# Breath Analysis: A Promising Tool for Disease Diagnosis--The Role of Sensors
## 3 Types of Nanomaterial-Based Sensors in Breath Analysis
### Chemiresistors
#### 3.1.2 Cross-Reactive Applications
This achieved low LOD and visual discrimination between the three analytes using polar plots (Figure 5); however, further statistical analysis is required [99]. The same group has also developed a 3 \(\times\) 3 sensor array based on WO\({}_{3}\), SnO\({}_{2}\), or In\({}_{2}\)O\({}_{3}\)-based thin films, Au NPs-decorated thin films and Au NP-decorated willi-like structures; the array efficiently discriminated ppt levels of H\({}_{2}\)S and ppp levels of NH\({}_{3}\) and NO in 80% of RH, being potentially applicable to halitosis, renal disorder, and asthma diagnosis, respectively [100]. The notable sensor sensitivity was attributed to the increased surface-to-volume ratio created by the Au NPs and the highly porous villi-like structure [100]. Apart from MNPs-decorated MOS, other promising types of hybrid materials have been studied; MOS for instance have been combined with graphene derivatives. An e-Nose based on graphene-doped TiO\({}_{2}\), NFs, and nano-ribbons was recently developed for ethanol, acetone, CO and NO detection, common biomarkers for _Staphylococcus aureus_ infection, diabetes, asthma, COPD, and cystic fibrosis (CF), respectively [101]. Breath-simulating samples of different VOCs-concentrations (respective to HC and patients of a selected disease) have also been studied, leading to effective discrimination of VOC concentrations. In another attempt for the development of an e-Nose, molecularly functionalized rGO layers with different amine-ligands, have been used for the discrimination of exhaled cancer biomarkers ethanol, 2-ethylhexanol, nonanal, and ethyl benzene [102]. The molecular ligands, serving as the organic sensing film, alter the adsorption capacity and conductivity of the rGO. Concerning CNTs-based cross-reactive sensor arrays, calixarene functionalization has permitted the detection of aromatic compounds (toluene, benzene, ethyl benzene, and xylenes) with high sensitivity [103]. Decoration with Au (1.5 nm), Pd (0.2 nm), and Cr (1.0 nm) has been used along with a pristine sensor element to effectively distinguish NH\({}_{3}\), ethanol, CO, and CO\({}_{2}\) using PCA [104]. Remarkably, in a more recent study, an array of nylon fibers wrapped with SWCNTs, MWCNTs, and ZnO QDs-SWCNTs has been developed as a flexible wearable sensor to be incorporated in face masks. Detection and effective discrimination of NH\({}_{3}\), ethanol, and formaldehyde [105], and common disease biomarkers (ethanol [101], formaldehyde [106], NH\({}_{3}\)[7]) was achieved [7]. SWCNTs-functionalization with semiconducting organic polymers, monomers or oligomers is also reported, especially for real-world sample experiments, discriminating successfully COPD patients from HC as well as selected analytes; however, larger clinical trials remain to be conducted (Table 2) [107]. The most common types of hybrid sensing layers are those composed of a conductive inorganic material, surrounded by an organic functional film where the gaseous analytes are adsorbed therefore changing the conductivity of the device [15]. CNTs, MNPs (e.g., Au) [15], or carbon black [15; 108] can be used as the conductive part while non-conducting molecular ligands (MCNPs) [51; 108; 109] or polymers [110] as the organic one. Such sensors offer the prospect of cross-reactive sensor-array development since the organic part is selected based on the chemical and physical properties of the VOCs [16]. Upon sensor exposure to gaseous biomarkers, the latter diffuse into the organic layer interacting with its functional groups [15]. Those interactions cause swelling of the organic matrix [15], posing a stress to the underlying NPs layer [41], thus increasing the inter-particle distance of the conducting NPs and the measured resistance [6]. In addition, the relative dielectric constants of the VOCs and the organic layer, all of which affect the permittivity of the organic matrix, change the measured resistance [6]. Molecularly-functionalized conducting nanomaterials have been extensively investigated for the cross-reactive detection of VOCs by [PERSON] et al.