Shear-induced platelet aggregation: 3D-grayscale microfluidics for repeatable and localized occlusive thrombosis.

Area of Science:

• Biomedical Engineering
• Hematology
• Cardiovascular Research

Background:

• Atherothrombosis, a major cause of myocardial infarction and stroke, involves shear-induced platelet aggregation (SIPA).
• Microfluidic assays are crucial for assessing thrombotic activity but face variability due to design parameters and endpoints.
• Standardization is needed for reliable point-of-care diagnostics and research tools.

Purpose of the Study:

• To investigate the impact of extrinsic design factors on the variability of a single endpoint in microfluidic thrombosis assays.
• To provide a quantified rationale for standardizing design parameters and endpoints in SIPA assays.
• To enhance the precision and specificity of diagnostic and benchtop microfluidic assays.

Main Methods:

• Employed a design of experiments approach to evaluate extrinsic factors.
• Assessed the influence of channel fabrication methods, surface coatings (collagen), and anticoagulants (heparin vs. citrate) on occlusion time variability.
• Utilized porcine whole blood in a high shear zone environment.

Main Results:

• Channel fabrication method and collagen surface coating significantly impacted the variability of occlusion time.
• Anticoagulant choice (heparin or citrate) did not significantly affect occlusion time variability.
• No tested factor significantly altered the mean occlusion time.
• Occlusive thrombus consistently formed within the initial third of the high shear zone.

Conclusions:

• Channel fabrication and collagen coating are critical factors influencing variability in microfluidic thrombosis assays.
• Standardizing these design elements can improve the precision and specificity of SIPA assays.
• Findings support the development of more reliable point-of-care diagnostics for atherothrombosis.