Molecular sensing transforms olfactory diagnosis in traditional Chinese medicine: a critical review

Abstract

Objectifying and standardizing diagnostic methods are essential steps toward the modernization and global recognition of traditional Chinese medicine (TCM). The “four diagnostic methods”, namely, inspection, auscultation and olfaction, inquiry, and palpation, constitute the fundamental diagnostic framework of TCM, among which olfactory diagnosis plays a vital role. This method relies on identifying characteristic odors from the breath or secretions of a patient to guide syndrome differentiation (Bian Zheng). However, conventional olfactory diagnosis remains highly subjective depending on the practitioner's experience, which results in inconsistent outcomes and challenges in reproducibility and quantification. The integration of medical science with modern sensing and analytical technologies provides a transformative pathway to overcome these limitations. Recent studies have shown that exhaled breath contains a complex spectrum of volatile organic compounds (VOCs) that collectively form a personalized “breathprint”, reflecting physiological and pathological states. Objective analysis of these VOCs enables quantifiable, evidence-based characterization of disease-related odors, thereby providing a scientific foundation for olfactory diagnostics in TCM. This review summarizes advancements in VOC detection methodologies, including gas chromatography-mass spectrometry (GC-MS) and electronic nose (e-nose) systems paired with data-driven analytical frameworks, to advance the transformation of traditional olfactory diagnosis in TCM into a standardized, evidence-based diagnostic paradigm.