Sniffing Disease: Chemiresistive Metal-Oxide Electronic Noses for Noninvasive Disease Diagnosis

Abstract

This review examines recent advances in chemiresistive metal-oxide semiconductor (MOS) gas sensors for noninvasive disease diagnosis through the detection of volatile organic compounds (VOCs) in exhaled breath and skin gas. The operating principle, based on oxygen chemisorption and desorption, is first outlined along with strategies for enhancing sensor performance, including nanostructuring, catalytic functionalization, and heterojunction engineering, which enable detection limits suitable for clinical analysis (sub-ppb range). To address limitations in sensitivity and selectivity, the integration of cross-reactive sensor arrays (electronic noses) with artificial intelligence–based pattern recognition, particularly deep neural networks (DNNs), is highlighted as a critical approach for classifying complex VOC signatures. Clinical case studies across major diseases—such as lung cancer (aromatic and alkane markers), diabetes (acetone), asthma (H2S), COVID-19 (multi-array DNN systems), and tuberculosis (multiple VOCs)—demonstrate high diagnostic accuracy, validating the technology’s potential as a rapid and low-cost screening tool. However, successful clinical implementation requires overcoming key challenges, including the standardization of sampling and pretreatment methods (e.g., end-tidal breath collection and humidity control), cross-site data generalization, mitigation of confounding variables, and improvement of long-term sensor stability. Future research should focus on advanced material systems and robust machine learning frameworks to realize universally applicable point-of-care diagnostic platforms.