PB0147 - Development of a microfluidic model to evaluate extracorporeal circuit material thrombogenicity

Background: Extracorporeal circuits, for example, extracorporeal membrane oxygenation, cardiopulmonary bypass, and dialysis circuits, require patients to receive systemic heparin to mitigate thrombosis caused by the circuit materials at low flow or stagnant regions such as tubing connectors. Despite the use of heparin and heparin coated circuits, thrombosis and severe bleeding events can still occur. Understanding how extracorporeal circuit materials cause thrombosis is critical to reduce thrombotic and bleeding events and our reliance on systemic heparin.

Aims: To develop a microfluidic model to evaluate extracorporeal circuit material thrombogenicity under flow.

Methods: Straight channel microfluidics incorporating control materials (glass and silicone) or the material of interest (polycarbonate (used for circuit connectors) and polyvinylchloride (PVC, used for circuit tubing)) were fabricated using standard photo and soft lithography. Whole blood anti-coagulated with clinically relevant levels of heparin (0.5-5IU/mL) was flowed through the channels at a shear strain rate of 50-2000s-1. Platelet adhesion on materials was observed in real-time using fluorescence microscopy.

Results: At a shear rate of 200s-1, platelet adhesion was highest on PVC where platelets accumulated over time. Platelet adhesion was lower on silicone and polycarbonate compared to PVC, with platelets observed adhering and accumulating initially, then detaching over time. Platelet adhesion to glass was the lowest compared to all hydrophobic polymers. Platelet adhesion was reduced by blocking the materials with albumin prior to blood contact. The same trends were observed at shear rates from 50-2000s-1.

Conclusion(s): Real-time visualisation of dynamic platelet events on extracorporeal circuit materials using clinically relevant shear rates and anticoagulation levels in a microfluidic model, revealed varying levels of platelet adhesion, accumulation, and detachment of different hydrophobic polymers. This model could be used to further understand platelet interactions during extracorporeal circuit thrombosis and for the development of anti-thrombogenic materials for extracorporeal circuits.