Real-time monitoring of adhesion and aggregation of platelets using thickness shear mode (TSM) sensor

Hemostasis is required to maintain vascular system integrity, but thrombosis, formation of a clot in a blood vessel, is one of the largest causes of morbidity and mortality in the industrialized world. Novel clinical and research tools for characterizing the hemostatic system are of continued interest, and the object of this research is to test the hypothesis that clinically relevant platelet function can be monitored using an electromechanical sensor. A piezoelectric thickness shear mode (TSM) biosensor coated with collagen-I fibers to promote platelet activation and adhesion was developed and tested for sensitivity to detect these primary events. Magnitude and frequency response of the sensor were monitored under static conditions at 37 °C, using platelet-rich plasma (PRP), and PRP with adenosine diphosphate (ADP), a clinical aggregation inhibitor (abciximab), or a collagen binding inhibitor. Sensors loaded with PRP exhibited a 3-stage response; no significant change in response for the first 20 min (Stage-1), followed by a larger drop in response (Stage-2) and subsequently, response gradually increased (Stage-3). Exogenous ADP stimulated an immediate Stage-2 response, while abciximab delayed and reduced the magnitude change of Stage-2. In the presence of collagen inhibitor, Stage-2 response was similar to that of control but was delayed by an additional 20 min. The obtained results, supported by epifluorescence and complementary SEM studies, demonstrated the selective sensitivity of TSM electromechanical biosensors to monitor platelet function and inhibition, particularly aggregation.