Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient

Area of Science:

• Biomedical Engineering
• Cardiovascular Physiology
• Hemostasis and Thrombosis

Background:

• Platelet aggregation is crucial for hemostasis, forming clots under varying hemodynamic conditions.
• Wall shear stress (τw) and transthrombus pressure gradient (ΔP) significantly influence platelet plug formation and bleeding control.
• Understanding these factors is vital for developing effective thrombosis treatments.

Purpose of the Study:

• To develop and utilize a novel microfluidic device for precisely controlling τw and ΔP during thrombus formation.
• To investigate the impact of controlled pressure gradients on clot structure, composition, and permeability.
• To quantify the convective removal of thrombogenic solutes like thrombin under varying pressure conditions.

Main Methods:

• Designed a computer-controlled microfluidic device to independently manipulate ΔP and τw.
• Utilized side-view visualization and fluorescent solutes to analyze thrombus growth and permeation.
• Employed a platelet-targeting thrombin sensor to measure intrathrombus thrombin levels.
• Quantified clot permeability on collagen and collagen/tissue factor surfaces.

Main Results:

• Increased ΔP significantly reduced thrombus height by up to 28% under arterial shear stress.
• A 62% decrease in intrathrombus thrombin was observed with increasing ΔP, indicating convective removal.
• Platelet deposits on collagen showed higher permeability (5.45 × 10⁻¹⁴ cm²) than platelet/fibrin clots on collagen/TF (2.71 × 10⁻¹⁴ cm²).

Conclusions:

• The microfluidic system effectively simulates in vivo hemodynamic conditions for thrombosis research.
• Pressure-driven permeation plays a critical role in regulating clot size and composition by removing thrombogenic factors.
• This model provides a platform for studying coupled platelet deposition and thrombin generation under controlled flow and pressure gradients.