Cation-π Interaction-Based Biointerface for Low-Cost PD-1 Detection Toward NSCLC Immunotherapy Monitoring

Abstract

Programmed death-1 (PD-1) is a key biomarker for monitoring therapeutic response and resistance in non-small cell lung cancer (NSCLC) immunotherapy. Achieving highly sensitive, real-time detection of PD-1 is crucial for early prediction of treatment resistance and disease recurrence. However, current methods such as ELISA suffer from limitations in sensitivity, speed, and cost. To address these challenges, we develop a label-free biosensor based on semiconducting single-walled carbon nanotube field-effect transistors (CNT-FETs). The sensing interface is designed by wrapping s-SWCNTs with poly[9-(1-octylnonyl)-9H-carbazole] (PCz), enabling immobilization of anti-PD-1 antibodies via cation-π interactions. XPS analysis confirms antibody immobilization via reversible binding energy shifts in C 1s and N 1s spectra upon salt treatment, consistent with cation-π interactions, further validated by NaCl and imidazole competition assays. Using this strategy, the sensor achieves a detection limit of 8.39 fg/mL for murine PD-1—three orders of magnitude lower than ELISA, along with good specificity and favorable regeneration capability. In human serum, it shows promising performance, with 12 out of 14 NSCLC patient samples (85.7%) exhibiting good linear correlation. With rapid response, low cost, and simple operation, this platform offers a reliable strategy for point-of-care PD-1 monitoring during NSCLC immunotherapy.