Journal
IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS
Volume 11, Issue 6, Pages 1459-1469Publisher
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TBCAS.2017.2739724
Keywords
Blood coagulation; capacitive sensor; dielectric coagulometry; dielectric spectroscopy; hemostasis; microfluidics; permittivity; point-of-care diagnostics; whole blood
Funding
- Case-Coulter Translational Research Partnership
- Advanced Platform Technology Center-a VA Research Center of Excellence-at the Case Western Reserve University
- NIH [5R01 HL121212]
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This paper describes the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy of human whole blood during coagulation. The sensor, termed ClotChip, employs a three-dimensional, parallel-plate, capacitive sensing structure with a floating electrode integrated into amicrofluidic channel. Interfaced with an impedance analyzer, the ClotChip measures the complex relative dielectric permittivity, epsilon(r), of human whole blood in the frequency range of 40 Hz to 100 MHz. The temporal variation in the real part of the blood dielectric permittivity at 1 MHz features a time to reach a permittivity peak, T-peak, as well as a maximum change in permittivity after the peak, Delta epsilon(r), (max), as two distinct parameters of ClotChip readout. The ClotChip performance was benchmarked against rotational thromboelastometry (ROTEM) to evaluate the clinical utility of its readout parameters in capturing the clotting dynamics arising from coagulation factors and platelet activity. T-peak exhibited a very strong positive correlation (r = 0.99, p<0.0001) with the ROTEM clotting time parameter, whereas Delta epsilon(r), (max) exhibited a strong positive correlation (r= 0.85, p<0.001) with the ROTEM maximum clot firmness parameter. This paper demonstrates the ClotChip potential as a point-of-care platform to assess the complete hemostatic process using < 10 mu L of human whole blood.
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