A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

Abstract

Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.

Bioprinted thrombosis-on-a-chip

“…This feature provides us with a unique flexibility in comparison with the device that reported thrombus formation achieved through the introduction of rigid stenosis and hence disturbed flow within a microfluidic chamber. 31 Another importance aspect associated with the thrombosis-on-a-chip platform described in this study lies in our ability to endothelialize the channels from within, in close adjacency to the fibroblast cells embedded within the hydrogel. This co-culture aspect of our platform allows for studying unique aspects of thrombosis, such as migration of fibroblasts, and the ability to study clot aging, thereby facilitating the construction of a fibrotic-clot-on-a-chip model that has not been achieved before.…”

Point-of-Care Diagnostics: Recent Developments in a Connected Age

“…A chip where reagent droplets were mixed electrostatically was demonstrated 227 . A microfluidic device allowing for control of shear rates and gradients in a fluid stream allowed for monitoring of whole blood hemostasis and platelet function 228 . An electrochemical sensor system that monitored liquid flow in porous materials without affecting real flow in paper samples was built, showing the ability to characterize wettability signatures for paper samples of different geometry or composition 229 .…”

Microfludic platforms for the evaluation of anti-platelet agent efficacy under hyper-shear conditions associated with ventricular assist devices

“…The device was used to evaluate the effects of IIb/IIIa, Ibα inhibitors, heparin and enoxaparin. A similar approach was used by Jain and co-authors [32] who replicated shear rates typical of stenotic vessels in microfluidic channels. Stenotic conditions were also replicated in the system proposed by Li and colleagues [33] who evaluated the effect of ASA and eptifibatide on thrombus formation in collagen-coated microchannels under arterial shear stress conditions.…”

“…Also, in studies where non-physiological shear conditions were considered, e.g. replicating stenotic vessels [32,33], flow conditions are still far from those occurring in VADs, which is characterized by “hypershear” and complex time-varying shear conditions.…”