title: A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function.
abstract: Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.|Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.|Vascular Biology Program, Departments of Pathology and Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Abhishek
authors.identifier: http://orcid.org/0000-0003-2235-5139
authors.initials: A
authors.lastname: Jain
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Graveline
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Waterhouse
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
authors.forename: Andyna
authors.initials: A
authors.lastname: Vernet
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Flaumenhaft
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.|Vascular Biology Program, Departments of Pathology and Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.|Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001780:Blood Coagulation Tests / Q000295:instrumentation* / Q000379:methods; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D056656:Lab-On-A-Chip Devices; D046210:Microfluidic Analytical Techniques; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods; D019095:Point-of-Care Systems; D033081:Shear Strength; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D000077284:Abciximab