Cascade redox cycling amplification enabled by COF-confined Co3O4 for enhanced immunosensing

Abstract

Herein, an enzyme-free and highly efficient sandwich-type electrochemical immunosensor for cTnI detection was developed using covalent organic framework (COF) confined Co₃O₄ nanoparticles (NPs) as the signal probe and enhancing the sensitivity with electrochemical-chemical-chemical (ECC) redox cycle amplification (RCA) strategy. The multifunctional COF, with high surface area and rich nitrogen, serves not only as a substrate material but also as a scaffold for Co²⁺ entrapment, enabling the confined growth and uniform distribution of ultrafine Co₃O₄ NPs as signal amplification platform, thereby providing abundant catalytic active sites for ECC redox cycling reactions. COF confined Co₃O₄ NPs with variable valence states (Co³⁺/Co²⁺) serve as a redox-active electrode material that can enhance the current signal substantially. The ECC redox cycle is triggered by the redox reaction between Co³⁺ at the electrode and electroactive hydroquinone (HQ), while HQ was regenerated by the reducing agent tris (2-carboxyethyl) phosphine (TCEP), resulting in a significant amplification of the current signal for cTnI analysis. The constructed immunosensor exhibited excellent performance with a wide linear range from 1 fg mL⁻¹ to 100 ng mL⁻¹, and a low detection limit of 0.88 fg mL⁻¹. Furthermore, the immunosensor successfully applied to detected cTnI in human serum, proving its clinical potential.