Novel impedance-based coagulation analysis device for point-of-care testing

Blood coagulation is a very complex biological process consisting in a strict interplay among several factors which finally results in a delicate thrombohemorrhagic balance. Alterations in the evolution of the coagulation cascade are the primary cause of different dangerous pathological conditions that over the last years interested an ever increasing number of patients. The main treatment consists in the administration of different drug therapies requiring periodic monitoring, therefore, specific tests to assess blood coagulation have been developed, particularly measuring clotting time. Standard laboratory tests are time and resource consuming, both for clinicians and patients, consequently affecting the quality of life. The result is a rising need of a low-cost, fast, and portable device able to perform clotting time tests such as the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT). The aim of this project is to develop a point-of-care (POC) device to analyze the coagulation cascade and its involved factors through a strongly innovative as well as promising technique: electrical transduction and impedance measurement. The starting point relied on an evaluation board from Analog Devices, the ADuCM350EBZ which mounts a powerful meter-on-chip specifically designed for biochemical applications and impedance measurement through a Discrete Fourier Transform (DFT) engine. The board was combined with a sensing element, i.e. a pair of electrodes, and a python application running on a host computer, for process handling and analysis of the results. The system continuously monitors the impedance value of a capillary blood sample from fingerstick until clot formation. Measurement parameters such as excitation and sampling frequency were optimized for the specific sample and different experimental conditions were explored, both in terms of chemical reagents employed to trigger the coagulation cascade, and type of electrodes to adopt as sensors in terms of geometry, materials and fabrication method. Concerning this, the study begins with Dropsens’ screen printed electrodes (SPE) fabricated on a ceramic substrate, moving then to an interdigitated solution, also screen printed, either in gold onto a glass surface or in silver on alumina. Both optionally coupled with a microfluidic system to ease the sample handling. Interdigitated gold electrodes were sputtered on a nitrocellulose substrate and tested as well. The adopted configurations gave promising results, with clotting time values compatible with the clinical range. Finally, a dedicated printed circuit board (PCB) was designed and fabricated to practically implement this impedance-based coagulation device in the form of a pen-drive. The created board enables a simple, low-cost and accurate sensing solution that lends itself to portability and ease-of-use, consequently having the potential to improve blood coagulation analysis and quality of life of patients under related therapies.