Application of SERS-based nanobiosensors to metabolite biomarkers of CKD

A clinical diagnosis of chronic kidney disease (CKD) is commonly achieved by estimating the serum levels of urea and creatinine (CR). Given the limitations of the conventional diagnostic assays, it is imperative to seek alternative, economical strategies for the detection of CKD-specific biomarkers with high specificity and selectivity. In this respect, surface-enhanced Raman spectroscopy (SERS) can be regarded as an ideal choice. SERS signals can be greatly amplified by noble metal nanoparticles (e.g., gold nanoparticles (GNPs)) of numerous sizes, shapes, and configurations to help achieve ultra-sensitive single molecule-level detection at 10^-15 M (up to 10 orders of magnitude more sensitive than fluorescence-based detection). The irregular geometry of GNPs with spike-like tips, dimers, and aggregates with small nanogaps (i.e., due to plasmon coupling such as Raman hot spots) play a pivotal role in enhancing the specificity and sensitivity of SERS. This review critically outlines the performance of SERS-based biosensors in the ultrasensitive detection of CKD biomarkers in various body fluids in terms of basic quality assurance parameters (e.g., limit of detection, figure of merit, enhancement factor, and stability of the biosensor). Moreover, the challenges and perspectives are described with respect to the expansion of such sensing techniques in practical clinical settings.