# Breath Analysis: A Promising Tool for Disease Diagnosis--The Role of Sensors
## 3 Types of Nanomaterial-Based Sensors in Breath Analysis
### Cross-Reactive Applications  
Non-functionalized [180; 181] or polymer-functionalized [129] SAW sensors have been combined with GC columns as detectors for the development of point-of-care diagnostic systems. BC [180], tuberculosis [181], and LC [129] patients for instance, have been effectively diagnosed with an accuracy of 79%, 84%, and 80%, respectively. SAW sensors have been also used for the detection of both polar and non-polar VOCs, after their modification with appropriate sensing films [6]. Cross-reactive SAW sensor arrays with polymeric coatings of different composition [182] or thickness [183] have been reported; SAW sensors coated with eight different polymeric films have achieved effective discrimination of chloroform, octane and xylene vapors as shown by radar plots, maintaining their performance for a period of 3 years [182]. Interestingly, 3 polyisobutylene films of varying thickness, namely 10, 50, and 100 nm, allowed for chloroform, chlorobenzene, o-dichlorobenzene, heptane, toluene, hexane, and octane discrimination by analyzing the transient responses characterized by analyte-specific kinetics variability (different stages of equilibrium attainment, for different coating thickness) [183]. Such polymer-based SAW sensors hold a great promise for potential breath analysis applications. CNTs, SWCNTs, and MWCNTs dispersed in ethanol or toluene for example, have been separately tested for ethanol, toluene, and ethyl acetate sensing at RT with a LOD of 1 ppm [184]. The main advantage of CNTs-modified sensors is the enhanced SAW sensor-sensitivity, due to the ability to sense variations not only in mass but also in conductivity [172]. Among hybrid materials, MWCNTs combined with other materials have achieved selectivity enhancement. Polyepichlorohydrin and polyurethane were combined with different MWCNTs percentages so as to develop a 4 sensor-array, for toluene and octane detection and differentiation using polar plots [185]. Notably, no response was observed for gases such as H\({}_{2}\), NH\({}_{3}\), NO\({}_{2}\), and CO, while toluene adsorption was far more enhanced than that of octane [185]. In a different publication, MWCNTs combined with nano-sized CeO\({}_{2}\) (100:1) have formed a semiconducting composite that achieved acetone and ethanol detection, with higher sensitivity for the former [186]. As far as MNPs-based hybrid materials are concerned, thiol containing calix4 arene-modified AuNRs and Ag nano-cubes (NCs) have been recently used in a 5-sensors array, for the detection of polar and non-polarVOCs in low ppm levels including the LC biomarker toluene. Chloroform and toluene were detected with greater sensitivity by the modified AuNRs and AgNPs respectively when compared to unmodified NPs (Table 2) [49]. Calix4 arene modification enhanced sensitivity largely due to the increase of the surface interaction area as well as the arrangement of the macrocyclic ligands (Figure 12) [49]. The use of pristine or Au NPs-functionalized zeolitic-imidazole-framework nanocrystals (ZIF-8 and ZIF-67) in a 4-sensor array for the discrimination of diabetes biomarkers (acetone, ethanol, and NH\({}_{3}\)) via PCA is another example of promising hybrid materials [138] (Table 2). Molecularly functionalized MOS-NPs are also reported in the literature. Using a layer of amino-terminated iron oxide NPs for instance, the VOCs butanol, isopropanol, toluene, and xylene were detected with a low LOD of 1, 12, 3, and 0.5 ppm, respectively, thus developing an effective sensing device of lower cost in comparison to MNPs-based sensing systems [187]. Iron oxide NPs have been also used in combination with polymers.