Skin emitted volatiles analysis for noninvasive diagnosis: the current advances in sample preparation techniques for biomedical application.

Human skin emits a series of volatile compounds from the skin due to various metabolic processes, microbial activity, and several external factors. Changes in the concentration of skin volatile metabolites indicate many diseases, including diabetes, cancer, and infectious diseases. Researchers focused on skin-emitted compounds to gain insight into the pathophysiology of various diseases. In the case of skin volatolomics research, it is noteworthy that sample preparation, sampling protocol, analytical techniques, and comprehensive validation are important for the successful integration of skin metabolic profiles into regular clinical settings. Solid-phase microextraction techniques and polymer-based active sorbent traps were developed to capture the skin-emitted volatile compounds. The primary advantage of these sample preparation techniques is the ability to efficiently and targetedly capture skin metabolites, thus improving the detection of the biomarkers associated with various diseases. In further research, polydimethyl-based patches were utilized for skin research due to their biocompatibility and thermal stability properties. The microextraction sampling tools coupled with high sensitive Gas Chromatography-Mass Spectrometer provided a potential platform for skin volatolomes, thus emerging as a state-of-the-art analytical technique. Later, technological advancements, including the design of wearable sensors, have enriched skin-based research as it can integrate the information from skin-emitted volatile profiles into a portable platform. However, individual-specific hydration, temperature, and skin conditions can influence variations in skin volatile concentration. Considering the subject-specific skin depth, sampling time standardization, and suitable techniques may improve the skin sampling techniques for the potential discovery of various skin-based marker compounds associated with diseases. Here, we have summarised the current research progress, limitations, and technological advances in skin-based sample preparation techniques for disease diagnosis, monitoring, and personalized healthcare applications.