Long-lived SERS Matrix for Real-Time Biochemical Detection Using "Frozen" Transition State

For the long-time tracking of biological events, maintaining the bioactivity of the analytes during the detection process is essential. Here, we show a versatile surface-enhanced Raman Scattering (SERS) platform, termed a superwettable-omniphobic lubricous porous SERS (SOLP-SERS) substrate. The SOLP-SERS substrate could generate a three-dimensional liquid "hotspots" matrix with an ultra-long lifetime (tens of days) by confining tiny amounts of liquids within the gaps between nanoparticles. Then, the analytes are trapped in the uniform liquid "hotspots", whose bioactivity can be well maintained over a long period of time during SERS detection. Limits of detection down to femtomolar levels were achieved for various molecules. More importantly, SERS signals were uniform within the substrate and remained stable for more than 30 days. As a proof-of-concept experiment, the dynamic detection of the polymerization of Aβ peptides into amyloids was monitored by the SOLP-SERS substrate within 48 h. Moreover, the exosomes secreted by breast cancer cells, an important biomarker of cancer, were also measured. These results demonstrate that the SOLP-SERS platform will provide new insights into the development of real-time biochemical sensors with ultrahigh sensitivity.