# 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
Molecularly-capped Au NPs and molecularly-coated random SWCNTs networks have been successfully developed for exhaled VOCs-biomarkers detection using real-world samples, usually in combination with chromatographic analysis of breath samples. Irritable bowel syndrome disease (IBS) [111], ovarian [44], colon, lung, gastric [16; 112], breast and prostate cancer [16; 42], chronic kidney diseases (CKD) [113], multiple sclerosis [62], Alzheimer's and Parkinson's diseases [15; 114] have been effectively diagnosed with such chemeissistors. In the case of multiple sclerosis e.g., PAH-coated SWCNTs sensor-arrays have exhibited sensitivity, specificity and accuracy percentages comparable to those of invasive and expensive techniques such as MRI and cerebrospinal fluid electrophoresis [62]. VOCs targeted for the diseases mentioned above are presented on Table 2. In a remarkable application of a MCNPs/SWCNTs-based chemie  
Figure 5: Polar plot of a 2 \(\times\) 4 sensor array response for (**a**) 10 ppm of acetone; (**b**) 1 ppm of NO\({}_{2}\) and; (**c**) 1 ppm of H\({}_{2}\)S and operation temperatures 300, 150, and 250 \({}^{\circ}\)C; (**d**) schematic representation of the parts of the sensor (2 \(\times\) 4 sensor array, back heater, chip carrier, and Au wires). The array shows good recovery and repeatability as well as high performance at sub ppb level, facilitating discrimination between the three biomarkers. Adapted with permission from Ref. [99]. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. sistor array (20 sensors), 17 different diseases (Table 2) were successfully discriminated, with 86% accuracy, based on the detection of a pattern of only 13 VOC whose concentration differed significantly between HC and/or different diseases [115]. More recently, a MCNPs-based chemiresistor was developed for COVID-19 detection, with remarkable diagnostic accuracy over healthy and non-COVID infected subjects [24]. Despite the fact that targeted VOCs were not listed in this study, the most notable VOCs for COVID-19 are probably methylpent-2-enal, 2,4-ocadiene, 1-chloroheptane, and nonanal (10-250 ppb) [25]. Interestingly, a tailor-made nanoscale artificial nose (NA-NOSE), based on this type of sensing films, has been developed by [PERSON] et al. [116]. NA-NOSE is composed of seven cross-reactive MCNPs-layers with different ligands, from which 6 are composed of spherical Au NPs and 1 of cubic Pt NPs. NA-NOSE seems to be promising for breath analysis, as it has been effectively used, e.g., for BC diagnosis [116]. Molecularly-modified Au, Pt, and Cu NPs have been used for the development of a 6-sensors array, to effectively diagnose the infectious disease human cutaneous _Leishmaniasis_ with a 98.2% accuracy, after identifying 9 potential biomarkers using GC/quadruple-TOF [109]. A representative example of MCNPs-based chemiresistors is presented in Figure 6.  
The size, composition, inter-particle distance, and periodicity of the NPs as well as the aggregate thermal stability of such sensors are essential yet easily controlled parameters [51]. However, one major drawback is humidity cross-sensitivity which is a major component of exhaled breath. Thus, sensor reliability and reproducibility for real samples analysis is of major concern. Humidity compensation is proposed as an effective solution, enhancing the diagnostic ability of the sensor [42]. Remarkably, hybrid composites based on polymers seem particularly promising as well. One of the most commonly studied commercial e-Noses i.e., Cyanose 320, consists of 32 chemiresistors based on composites of carbon black conducting particles and different polymeric films [117; 118]. Cyanose 320 has been effectively used amongst others, for the  
Figure 6: Schematic representation of a MCNPs-based chemiresistor, programmed according to the VOCs identified as inflammatory bowel and irritable bowel syndrome disease biomarkers. The sensor was exposed to simulated, HC and patient breath samples.