Monitoringin vitrothrombus formation with novel microfluidic devices

Abstract

Cardiovascular disease is a major cause of mortality globally and is subject to ongoing research to improve clinical treatment. It is established that activation of platelets and coagulation are central to thrombosis, yet at different extents in the arterial and venous system. In vitro perfusion chamber technology has contributed significant knowledge on the function of platelets in the thrombotic process under shear conditions. Recent efforts to downscale this technique with a variety of microfluidic devices has opened new possibilities to study this process under precisely controlled flow conditions. Such microfluidic devices possess the capability to execute platelet function tests more quickly than current assays, while using small blood samples. Gradually becoming available to the clinic now, they may provide a new means to manage the treatment of cardiovascular diseases, although accurate validation studies still are missing. This review highlights the progress that has been made in monitoring aspects of thrombus formation using microfluidic devices.

Counting and Tracking: Development and Use of New Methods for Detailed Analysis of Thrombus Formation

“…However, there might be constraints on the geometry based on the used construction materials or the geometry needed to achieve a uniform shear rate distribution within the flow chamber (70). In its simplest form, the flow chamber is a rectangular channel through which blood is pulled or pushed to achieve a specific shear rate.…”

“…The earliest test of platelet function, in vivo bleeding time, was performed by Duke in the early 1900s (70). The test has been continually used but is highly affected by both the patient and the laboratory personnel, and later studies have shown that the test is less suitable for diagnostic purposes (71).…”

“…His device was an annular chamber with an activating surface from a rabbit artery. About a decade later a parallel plate flow chamber made of glass coverslips was developed by Sakariassen (70,80).…”

“…The wide variety of design options makes it possible to construct advanced flow chambers adapted to specific research questions (70). Such designs may include obstructions to simulate a stenosis (66,67), microarrays of protein spots to evaluate adhesion and concentration thresholds (83,84) or coupled parallel channels for simplified dose-response and inhibitor evaluations (85,86).…”

“…Standard methods for quantifying platelet adhesion and thrombus formation invitro or in animal models are based on either fluorescent intensity, thrombus surface area or thrombus volume (70,75,81,82). The result from all of these techniques are affected by the settings during image acquisition, may be operator dependent and require manual assessments, and thereby increase the variability of the results, hinder standardisation and comparison between different laboratories.…”