The quest for non-invasive, rapid, and highly sensitive diagnostic technologies has catalyzed the development of breath-based biosensing platforms. Exhaled human breath contains a complex array of volatile organic compounds (VOCs) that reflect metabolic and pathological changes, offering a rich source of real-time biomarkers. This review comprehensively examines the biochemical origins and disease-specific signatures of VOCs, alongside a comparative assessment of breath with other biofluids such as blood, saliva, and urine. Particular emphasis is placed on emerging quantum nanomaterials including quantum dots, MXenes, black phosphorus, and perovskite nanocrystals which offer exceptional sensitivity, selectivity, and room-temperature operability in VOC detection. We explore signal transduction mechanisms such as fluorescence quenching, chemiresistive sensing, and resonance energy transfer, and highlight their integration into smart diagnostic platforms enabled by artificial intelligence, microfluidics, and IoT technologies. Applications across metabolic disorders, cancers, respiratory diseases, and hepatic dysfunctions are critically analyzed. Finally, current limitations in VOC standardization, sensor degradation, and environmental interference are discussed, with a forward-looking perspective on clinical translation. This review offers a unified framework bridging material innovation, breathomics, and digital health, underscoring the transformative potential of quantum nanomaterial-enabled breath sensors for next-generation personalized diagnostics. • Quantum nanomaterials revolutionize breath-based diagnostics for non-invasive disease detection. • VOC biomarkers in exhaled breath enable real-time metabolic health monitoring. • Advanced sensing via quantum dots, MXenes, and perovskites ensures superior sensitivity. • AI-integrated breathomics platforms enhance diagnostic precision and clinical applicability. • Emerging nanomaterial biosensors advance personalized, portable, and point-of-care healthcare.
Singh et al. (Sun,) studied this question.