Microfluidic device for extreme shear rates and elongational flows (Diamond, SL)

Purpose: Microfluidic devices allow the generation of extreme shear rates useful for the study of thrombosis in severely stenosis coronary syndromes (Colace, 2013, Colace, 2013, Colace, 2012).  In assisted circulation pumps such as left ventricle assist devices (LVADs), extreme shear rates can cause depletion of von Willebrand factor (vWF), hemolysis, and platelet activation.  The ability to generate wall shear rates on the order of 105 s-1 using small sub-mL volumes of blood is enabled with microfluidics.

Method of Fabrication/Use: An extreme contraction/expansion device was fabricated in PDMS to study von Willebrand function in plasma and whole blood flow (Colace 2013, Colace 2013).  A vacuum holds the device to glass which was pre-patterned with fibrillar collagen to promote vWF capture.

Von Willebrand Factor fibers deposit on surfaces of collagen type 1 in a microfluidic model of coronary stenosis. (A-D) Platelet free plasma (5 mM EDTA) was perfused through a microfluidic channel over a collagen at the indicated wall shear rate (arrow, flow direction).  E, Computational fluid dynamics defined the wall shear rates in the outlet of the stenosis channel. F,  The colors indicate local wall shear rate and are equivalent to the scale bar in E.  G, The local wall shear rate along the central axis of the stenosis channel (dotted white line in F) indicates a steep gradient in shear rate (1,000 s-1 to 125,000 s-1) at the inlet and outlet.

Von Willebrand Factor fibers deposit on surfaces of collagen type 1 in a microfluidic model of coronary stenosis. (A-D) Platelet free plasma (5 mM EDTA) was perfused through a microfluidic channel over a collagen at the indicated wall shear rate (arrow, flow direction). E, Computational fluid dynamics defined the wall shear rates in the outlet of the stenosis channel. F, The colors indicate local wall shear rate and are equivalent to the scale bar in E. G, The local wall shear rate along the central axis of the stenosis channel (dotted white line in F) indicates a steep gradient in shear rate (1,000 s-1 to 125,000 s-1) at the inlet and outlet.

Results: The Diamond Lab has used this device to study extreme hemodynamics. Distinct from viscometers or recirculation systems that shear blood or its components for many seconds, we deployed microfluidic devices for single-pass perfusion of whole blood or platelet free plasma (PFP) over fibrillar collagen type 1 surfaces (< 10 msec transit time) at pathological gw or spatial wall shear rate gradients (grad gw).   Long vWF fibers (>20 mm) bound to collagen were observed with fluorescent anti-vWF at gw > 30,000 s-1 during perfusion of PFP (citrate, EDTA, or recalcified with PPACK to inhibit thrombin), a process occurring at constant gw and enhanced at 0 Ca2+ possibly through vWF A2 destabilization.

References

Colace TV, Diamond SL. Direct Observation of von Willebrand Factor Elongation and Fiber Formation on Collagen During Acute Whole Blood Exposure to Pathological Flow. Arteriosclerosis Thrombosis and Vascular Biology Jan 2013; 33 (1): 105-113.

Colace TV, Muthard RW, Diamond SL. Thrombus growth and embolism on tissue factor-bearing collagen surfaces under flow: role of thrombin with and without fibrin. Arterioscler Thromb Vasc Biol Jun 2012; 32 (6): 1466-1476.

Colace TV, Tormoen GW, McCarty OJ, Diamond SL. Microfluidics and coagulation biology. Annu Rev Biomed Eng 2013; 15 283-303.

 

 

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