A Hybrid Phospholipid Monolayer-Based Interface for Interaction-Enhanced Electrical Detection in Biofluids

Charge interactions at the sensing interface are pivotal for efficient signal transduction. However, in biofluids, charge screening and nonspecific adsorption induced by counterions and biomolecules can negatively affect the signal transduction between the interface and electrode. In this work, we demonstrate that counterion screening and nonspecific adsorption can be mitigated by regulating the surface charge density and composition of the sensing interface, thereby improving signal transduction performance. We constructed an interfacial model with an adjustable surface charge based on a hybrid phospholipid monolayer (HPM) to investigate the interactions between interfacial charge distribution, counterion screening, and nonspecific adsorption. The signal transduction capacity of the sensing interface was enhanced by doping unsaturated long-chain molecules within the HPM. Molecular dynamics simulations and density-functional theory calculations confirmed that an appropriate surface charge density and the doping of conjugated molecules are crucial for efficient signal transduction. We applied this sensing interface for the highly sensitive detection of myocardial injury biomarkers (MIBs), achieving a detection limit (LoD) as low as 0.92 pg/mL. Our findings reveal the underlying mechanism of efficient signal transduction at the sensing interface, highlighting the relationships between the interface composition and performance in electrical biosensing.