Self-Concentrated Surface-Enhanced Raman Scattering-Active Droplet Sensor with Three-Dimensional Hot Spots for Highly Sensitive Molecular Detection in Complex Liquid Environments

In this work, a surface-enhanced Raman scattering (SERS)-active droplet with three-dimensional (3D) hot spots prepared from a superhydrophobic SERS substrate, which is inspired by the nut wizard strategy, was developed for ultrasensitive detection in complex liquid environments. The SERS substrate was composed of silver-capped parylene C-coated carbon nanoparticles (Ag-PC@CNPs). Such a SERS substrate was prepared by candle-soot deposition to provide a porous carbon nanoparticle layer followed by deposition of a parylene C film to protect the CNPs and then sputtering of silver nanoparticles. Similar to a nut wizard, a droplet rolling on the Ag-PC@CNP-coated substrate picked up the Ag-PC@CNPs. In this way, a self-concentrated and extremely sensitive SERS-active droplet sensor with 3D hot spots was formed. The sensor did not require precise laser focusing and showed relatively high repeatability and much higher sensitivity than those of a corresponding SERS substrate with two-dimensional hot spots. The sensor also achieved high sensitivity and specificity in complex liquid environments; in addition, bovine serum albumin with a concentration as low as 1 pM can be achieved. Consequently, an extremely simple, flexible, and highly sensitive SERS detection technique applicable to liquid biopsy analysis is anticipated.