Cargando…

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

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 inaccur...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963439/
https://www.ncbi.nlm.nih.gov/pubmed/27464497
http://dx.doi.org/10.1007/s10544-016-0095-6
_version_ 1782444952179965952
author 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.
author_facet 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.
author_sort Jain, Abhishek
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10544-016-0095-6) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4963439
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-49634392016-08-18 Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium 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. Biomed Microdevices Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10544-016-0095-6) contains supplementary material, which is available to authorized users. Springer US 2016-07-27 2016 /pmc/articles/PMC4963439/ /pubmed/27464497 http://dx.doi.org/10.1007/s10544-016-0095-6 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
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.
Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
title Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
title_full Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
title_fullStr Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
title_full_unstemmed Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
title_short Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
title_sort assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963439/
https://www.ncbi.nlm.nih.gov/pubmed/27464497
http://dx.doi.org/10.1007/s10544-016-0095-6
work_keys_str_mv AT jainabhishek assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT vandermeerandriesd assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT papaannelaure assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT barrilericcardo assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT laiangela assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT schlechterbenjaminl assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT otienomonicaha assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT loudencalverts assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT hamiltongeraldinea assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT michelsonaland assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT frelingerandrewl assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium
AT ingberdonalde assessmentofwholebloodthrombosisinamicrofluidicdevicelinedbyfixedhumanendothelium