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

Abhishek Jain, Andries Dirk van der Meer, Anne-Laure Papa, Riccardo Barrile, Angela Lai, Benjamin L. Schlechter, Monicah A. Otieno, Calvert S. Louden, Geraldine A. Hamilton, Alan D. Michelson, Andrew L. Frelinger, Donald E. Ingber

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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.
Original languageEnglish
Article number73
Pages (from-to)73-
Number of pages7
JournalBiomedical microdevices
Volume18
Issue number73
DOIs
Publication statusPublished - 2016

Fingerprint

Lab-On-A-Chip Devices
Platelets
Point-of-Care Systems
Microfluidics
Endothelium
Thrombosis
Blood
Blood Platelets
Hemostasis
Equipment and Supplies
Biomimetic Materials
Clinical laboratories
Vascular Endothelium
Biomimetics
Microvessels
Cell culture
Shear stress
Assays
Cell Culture Techniques
Monitoring

Keywords

  • METIS-317467
  • IR-100922

Cite this

Jain, Abhishek ; van der Meer, Andries Dirk ; 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. In: Biomedical microdevices. 2016 ; Vol. 18, No. 73. pp. 73-.
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Jain, A, van der Meer, AD, Papa, A-L, Barrile, R, Lai, A, Schlechter, BL, Otieno, MA, Louden, CS, Hamilton, GA, Michelson, AD, Frelinger, AL & Ingber, DE 2016, 'Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium' Biomedical microdevices, vol. 18, no. 73, 73, pp. 73-. https://doi.org/10.1007/s10544-016-0095-6

Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium. / Jain, Abhishek; van der Meer, Andries Dirk; 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.

In: Biomedical microdevices, Vol. 18, No. 73, 73, 2016, p. 73-.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium

AU - Jain, Abhishek

AU - van der Meer, Andries Dirk

AU - Papa, Anne-Laure

AU - Barrile, Riccardo

AU - Lai, Angela

AU - Schlechter, Benjamin L.

AU - Otieno, Monicah A.

AU - Louden, Calvert S.

AU - Hamilton, Geraldine A.

AU - Michelson, Alan D.

AU - Frelinger, Andrew L.

AU - Ingber, Donald E.

N1 - Open access

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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KW - IR-100922

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DO - 10.1007/s10544-016-0095-6

M3 - Article

VL - 18

SP - 73-

JO - Biomedical microdevices

JF - Biomedical microdevices

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ER -