Platelet adhesion is an essential function following vascular injury. Pathological conditions triggering vascular alterations and blood flow disturbances transform this beneficial process into a disease mechanism resulting in occlusion or inadequate clotting. Fluid shear stress influences the functionality of platelet adhesion receptors. Functional Fluidic’s proprietary whole blood thrombosis assays investigate kinetic platelet adhesion and aggregation on different substrates during physiologic shear flow. Time-lapse imaging is acquired and analyzed. Preclinical compound assessment for anti-platelet and anti-thrombotic compounds can be evaluated.
Our flow-based thrombus assay can facilitate the screening of potential anti-platelet, anti-coagulant and thrombolytic agents through real-time measurement of platelet adhesion and aggregation, real-time measurement of thrombus formation in the presence or absence of coagulation, real-time measurement of platelet shape change and thrombus stabilization as well as end-stage measurement after thrombus formation.
The potential clinical application of our partners’ test compounds on thrombosis formation in whole (human or animal) blood can be assessed on selected extracellular matrix protein-coated surfaces (thrombogenic surfaces such as collagen, fibronectin, vWF or fibrinogen-coated) under flow conditions of low (venous) and high (arterial) or other predefined pathophysiological shear rates.
The following video shows a time lapse of ex vivo aspirin-treated or non-treated human blood sample flowed on collagen-coated micro-channels. In the upper channel, we have a sample without aspirin added. In the lower channel we have the same sample with aspirin added showing a dose response:
Blood samples (whole or isolated platelets) are pre-treated with a drug of interest, and then subjected to physiologic arterial flow across a substrate of interest. A series of photomicrographs of fluorescently labeled blood are analyzed to determine the kinetics of thrombosis formation (lag time, max rate of thrombosis, area under the curve, and maximum amplitude).
Parallel microfluidic channels can assess both platelet function and coagulation within the same experiment at predefined shear rates. These flow-based thrombosis assays are also in identifying the roles of antagonist or agonist on platelet receptors and signaling proteins in thrombus formation.