"Yan","year":"2024","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"2026100608082799600_cit15","doi-asserted-by":"publisher","first-page":"6740","DOI":"10.1021\/ac400688f","article-title":"Cell-Based Drug Combination\nScreening with a Microfluidic\nDroplet Array System","volume":"85","author":"Du","year":"2013","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit16","doi-asserted-by":"publisher","first-page":"11558","DOI":"10.1021\/acs.analchem.0c00273","article-title":"Inertial\nMicrofluidic Purification of Floating Cancer Cells for Drug Screening\nand Three-Dimensional Tumor Models","volume":"92","author":"Zhang","year":"2020","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit17","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88830.3","article-title":"Exploration of drug\nresistance mechanisms in triple negative breast\ncancer cells using a microfluidic device and patient tissues","volume":"12","author":"Lim","year":"2024","journal-title":"eLife"},{"key":"2026100608082799600_cit18","doi-asserted-by":"publisher","first-page":"13969","DOI":"10.1021\/acs.analchem.8b03456","article-title":"A Plug-and-Play,\nDrug-on-Pillar Platform for Combination Drug Screening Implemented\nby Microfluidic Adaptive Printing","volume":"90","author":"Li","year":"2018","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit19","doi-asserted-by":"publisher","first-page":"4749","DOI":"10.1039\/D1LC00895A","article-title":"Cancer\ndrug screening with an on-chip multi-drug dispenser in digital microfluidics","volume":"21","author":"Zhai","year":"2021","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit20","doi-asserted-by":"publisher","first-page":"2000126","DOI":"10.1002\/biot.202000126","article-title":"A Novel Wick-Like Paper-Based Microfluidic Device for\n3D Cell Culture and Anti-Cancer Drugs Screening","volume":"16","author":"Fu","year":"2021","journal-title":"Biotechnol. J."},{"key":"2026100608082799600_cit21","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202514775","article-title":"A Microwell Array Embedded Microfluidic\nGradient Platform for Drug Screening on Tumor Spheroids","volume":"22","author":"Liu","year":"2026","journal-title":"Small"},{"key":"2026100608082799600_cit22","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3390\/mi11030322","article-title":"Selective Retrieval of Individual Cells from Microfluidic\nArrays Combining Dielectrophoretic Force and Directed Hydrodynamic\nFlow","volume":"11","author":"Thiriet","year":"2020","journal-title":"Micromachines"},{"key":"2026100608082799600_cit23","doi-asserted-by":"publisher","first-page":"19117","DOI":"10.1021\/acs.analchem.4c04633","article-title":"Microfluidic Chip for Cell Fusion and In Situ Separation\nof Fused Cells","volume":"96","author":"Bai","year":"2024","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit24","doi-asserted-by":"publisher","first-page":"9932","DOI":"10.1021\/acs.analchem.9b01604","article-title":"Nondestructive identification\nand accurate isolation\nof single cells through a chip with raman optical tweezers","volume":"91","author":"Fang","year":"2019","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit25","doi-asserted-by":"publisher","first-page":"3936","DOI":"10.1021\/acsami.9b17575","article-title":"Photoactivated\nSelective\nRelease of Droplets from Microwell Arrays","volume":"12","author":"Han","year":"2020","journal-title":"ACS\nAppl. Mater. Interfaces"},{"key":"2026100608082799600_cit26","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1039\/D4LC00736K","article-title":"Large-scale\nacoustic single cell trapping and selective releasing","volume":"25","author":"Zhang","year":"2025","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit27","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2022.124044","article-title":"Single-cell\nsorting using integrated pneumatic valve droplet microfluidic chip","volume":"253","author":"Zhou","year":"2023","journal-title":"Talanta"},{"key":"2026100608082799600_cit28","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.talanta.2018.09.085","article-title":"A microfluidic platform\nwith pneumatically switchable\nsingle-cell traps for selective intracellular signals probing","volume":"192","author":"Wang","year":"2019","journal-title":"Talanta"},{"key":"2026100608082799600_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2022.132198","article-title":"A self-driven\ncarbon-doped high-density microwell array for single cell analysis","volume":"368","author":"Wu","year":"2022","journal-title":"Sens. Actuators, B"},{"key":"2026100608082799600_cit30","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1039\/D3LC00922J","article-title":"Selective expansion\nof renal cancer stem cells using\nmicrofluidic single-cell culture arrays for anticancer drug testing","volume":"24","author":"Wang","year":"2024","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2022.123976","article-title":"Fabrication of single cell microarrays\non a double-layered hydrogel for mitochondrial activity monitoring","volume":"253","author":"Cho","year":"2023","journal-title":"Talanta"},{"key":"2026100608082799600_cit32","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1021\/acs.analchem.5b04681","article-title":"Droplet Microfluidic\nPlatform for the Determination of Single-Cell Lactate Release","volume":"88","author":"Mongersun","year":"2016","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit33","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1039\/c4lc00303a","article-title":"Deformability-based\nmicrofluidic cell pairing and fusion","volume":"14","author":"Dura","year":"2014","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit34","doi-asserted-by":"publisher","first-page":"10733","DOI":"10.1021\/acs.analchem.0c02006","article-title":"Exosome Purification and Analysis\nUsing a Facile Microfluidic Hydrodynamic\nTrapping Device","volume":"92","author":"Tayebi","year":"2020","journal-title":"Anal. Chem."