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dc.contributor.authorBerry, Jess
dc.contributor.authorPeaudecerf, François J
dc.contributor.authorMasters, Nicole A
dc.contributor.authorNeeves, Keith B
dc.contributor.authorGoldstein, Raymond
dc.contributor.authorHarper, Matthew
dc.date.accessioned2021-08-10T23:30:22Z
dc.date.available2021-08-10T23:30:22Z
dc.date.issued2021-10-26
dc.identifier.issn1473-0197
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/326473
dc.description.abstractCardiovascular disease remains one of the world's leading causes of death. Myocardial infarction (heart attack) is triggered by occlusion of coronary arteries by platelet-rich thrombi (clots). The development of new anti-platelet drugs to prevent myocardial infarction continues to be an active area of research and is dependent on accurately modelling the process of clot formation. Occlusive thrombi can be generated in vivo in a range of species, but these models are limited by variability and lack of relevance to human disease. Although in vitro models using human blood can overcome species-specific differences and improve translatability, many models do not generate occlusive thrombi. In those models that do achieve occlusion, time to occlusion is difficult to measure in an unbiased and objective manner. In this study we developed a simple and robust approach to determine occlusion time of a novel in vitro microfluidic assay. This highlighted the potential for occlusion to occur in thrombosis microfluidic devices through off-site coagulation, obscuring the effect of anti-platelet drugs. We therefore designed a novel occlusive thrombosis-on-a-chip microfluidic device that reliably generates occlusive thrombi at arterial shear rates by quenching downstream coagulation. We further validated our device and methods by using the approved anti-platelet drug, eptifibatide, recording a significant difference in the "time to occlude" in treated devices compared to control conditions. These results demonstrate that this device can be used to monitor the effect of antithrombotic drugs on time to occlude, and, for the first time, delivers this essential data in an unbiased and objective manner.
dc.description.sponsorshipSchlumberger Chair Fund
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherRoyal Society of Chemistry (RSC)
dc.rightsAll rights reserved
dc.titleAn "occlusive thrombosis-on-a-chip" microfluidic device for investigating the effect of anti-thrombotic drugs.
dc.typeArticle
prism.publicationDate2021
prism.publicationNameLab Chip
dc.identifier.doi10.17863/CAM.73924
dcterms.dateAccepted2021-08-05
rioxxterms.versionofrecord10.1039/d1lc00347j
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-09-15
dc.contributor.orcidPeaudecerf, François J [0000-0003-0295-4556]
dc.contributor.orcidNeeves, Keith B [0000-0001-7546-4588]
dc.contributor.orcidGoldstein, Raymond [0000-0003-2645-0598]
dc.contributor.orcidHarper, Matthew [0000-0002-4740-637X]
dc.identifier.eissn1473-0189
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (207510/Z/17/Z)
pubs.funder-project-idNational Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N002350/1)
cam.issuedOnline2021
cam.orpheus.successMon Sep 27 07:30:39 BST 2021 - Embargo updated
cam.orpheus.counter6
rioxxterms.freetoread.startdate2022-09-15


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