Ultrasensitive Optoelectronic Quantification of Erlotinib in Metastatic Pancreatic Adenocarcinoma Based on BiOBr/Bi2Te3 Heterojunction for Therapeutic Efficacy Assessment

Abstract Therapeutic drug monitoring of erlotinib in metastatic pancreatic ductal adenocarcinoma (PDAC) is critically constrained by the reliance on centralized instrumentation incompatible with point-of-care deployment. Here, a BiOBr/Bi2Te3 type II staggered heterojunction was rationally designed as a photoelectrochemical (PEC) sensing platform for ultrasensitive erlotinib quantification. The heterojunction, fabricated via secondary solvothermal assembly, was confirmed by XRD/Rietveld refinement, XPS, and HRTEM to form an intimate sheet-on-sheet architecture. PDOS calculations revealed that the staggered band alignment drives vectorial electron transfer from the Bi2Te3 CB to the BiOBr CB via common-cation orbital bridging, yielding a 2.85-fold photocurrent enhancement relative to pristine BiOBr. The PEC sensor exhibited a linear response of 0.1–20 μM (R2 = 0.9981), a sensitivity of 0.7371 μA·cm–2·μM–1, a limit of detection of 9.3 nM, excellent selectivity over biological interferents (<8% cross-response), and recoveries of 93.8%–104.9% in spiked human serum. Integration of sensor-derived pharmacokinetic parameters with a retrospective institutional cohort of 200 metastatic PDAC patients through explainable machine learning (Gradient Boosting AUC = 0.942 ± 0.046; XGBoost AUC = 0.933 ± 0.053)) demonstrated that optoelectronic exposure metrics significantly improved therapeutic response prediction, Kaplan–Meier survival stratification, and decision curve net benefit, establishing a closed-loop analytical-to-clinical framework for precision erlotinib therapy.