Graphene-Enabled Breathomics: A Translational Roadmap from Fundamental Physics to Non-Invasive Point-of-Care Diagnostics.

Selective molecular recognition of trace volatile biomarkers in humid breath remains a fundamental coordination challenge at graphene interfaces. While exhaled breath contains a complex matrix of more than 3500 volatile organic compounds, clinical transition has been largely challenged by the selectivity-humidity paradox. This review traces the evolution of graphene transduction platforms from fundamental quantum phenomena to coordination-governed interfacial engineering strategies enabling selective molecular recognition. It critically analyzes the atomic-level interactions governing the interface, specifically how sublattice symmetry breaking, metal-ligand interactions, competitive water coordination, and 1/f noise spectroscopy enable detection limits at the parts-per-trillion level. It details nanoengineering strategies for superior performance, tracing the shift from pristine graphene to 2D/2D heterostructures and organic-functionalized scaffolds that introduce defined coordination environments to regulate analyte binding and suppress humidity interference. These coordination-engineered platforms are linked with clinical targets such as oncology and metabolic disorders, while machine intelligence serves as a supporting analytical layer within the sensor intelligence paradigm. Crucially, it addresses the path to clinical translation, emphasizing first-in-human safety milestones, green synthesis, and economic scalability afforded by adopting laser-induced graphene. By unifying 2D-material physics, coordination-driven selectivity, and sensor intelligence, graphene breathomics provides a chemically grounded framework for decentralized, personalized diagnostic technologies.