Gold Nanoisland Microelectrode Micro-Aptamer Sensor with SWASV Readout for EGFR-Positive Lung Cancer Exosomes

Non-small cell lung cancer (NSCLC) requires highly sensitive liquid biopsy tools capable of detecting EGFR driven disease and resistance mutations such as T790M, which often evade conventional circulating free DNA assays. Exosomes provide a more reliable biomarker due to their abundance, stability, and enrichment of tumor specific EGFR cargo. Here, we report an ultrasensitive electrochemical microaptasensor specifically designed for the quantitative detection of EGFR positive lung cancer exosomes. The innovation of this work lies in the integration of a thermally dewetted gold nanoisland microelectrode (AuNI ME) which offers a large and Au(111) enriched electroactive surface for high density aptamer immobilization. Additionally, the system utilizes a dual aptamer AND gate recognition strategy using EGFR and CD63 aptamers to ensure exceptional specificity along with a cadmium sulfide quantum dot (CdS QD) amplification system quantified via square wave anodic stripping voltammetry (SWASV). This multi tiered amplification architecture combines nanostructured electrode design, orthogonal dual aptamer recognition, and QD based metal ion amplification to result in a remarkably low limit of detection of 150 particles/mL. This performance outperforms ELISA, NTA, and recent electrochemical exosome assays. The sensor exhibits excellent selectivity, reproducibility, and stability, and demonstrates high recovery ranging from 97.8% to 105.0% in spiked human serum samples. These results highlight the translational potential of this platform as a noninvasive tool for early NSCLC diagnosis and real time therapeutic monitoring.