An antifouling electrochemical biosensor based on covalent organic framework-iridium nanocomposite functionalized with designed peptide for the detection of β-Amyloid in serum

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder closely associated with the aggregation of β-Amyloid (Aβ) peptides, particularly Aβ 1–42. Electrochemical biosensors hold great potential for serological Aβ 1–42 detection due to their high sensitivity and rapid response capability. However, their performances in complex matrices such as serum are compromised by biofouling and signal interference. The biosensors with functional peptide-modified interfaces, leveraging Ir–S coordination, have had improved antifouling performance and stability. Nevertheless, conventional iridium nanoparticle (IrNPs) electrodeposition often yields heterogeneous structures with poor uniformity, limiting the consistency and sensitivity of such platforms. To address this, we developed an innovative electrochemical biosensor based on a covalent organic framework (COF)-mediated interface. Using TpPa-1 COF (Tp: 1,3,5-triformylphloroglucinol; Pa: p-phenylenediamine) as a structural template, we achieved uniform and high-density loading of IrNPs (IrNPs@COF). The functional peptides were subsequently assembled via robust Ir–S coordination, creating a synergistic antifouling sensing platform. This biosensor enables ultrasensitive and selective detection of Aβ 1–42 in serum, demonstrating significant potential for reliable early diagnosis of AD.