TL;DR
A cascade-driven dual-signal attenuation strategy that holds great promise for high‑performance electrochemical biosensing in complex biological samples.
In sensing analysis, controlling signal switch through targets is a key method to ensure detection sensitivity. To improve the control effect, an antifouling sensor based on controlled-release and co-reaction catalytic strategies was designed. Concretely, the gel interface with the biocompatible red cell membrane as the skeleton was developed to resist the non-specific adsorption of interfering proteins in the serum environment. Secondly, due to the strong specific binding of antigens and antibodies, S QDs were released from the cavity of mesoporous SiO2, thereby achieving target-induced signal self-on. At the same time, Pd NCs encapsulated in the antifouling hydrogel were used for autocatalysis of luminescence signals to achieve highly responsive signal-on. The integration of interface antifouling and controlled release effectively avoided the adverse interferences from external environment and background signals, improving the reliability of target-induced responses, and the highly responsive signal-on mode endowed the biosensor with high sensitivity. Based on this, the constructed biosensor realized trace detection of squamous cell carcinoma antigen in a wide detection range of 100 fg/mL ∼1 μg/mL, with a detection limit of 27.7 fg/mL, meeting the needs of early clinical diagnosis of related cancers. The proposed biosensing platform based on cell membrane antifouling and highly responsive signal-on provides a powerful tool for the applications in clinical diagnose and other biological detection scenarios.
Electrocatalytically amplified electrochemical immunosensing is a powerful strategy for sensitive and interference-free detection of biomarkers. Herein, we report a high-performance electrochemical immunosensor enabled by a hierarchical hybrid architecture comprising Ru nanodots anchored on titanium oxynitride nanoflakes dispersed on graphene oxide (Ru/TiON-GO), linked via APTES to biorecognition building blocks. The engineered heterostructure exhibits advanced electrocatalytic activity, arising from synergistic electronic coupling between Ru nanodots and the highly conductive TiON-GO support, effectively promoting interfacial electron transport between the electrocatalytic surface and the [Fe(CN)6]3-/4- redox probe. Leveraging this electrocatalytic platform, a prostate-specific antigen (PSA) impedimetric immunosensor was constructed, achieving a limit of detection of 0.06 ng mL-1 (2.3 pM) and a wide linear response covering clinically relevant concentration range. The immunosensor demonstrates excellent selectivity in human serum, operating in interference-free mode even in the presence of common coexisting biomolecules, highlighting suitability for medical diagnostics. Density functional theory calculations further elucidate the origin of the enhanced electrocatalytic performance, with charge density difference plots and density of states analysis revealing Ru-driven electron redistribution and increased density of states near the Fermi level. This work establishes the Ru/TiON-GO nanocomposite as a robust electrocatalytic platform for advanced immunosensing applications, paving the way toward next-generation electrochemical diagnostic devices.
The precise detection of CA19-9 is paramount for early cancer diagnosis and clinical monitoring. However, traditional immunoassays are often hampered by their heavy reliance on matched antibody pairs and the insufficient sensitivity of enzymatic amplification systems. To address these limitations, we report a novel, enzyme-free surface-enhanced Raman scattering (SERS) platform based on a "dual-hotspot amplification" strategy. The core innovation lies in exploiting the dual-connectivity of phenylboronic acid (PBA) to achieve precise hotspot modulation via a multi-cycle assembly. By utilizing D-glucose as a reversible molecular bridge, this strategy successfully breaks the traditional "one-to-one" linear binding limit of PBA. It facilitates a synergistic transition from heterogeneous binding, which anchors nanoprobes to a BSA@CPBA macromolecular scaffold, to homogeneous binding that drives continuous inter-particle cross-linking. This cycle-dependent assembly transforms individual immune recognition events into a highly coupled 3D dendritic plasmonic network, resulting in progressive accumulation of plasmonic hotspots and amplified macroscopic SERS signals. Under optimized conditions, the proposed sensor achieves an exceptionally low limit of detection of 6.2 × 10-5 U/mL and a wide linear dynamic range spanning five orders of magnitude (10-4 to 10 U/mL). Furthermore, the platform demonstrates outstanding specificity and excellent reproducibility (RSD = 8.34%). Practical utility was validated in human serum samples with near-ideal recovery rates (98.67%-103.87%) and excellent agreement with clinical chemiluminescence immunoassays. This modular and cost-effective approach not only enhances detection sensitivity but also provides a useful design concept for the ultrasensitive analysis of carbohydrate-derived biomarkers.