# Breath Analysis: A Promising Tool for Disease Diagnosis--The Role of Sensors
## 3 Types of Nanomaterial-Based Sensors in Breath Analysis
### Selective and Cross-Reactive Applications
#### 3.5.4 Surface Enhanced Raman Spectroscopy (SERS)-Based Sensors  
Another, more widespread optical-sensor application of the LSPR phenomenon in MNPs, is SERS [36], i.e., the enhancement of Raman signals due to the LSPR phenomenon. SERS is a vibrational spectroscopic technique [197] that permits single-molecule detection, and has been investigated among others for VOCs detection [198].  
Functionalization of different MNPs with appropriate molecules has been reported for selective VOC-detection. Aldehydes detection as LC biomarkers by SERS-based sensors seems promising [198,199]. Dendritic Ag nanocrystals coated with the aldehyde-selective probe molecule \(p\)-aminothiophen have achieved low LOD (ppb range) in the presence of confounding LC biomarkers (hydrocarbons, alcohols, ketones, esters, nitrogen, and aromatic compounds) [199]. NO, on the other hand, serves as a biomarker for asthma [36], hypertension, arteriosclerosis, diabetes, and rheumatoid arthritis [197]. NO detection has been achieved by \(o\)-Phenylenediamine-modified Au NPs which have permitted selective chemical reaction between functionality moieties and NO, leading to nano-probe SERS variations; such sensors have achieved a LOD of 1.7 \(\times\) 10\({}^{-7}\) M, in the presence of H\({}_{2}\)S and CO [197].  
As it can be observed, SERS-based sensors have been developed for the selective detection of a specific VOC or classes of VOCs, rather than cross-reactive detection. Notably, optical sensors are not preferred for e-Nose development, mainly due to their size and complex signal conditioning [40].  
On Table 2 representative examples for different types of sensor-arrays, using conventional materials or nanomaterials, are presented. Sensitivity, selectivity, and discriminant accuracy of the sensor arrays highlight their promising application as diagnostic tools. It can be observed that the incorporation of nanomaterials in the sensing element ameliorates the sensing performance (i.e., sensitivity, LOD), while appropriate modification permits the desired cross-selectivity. Sufficient LOD, similar to the usual concentration of VOCs in exhaled breath, is achieved by all sensor types. As far as MOS-based sensors are concerned, it is apparent that their main drawback towards all the other categories is their increased operating temperature. Chemiresistors are probably the most investigated gas sensor type for cross-reactive systems, incorporating different (nano)materials, being particularly attractive for the diagnosis of a wide range of diseases. Remarkably, most of the branded e-Noses that have been developed and tested for breath analysis applications, presented on Table 3, appertain to chemiresistors (AeoNose, Cyranose 320, SpiroNose, DiagNose, and Common Invent e-Nose). Another noteworthy information presented on Table 2 is the variety of data analysis and machine learning techniques used among the different studies, in the absence of which the discrimination of subjects would be infeasible.