title: Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium.
abstract: The vascular endothelium and shear stress are critical determinants of physiological hemostasis and platelet function in vivo, yet current diagnostic and monitoring devices do not fully incorporate endothelial function under flow in their assessment and, therefore, they can be unreliable and inaccurate. It is challenging to include the endothelium in assays for clinical laboratories or point-of-care settings because living cell cultures are not sufficiently robust. Here, we describe a microfluidic device that is lined by a human endothelium that is chemically fixed, but still retains its ability to modulate hemostasis under continuous flow in vitro even after few days of storage. This device lined with a fixed endothelium supports formation of platelet-rich thrombi in the presence of physiological shear, similar to a living arterial vessel. We demonstrate the potential clinical value of this device by showing that thrombus formation and platelet function can be measured within minutes using a small volume (0.5 mL) of whole blood taken from subjects receiving antiplatelet medications. The inclusion of a fixed endothelial microvessel will lead to biomimetic analytical devices that can potentially be used for diagnostics and point-of-care applications.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, CLSB 5, Boston, MA, 02115, USA.|Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Jain
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, CLSB 5, Boston, MA, 02115, USA.|MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Andries D
authors.initials: AD
authors.lastname: van der Meer
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, CLSB 5, Boston, MA, 02115, USA.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Papa
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, CLSB 5, Boston, MA, 02115, USA.|Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Barrile
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Lai
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Schlechter
authors.affiliation: Janssen Pharmaceutical Research and Development, Pre-Clinical Development and Safety, Spring House, PA, USA.
authors.forename: Monicah A
authors.initials: MA
authors.lastname: Otieno
authors.affiliation: Janssen Pharmaceutical Research and Development, Pre-Clinical Development and Safety, Spring House, PA, USA.
authors.forename: Calvert S
authors.initials: CS
authors.lastname: Louden
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, CLSB 5, Boston, MA, 02115, USA.|Emulate Inc., 210 Broadway St., Cambridge, MA, USA.
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: Hamilton
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Michelson
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Frelinger
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, CLSB 5, Boston, MA, 02115, USA. don.ingber@wyss.harvard.edu.|Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.|Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D001792:Blood Platelets / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005337:Fibrin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019095:Point-of-Care Systems; D013314:Stress, Mechanical; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D010975:Platelet Aggregation Inhibitors; D005337:Fibrin
keywords: Biomedical technology; Hemostasis; Lab-on-a-Chip; Platelet function tests; Thrombosis; Vascular endothelium