PEC/EC dual-signal amplification based on Cd-doped MoS(2) nanoflowers for highly accurate sensing of NT-proBNP in serum samples.

The increasing global prevalence of heart failure (HF) underscores the urgent need for highly sensitive and reliable detection of biomarkers. The detection of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a gold-standard diagnostic marker is significantly important. Conventional detection strategies, predominantly based on sandwich immunoassays in a single-mode format, are often compromised by susceptibility to interference and limited robustness. Additionally, accurate detection poses significant challenges due to the low concentrations of NT-proBNP released by patients with early-stage heart failure, compounded by the complexity of biological matrices. To address these issues, we developed a photoelectrochemical/electrochemical (PEC/EC) dual-mode aptasensor by combining Au nanoparticles (Au NPs)@dsDNA embedded with methylene bule (MB) and the CdS quantum dot/Cd-doped MoS nanoflowers (CdS/Cd-MoS NFs) heterojunction. This system enabled synchronous PEC (via chronoamperometry) and EC (via differential pulse voltammetry) detection of NT-proBNP in a single electrode and single solution after NT-proBNP binding. Herein, Cd-MoS NFs, which exhibit high photoelectrochemical efficiency and electrochemical conductivity, were employed to simultaneously amplify both PEC and EC responses. This dual-signal amplification strategy greatly enhances detection sensitivity, demonstrating ultra-sensitive detection limits (0.062 pg/mL for PEC and 0.055 pg/mL for EC) and a broad dynamic range (0.0001-100 ng/mL). Furthermore, the proposed aptasensor demonstrates high specificity and excellent performance in serum samples, showing strong agreement with clinical reference data from hospitals. It also provides superior resolution in the low-abundance range compared to conventional chemiluminescence immunoassay. The dual-mode design improves detection reliability through intrinsic signal cross-validation. Therefore, this biosensor shows strong potential for application in the early heart failure diagnosis.