# Breath Analysis: A Promising Tool for Disease Diagnosis--The Role of Sensors
## 3 Types of Nanomaterial-Based Sensors in Breath Analysis
### Selective Applications  
QCM sensors are used extensively for selective gas detection and are potentially applicable in breath analysis. As an example of MOS based sensors, ZnO has been used in the form of NWs [168] and vertically-aligned NRs [169] for NH\({}_{3}\) detection, permitting the development of reproducible and stable systems in both cases as well as increased selectivity against liquefied petroleum gas, N\({}_{2}\)O, CO, NO\({}_{2}\), and CO\({}_{2}\) in the case of NRs. Notably, VOC detection with MOS-QCM sensors is feasible at RT (despite the use of MOS) since it is directly connected to mass-changes [169]. Concerning polymeric materials, for the selective detection of NH\({}_{3}\)[170] and formaldehyde [171], the use of polymeric NFs based on poly(acrylic acid)/poly(vinyl alcohol) (PAA/PVA) [170] and polyethylenimine (PEI)/PVA [171], respectively, has been demonstrated. More recently, a Si NPs-containing methacrylate acid-based MIP-composite was reported to selectively detect hexanal as LC biomarker in the presence of trimethyl amine, NH\({}_{3}\), ethanol, acetone, acetic acid, and diethyl ether, due to analyte binding through hydrogen bonding formation [74].  
Cross-Reactive Applications  
In the case of cross-reactive applications, hybrid and especially polymeric/macrocyclic sensing materials are investigated. TiO\({}_{2}\)NPs-decorated MWCNTs and cobalt (II) phthalocyanine-silica, for instance, have been used as sensing elements in a 3 sensor array, along with a bare QCM sensor; this was used for simultaneous acetone and NO detection, which serve as diabetes and asthma biomarkers, respectively [139]. No response was observed by the bare sensor, while analyte adsorption to the modified sensors is attributed to analyte-sensing film coordination interactions [139]. Concerning polymeric materials, eight different polythiophene derivatives have achieved acetic acid, toluene, acetone, \(p\)-xylene, ethanol, 1-octanol, acetonitrile, and water discrimination based on VOC-polarity, with a LOD at ppm levels; prediction of toluene concentration in mixtures with ethanol was also permitted [173]. Macrocyclic calixarene derivatives, on the other hand, have achieved the detection of 16 VOCs belonging to ketones, alcohols, aromatic, and chlorinated compounds, at ppm levels, due to \"host-guest\" interactions. Sensor sensitivity and selectivity were dependent on the number and functional groups of calixarene derivatives [174]. In a more recent application, 13 different MIPs of different compositions and cavity structures were studied for the detection of hexanal, nonanal, and benzaldehyde, which are common cancer biomarkers. A combination of five sensors led to the most effective VOC discrimination while sensor-array performance was found to be dependent on both molecular imprinting and matrix effect [73].  
Metalloporphyrin-based cross-reactive QCM sensors seem as the most promising QCM sensors (Table 2) while they have been also applied in real breath samples [130; 131; 132; 133; 134]. Such e-Noses have been examined for asthma [131], COPD [130], halitosis [135], LC [132; 133; 175], and tuberculosis [134] diagnosis with particularly promising diagnostic performance. Similarly, an anthocyanin-based QCM sensor called BIONOTE e-Nose has been developed by [PERSON] et al. [176] and was recently studied for use in asthma diagnosis of children, with the aim to assess the within and between-day repeatability of obtained measurements; values similar to those of conventional methods were achieved (Table 2) [136].