{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:01:35Z","timestamp":1790413295223,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Following injury and infection, neutrophils are guided to the affected site by chemoattractants released from injured tissues and invading microbes. During this process (chemotaxis), neutrophils must integrate multiple chemical signals, while also responding to physical constraints and prioritizing their directional decisions to generate an efficient immune response. In some clinical conditions, human neutrophils appear to lose the ability to chemotax efficiently, which may contribute both directly and indirectly to disease\u00a0pathology. Here, a range of microfluidic designs is utilized to test the sensitivity of chemotaxing neutrophils to various perturbations, including binary decision-making in the context of channels with different chemoattractant gradients, hydraulic resistance, and angle of approach. Neutrophil migration in long narrow channels and planar environments is measured. Conditions in which neutrophils are significantly more likely to choose paths with the steepest chemoattractant gradient and the most direct approach angle, and find that migration efficiency across planar chambers is inversely correlated with chamber diameter. By sequential measurement of neutrophil binary decision-making to different chemoattractant gradients, or chemotactic index in sequential planar environments, data supporting a model of biased random walk for neutrophil chemotaxis are presented.<\/jats:p>","DOI":"10.1002\/jlb.3ma0122-378rr","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T19:41:29Z","timestamp":1643658089000},"page":"1175-1184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Multifactorial assessment of neutrophil chemotaxis efficiency from a drop of blood"],"prefix":"10.1093","volume":"111","author":[{"given":"Felix","family":"Ellett","sequence":"first","affiliation":[{"name":"BioMEMS Resource Center, Division of Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika L","family":"Marand","sequence":"additional","affiliation":[{"name":"BioMEMS Resource Center, Division of Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Irimia","sequence":"additional","affiliation":[{"name":"BioMEMS Resource Center, Division of Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.coph.2011.06.007","article-title":"The role of TLRs in neutrophil activation","volume":"11","author":"Prince","year":"2011","journal-title":"Current opinion in pharmacology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nri.2016.49","article-title":"Neutrophil migration in infection and wound repair: going forward in reverse","volume":"16","author":"De Oliveira","year":"2016","journal-title":"Nature Reviews Immunology"},{"key":"2023032108503864000_","first-page":"807","article-title":"Depressed neutrophil chemotaxis in children suffering blunt trauma","volume":"93","author":"Krause","year":"1994","journal-title":"Pediatrics"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"e11921","DOI":"10.1371\/journal.pone.0011921","article-title":"Burn injury reduces neutrophil directional migration speed in microfluidic devices","volume":"5","author":"Butler","year":"2010","journal-title":"PloS one"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1142\/S2339547813500040","article-title":"Measuring neutrophil speed and directionality during chemotaxis, directly from a droplet of whole blood","volume":"1","author":"Hoang","year":"2013","journal-title":"Technology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/MOH.0b013e32833338f3","article-title":"Effects of sepsis on neutrophil chemotaxis","volume":"17","author":"Reddy","year":"2010","journal-title":"Current opinion in hematology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41551-018-0208-z","article-title":"Diagnosis of sepsis from a drop of blood by measurement of spontaneous neutrophil motility in a microfluidic assay","volume":"2","author":"Ellett","year":"2018","journal-title":"Nature biomedical engineering"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jcrc.2020.01.020","article-title":"The role of neutrophil chemotaxis activity as an immunologic biomarker to predict mortality in critically-ill patients with severe sepsis","volume":"56","author":"Srisawat","year":"2020","journal-title":"Journal of critical care"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep29410","article-title":"Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus","volume":"6","author":"Hou","year":"2016","journal-title":"Scientific reports"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","DOI":"10.1016\/j.tcb.2020.08.002","article-title":"All roads lead to directional cell migration","author":"Shellard","year":"2020","journal-title":"Trends in cell biology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s00109-011-0784-9","article-title":"Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation","volume":"89","author":"McDonald","year":"2011","journal-title":"Journal of molecular medicine"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1084\/jem.115.3.453","article-title":"The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes","volume":"115","author":"Boyden","year":"1962","journal-title":"The Journal of experimental