Dual-Mode SERS and Colorimetric Sensor for Lung Cancer VOC-Biomarker Detection Using Hydrogel Patches
Hexanal, a volatile organic compound (VOC), is a potential biomarker for the early detection of lung cancer. In this study, we developed a dual-mode flexible biosensor that integrates surface-enhanced Raman scattering (SERS) and colorimetric detection for the quantitative analysis of hexanal in human exhaled breath. The biosensor employs Ag nanocubes wrapped with Co-Ni layered double hydroxide (AgNCs@Co-Ni LDH) as a functional matrix, offering both superior SERS enhancement and efficient VOC adsorption properties. To achieve selective detection, AgNCs@Co-Ni LDH were incorporated into agarose hydrogels along with 3-methyl-2-benzothiazolinone hydrazone (MBTH). The resulting MBTH-AgNCs@Co-Ni LDH/hydrogel-patch facilitate the oxidation of hexanal, enabling simultaneous colorimetric and SERS signal generation, while producing acrizine, a blue-colored reaction product. This hydrogel-based dual-mode sensing platform exhibits high selectivity, excellent stability, and precision in SERS-based hexanal detection. The detection limit for the SERS method was determined to be as low as 3.34x10-13 M. Furthermore, developed and optimized compact CNN-based multi-terminal intelligent recognition system for enhanced hydrogel-patch detection through AI-driven, portable, and real-time colorimetric analysis. Therefore, this work not only enables the effective detection of hexanal in the exhaled breath of suspected lung cancer patients, underscoring its potential for early lung cancer screening, but also establishes a foundation for the development of multimodal hydrogel biosensors for broader applications in disease diagnosis.