Laser‐Induced Graphene/AuNPs‐Gated OECT Biosensor for Sensitive Detection of PD‐L1‐Positive Exosomes Associated With Non‐Small Cell Lung Cancer

ABSTRACT

Lung cancer remains a major cause of cancer‐related mortality worldwide, and non‐small cell lung cancer (NSCLC) accounts for the largest proportion of diagnosed lung cancer cases. Exosomal programmed death‐ligand 1 (PD‐L1) has attracted increasing attention as a potential liquid‐biopsy biomarker associated with tumor immune regulation; however, its sensitive and low‐cost detection in complex biological samples remains challenging. Herein, we report a laser‐induced graphene (LIG)‐enabled organic electrochemical transistor (OECT) biosensor for ultrasensitive detection of exosomal PD‐L1 associated with NSCLC. Three‐dimensional porous LIG electrodes were directly fabricated on poly(ether ether ketone) substrates by laser writing, and stable OECT devices were obtained by optimizing the fabrication parameters. To improve biorecognition and interfacial signal transduction, Au nanoparticles were introduced onto the LIG gate for subsequent covalent immobilization of PD‐L1 aptamers. The resulting device exhibited a maximum transconductance of 2.62 mS, an on/off ratio of 52.8, and fast switching characteristics. Using PD‐L1‐positive exosomes derived from PD‐L1‐overexpressing A549 cells as model targets, the biosensor showed a concentration‐dependent response over 0.1–5000 pg mL ⁻¹ with excellent linearity based on offset‐voltage analysis ( R ²  = 0.9922). Device‐to‐device reproducibility, gate‐to‐gate variation, blank/low‐concentration discrimination, and storage stability of the functionalized gates were further evaluated to support analytical reliability. Preliminary clinical assessment using whole‐blood samples from 15 pathologically confirmed patients with NSCLC and 3 healthy controls showed distinguishable normalized responses between the two groups. Exploratory statistical analysis using a two‐sided Mann–Whitney U test indicated a significant difference between the healthy‐control and NSCLC groups ( U  = 0 and p  = 0.0025), with lower mean normalized response values observed in the NSCLC group than in the healthy‐control group (−0.3799 vs. −0.1926). This LIG/AuNPs‐gated OECT biosensing platform provides a sensitive, low‐sample‐consumption, and low‐cost strategy for exosomal PD‐L1 analysis, offering a potential technical basis for further liquid‐biopsy‐related biomarker studies.