# Enhancing Disease Diagnosis: Biomedical Applications of Surface-Enhanced Raman Scattering
## 5 Applications of SERS in Disease Diagnostics
### Microbial Infections-Pathogen Detection
Apparently the short time at which AMR was detected in this study [17] may help to prevent or cure opportunistic infections during surgeries and organ transplants, and to avoid the use of broad spectrum antibiotics which contribute to increase in AMR. In the coming years, in situ SERS needs validation through multicentral tests for AMR in a large cohort of clinical isolates and antibiotics using standardised protocols. Also, the Raman vibrational modes for heavy water (D\({}_{2}\)O) are well established [124], and several authors have probed the general metabolic activity of microbial community members capable of degrading environmental contaminants [124; 125]. Similarly, D\({}_{2}\)O can be incorporated to AMR studies to probe the metabolic activity of sensitive and resistant microbes for in-depth assessment and elucidation of bactericidal and bacteriostatic effects of common and novel antibiotics. Since SERS spectral data provides information on the structural properties of biomolecules, probing cells with D\({}_{2}\)O in a time course fashion may identify novel (multi)-resistant prokaryotes, offer kinetics and mechanistic insights into AMR and treatment prognosis. In addition, it may reveal valuable biochemical changes in pathogens due to the regulation of drug metabolism to guide the next generation therapeutics. The label-free SERS approach can also be complemented by label-based SERS to allow high-level multiplexed analysis of pathogens in patient samples. Renishaw Diagnostics recently developed a cutting edge robust SERS-based multiplex tool called Fungiplex assay [126]. This is perhaps the greatest milestone in recent years which has pushed SERS toward routine clinical use. In its trial phase, a Fungiplex assay reproducibly detected and identified blood-derived DNA for 12 _Candida_ and _Aspergillus_ pathogens ex vivo in a single run. Following this, several researchers have launched ultrasensitive assays of clinical quality for the isolation and quantitative detection of antibiotic resistant bacteria at 10 cfu/mL [73], DNA of meningitis-associated pathogens at \(\sim\)21 pM [31], viruses at 10 pg/mL in serum [127] and deadly Ebola virus in blood [128], in 3-plexed analysis, to confirm the potential of SERS to meet workflow demands for real-time PoC diagnostics. When coupled to rapidly emerging novel devices--lab-on-a-chip [129; 130], microbial- and nano-barcoding [131; 132]--SERS has better stability, ruggedness and analytical performance. This makes SERS undoubtedly exploitable for  
Figure 3: **(I)** In situ SERS spectral profiles of sensitive wild type _E. coli_ K-12 TOP-10 and K-12 DSM. Strains (\(n=116\)) treated with **(a)** Polymorphism B and **(b)** Ampicillin, harvested at different time points. By visual inspection, the intensity of SERS bands decreased while new bands appeared with increasing time in both cases. **(II)** SERS images showing increasing concentrations of dead _E. coli_ cells, A. 0%, B. 5%, C. 25%, D. 50%, E. 75% and F. 100%, quantified by 735 cm\({}^{-1}\) band, clearly indicating that no SERS signals were detected on dead cells. Colour code: Blue = live cell and white = dead cell. Reprinted with permission from [PERSON] et al. [17]. Copyright © 2017, American Chemical Society. in-field investigations of multiple conflicting coinfections in vivo, especially in remote areas which are highly susceptible to outbreaks of communicable diseases [128].