A Caenorhabditis elegans-based whole-organism microfluidic biosensing platform for detecting lung cancer cell-derived volatile organic compounds

초록

Volatile organic compounds (VOCs) released from cancer cells are being explored as non-invasive readouts for cancer-associated states. However, translating complex VOC profiles into practical and biologically interpretable detection platforms remains challenging. Here, we developed a Caenorhabditis elegans-based whole-organism microfluidic biosensing platform for lung cancer cell-derived VOC detection. The polydimethylsiloxane chip operates on standard nematode growth medium (NGM) plates, preserving crawling-based chemotaxis while providing a standardized geometry for paired comparison of a matched reference medium or vehicle and the corresponding conditioned-medium or VOC test sample. Using this platform, wild-type C. elegans generated a quantifiable chemotactic response that distinguished SK-MES-1 lung cancer cell-conditioned medium from MRC-5 non-malignant lung fibroblast-conditioned medium and DMEM-only controls, with attraction observed over a dilution range of 10(-)& sup3; to 10(-)(7). Gas chromatography-mass spectrometry profiling revealed candidate VOC cues enriched in SK-MES-1-conditioned medium, which were putatively assigned to ethylbenzene, p-xylene, cyclohexanol, o-xylene, and decamethylcyclopentasiloxane. Purified-compound assays revealed compound-specific behavioral responses, with ethylbenzene and o-xylene producing attraction-like responses and p-xylene, cyclohexanol, and decamethylcyclopentasiloxane producing avoidance-associated responses. odr-3(n2150) mutants showed loss or reversal of the wild-type attraction response, supporting the involvement of ODR-3-dependent olfactory signaling. Early-life olfactory imprinting further amplified adult chemotactic responses. These results support the feasibility of a C. elegans-based whole-organism biosensing framework that integrates microfluidic standardization, candidate VOC profiling, genetic pathway analysis, and olfactory plasticity, providing a foundation for future lung cancer-associated VOC detection using patient-derived samples.

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