medicine"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1083\/jcb.75.2.606","article-title":"Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors","volume":"75","author":"Zigmond","year":"1977","journal-title":"The Journal of cell biology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1242\/jcs.99.4.769","article-title":"A new direct-viewing chemotaxis chamber","volume":"99","author":"Zicha","year":"1991","journal-title":"Journal of cell science"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"066001","DOI":"10.1088\/1478-3975\/12\/6\/066001","article-title":"Inference of random walk models to describe leukocyte migration","volume":"12","author":"Jones","year":"2015","journal-title":"Physical biology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.molimm.2012.12.008","article-title":"Intraluminal crawling versus interstitial neutrophil migration during inflammation","volume":"55","author":"Pick","year":"2013","journal-title":"Molecular immunology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10544-015-9998-x","article-title":"Integrin associated proteins differentially regulate neutrophil polarity and directed migration in 2D and 3D","volume":"17","author":"Yamahashi","year":"2015","journal-title":"Biomedical microdevices"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.tibtech.2018.03.011","article-title":"Inflammation-on-a-chip: probing the immune system ex vivo","volume":"36","author":"Irimia","year":"2018","journal-title":"Trends in biotechnology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nbt712","article-title":"Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device","volume":"20","author":"Jeon","year":"2002","journal-title":"Nature biotechnology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/792163","article-title":"Drift-diffusion analysis of neutrophil migration during inflammation resolution in a zebrafish model","author":"Holmes","year":"2012","journal-title":"Advances in hematology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fimmu.2019.00359","article-title":"Super-low dose lipopolysaccharide dysregulates neutrophil migratory decision-making","volume":"10","author":"Boribong","year":"2019","journal-title":"Frontiers in immunology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep36440","article-title":"A microfluidic device for measuring cell migration towards substrate-bound and soluble chemokine gradients","volume":"6","author":"Schwarz","year":"2016","journal-title":"Scientific reports"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"21006","DOI":"10.1073\/pnas.1317441110","article-title":"Biased migration of confined neutrophil-like cells in asymmetric hydraulic environments","volume":"110","author":"Prentice-Mott","year":"2013","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0955-0674(02)00310-1","article-title":"Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass","volume":"14","author":"Weiner","year":"2002","journal-title":"Current opinion in cell biology"},{"key":"2023032108503864000_","first-page":"1","article-title":"Chemotaxing neutrophils enter alternate branches at capillary bifurcations","volume":"11","author":"Wang","year":"2020","journal-title":"Nature communications"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1039\/c0ib00011f","article-title":"Directional decisions during neutrophil chemotaxis inside bifurcating channels","volume":"2","author":"Ambravaneswaran","year":"2010","journal-title":"Integrative Biology"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"e6842","DOI":"10.1371\/journal.pone.0006842","article-title":"Navigation of chemotactic cells by parallel signaling to pseudopod persistence and orientation","volume":"4","author":"Bosgraaf","year":"2009","journal-title":"PloS one"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.devcel.2016.06.031","article-title":"Leading from the back: the role of the uropod in neutrophil polarization and migration","volume":"38","author":"Hind","year":"2016","journal-title":"Developmental cell"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.cell.2011.10.050","article-title":"Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration","volume":"148","author":"Houk","year":"2012","journal-title":"Cell"},{"key":"2023032108503864000_","doi-asserted-by":"crossref","first-page":"e3000457","DOI":"10.1371\/journal.pbio.3000457","article-title":"Cell confinement reveals a branched-actin independent circuit for neutrophil polarity","volume":"17","author":"Graziano","year":"2019","journal-title":"PLoS biology"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.3MA0122-378RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.3MA0122-378RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/111\/6\/1175\/49467149\/jlb11083.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/111\/6\/1175\/49467149\/jlb11083.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T16:26:48Z","timestamp":1700152008000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/111\/6\/1175\/6885182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,31]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,1,31]]},"published-print":{"date-parts":[[2022,5,23]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.3ma0122-378rr","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,6]]},"published":{"date-parts":[[2022,1,31]]},"assertion":[{"value":"2021-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}