Application of microfluidic devices in studies of thrombosis and hemostasis

Abstract

Due to the importance of fluid flow during thrombotic episodes, it is quite appropriate to study clotting and bleeding processes in devices that have well-defined fluid shear environments. Two common devices for applying these defined shear stresses include the cone-and-plate viscometer and parallel-plate flow chamber. While such tools have many salient features, they require large amounts of blood or other protein components. With growth in the area of microfluidics over the last two decades, it has become feasible to miniaturize such flow devices. Such miniaturization not only enables saving of precious samples but also increases the throughput of fluid shear devices, thus, enabling the design of combinatorial experiments and making the technique more accessible to the larger scientific community. In addition to simple flows that are common in traditional flow apparatus, more complex geometries that mimic stenosed arteries and the human microvasculature can also be generated. The composition of the microfluidics cell substrate can also be varied for diverse basic science investigations, and clinical investigations that aim to assay either individual patient coagulopathy or response to anti-coagulation treatment. This review summarizes the current state of the art for such microfluidic devices and their applications in the field of thrombosis and hemostasis.

Imaging Platelet Processes and Function—Current and Emerging Approaches for Imaging in vitro and in vivo

“…Many laboratories have used microfluidic systems to monitor thrombus formation, demonstrate the effects of fluid shear stress and define molecular events involved (110)(111)(112)(113)(114). Microfluidic studies have assessed thrombus formation in healthy donors (50, 115) and patients afflicted with von Willebrand disease, hemophilia, or thrombocytopenia (114,116), and used to tease out points of difference between immobilized ligands.…”

Technology Advancements in Blood Coagulation Measurements for Point-of-Care Diagnostic Testing

“…Microfluidic viscometers have been shown to enable highly precise physiological measurement of blood coagulation with using just a few microliters of blood. For instance, they were applied in order to study the mechanisms underlying thrombus formation in micro channels resembling the human microvasculature (Colace et al, 2013;Branchford et al, 2015;Nagy et al, 2017;Zhang and Neelamegham, 2017). There are different types of microfluidic viscometers that work based on the measurement of pressure/velocity, surface tension, vibrating element frequency, and drag force (Gupta et al, 2016;Judith et al, 2018).…”

In vitro flow based systems to study platelet function and thrombus formation: Recommendations for standardization: Communication from the SSC on Biorheology of the ISTH

“…Blood flow assays also shaped our thinking around additional functions of key platelet receptors that may have been overlooked in classical assays, most notably glycoprotein (GP)Ib‐IX‐V and integrin αIIbβ3 proposed to act as mechanoreceptors . Finally, blood flow assays have the potential to: (a) screen for hereditary or acquired platelet‐related pathologies, (b) assess the effectiveness of novel anti‐platelet therapies, and (c) evaluate the importance of the coagulation cascade in hemostasis and thrombosis …”

“…5,6 Finally, blood flow assays have the potential to: (a) screen for hereditary or acquired platelet-related pathologies, (b) assess the effectiveness of novel anti-platelet therapies, and (c) evaluate the importance of the coagulation cascade in hemostasis and thrombosis. [7][8][9][10] The so named "in vitro thrombosis model" is a frequently used assay to study the formation of 3D aggregates under flow. 11 It involves perfusing anticoagulated whole blood over fibrillar collagen in a flow geometry of rectangular cross-section, such as glass microcapillaries or parallel-plate flow chambers.…”