Fc@ZeNose platform for the detection of four physiologically relevant breath biomarkers: a case study using ethanol, isopropanol, acetic acid, and acetone†

Metabolomics allows the analysis of metabolites in biological samples to identify biomarkers associated with metabolic processes, and among these volatile organic compounds (VOCs) have emerged as a significant component in non-invasive diagnostics playing a crucial role in understanding physiological and pathological conditions. The changes in metabolic pathways that occur in biological systems during disease states result in the generation of VOCs as end products or intermediate products. These are then transported to the lungs via the circulatory system and presented into breath at the alveolar membrane. This direct link between metabolic changes and exhaled VOCs has driven growing interest in breathomics, a non-invasive approach to disease diagnosis and monitoring. Among numerous gas sensing technologies that have been explored, electrochemical sensors have demonstrated high sensitivity, cost-effectiveness, real-time monitoring, and miniaturization capabilities. In this work, we have developed a ferrocene (Fc) encapsulated zeolitic imidazole framework −8 (ZIF-8) for the detection of 4 physiologically relevant VOCs: ethanol, isopropanol, acetic acid, acetone, utilizing chronoamperometry as the transduction principle. The material characterization was performed using X-ray photoelectron spectroscopy, powder X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray analysis, and thermogravimetric analysis to confirm the morphological properties of Fc@ZIF-8. The dose-dependent response curves were established for each VOC, demonstrating linearity and the sensor's detection capabilities. Additionally, the sensor's accuracy was confirmed with spike and recovery experiments, achieving recovery rates within the CLSI guideline range of 80–120%.