Metabolomics can be defined as the systematic study of the unique chemical fingerprints that specific cellular and physiological processes leave behind. For the scope, it encompasses a set of analytical methods to detect low molecular weight metabolites in biological samples that are linked to specific health or disease conditions. The collections of compounds form the so-called metabolic profiles usually containing hundreds of different compounds. Ultimately, metabolomics studies are aimed at finding the alteration of the metabolic profile due to specific conditions or diverse pathologies from cancer, to infective diseases.The volatilomics is the case of metabolomics concerned with the small metabolites that are volatile or semi-volatile. The human volatilome can be studied in different human samples such as breath, skin, urines, saliva, and feces.The study of volatile compounds is an important topic of analytical chemistry. Thus, several analytical instruments and methods are available for the investigation of the volatilome5. In general, the scope of the analysis is the detection of the quality and the quantity of the molecules contained in a sample. To achieve this scope these instruments are made by a step of separation and a detector.Analytical machines are generally bulky, costly, and they require specialized staff to be operated and to interpret the data. For these reasons, volatilomics is greatly fascinated by the possibility to replace the analytical machines with sensors. Sensors are devices small enough to be directly connected to electronic platforms.In sensors the separation stage of the analytical instruments is replaced by the affinity of the sensor respect to the molecules composing the sample. however, differently form mass spectrometers. sensors always produce a signal that is related to the totality of the molecules at which it is exposed. Thus, sensors may be selective, when the affinity towards one molecular species overcome the affinity towards all the others, or non-selective when the affinities are comparable. Thus, in principle to replace a GC, an ensemble of sensors each selective to a different species is necessary.The development of sensors for volatilomics found an unexpected inspiration from nature, and more specifically, from olfaction. One of the most striking characteristics of olfaction is the capability to sense many different odors with a limited set of different receptors. It has been surmised that human, with only 388 different receptors, can detect more than one trillion of odor stimuli. The principle of odor identification in olfaction is ruled by the so-called combinatorial selectivity. since a single compound may be sensed by more receptors and more receptors may sense the same compound, the identification of an odor is accomplished by the pattern of responses of the whole set of receptors.Porphyrinoids have been found to be an exceptional material for electronic noses because theie molecular structure made of modular blocks such as the central metal atom, the aromatic ring, and the peripheral motifs can be modified giving rise to a large variety of sensitivity patterns.Porphyrins have been extensivelly used in volatilomics, in the first implementation, as the functional layer of quartz microbalances. In 2003 an array made of porphyrins and corroles demonstrated that lung cancer could be diagnosed from the analysis of breath. This first evidence was followed by other applications aimed at diagnosis tuberculosisfrom breath, lung cancerand kidney cancerfrom urines and COVID-19 from serum. Additionally, these sensors were used to study malariaand stem cellsproliferation in murine models.Recently, quartz microbalance sensors were challenged by the possibility to develop porphyrins-based impedance sensors. The introduction of these sensors is expected to reduce the costs of production and to result into more simple and widely usable devices. For instance, a capacitive sensor array made of porphyrinoids coated silica particles was used to detect COVID-19 from the VOCs released by serum, and Porphyrins-doped PEDOT was implemented in facemasksand used to diagnose chronic kidney diseases.In the presentation, the rationale of these developments will be presented, and somne noteworthy case studies will be discussed.
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