Novel Paper Based Hand-Fabricated Point of Care Prothrombin Time Sensing Platform Using Pencil and Correction Pen

摘要

Cardiovascular diseases (CVDs) are reported to be the leading cause of death worldwide by World Health Organization (WHO) with an approximate of 31% of global deaths. Consequently, it has been noted that the largest sector of population which experiences coagulation or hemostatic imbalances or undergo oral anticoagulation therapy (OAT) are the major sector susceptible to the risk of mortality due to cardiovascular ailments such as atherosclerosis, deep vein thrombosis (DVT), stroke etc. These candidates are prescribed or administered using oral anticoagulation therapy (OAT) and are advised to take the Prothrombin Time (PT) test respectively. Prothrombin Time (PT) analyzers are the type of haemostasis analyzer mainly catering to the coagulation following the extrinsic pathways. Additionally, the candidates under OAT requires routine administration of the coagulation status for proper dosage of warfarin or its derivatives which shares a very narrow therapeutic window. A slight amount of imbalance in the coagulation chemistry can disrupt the cardiovascular functioning, hence a routine monitoring is strongly mandated by cardiac surgeons. It is important to realize a simplified hand held, low cost point of care solution for diagnosing hemostasis or coagulation status to cater both the rural and urban sectors resulting in lower casualties due to coagulation imbalance. The respective work proposes a handheld point of care PT sensing paper sensor using very inexpensive pencil and correction pen and Whattman filter paper. In addition the sensor has enhanced capability of carrying our sensitive detection of coagulation status compared to the existing complex and expensive sensors developed through a variety of methods like screen printing, lithography, flexography printing, wax printing, PDMS printing, stamping etc. The proposed device consists of two pencil marks as electrodes. The device is illustrated in Figure 1. The sensor monitors a change in impedance (resistance) w.r.t time. Blood being an ionic fluid whose chemistry changes with the ionic interactions during the process of coagulation results in a direct correlation of the coagulation process to the respective impedimetric signatures. The synthetic coagulation behavior and the response of the device has been measure using nail paint as an analyte. The points of maximum changes in resistance (first and second) denotes the application of the analyte to the sensor and initiation of coagulation or solidification respectively (shown in Figure 2) from which the coagulation time is further derived. Lab View has been used as an interfacing platform for processing the respective resistive data and generating corresponding coagulation status. Thus, the particular PDE-PAD (pencil drawn electrodes-paper-based analytical devices) can be considered as a promising future device for low cost sensitive detection platform for a point of care PT diagnosis.