Flexible electrochemical microelectrodes integration in clot-in-chip devices for calcium monitoring

Recent advances in the medical research field have expanded into the use of microfluidics devices, offering innovative solutions for healthcare challenges. Precise control over fluid manipulation at small scales and significant sample volume reduction are just some of the different benefits introduced by these advanced microdevices. In the framework of the European project ANGIE (MAgnetically steerable wireless Nanodevices for the tarGeted delivery of therapeutic agents in any vascular rEgion of the body), focus on exploring the potential use of mobile microrobotic platforms for clot removal. The use of microfluidic devices is key to control the generation of blood clots in confined spaces. By exploiting controlled diffusion conditions in microfluidic technologies, it is possible to obtain biomimetic blood clots in chip that are of great interest as model systems to study stroke-related diseases. Currently, stroke treatment involves either mechanical treatments (e.g. thrombectomy) or rtPA administration treatment to remove clots. While thrombectomy is not applicable in small vessels, the side effects and limited window of use associated with rtPA make its effectiveness challenging. The use of microrobotic platforms to improve clot dissolution by achieving localized drug delivering is demonstrated in clot-in-chip devices, where calcium is used as triggering agent for the coagulation cascade. To fully understand blood clot generation, it is key to understand calcium permeation through a polydimethylsiloxane (PDMS) membrane located inside a two-layer microfluidic device hereby used. This study aims to develop a lab-on-chip device with integrated miniaturized sensing elements to gather important information over clot generation in chip in order to further reproduce them and better understand the coagulation dynamics. Towards that aim, different analytical methods are explored, being mainly focused on electrochemical detection systems. In that line, we studied both screen-printed electrodes and flexible microelectrodes, this last being integrated in the microfluidic devices to enable real-time and in situ calcium detection with quantitative analysis. These advancements highlight the transformative potential of microfluidic technologies in medical research and healthcare, providing valuable pathways for targeted and more effective stroke treatments.