Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium

• Published in: Biomedical microdevices Vol. 18; no. 4; pp. 73 - 7
• Main Authors: Jain, Abhishek, van der Meer, Andries D., Papa, Anne-Laure, Barrile, Riccardo, Lai, Angela, Schlechter, Benjamin L., Otieno, Monicah A., Louden, Calvert S., Hamilton, Geraldine A., Michelson, Alan D., Frelinger, Andrew L., Ingber, Donald E.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2016; Springer Nature B.V
• Subjects: Assessments; Biological and Medical Physics; Biomedical Engineering and Bioengineering; Biomedical materials; Biomimetics; Biophysics; Biotechnology; Blood; Blood Platelets - drug effects; Continuous flow; Devices; Diagnostic systems; Endothelial Cells - drug effects; Endothelium; Endothelium, Vascular - drug effects; Engineering; Engineering Fluid Dynamics; Fibrin - metabolism; Formations; Hemostasis; Hemostatics; Human Umbilical Vein Endothelial Cells; Humans; In vivo methods and tests; Lab-On-A-Chip Devices; Microfluidic devices; Microfluidics; Nanotechnology; Organic chemistry; Physiology; Platelet Aggregation Inhibitors - pharmacology; Platelets; Point-of-Care Systems; Shear stress; Stress, Mechanical; Thromboembolism; Thrombosis; Thrombosis - blood; Thrombosis - diagnosis; Thrombosis - drug therapy; Vascular endothelium; Platelet function tests; Hemostasis; Thrombosis; Biomedical technology; Lab-on-a-Chip
• ISSN: 1387-2176; 1572-8781
• DOI: 10.1007/s10544-016-0095-6

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.