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Updated: Oct 20, 2025
In Vitro Microfluidic Disease Model to Study Whole Blood-Endothelial Interactions and Blood Clot Dynamics in Real-Time
Published on: May 24, 2020
An "occlusive thrombosis-on-a-chip" microfluidic device for investigating the effect of anti-thrombotic drugs
Jess Berry1, François J Peaudecerf2, Nicole A Masters3
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK. mth29@cam.ac.uk.
Insights
Researchers developed a novel microfluidic device to accurately measure clot formation time in blood. This thrombosis-on-a-chip model overcomes limitations of previous assays, enabling objective assessment of anti-platelet drug efficacy.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Hematology
Background:
- Cardiovascular disease is a leading cause of death, often caused by arterial clots.
- Accurate modeling of clot formation is crucial for developing new anti-platelet drugs.
- Existing in vitro models often fail to generate occlusive thrombi or measure occlusion time objectively.
Purpose of the Study:
- To develop a novel microfluidic device for reliable, in vitro clot formation modeling.
- To objectively measure the time to occlusion in a thrombosis assay.
- To validate the device's utility in assessing anti-platelet drug effects.
Main Methods:
- Development of a thrombosis-on-a-chip microfluidic device designed to generate occlusive thrombi at arterial shear rates.
- Implementation of a method to quench downstream coagulation, preventing off-site clot formation.
- Validation using the anti-platelet drug eptifibatide to measure "time to occlude".
Main Results:
- The novel microfluidic device reliably generates occlusive thrombi.
- The device successfully measured a significant difference in "time to occlude" with eptifibatide treatment.
- Off-site coagulation was identified as a confounding factor in previous models.
Conclusions:
- The developed thrombosis-on-a-chip device provides an unbiased and objective method for measuring clot occlusion time.
- This assay is suitable for monitoring the efficacy of antithrombotic drugs.
- The device advances in vitro modeling for cardiovascular disease research.
Abstract:
Cardiovascular 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.
