Sensors and microsystems for biomedical applications

This doctoral thesis develops two complementary research lines in the field of sensors and microsystems for biomedical applications, relying on Complementary Metal-Oxide-Semiconductor (CMOS) integrated circuits and Micro Electro Mechanical Systems (MEMS) technologies, and united by the need to bring precision instrumentation where conventional clinical methods cannot act. The first contribution addresses the clinically relevant problem of continuous respiratory monitoring in patients affected by chronic conditions such as Chronic Obstructive Pulmonary Disease (COPD), asthma, and sleep-disordered breathing. Reference clinical techniques guarantee high diagnostic accuracy but are incompatible with prolonged acquisition in real-life conditions. To overcome this limitation, a wearable system was developed based on the SENSIPLUS platform, a CMOS integrated circuit for thoracic electrical bioimpedance measurements, integrated with a MEMS microphone for acoustic sensing of respiratory sounds. The system was metrologically characterized, validated against a certified clinical spirometer, and equipped with multimodal fusion algorithms for real-time estimation of respiratory rate, ventilatory cycle phases, and apneic events. The proposed architecture is oriented toward home telemonitoring and Internet of Medical Things (IoMT) applications, with potential impact on the management of acute exacerbations and the personalization of respiratory therapies. The second contribution lies in the domain of precision biological micromanipulation, a field with broad biomedical relevance spanning single-cell isolation, ophthalmic and vascular microsurgery, tissue engineering, and targeted drug delivery. Electrostatically actuated Silicon-on-Insulator (SOI) MEMS microgrippers were designed, modeled, and characterized, developing an analytical and numerical framework for estimating contact forces and mechanical properties of biological samples. The system was successfully applied to the manipulation of marine microorganisms, demonstrating the ability to interact with fragile biological objects in a controlled and non-destructive way. Novel architectures with modular features were further designed, together with a cooperative four-manipulator microstation, conceived for integrated mechanical stimulation and sensing, pick-and-place operations, coordinated manipulation and transport of biological microobjects within a shared workspace.