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Design and Utility of a Point-of-Care Microfluidic Platform to Assess Hematocrit and Blood Coagulation

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Abstract

Purpose

To develop a small volume whole blood analyzer capable of measuring the hematocrit and coagulation kinetics of whole blood.

Methods and Results

A co-planar microfluidic chamber designed to facilitate self-driven capillary action across an internal electrical chip was developed and used to measure the electric parameters of whole human blood that had been anticoagulated or allowed to clot. To promote blood clotting, select chip surfaces were coated with a prothrombin time (PT) reagent containing lipidated tissue factor (TF), which activates the extrinsic pathway of coagulation to promote thrombin generation and fibrin formation. Whole human blood was added to the microfluidic device, and voltage changes within the platform were measured and interpreted using basic resistor-capacitor (RC) circuit and fluid dynamics theory. Upon wetting of the sensing zone, a circuit between two co-planar electrodes within the sensing zone was closed to generate a rapid voltage drop from baseline. The voltage then rose due to sedimentation of red blood cells (RBC) in the sensing zone. For anticoagulated blood samples, the time for the voltage to return to baseline was dependent on hematocrit. In the presence of coagulation, the initiation of fibrin formation in the presence of the PT reagent prevented the return of voltage to baseline due to the reduced packing of RBCs in the sensing zone.

Conclusions

The technology presented in this study has potential for monitoring the hematocrit and coagulation parameters of patient samples using a small volume of whole blood, suggesting it may hold clinical utility as a point-of-care test.

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Acknowledgments

We thank Katrina Sloma, Ken Vandehey, Manish Giri and Chantelle Domingue from the Division of Research and Development, Microfluidic Technology, HP Inc. for manufacturing and supplying chips and providing electrical signal-processing software and technical support. This work was supported by grants from the National Institutes of Health (R01HL101972, R01GM116184 and F31HL13623001) and an unrestricted research contract from HP Inc. O.J.T. McCarty is an American Heart Association Established Investigator (13EIA12630000).

Conflict of interest

HP Inc. has pending patents for microfluidic device and chip technology concept and software described. R.M. White was employed by HP, Inc. during this study. J. Zilberman-Rudenko, D.A. Zilberman, H.H.S. Lakshmanan, R.A. Rigg, J.J. Shatzel, J. Maddala and O.J.T. McCarty have no conflicts of interests. Potential conflicts of interest have been reviewed and managed by the Oregon Health and Science University Conflict of Interest in Research Committee.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was received from all human blood donors. This article does not contain any studies with animals performed by any of the authors.

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Authors and Affiliations

  1. Biomedical Engineering, School of Medicine, Oregon Health and Science University, 3303 SW Bond Ave, Portland, OR, 97239, USA

    Jevgenia Zilberman-Rudenko, Rachel M. White, Dmitriy A. Zilberman, Hari H. S. Lakshmanan, Rachel A. Rigg, Joseph J. Shatzel, Jeevan Maddala & Owen J. T. McCarty

  2. Division of Research and Development, Microfluidic Technology, HP Inc., Corvallis, OR, USA

    Rachel M. White

  3. Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV, USA

    Hari H. S. Lakshmanan & Jeevan Maddala

  4. Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR, USA

    Joseph J. Shatzel & Owen J. T. McCarty

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  1. Jevgenia Zilberman-Rudenko
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  2. Rachel M. White
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  3. Dmitriy A. Zilberman
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Correspondence to Jevgenia Zilberman-Rudenko.

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Associate Editor Michael R. King oversaw the review of this article.

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Zilberman-Rudenko, J., White, R.M., Zilberman, D.A. et al. Design and Utility of a Point-of-Care Microfluidic Platform to Assess Hematocrit and Blood Coagulation. Cel. Mol. Bioeng. 11, 519–529 (2018). https://doi.org/10.1007/s12195-018-0541-z

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