# Enhancing Disease Diagnosis: Biomedical Applications of Surface-Enhanced Raman Scattering
## 5 Applications of SERS in Disease Diagnostics
### Microbial Infections-Pathogen Detection  
Microbes are found everywhere in large quantities and complex consortia where they perform specialised functions that play a vital role in ecosystems on which humans depend--quite often within the superorganism host [103]. However, it is well known that a small proportion of microbes such as bacteria, fungi and protozoa are responsible for foodborne, waterborne and tuberculosis which contribute to high mortality and morbidity rates globally [104]. Although local and international guidelines for combatting diseases are available, microbial infections are still unacceptably high worldwide with a significant burden borne by the developing world. Just recently perhaps the largest outbreak of listeriosis, a foodborne infection contracted through consumption of food contaminated with _Listeria monocytogenes_ bacterium, which occurred in South Africa [105]. The number of affected confirmed laboratory cases was estimated at 674 with 183 deaths recorded. On the other hand, waterborne infections are reported to be associated with gastroenteritis cases that claim 2 million deaths per year globally, and the number of deaths is likely to increase every hour that therapeutic treatment is delayed [106]. At the time of writing this review, it was reported that at least 54% of chicken meat sold in Germany supermarkets and 79% of those in slaughter houses were contaminated with _Campylobacter_ spp. pathogens [107]. Due to the dramatic increase in incidence rates driven by quick transmission, spread and antimicrobial resistance (AMR) of acute infections, there is an urgent demand for rapid and ultrasensitive tools to characterise pathogens to protect public health and to prevent potential bioterrorism. Furthermore, unequivocal identification and differentiation of pathogens, especially at the PoC, will certainly offer an opportunity to trace the origin of fatal sporadic infections in order to design effective immediate and long-term corrective action. Until very recently, routine microbial diagnostics were dominated by traditional platforms based on culturing, biochemical tests and colony counting [108]. However, these methods are inherently time-consuming, laborious and centralised (i.e., tests are done in dedicated laboratories rather than on site), as well as sometimes being inapplicable depending on pathogenic species under investigation. For example, bacteria such as _Mycobacterium tuberculosis_ may take several days to weeks to form visible colonies, while selective _Campylobacter_ spp. are biochemically unreactive [109; 110]. Alternatively, immunoassay and molecular tools based on ELISA and PCR have shown much improved rapidity and applicability [111; 112]. These techniques have better detection limits, offer accurate phylogenetic identity and classification and allow for simultaneous detection of multiple pathogens provided several antibodies or primers are employed. Although ELISA and PCR have found extensive use in clinical diagnostics they are costly, labour-intensive, require trained personnel and have long turnaround times necessitated by pretreatment and enrichment steps. PCR in particular is prone false positive tests due to cross contamination from the environment and during sample collection, omits phenotypic characteristics of pathogens and fails to differentiate viable from nonviable infectious pathogens since the genetic material is always present in live or dead microbial cells. Moreover, the analytical merit of PCR based on exponential amplification of genetic materials can be a devastating disadvantage in case of sample contamination [108]. To bridge the gap, intrinsically robust SERS protocols with little or no sample preparation could be applied widely for reliable and noninvasive biosensing of microbial infections. The objective of using SERS is to obtain unique \"whole-organism\" metabolic fingerprints to discern intrinsic biochemical content and dynamics of microbial cells.