Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients

Abstract

Introduction: Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited in vitro methods exist for assessing the effects of anticoagulants on hemostasis, the development of novel therapies to safely prevent thrombosis in COVID-19 patients relies on preclinical animal models and early phase human trials. Herein we present the design of a microfluidic “bleeding chip” to evaluate the effects of antithrombotic therapies on hemostatic plug formation in vitro. Methods: The design of the microfluidic device consists of two orthogonal channels: an inlet that serves as a model blood vessel, and a bleeding channel to model hemostatic plug formation at sites of compromised endothelial barrier function. This is achieved by placing a series of 3 pillars spaced 10 μm apart at the intersection of the two channels. The pillars and bleeding channel are coated with the extracellular matrix protein collagen. Results: Perfusion of human whole blood through the microfluidic bleeding chip led to initial platelet adhesion and aggregation at the pillars followed by hemostatic plug formation and occlusion of the bleeding channel. Conclusions: Safe and effective mitigating agents are needed for treatment and prevention of thrombotic complications in COVID-19 patients. This simple microfluidic device holds potential to be developed into a tool for assessing the effects of anticoagulant therapy on hemostasis.