Application of a strain rate gradient microfluidic device to von Willebrand's disease screening

Brazilek, R, Tovar Lopez, F, Wong, A, Tran, H, Davis, A, McFadyen, J, Kaplan, Z, Chunilal, S, Jackson, S, Nandurkar, H, Mitchell, A and Nesbitt, W 2017, 'Application of a strain rate gradient microfluidic device to von Willebrand's disease screening', Lab on a Chip, vol. 17, no. 15, pp. 2595-2608.

Document type: Journal Article
Collection: Journal Articles

Title Application of a strain rate gradient microfluidic device to von Willebrand's disease screening
Author(s) Brazilek, R
Tovar Lopez, F
Wong, A
Tran, H
Davis, A
McFadyen, J
Kaplan, Z
Chunilal, S
Jackson, S
Nandurkar, H
Mitchell, A
Nesbitt, W
Year 2017
Journal name Lab on a Chip
Volume number 17
Issue number 15
Start page 2595
End page 2608
Total pages 14
Publisher Royal Society of Chemistry
Abstract Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relatively large blood volumes, have low throughput, are time-consuming, and do not incorporate the physiologically relevant effects of haemodynamic forces. We developed a microfluidic device incorporating micro-contractions that harnesses well-defined haemodynamic strain gradients to initiate platelet aggregation in citrated whole blood. The microchannel architecture has been specifically designed to allow for continuous real-time imaging of platelet aggregation dynamics. Subjects aged ≥18 years with previously diagnosed VWD or who presented for evaluation of a bleeding disorder, where the possible diagnosis included VWD, were tested. Samples were obtained for device characterization as well as for pathology-based testing. Platelet aggregation in the microfluidic device is independent of platelet amplification loops but dependent on low-level platelet activation, GPIb/IX/V and integrin α IIb β 3 engagement. Microfluidic output directly correlates with VWF antigen levels and is able to sensitively detect aggregation defects associated with VWD subtypes. Testing demonstrated a strong correlation with standard clinical laboratory-based tests. Head-to-head comparison with PFA100® demonstrated equivalent, if not improved, sensitivity for screening aggregation defects associated with VWD. This strain rate gradient microfluidic prototype has the potential to be a clinically useful, rapid and high throughput-screening tool for VWD as well as other strain-dependent platelet disorders. In addition, the microfluidic device represents a novel approach to examine the effects of high magnitude/short duration (ms) strain rate gradients on platelet function.
Subject Medical Devices
Medical Biotechnology Diagnostics (incl. Biosensors)
Keyword(s) Function Analyzer PFA-100
Flow-Based Assays
Thrombus Formation
Global Assessment
DOI - identifier 10.1039/c7lc00498b
Copyright notice © 2017 The Royal Society of Chemistry.
ISSN 1473-0197
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