A generalizable dual-mode photoelectrochemical–colorimetric biosensing platform based on a CuInS2/Zn0.5Cd0.5S heterojunction for drug monitoring via Exo I-assisted target recycling and ion exchange

A generalizable photoelectrochemical (PEC)-colorimetric dual-mode aptasensor was developed for drug monitoring based on a CuInS 2 /Zn 0.5 Cd 0.5 S (CIS/ZCS) heterojunction, combined with Exonuclease I (Exo I)-assisted target-induced cycle amplification and an ion- exchange reaction. The CIS/ZCS heterojunction was prepared via a mild in-situ growth method and exhibited significantly enhanced PEC activity. In the presence of the target (Amoxicillin, AMX, as a sample), Exo I cleaved the CuO-labeled aptamer (CuO-Apt), releasing CuO and enabling cyclic signal amplification. Under acidic conditions, the released CuO generated Cu 2+ ions, which subsequently underwent an ion-exchange reaction with CIS/ZCS. Increasing the target concentration led to a decrease in photocurrent and a visible color change at the electrode interface from yellow to dark, enabling both PEC and colorimetric detection. Under optimal conditions, the PEC mode achieved a linear range from 1 pM to 10 μM with a limit of detection (LOD) of 0.146 pM (S/N = 3), while the colorimetric mode exhibited a linear range from 0.1 nM to 10 μM with an LOD of 87.15 pM. After oral drug administration, urine samples were collected from humans and blood samples were collected from mice at different time points. Good results were obtained in both cases, highlighting the potential of the sensor for therapeutic drug monitoring and pharmacokinetic studies. Additionally, by changing the ligands, the proposed platform could be extended to specific monitoring applications for other analytes. This has been experimentally verified by using ampicillin as an additional model analyte.