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

• Published in: Cellular and molecular bioengineering 2018-12, Vol.11 (6), p.519-529
• Main Authors: Zilberman-Rudenko, Jevgenia, White, Rachel M., Zilberman, Dmitriy A., Lakshmanan, Hari H. S., Rigg, Rachel A., Shatzel, Joseph J., Maddala, Jeevan, McCarty, Owen J. T.
• Format: Article
• Language: English
• Subjects: Biological and Medical Physics; Biomaterials; Biomedical Engineering and Bioengineering; Biomedical Engineering/Biotechnology; Biophysics; Blood coagulation; Capillarity; Cell Biology; Clotting; Coagulation; Detection; Electric potential; Engineering; Erythrocyte sedimentation rate; Erythrocytes; Fibrin; Fluid dynamics; Hematocrit; Hydrodynamics; Microfluidics; Parameters; Prothrombin; Reagents; Sedimentation; Thrombin; Tissue factor; Voltage; Voltage drop
• ISSN: 1865-5025; 1865-5033
• DOI: 10.1007/s12195-018-0541-z

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.