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A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function

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  • Abhishek Jain

    (Wyss Institute for Biologically Inspired Engineering, Harvard University
    Beth Israel Deaconess Medical Center and Harvard Medical School
    Vascular Biology Program, Boston Children’s Hospital and Harvard Medical School)

  • Amanda Graveline

    (Wyss Institute for Biologically Inspired Engineering, Harvard University)

  • Anna Waterhouse

    (Wyss Institute for Biologically Inspired Engineering, Harvard University)

  • Andyna Vernet

    (Wyss Institute for Biologically Inspired Engineering, Harvard University)

  • Robert Flaumenhaft

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Donald E. Ingber

    (Wyss Institute for Biologically Inspired Engineering, Harvard University
    Vascular Biology Program, Boston Children’s Hospital and Harvard Medical School
    Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University)

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.

Suggested Citation

  • Abhishek Jain & Amanda Graveline & Anna Waterhouse & Andyna Vernet & Robert Flaumenhaft & Donald E. Ingber, 2016. "A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10176
    DOI: 10.1038/ncomms10176
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    Cited by:

    1. Meredith E. Fay & Oluwamayokun Oshinowo & Elizabeth Iffrig & Kirby S. Fibben & Christina Caruso & Scott Hansen & Jamie O. Musick & José M. Valdez & Sally S. Azer & Robert G. Mannino & Hyoann Choi & Da, 2023. "iCLOTS: open-source, artificial intelligence-enabled software for analyses of blood cells in microfluidic and microscopy-based assays," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Narges Ahmadi & Jieun Lee & Chirag Batukbhai Godiya & Jong-Man Kim & Bum Jun Park, 2024. "A single-particle mechanofluorescent sensor," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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