Advances in Functional Nucleic Acid SERS Sensing Strategies

Functional nucleic acids constitute a distinct category of nucleic acids that diverge from conventional nucleic acid amplification methodologies. They are capable of forming intricate hybrid structures through Hoogsteen and reverse Hoogsteen hydrogen bonding interactions between double-stranded and single-stranded DNA, thereby broadening the spectrum of DNA interactions. In recent years, functional DNA/RNA-based surface-enhanced Raman spectroscopy (SERS) has emerged as a potent platform capable of ultrasensitive and multiplexed detection of a variety of analytes of interest. This review aims to elucidate the operational principles of several functional nucleic acids in SERS detection, including DNAzymes, G-quadruplexes, aptamers, CRISPR, origami etc., alongside the design methodologies and practical applications of functional DNA/RNA-based SERS sensing. Initially, an overview is summarized encompassing the structural attributes and SERS sensing mechanisms inherent to diverse functional DNA/RNA. Following this, various innovative strategies for constructing functional nucleic acid-based SERS sensors are illustrated in detail, aimed at improving the present detection capabilities. A comprehensive summing up is then conducted on the applications of these sensors in crucial fields, such as disease diagnosis, environmental monitoring, and food safety detection, with a particular focus on SERS sensitivity, specificity, and analytical versatility. Finally, conclusive remarks are offered along with an exploration of the existing challenges and prospective avenues for future research in this developed field.