Lung cancer remains a global health concern, demanding the development of noninvasive, prompt, selective, and point-of-care diagnostic tools. Correspondingly, breath analysis using nanobiosensors has emerged as a promising noninvasive nose-on-chip technique for the early detection of lung cancer through monitoring diversified biomarkers such as volatile organic compounds/gases in exhaled breath. This comprehensive review summarizes the state-of-the-art breath-based lung cancer diagnosis employing chemiresistive-module nanobiosensors supported by theoretical findings. It unveils the fundamental mechanisms and biological basis of breath biomarker generation associated with lung cancer, technological advancements, and clinical implementation of nanobiosensor-based breath analysis. It explores the merits, challenges, and potential alternate solutions in implementing these nanobiosensors in clinical settings, including standardization, biocompatibility/toxicity analysis, green and sustainable technologies, life-cycle assessment, and scheming regulatory modalities. It highlights nanobiosensors' role in facilitating precise, real-time, and on-site detection of lung cancer through breath analysis, leading to improved patient outcomes, enhanced clinical management, and remote personalized monitoring. Additionally, integrating these biosensors with artificial intelligence, machine learning, Internet-of-things, bioinformatics, and omics technologies is discussed, providing insights into the prospects of intelligent nose-on-chip lung cancer sniffing nanobiosensors. Overall, this review consolidates knowledge on breathomic biosensorbased lung cancer screening, shedding light on its significance and potential applications in advancing state-of-the-art medical diagnostics to reduce the burden on hospitals and save human lives.
