Integrated microfluidic multiple electrode aggregometry for point-of-care platelet function analysis

Lab Chip. 2024 Oct 9;24(20):4859-4868. doi: 10.1039/d4lc00469h.

Abstract

Point-of-care (POC) platelet function analysis can enable timely and precise management of bleeding and clotting in emergency rooms, operation rooms and intensive care units. However, POC platelet testing is currently not commonly performed, due to the complexity of sample preparation and limitations of existing technologies. Here, we report the development of an integrated microfluidic multiple electrode aggregometry (μMEA) sensor which uses multi-frequency impedance measurement of an embedded microelectrode array to perform platelet aggregometry directly from whole blood, sensing and measuring platelet activation in a label-free manner and without requiring any additional sample preparation. Additionally, the sensor incorporates blood flow during the assay to account for physiological flow and shear conditions. We show that the impedance signal from the sensor can be used to accurately detect and quantify platelet aggregation in a label-free manner, which was further validated by simultaneous fluorometric measurement and visualization of platelet aggregation. Further, we optimized the sensitivity and repeatability of the sensor using its frequency response and demonstrated that the sensor could be used to characterize drug dose-response in antiplatelet therapy with a frequency-tunable dynamic range. We also demonstrate that the sensor provides high sensitivity to perform platelet aggregometry under thrombocytopenic or low platelet count conditions. The μMEA sensor could thus enable POC platelet function analysis across several clinical applications.

MeSH terms

  • Blood Platelets / cytology
  • Blood Platelets / drug effects
  • Blood Platelets / physiology
  • Electrodes
  • Equipment Design
  • Humans
  • Lab-On-A-Chip Devices
  • Microelectrodes
  • Microfluidic Analytical Techniques* / instrumentation
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation* / drug effects
  • Platelet Function Tests* / instrumentation
  • Platelet Function Tests* / methods
  • Point-of-Care Systems*

Substances

  • Platelet Aggregation Inhibitors