Electrochemical Disposable Biosensor to Monitor Dabigatran in Point-of-Care Anticoagulation Therapy

Abstract

Dabigatran etexilate, an oral prodrug, is often used to treat complications linked to thrombosis. Dabigatran (DAB, active form) does not need to be monitored. However, there are several conditions, such as reduced renal function, traumatic bleeding, emergency surgery, the need for thrombolytic therapy in acute stroke, or the requirement to use other forms of anticoagulation, where knowing the concentration of DAB in the blood is indispensable. Unfortunately, there are no convenient DAB-specific point-of-care tests available. To solve this problem, two disposable sensors were constructed and optimised in this work to detect the anticoagulant drug DAB using novel co-facing disposable electrodes, which allows a calibration-free quantitation of the electroactive mediator concentration. A trypsin-based sensor was evaluated. This sensor performed well in a 10 mM Tris buffer (pH 8.8) solution. However, trypsin was inhibited by alpha-1 antitrypsin when a plasma sample was introduced into the sensor. This problem was overcome by plasma filtration. This sensor showed a detection limit of 50.7 ng mL−1 DAB in plasma and a quantification range of 177–500 ng mL−1. A thrombin-based sensor was also constructed. This sensor performed well in ten-fold diluted plasma, overcoming the filtration problem observed with the trypsin-based sensor. This sensor showed a detection limit of 9.6 ng mL−1 DAB in plasma and a quantification range of 11.5–140 ng mL−1. Its extensive pH stability range, the possibility of working at physiological pH, low volume, low cost, and fast turnaround response (less than 20 s) make the calibration-free thrombin-based sensor a suitable point-of-care test to measure DAB concentration in the blood.

Electrochemical Monitoring in Anticoagulation Therapy

“…Recently, our group developed an assay for dabigatran using disposable gold co-facing electrodes (Figure 3), which allowed for the calibration-free quantification of the electroactive mediator concentration [56,57]. The working principle of the sensor involves measuring the activity of thrombin using the specific substrate Tos-Gly-Pro-Arg-ACP, which contains the redox active group 4-amino-2-chlorophenol (ACP).…”

“…The sensor encompasses both the therapeutic range and clinically relevant concentrations, which is significant in emergencies. Concentrations of dabigatran ≤ 30-50 ng mL −1 are considered safe for emergency surgeries in individuals undergoing dabigatran therapy, underscoring the importance of this sensor [56]. Much research has been dedicated to detecting thrombin as a vital coagulation factor.…”

“…WE = working electrode, CE = counter electrode, and pseudo-RE = Au pseudo-reference electrode. Adapted from references[56][57][58].…”

Effect of Hydrogen Plasma Treatment on the Sensitivity of ZnO Based Electrochemical Non-Enzymatic Biosensor

“…Electrochemical biosensors are attractive devices with respect to analyzing the content of a biological sample due to their ability to directly convert a biological event into an electrical signal. The advantages of electrochemical biosensors include their miniaturisation, wide detection limits, simplicity, and reliability [ 31 , 32 ].…”