Abstract: A Review of Hemostasis and Thrombosis Microfluidics

Hemostasis is the vital first step in the process of wound healing. After an injury to a blood vessel restoring hemostasis involves vessel contraction, the formation of a temporary platelet plug, and fibrin formation in which a clot or plug forms at the injury site. Thrombosis is the process of obstructing the blood flow from circulating normally, via thrombus formation. Thrombosis and hemostasis can be understood through the biochemical reactions which give rise to clotting. These reactions, which involve interdependent interaction chemistry between blood cells, endothelial cells, extravascular proteins, and soluble factors in the blood are collectively known as the coagulation cascade. In addition to the interdependent chemistry, other environmental factors associated with the hemodynamics of blood are known to affect the balance of thrombosis and hemostasis including the geometry of the vessel, the shear rate, and turbulence. Analyzing the effects of each of these important factors clinically and at scale is difficult due to the complex and non-stochastic nature of clotting. Microfluidics is a useful tool to study thrombosis and hemostasis because the small dimensions allow for less blood volume to be used, laminar flow to be maintained, and sensitivity increased due to lowered detection limits. These devices can be used to gain insight into how specific factors affect coagulation. Microfluidic devices offer not only the convenience of reduced size, and therefore smaller volumes of blood needed for analysis, but also offer the ability to control biological and shear conditions within the device to mimic various hematologic processes in near-patient settings. Microfluidic devices, being easily and reproducibly manufactured, offer the potential to create personalized chips for individual patients. With the simple addition of fluorescence or brightfield microscopy, microfluidic devices allow for real-time visualization of clot formation making them a useful tool for antithrombotic drug development and clinical monitoring. With its customizability, many other characterization options can be easily incorporated into the device system through the addition of pressure sensors, CCD cameras, electrodes for impedance measurements, photodetectors, and electromagnets for clot analysis. With the vast potentials of laboratory microfluidics and increased interest in understanding the underpinnings of blood clotting, there is a significant need to synthesize the literature and understand the increasing volume of results in a systematic framework. To start the process of synthesis, we have written a literature review that showcases recent relevant work and information in a framework organized around applications such as clinical, point of care, laboratory R&D, and microphysical models in hopes to encourage further research and interest in the field of thrombosis and hemostasis microfluidics. Along with applications, the ease of fabrication is demonstrated in the review through the presentation of various methods. And evaluation methods are highlighted to illustrate the versatility of uses and application capabilities of microfluidic devices. With this, the review aims to emphasize the benefits of microfluidics as a tool for hemostasis and thrombosis evaluation.