Magneto-electrochemical biosensing for pathogen detection using nuclease-responsive nanohybrids

Abstract The development of sustainable and highly sensitive diagnostic platforms is critical for rapid pathogen identification and effective disease management. Here, a green, magneto-electrochemical biosensing strategy is reported for the selective detection of Streptococcus pneumoniae based on pathogen-specific nuclease activity. Uniform organic–inorganic hybrid polyhedral oligomeric silsesquioxane (POSS) nanoparticles were synthesized via an ultrafast UV-initiated emulsion polymerization within 5 min using an eco-friendly approach. The nanoparticles were sequentially functionalized by in situ deposition of superparamagnetic iron oxide nanoparticles and biomimetic polydopamine coating, enabling robust and high-density immobilization of nuclease-responsive oligonucleotide probes. The resulting PDA@SPION/POSS nanohybrids exhibit controlled size, preserved structural integrity, and strong superparamagnetic behavior, allowing efficient magnetic manipulation and electrochemical signal transduction. Upon exposure to S. pneumoniae , nuclease-mediated probe cleavage produces a pronounced electrochemical response, enabling label-free detection over a wide dynamic range (10 2 –10⁸ CFU mL⁻¹) with a detection limit of 10 2 CFU mL⁻¹. High selectivity against non-target bacteria highlights the specificity of the enzymatic recognition mechanism. This work establishes a sustainable and amplification-free biosensing platform with strong potential for rapid clinical diagnostics. Graphical abstract