A tri-modal biosensor based on alkyne-functionalized gold nanoparticles and molecular beacon for detection of resistance-related point mutations in epidermal growth factor receptor-tyrosine kinase inhibitors.

BACKGROUND

Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) is frequently driven by point mutations such as EGFR T790M. This poses a major clinical challenge that significantly compromises treatment efficacy and patient survival. Conventional detection methods often rely on single-mode signaling and lack built-in validation, which limits their reliability and accessibility, particularly in resource-limited settings.

METHODS AND

RESULTS

We developed a tri-modal biosensor that integrates alkynyl-modified gold nanoparticles (Alk-GNP) with a molecular beacon (MB) for the multiplexed detection of EGFR T790M. The optimized system simultaneously responds to the target mutation through three distinct modes: photothermal response, colorimetric shift, and fluorescence emission, achieving detection limits of 16.81 nM, 2.41 nM, and 0.80 nM, respectively. The fluorescence modality served as the primary detection mode due to its high sensitivity, while photothermal and colorimetric signals provided real-time cross-validation to enhance overall reliability. Furthermore, the smartphone-compatible photothermal and colorimetric outputs enable portable and point-of-care data analysis, an essential feature of next-generation biosensing platforms.

CONCLUSIONS

This work presents a diagnostic tool that integrates tri-modal signal outputs with built-in cross-validation, which may have implications for guiding treatment decisions in NSCLC.