Flexible and Printed Capacitive Sensor with Graphene Oxide As Active Layer for Prothrombin Time Measurement
Authors: Schuck Ariadna , Kim Hyo Eun , Kim Yong-Sang 
Published: July 2021

Prothrombin time test is commonly used to monitor and regulate the coagulation cascade process in various clinical conditions, such as cardiac surgery or recurrent thrombosis [1]. After the extrinsic pathway is triggered by the thromboplastin reagent (tissue), several biochemical interactions between the blood factors occur [2]. Graphene materials are widely used for biosensor applications since they present high sensitivity and excellent mechanical and electrical properties [3]. To monitor these cascade effects based on the change of the electrical properties, we developed a printed and flexible electrochemical sensor using conductive ink as electrodes and graphene oxide as an active layer. The silver nanoparticle electrodes were printed on a glossy paper substrate by an inkjet printer and sintered at 75 °C for 30 min. A vinyl chamber was plotted and attached over the substrate. Graphene oxide (GO) was drop-casted (1-, 2-, 3-layers) over the active area in several devices and then dried at 75 °C for 15 min. For the electrical characterization, phosphate-buffered saline (PBS; pH 7.4) solution was injected in the chamber and the capacitance of the device was measured by a parameter analyzer while applying a DC bias of 10 mV in a frequency of 1 kHz. Next, the paper chip was cleaned, and the thromboplastin reagent (10 µL) was inserted. Then, during the capacitance measurement, the human plasma was mixed to the reagent inside the chamber. The devices without the active layer presented higher capacitance values (Figure 1) than the ones with graphene oxide while using PBS solution as an analyte. For the prothrombin test, a change in the capacitance values (Figure 2(a)) was monitored for each fabricated device. However, there were different behaviors in the capacitance curves, indicating that the thickness of the graphene oxide affects the sensitivity of the system while monitoring the clotting formation. Also, the fibrin clot formation increases viscosity, consequently increasing the electrical impedance over the active layer. Considering the capacitance curves for 5 min (Figure 1b-d)), the devices with 2- and 3-layers of graphene oxide demonstrated a better response to the biochemical reaction that was happening in the plasma after the addition of the reagent. The future studies are related to improving the fabrication process of the active layer enhancing reproducibility and sensitivity. Then, a fully-printed sensor will be developed for coagulation test using a small volume of whole blood samples. And a mathematical implementation will be used to determine the exact prothrombin time based on the slope of the response curve.

References

[1] M.I. Meesters, G. Kuiper, A.B.A. Vonk, S.A. Loer, C. Boer, Validation of a point-of-care prothrombin time test after cardiopulmonary bypass in cardiac surgery, Anaesthesia. 71 (2016) 1163–1168. https://doi.org/10.1111/anae.13591.

[2] S. Palta, R. Saroa, A. Palta, Overview of the coagulation system, Indian J. Anaesth. 58 (2014) 515–523. https://doi.org/10.4103/0019-5049.144643.

[3] R. Alrammouz, J. Podlecki, A. Vena, R. Garcia, P. Abboud, R. Habchi, B. Sorli, Highly porous and flexible capacitive humidity sensor based on self-assembled graphene oxide sheets on a paper substrate, Sensors Actuators B Chem. 298 (2019) 126892. https://doi.org/10.1016/j.snb.2019.126892.

Figure 1