Background: Myocardial infarction is triggered by occlusion of coronary arteries by platelet-rich thrombi. Development of new anti-platelet drugs to prevent myocardial infarction depends on accurate models of thrombosis. In vivo animal models produce variable results and only have limited relevance to human disease. Few in vitro models using human blood generate occlusive thrombi; those that do generate occlusive thrombi do not allow quantitive assessment of antithrombotic compounds.

Aims: Development of a novel “arterial thrombosis-on-a-chip” microfluidic system that allows quantitative measurement of occlusion time.

Methods: A microfluidic chip was iteratively designed, and fabricated using soft lithography. Within the chip, a collagen and tissue factor patch triggers thrombosis in whole human blood flowed at arterial shear. Thrombus growth is monitored using confocal microscopy. Occlusion time is measured in a simple, robust way using a balance.

Results: Initial experiments confirmed that addition of a bifurcation into a microfludic chip allows occlusion to occur. However, further analysis highlighted that this occlusion can be caused by off-site coagulation, obscuring the effect of anti-platelet drugs. We therefore designed a microfluidic device that generates biologically relevant occlusive thrombi by quenching downstream coagulation. We validated our device by using the approved anti-platelet drug eptifibatide, demonstrating that our device can be used to monitor the effect of antithrombotic drugs on occlusion time in an unbiased manner.

Conclusions: We have developed a novel arterial thrombosis-on-a-chip device that allows biologically relevant occlusive thrombi to form, and that can be used to assess the effect of anti-thrombotic compounds on occlusion time.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/development-of-a-novel-arterial-thrombosis-on-a-chip-microfluidic-device/