},{"key":"2026100608082799600_cit35","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1039\/C9LC00036D","article-title":"Hydrodynamic shuttling\nfor deterministic high-efficiency multiple single-cell capture in\na microfluidic chip","volume":"19","author":"He","year":"2019","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit36","doi-asserted-by":"publisher","first-page":"7929","DOI":"10.1021\/acs.langmuir.2c00341","article-title":"Quantification\nof Intracellular Proteins in Single Cells Based on Engineered Picoliter\nDroplets","volume":"38","author":"Liu","year":"2022","journal-title":"Langmuir"},{"key":"2026100608082799600_cit37","doi-asserted-by":"publisher","DOI":"10.1063\/5.0250472","article-title":"Hydrodynamic\nefficient cell capture and pairing method on microfluidic cell electrofusion\nchip","volume":"9","author":"Wang","year":"2025","journal-title":"APL. Bioeng."},{"key":"2026100608082799600_cit38","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1073\/pnas.0606625104","article-title":"A trap-and-release\nintegrated microfluidic system for\ndynamic microarray applications","volume":"104","author":"Tan","year":"2007","journal-title":"Proc. Natl.\nAcad. Sci. U.S.A."},{"key":"2026100608082799600_cit39","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1039\/C2LC20911J","article-title":"Microfluidic\nsingle-cell cultivation chip with controllable immobilization and\nselective release of yeast cells","volume":"12","author":"Zhu","year":"2012","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit40","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1039\/D1LC00302J","article-title":"A microfluidic device\nenabling deterministic single cell trapping and release","volume":"21","author":"Chai","year":"2021","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit41","doi-asserted-by":"publisher","first-page":"3686","DOI":"10.1039\/D1LC00463H","article-title":"Planar hydrodynamic traps and buried\nchannels for bead and cell trapping and releasing","volume":"21","author":"Lipp","year":"2021","journal-title":"Lab Chip"},{"key":"2026100608082799600_cit42","doi-asserted-by":"publisher","first-page":"4540","DOI":"10.1182\/blood.V110.11.4540.4540","article-title":"Transcriptional Changes Induced by\nImatinib and Nilotinib in the Chronic Myelogenous Leukemia (CML) Cell\nLine K562","volume":"110","author":"Neumann","year":"2007","journal-title":"Blood"},{"key":"2026100608082799600_cit43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000512","article-title":"Transcriptional\nProfiling of the\nDose Response: A More Powerful Approach for Characterizing Drug Activities","volume":"5","author":"Ji","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2026100608082799600_cit44","doi-asserted-by":"publisher","first-page":"6187","DOI":"10.1038\/s41598-021-85734-0","article-title":"Efficiency of nilotinib to target\nchronic phase-chronic myeloid leukaemia primary mature CD34\u2013\nand immature CD34+ cells","volume":"11","author":"Berger","year":"2021","journal-title":"Sci. Rep."},{"key":"2026100608082799600_cit45","doi-asserted-by":"publisher","first-page":"eaan4368","DOI":"10.1126\/science.aan4368","article-title":"The target landscape of clinical kinase drugs","volume":"358","author":"Klaeger","year":"2017","journal-title":"Science"},{"key":"2026100608082799600_cit46","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1476-4598-9-22","article-title":"Effects of nilotinib\non regulatory T cells: the dose matters","volume":"9","author":"Fei","year":"2010","journal-title":"Mol.\nCancer"},{"key":"2026100608082799600_cit47","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.966182","article-title":"Cardiovascular adverse\nevents in chronic myeloid leukemia patients\ntreated with nilotinib or imatinib: A systematic review, meta-analysis\nand integrative bioinformatics analysis","volume":"9","author":"Li","year":"2022","journal-title":"Front.\nCardiovasc. Med."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c03273","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/39\/28905\/68587625\/acs.analchem.6c03273.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/39\/28905\/68587625\/acs.analchem.6c03273.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:20:21Z","timestamp":1791289221000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/39\/28905\/5434717\/Hydrodynamic-Cell-Capture-and-Release-Microfluidic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":47,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,10,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c03273","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}