Probing Biointerfaces with QCM‑D and Electrochemistry: Opportunities and Challenges toward Integrated EQCM‑D Biosensing.

Biosensing has garnered significant attention due to the demand for early disease diagnosis and the interest in biological interfaces where gravimetric response, hydration, mechanical deformation, and charge transfer are intrinsically coupled and dynamically evolving. Quartz crystal microbalance with dissipation monitoring (QCM-D) and electrochemical techniques provide complementary access to interfacial mechanical and electrical properties, yet each alone faces limitations in interpreting the complexity. This review summarizes recent advances in QCM-D- and electrochemistry-based biosensing, discussing strategies for their coupling, with a particular focus on electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D). By enabling simultaneous gravimetric, viscoelastic, and electrochemical measurements at the same interface, EQCM-D offers unique opportunities for real-time correlation of biointerfacial processes. We further highlight emerging challenges in data interpretation arising from the active roles of water and ions and discuss future perspectives toward correlative multimodal EQCM-D platforms for quantitative biosensing and bioelectrochemical studies.