# Enhancing Disease Diagnosis: Biomedical Applications of Surface-Enhanced Raman Scattering
## 5 Applications of SERS in Disease Diagnostics  
### Cancer  
Cancer is a major public health concern and an economic burden globally. Recent research indicates that 17.5 million cancer cases were recorded worldwide in 2015, culminating in 8.7 million deaths [78]. Unfortunately the number of cancer cases increased sharply after two years in 2018 making cancer the second most common cause of death worldwide [79]. Cancer is a collective term used to describe malignancies characterised by rapid abnormal growth of cells which invade other parts of the body. At the onset of cancer, specific biochemical molecules (e.g., proteins) are elevated or decreased in cancer patients and such dynamics serve as biomarkers for various types of cancers [80]. The early diagnosis of cancer, especially before metastasis, correlates well with the effectiveness of therapy, improved patient survival rates and prognosis. To this end, significant effort has been devoted towards the development of molecular biosensing platforms in recent years to meet the ever-demanding diagnostics of cancers in human cells, tissues and biofluids. Among these, immunoassay exhibit considerably high sensitivity and so they are commonly used as noninvasive strategies to measure biomarkers based on antibody-antigen interactions at different stages of cancer development [81]. The early work to highlight the diagnostic potential of immunoassays used radioisotopes to label antigens and antibodies to trace dynamics in target markers and metabolism indicative of cancers [82]. Unsurprisingly, the use of radioisotope immunoassay (RIA) in clinics declined due to environmental health and safety hazards, in addition to costly specialised laboratory facilities and waste disposal routes for radioactive materials. Enzymes are now commonly used as reporters in the enzyme-linked immunosorbent assay (ELISA). ELISA is safer, simpler, rapid and the gold standard assay used for routine analysis of protein cancer biomarkers. Several authors have documented the utility of ELISA in cancer studies [83; 84]. For instance, [PERSON] et al. detected low levels of CA15-3 glycoprotein antigen mainly observed in patients with breast cancer using anti-CA15-3-horseradish peroxidase conjugate chemically bonded to an Au solid substrate [85]; whereas [PERSON] et al. investigated colorectal cancer by accurately measuring autoimmune responses of IgM and IgG antibodies in human serum [86]. Nonetheless, long analysis times and high cost of commercial ELISA test kit limit the application of ELISA. Alternatively, fluorescence-based portable biosensors are well developed and extensively applied as readout assays. In terms of quantum yield, fluorescence has a large absorption cross-section, thus fluorescent immunoassay (FIA) has excellent sensitivity which enables detection of cancer biomarkers at clinically desirable LODs [87; 88]. However, FIA has several drawbacks: difficulty with labelling recognition or target species, limited multiplexing due to frequent spectral overlap caused by broad emission bands, as well as photobleaching and nonspecific binding, especially at low analyte levels. SERS has vital advantages over traditional immunoassays used in clinical biochemistry: it exhibits multiplexing ability with a single excitation laser and ultrasensitivity leading to absolute quantitative detection [10] and, if optimized, correctly rivals gold standard assays. Recently, reproducible substrates based on antibody-conjugated hollow Au nanospheres and magnetic beads were applied for rapid sensing of carcinoembryonic antigen (CEA)--a biomarker of lung cancer [89]. In this study, the SERS assay detected low amount (1 pg/mL) of CEA accurately, which was 1000-fold more sensitive than ELISA. Since the amount of CEA is clinically determined to be about 10 ng/mL in malignant cases [80], SERS detected subinfectious regime suitable for monitoring and predicting inception of lung cancer to avoid increased risk of severe metastasis.