Why, When and Where Blood Clots: Organ-on-Chip Approaches in the Assessment of Hemostasis and Thrombosis

Personalized diagnostics and precise monitoring of hemostasis in extracorporeal devices has been challenging partly because current devices fail to mimic the fluid mechanics of blood clotting as it occurs in vivo, and fail to include the contributions of the endothelium. I will present a bioinspired microfluidic device that mimics the architecture of a vascular bed and permits physiological and automated analysis of hemostasis and platelet function. We have tested it for in vitro use on blood samples of patients who are on antiplatelet medication and who suffer from congenital bleeding disorders; and pig models to demonstrate that it can be integrated to extracorporeal devices, such as dialysis or cardiac assist devices. We have also discovered a way to include chemically preserved endothelium for the assessment of thrombosis, permitting translation into clinical settings without requiring the stringent conditions of living cell culture.

Secondly, clotting in the lung is a cause of significant patient mortality, yet there are no effective models that can predict pulmonary thrombosis or permit analysis of its underlying pathophysiology. I will show that a lung alveolus-on-chip microfluidic culture device containing human primary alveolar epithelium interfaced with human vascular endothelium can be used to study organ-level contributions to pulmonary thromboinflammation. This model can detect inhibition of endothelial activation and clot formation induced by potential new antithrombotic therapeutics that is nearly impossible to do with animal models and offers a potentially valuable new tool for preclinical research and drug development.