An impedance-based chemiresistor for the real-time detection of gut microbiota-generated short-chain fatty acids

Short-chain fatty acids (SCFAs) are key molecules produced by gut bacteria in the intestine, that are absorbed into the bloodstream and strongly influence human health. SCFA disruption and imbalances have been linked to many diseases; however, they are seldom used diagnostically as their detection requires extensive sample preparation and expensive equipment. In this work, an electrochemical sensor was developed to enable real-time, quantitative measurement of SCFAs from complex samples in liquid phase without the need for extraction, evaporation, or destruction. An impedance-based sensor for in vitro detection of acetic acid, propionic acid, and butyric acid (accounting for more than 95% of SCFAs in the intestine) was fabricated by the deposition of a ZnO and polyvinyl alcohol (PVA) on the surface of a microfabricated interdigitated gold electrode. The sensor was first exposed to a broad, physiologically relevant range of concentrations of SCFAs in isolation (0.5-20 mg/ml) and unlike previously published SCFA sensors that could detect only in gas form with the aid of evaporation, it was able to detect them directly in the liquid phase at room temperature. Electrochemical impedance spectroscopy analysis was then applied to the mixture of SCFAs prepared at different ratios and in complex media at concentrations ranging from 0.5 to 10 mg/ml, which showed the capability of the sensor to measure SCFAs in experimentally relevant mixture. The recorded faradaic responses were then used to train a fit-to-data model to utilize the sensor to screen human bacterial isolates and detect which species secrete SCFAs in vitro. This work will allow for the rapid and non-destructive determination of the levels of SCFAs in complex biological samples, providing a miniaturized, highly stable, and highly sensitive sensor for real-time monitoring applications.