SERS immuno- and apta-assays in biosensing/bio-detection: Performance comparison, clinical applications, challenges

Surface Enhanced Raman Spectroscopy is increasingly used as a sensitive bioanalytical tool for detection of variety of analytes ranging from viruses and bacteria to cancer biomarkers and toxins, etc. This comprehensive review describes principles of operation and compares the performance of immunoassays and aptamer assays with Surface Enhanced Raman scattering (SERS) detection to each other and to some other bioassay methods, including ELISA and fluorescence assays. Both immuno- and aptamer-based assays are categorized into assay on solid substrates, assays with magnetic nanoparticles and assays in laminar flow or/and strip assays. The best performing and recent examples of assays in each category are described in the text and illustrated in the figures. The average performance, particularly, limit of detection (LOD) for each of those methods reflected in 9 tables of the manuscript and average LODs are calculated and compared. We found out that, on average, there is some advantage in terms of LOD for SERS immunoassays (0.5 pM median LOD of 88 papers) vs SERS aptamer-based assays (1.7 pM median LOD of 51 papers). We also tabulated and analyzed the clinical performance of SERS immune and aptamer assays, where selectivity, specificity, and accuracy are reported, we summarized the best examples. We also reviewed challenges to SERS bioassay performance and real-life application, including non-specific protein binding, nanoparticle aggregation, limited nanotag stability, sometimes, relatively long time to results, etc. The proposed solutions to those challenges are also discussed in the review. Overall, this review may be interesting not only to bioanalytical chemist, but to medical and life science researchers who are interested in improvement of bioanalyte detection and diagnostics.