Controllable nanopore SERS platform for single-molecule level biosensing

Abstract

Surface-enhanced Raman spectroscopy (SERS) is a significant analytical technique based on the interaction between light, nanostructures, and molecules. Its enhancement efficiency relies on the “hot spots” generated by the synergistic action of localized electromagnetic fields and charge transfer at the SERS substrate surface. However, due to the uneven enhancement characteristics and distribution of these hot spots, only a limited number of target molecules can be effectively enhanced. The “confined space effect” of the nanopore structure further enhances the localization accuracy of hotspots and increases molecular enrichment in hotspot regions, thereby providing new opportunities for single-molecule (SM) analysis. First, this review outlines the development of SERS technology and summarizes the research directions since the turn of the century. It then discusses the enhancement mechanisms of SERS and the key factors influencing the hotspots in nanopore-based SERS. From the perspectives of material systems and pore morphology, this article focuses on two types of SERS substrates: porous pure metals and porous metal-nonmetal composites. It systematically explores the preparation strategies and performance of porous SERS platforms from the viewpoint of two types of pore structures: random disorder and regular order. Furthermore, the paper analyzes the significant progress of nanopore structures in SM SERS-based quantitative analysis. The review also covers the application of porous SERS platforms in healthcare, particularly in sensing research related to prevention, screening, and prognosis, including areas such as health prevention detection, gas molecule detection, liquid biopsy, and tumor imaging and therapy. Finally, based on current research, the review presents key insights on nanopore SERS substrates.