Phase-transited BSA and cyclic-peptide antifouling interface for ultrasensitive PD-L1 detection in undiluted serum

Soluble programmed death-ligand 1 (sPD-L1) is a promising non-invasive biomarker for early cancer diagnosis and immunotherapy monitoring. However, electrochemical detection of sPD-L1 in serum remains challenging due to severe biofouling that compromises sensitivity and specificity. We developed a one-step, dual-antifouling electrochemical interface by co-assembling phase-transited bovine serum albumin (PTB) and a cyclic multifunctional peptide (CP). PTB forms a dense, amyloid-like nanofilm that acts as a robust protein shield, while CP introduces a zwitterionic antifouling loop and a PD-L1-binding motif. This synergistic architecture significantly suppresses non-specific protein adsorption while enabling oriented target recognition. The sensor achieves a detection limit of 37.4 pg/mL and accurately distinguishes cancer patients from healthy individuals using neat serum without dilution or pretreatment. The PTB/CP dual-antifouling platform offers a simple, sensitive, and clinically translatable strategy for sPD-L1 detection, with broad potential for point-of-care cancer diagnostics and immune monitoring.