In microfluidico: Recreating in vivo hemodynamics using miniaturized devices

Issue title: Special Issue in Recognition of Dr. Harry L. Goldsmith, Distinguished Editor 1994–2014

Article type: Review Article

Authors: Zhu, Shu^a | Herbig, Bradley A.^a | Li, Ruizhi^a | Colace, Thomas V.^a | Muthard, Ryan W.^a | Neeves, Keith B.^b | Diamond, Scott L.^{a; *}

Affiliations: [a] Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA | [b] Department of Chemical and Biomolecular Engineering, Colorado School of Mines, Golden, CO, USA

Correspondence: [*] Address for correspondence: Scott L. Diamond, 3340 Smith Walk, 1020 Vagelos Lab, Philadelphia, PA 19104, USA. Fax: +1 215 573 7227; E-mail: sld@seas.upenn.edu.

Abstract: Microfluidic devices create precisely controlled reactive blood flows and typically involve: (i) validated anticoagulation/pharmacology protocols, (ii) defined reactive surfaces, (iii) defined flow-transport regimes, and (iv) optical imaging. An 8-channel device can be run at constant flow rate or constant pressure drop for blood perfusion over a patterned collagen, collagen/kaolin, or collagen/tissue factor (TF) to measure platelet, thrombin, and fibrin dynamics during clot growth. A membrane-flow device delivers a constant flux of platelet agonists or coagulation enzymes into flowing blood. A trifurcated device sheaths a central blood flow on both sides with buffer, an ideal approach for on-chip recalcification of citrated blood or drug delivery. A side-view device allows clotting on a porous collagen/TF plug at constant pressure differential across the developing clot. The core-shell architecture of clots made in mouse models can be replicated in this device using human blood. For pathological flows, a stenosis device achieves shear rates of >100,000 s−1 to drive plasma von Willebrand factor (VWF) to form thick long fibers on collagen. Similarly, a micropost-impingement device creates extreme elongational and shear flows for VWF fiber formation without collagen. Overall, microfluidics are ideal for studies of clotting, bleeding, fibrin polymerization/fibrinolysis, cell/clot mechanics, adhesion, mechanobiology, and reaction-transport dynamics.

Keywords: Harry Goldsmith, microfluidics, hemorheology, platelet, von Willebrand factor

DOI: 10.3233/BIR-15065

Journal: Biorheology, vol. 52, no. 5-6, pp. 303-318, 2015