Calibration-free electrochemical sensor to monitor factor-Xa inhibitors at the point-of-care anticoagulation therapy

Abstract

This article presents a novel proof of concept for the blood plasma quantification of clinically relevant concentrations of direct oral anticoagulants, DOACs, including rivaroxaban and edoxaban, as well as low-molecular-weight heparins, LMWHs, such as enoxaparin and dalteparin, utilising a calibration-free disposable electrochemical sensor with co-facing electrodes. A dose-response curve was generated for rivaroxaban and edoxaban to demonstrate the sensor's ability to detect ≥9.00 ng mL−1 rivaroxaban and quantify it in the 11.0–140 ng mL−1 range. Similarly, the lower detection limit for edoxaban was 12.9 ng mL−1, with a quantification range of 16.8–140 ng mL−1. The significance of this sensor lies in its ability to quantify rivaroxaban and edoxaban below 30 ng mL−1, which is crucial in emergency care centres when patients undergoing DOAC therapy require emergency surgery or reversal of DOACs due to bleeding or ischemic stroke. Furthermore, the sensor can detect ≥0.016 IU mL−1 enoxaparin and ≥0.013 IU mL−1 dalteparin and quantify them in the 0.025–0.75 and 0.019–0.75 IU mL−1 range, respectively. Additionally, a dose-response curve was presented to demonstrate the potential ability of this sensor to quantify factor-Xa inhibitors independently of which DOACs or LMWHs are used. With the assay completed in less than 30 s using a minimal volume of 7 μL sample, the possibility to work at physiological pH and under calibration-free format makes this assay an excellent candidate for point-of-care testing.