How to Manage the Humidity of Biological Samples to Reduce Interference on Chemical Sensors

High humidity in biological gas samples (e.g., exhaled breath or headspace from biological fluids) can mask the detection of volatile compounds at low concentrations, reducing sensitivity and stability of chemical sensors. Though progress has been made in developing new sensor systems, unless humidity interference is well addressed, chemical sensors cannot be validated for clinical use. This review aims to provide a practical guide for researchers working in the field of chemical sensors for clinical diagnosis, where managing sample humidity is particularly critical to ensure good diagnostic accuracy. In this review, we analyzed the mechanisms of humidity interference with chemical sensors and discussed sampling strategies to mitigate it in biological sample analysis. Building on dehumidification strategies developed for well-established analytical techniques, we translate these insights to evaluate their possible application to chemical sensor analysis. We critically reviewed five sampling strategies to manage humidity: condensation, permeation, desiccants, dry dilution, and water trap. The operating principles, applications, as well as the advantages, limitations, and contamination risks of each technique are discussed. In practice, each method entails tradeoffs between residual humidity and analyte recovery, requiring careful selection depending on the application. Thoughtfully implemented, these strategies convert humidity from a confounder into a controlled variable, enabling safer and more reliable measurements.