Assessment of whole blood coagulation with a microfluidic dielectric sensor

J Thromb Haemost. 2018 Oct;16(10):2050-2056. doi: 10.1111/jth.14244. Epub 2018 Sep 25.

Abstract

Essentials ClotChip is a novel microsensor for comprehensive assessment of ex vivo hemostasis. Clinical samples show high sensitivity to detecting the entire hemostatic process. ClotChip readout exhibits distinct information on coagulation factor and platelet abnormalities. ClotChip has potential as a point-of-care platform for comprehensive hemostatic analysis.

Summary: Background Rapid point-of-care (POC) assessment of hemostasis is clinically important in patients with a variety of coagulation factor and platelet defects who have bleeding disorders. Objective To evaluate a novel dielectric microsensor, termed ClotChip, which is based on the electrical technique of dielectric spectroscopy for rapid, comprehensive assessment of whole blood coagulation. Methods The ClotChip is a three-dimensional, parallel-plate, capacitive sensor integrated into a single-use microfluidic channel with miniscule sample volume (< 10 μL). The ClotChip readout is defined as the temporal variation in the real part of dielectric permittivity of whole blood at 1 MHz. Results The ClotChip readout exhibits two distinct parameters, namely, the time to reach a permittivity peak (Tpeak ) and the maximum change in permittivity after the peak (Δεr,max ), which are, respectively, sensitive towards detecting non-cellular (i.e. coagulation factor) and cellular (i.e. platelet) abnormalities in the hemostatic process. We evaluated the performance of ClotChip using clinical blood samples from 15 healthy volunteers and 12 patients suffering from coagulation defects. The ClotChip Tpeak parameter exhibited superior sensitivity at distinguishing coagulation disorders as compared with conventional screening coagulation tests. Moreover, the ClotChip Δεr,max parameter detected platelet function inhibition induced by aspirin and exhibited strong positive correlation with light transmission aggregometry. Conclusions This study demonstrates that ClotChip assesses multiple aspects of the hemostatic process in whole blood on a single disposable cartridge, highlighting its potential as a POC platform for rapid, comprehensive hemostatic analysis.

Keywords: blood coagulation; blood coagulation disorders; blood coagulation factor inhibitors; blood coagulation tests; platelet function tests.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / pharmacology
  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / diagnosis*
  • Blood Coagulation Factors / metabolism
  • Blood Coagulation*
  • Case-Control Studies
  • Dielectric Spectroscopy
  • Equipment Design
  • Humans
  • Lab-On-A-Chip Devices*
  • Microfluidic Analytical Techniques / instrumentation*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Point-of-Care Testing*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Transducers*
  • Whole Blood Coagulation Time / instrumentation*

Substances

  • Blood Coagulation Factors
  • Platelet Aggregation Inhibitors
  • Aspirin