SERS-based methods for the detection of genomic biomarkers of cancer

Genomic biomarkers of cancer are based on changes in nucleic acids, which include abnormal expression levels of some miRNAs, point mutations in DNA sequences, and altered levels of DNA methylation. The presence of tumor-related nucleic acids in body fluids (blood, saliva, or urine) makes it possible to achieve a non-invasive early-stage cancer diagnosis. Currently existing techniques for the discovery of nucleic acids require complex, time-consuming, costly assays and have limited multiplexing abilities. Surface-enhanced Raman spectroscopy (SERS) is a vibrational spectroscopy technique that is able to provide molecular specificity combined with trace sensitivity. SERS has gained research attention as a tool for the detection of nucleic acids because of its promising potential: label-free SERS can decrease the complexity of assays currently used with fluorescence-based detection due to the absence of the label, while labeled SERS may outperform the gold standard in terms of the multiplexing ability. The first papers about SERS-based methods for the measurement of genomic biomarkers were written in 2008, and since then, more than 150 papers have been published. The aim of this paper is to review and evaluate the proposed SERS-based methods in terms of their level of development and their potential for liquid biopsy application, as well as to contribute to their further evolution by attracting research attention to the field. This goal will be reached by grouping, on the basis of their experimental protocol, all the published manuscripts on the topic and evaluating each group in terms of its limit of detection and applicability to real body fluids. Thus, the methods are classified according to their working principles into five main groups, including capture-based, displacement-based, sandwich-based, enzyme-assisted, and specialized protocols.