Peptide cleavage-mediated photoelectrochemical signal on-off via CuS electronic extinguisher for PSA detection

In this work, a peptide-based photoelectrochemical (PEC) biosensor was constructed based on CdTe/TiO₂ sensitized structure as electrode and CuS nanocrystals as signal amplifier for the ultrasensitive detection of protein. After peptide was fixed to the CdTe/TiO₂ electrode surface, the double-helix DNA (dsDNA) was immobilized at the end of the peptide and used as a carrier to immobilize the doxorubicin-copper sulfide nanocrystals (Dox-CuS) conjugates. As a proof of concept, prostate specific antigen (PSA) has been chosen as the model. In absence of PSA, CuS nanocrystals could consume electron donors and exciting light energy. Additionally, the steric hindrance effect of biomacromolecules hindered the movement of electron donors to the photoelectrode. Eventually, the photoelectric response signal was reduced, and the biosensor was in a "signal off" state. When PSA existed, the PSA specifically cleaved the peptide, and DNA/Dox-CuS probes were released from the electrode surface, resulting in a "signal on" state. The PEC biosensor revealed good specificity, stability, and reproducibility, and it exhibited excellent application in PSA analysis with a linear range from 0.005 to 20 ng mL^-1 and a low detection limit of 0.0015 ng mL^-1. This PEC biosensor may have potential applications in bioanalysis, disease diagnostics, and clinical biomedicine.