Abstract
High-shear stimulation is well known as one of the key factors affecting platelet activation and aggregation, which can lead to the formation of a thrombus. In one of our previous studies, we introduced migration distance-based platelet function analysis in a microfluidic system. In this study, we set out to examine the effects of stirring on shear-induced platelet activation and aggregation in a chamber system by using a rotating stirrer. We found that the rotating stirrer caused not only rotational shear flow but also a strong radial secondary flow. The latter flow led to efficient mixing in the chamber. Moreover, the rotational flow led to the generation of shear stress, the magnitude of which can be controlled to activate the platelets. Activated platelets tend to aggregate themselves. The maximum platelet aggregation was observed at a critical shear rate of 3100 s−1, regardless of the stirrer shape. Furthermore, the time taken to attain maximum aggregation was significantly shortened when using a wide stirrer (30 s) instead of a narrow one (180 s). When using a flat stirrer, the non-uniform shear field in the chamber system was resolved with the radial secondary flow-induced mixing; thus, most of the platelets were homogenously activated. The stirring-induced platelet activation mechanism was experimentally confirmed in a microfluidic system for a platelet aggregation test while monitoring the migration distance until the microfluidic channel is occluded. Our findings indicate that the present system, consisting of a rotating stirrer and a confined chamber, provides effective shear stimulation for activating platelets and inducing platelet aggregates.
Highlights
Platelets are important blood cells whose function is closely related to hemostasis
High-shear stimulation is well known as one of the key factors affecting platelet activation and aggregation, which can lead to the formation of a thrombus
In one of our previous studies, we introduced migration distance-based platelet function analysis in a microfluidic system
Summary
Platelets are important blood cells whose function is closely related to hemostasis. Platelet aggregation is caused by platelet activation, which is associated with direct contact with agonists, such as subendothelial collagen,[1–3] as well as an abnormally high shear stress.[4–7] A recent study showed that mechanical shear stimulation plays a dominant role in platelet aggregation and thrombus growth.[6,8] It is known that a pathological shear stress of 8 Pa is sufficient to activate platelets and induce the formation of a thrombus.[8–10]. The most widely used clinical diagnostic instruments for SIPA tests that uses a high shear rate (c_ > 5000 sÀ1).[12,13,15] In this device, a blood sample flows through a capillary (d 1⁄4 200 lm), in which platelets may be activated. A recent study[18] raised an issue that insufficient shear rate generation might be the cause of failure of platelet function tests to guide personalized antithrombotic medication. To overcome these limitations, there is a need for a simple and efficient shear-generating mechanism. The stirring-induced platelet activation mechanism was applied and verified for a platelet aggregation test in a novel microfluidic system
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