Non-invasive biosensing of health-related biomarkers in biofluids using electrochemical platforms

This doctoral thesis investigates the development of innovative electrochemical biosensors for the non-invasive monitoring of clinically relevant biomarkers in biofluids, with particular focus on saliva and interstitial fluid. The work explores multiple sensing platforms, including amperometric sensors and organic electrochemical transistors (OECTs), characterized by different levels of structural complexity, functionalization strategies, and application formats, from label-free systems to devices incorporating biorecognition elements, to wearable, skinconformable devices. Driven by the increasing demand for point-of-care (POC) diagnostic technologies enabling real-time and minimally invasive monitoring, the research addresses three representative case studies targeting key analytes. First, a label-free OECT platform based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) was developed for uric acid detection in human saliva. Operating in potentiodynamic mode, the sensor requires neither surface functionalization nor sample pretreatment. Its analytical performance was validated against a reference method and confirmed in real saliva samples, demonstrating high sensitivity, reproducibility, and compatibility with portable electronics. Second, to enable detection of non-electroactive biomarkers, molecularly imprinted polymers (MIPs) were integrated into the OECT architecture to selectively detect lysozyme. This approach combines the intrinsic signal amplification of OECTs with the molecular selectivity of MIPs, enhancing specificity without compromising device performance. Finally, fully inkjet-printed PEDOT:PSS electrodes were developed for glucose sensing. Both amperometric and OECT-based configurations were functionalized with glucose oxidase and systematically optimized. The devices were miniaturized and integrated into a tattoo-like wearable platform for skin application, enabling non-invasive glucose monitoring via reverse iontophoresis. The outcomes of this research demonstrate the versatility, adaptability, and cost-effectiveness of electrochemical platforms for non-invasive biosensing. Through a combination of material engineering, device design, and analytical validation, the thesis contributes to advancing nextgeneration diagnostic tools suitable for real-world, decentralized healthcare settings. The technologies developed herein show strong potential for improving chronic disease management, enabling personalized healthcare, and supporting telemedicine solutions.