Detecting target analytes with high specificity and sensitivity in any fluid is of fundamental importance to analytical science and technology. Surface-enhanced Raman scattering (SERS) has proven to be capable of detecting single molecules with high specificity, but achieving single-molecule sensitivity in any highly diluted solutions remains a challenge. Here we demonstrate a universal platform that allows for the enrichment and delivery of analytes into the SERSsensitive sites in both aqueous and nonaqueous fluids, and its subsequent quantitative detection of Rhodamine 6G (R6G) down to ∼75 fM level (10 −15 mol·L −1 ). Our platform, termed slippery liquidinfused porous surface-enhanced Raman scattering (SLIPSERS), is based on a slippery, omniphobic substrate that enables the complete concentration of analytes and SERS substrates (e.g., Au nanoparticles) within an evaporating liquid droplet. Combining our SLIPSERS platform with a SERS mapping technique, we have systematically quantified the probability, p(c), of detecting R6G molecules at concentrations c ranging from 750 fM (p > 90%) down to 75 aM (10 −18 mol·L −1 ) levels (p ≤ 1.4%). The ability to detect analytes down to attomolar level is the lowest limit of detection for any SERS-based detection reported thus far. We have shown that analytes present in liquid, solid, or air phases can be extracted using a suitable liquid solvent and subsequently detected through SLIPSERS. Based on this platform, we have further demonstrated ultrasensitive detection of chemical and biological molecules as well as environmental contaminants within a broad range of common fluids for potential applications related to analytical chemistry, molecular diagnostics, environmental monitoring, and national security.spectroscopy | sensing | SERS | slippery surfaces | nanoparticles

A hydrophilic directional slippery rough surface outperforms conventional liquid-repellent surfaces in water harvesting.