Microfluidic devices for studies of shear-dependent platelet adhesion

Area of Science:

• Biomedical Engineering
• Hematology
• Microfluidics

Background:

• Platelet adhesion to blood vessel walls is shear stress-dependent, crucial for hemostasis.
• Conventional assays require large blood volumes, limiting studies with small samples like those from a single mouse.
• Investigating platelet receptor function, such as integrin alphaIIbbeta3, is vital for understanding aggregation and thrombus formation.

Purpose of the Study:

• To develop novel microfluidic devices for dynamic platelet adhesion assays.
• To enable these assays with minimal blood volumes (<100 microliters) suitable for single-mouse samples.
• To investigate the role of integrin alphaIIbbeta3 domains in platelet adhesion under varying shear stresses.

Main Methods:

• Fabrication of two PDMS-based microfluidic devices for platelet adhesion.
• Utilizing devices with varying shear stress across multiple chambers and simultaneous imaging capabilities.
• Performing dynamic platelet adhesion assays with whole blood from wild-type and genetically modified mice.

Main Results:

• The microfluidic devices successfully replicated published platelet adhesion data.
• Absence of integrin alphaIIbbeta3 significantly impaired platelet adhesion across all shear stresses.
• A mutation in the intracellular domain of integrin alphaIIbbeta3 reduced adhesion primarily at moderate to high shear stresses.

Conclusions:

• The developed microfluidic devices offer a low-volume solution for dynamic platelet adhesion studies.
• These devices facilitate research involving genetically modified model organisms and clinical applications, including neonatal blood analysis.
• The findings highlight the differential roles of integrin alphaIIbbeta3 domains in shear-dependent platelet adhesion.