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

Rose J. Brazilek, Francisco J. Tovar-Lopez, Angus K. T. Wong, Huyen Tran, Amanda S. Davis, James D. McFadyen, Zane Kaplan, Sanjeev Chunilal, Shaun P. Jackson, Harshal Nandurkar, Arnan Mitchell, Warwick S. Nesbitt

Research output: Contribution to journalArticleResearchpeer-review

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 αIIbβ3 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.

Original languageEnglish
Pages (from-to)2595-2608
Number of pages14
JournalLab on a Chip
Volume17
Issue number15
DOIs
Publication statusPublished - 2017

Cite this

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title = "Application of a strain rate gradient microfluidic device to von Willebrand's disease screening",
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 αIIbβ3 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{\circledR} 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.",
author = "Brazilek, {Rose J.} and Tovar-Lopez, {Francisco J.} and Wong, {Angus K. T.} and Huyen Tran and Davis, {Amanda S.} and McFadyen, {James D.} and Zane Kaplan and Sanjeev Chunilal and Jackson, {Shaun P.} and Harshal Nandurkar and Arnan Mitchell and Nesbitt, {Warwick S.}",
year = "2017",
doi = "10.1039/c7lc00498b",
language = "English",
volume = "17",
pages = "2595--2608",
journal = "Lab on a Chip",
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publisher = "The Royal Society of Chemistry",
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}

Application of a strain rate gradient microfluidic device to von Willebrand's disease screening. / Brazilek, Rose J.; Tovar-Lopez, Francisco J.; Wong, Angus K. T.; Tran, Huyen; Davis, Amanda S.; McFadyen, James D.; Kaplan, Zane; Chunilal, Sanjeev; Jackson, Shaun P.; Nandurkar, Harshal; Mitchell, Arnan; Nesbitt, Warwick S.

In: Lab on a Chip, Vol. 17, No. 15, 2017, p. 2595-2608.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Application of a strain rate gradient microfluidic device to von Willebrand's disease screening

AU - Brazilek, Rose J.

AU - Tovar-Lopez, Francisco J.

AU - Wong, Angus K. T.

AU - Tran, Huyen

AU - Davis, Amanda S.

AU - McFadyen, James D.

AU - Kaplan, Zane

AU - Chunilal, Sanjeev

AU - Jackson, Shaun P.

AU - Nandurkar, Harshal

AU - Mitchell, Arnan

AU - Nesbitt, Warwick S.

PY - 2017

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N2 - 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 αIIbβ3 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.

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