title: In microfluidico: Recreating in vivo hemodynamics using miniaturized devices.
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.
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Herbig
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Li
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Colace
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Muthard
authors.affiliation: Department of Chemical and Biomolecular Engineering, Colorado School of Mines, Golden, CO, USA.
authors.forename: Keith B
authors.initials: KB
authors.lastname: Neeves
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Diamond
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000502:physiology; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D008904:Miniaturization; D013925:Thromboplastin / Q000737:chemistry / Q000378:metabolism; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D003094:Collagen; D013925:Thromboplastin
keywords: Harry Goldsmith; hemorheology; microfluidics; platelet; von Willebrand factor