The design and application of liquid interfacial plasmonic platform is still in its infancy but is an exciting topic in tunable optical devices, sensors, and catalysis. Here, we developed an interfacial surface-enhanced Raman scattering (SERS) platform through the large-scale self-assembly of gold nanoparticle (GNP) arrays at the cyclohexane (CYH)/water interface for detecting trace drug molecules in the urine of humans. The molecules extracted by the CYH phase from a urine sample were directly localized into the self-organized plasmonic hotspots, yielded excellent Raman enhancement, and realized the substrate-free interfacial SERS detection. Synchrotron radiation small-angle X-ray scattering (SR-SAXS) experiments reveals a good uniformity of approximately 2-3 nm interparticle distance in the GNP arrays. SERS colocalization experiments demonstrated that amphetamine molecules of different concentration levels could be loaded into the interfacial GNP arrays and realized the coassembly together with nanoparticles at the liquid/liquid interface. Interfacial GNP arrays with dynamic nanogaps in liquid interfacial structure can make surrounding molecules easily diffuse into the nanogaps. In contrast, the fixed GNP arrays on Si wafer were more irregular, such as multilayer stack, random aggregates, and voids, during the drying process. When the drugs directly participate in the self-assembly process, it becomes easier for analytes diffusing into the nanogaps of GNP arrays, produces a concentration effect, and amplified the SERS sensitivity. This feature also enables molecules to be adsorbed evenly in the arrays and makes a more uniform distribution of both the analytes and GNPs in the liquid interface and realizes the significant increase in signal reproducibility. Interfacial SERS produced a standard deviation of 12.5% at 1001 cm(-1) peak of methamphetamine (MAMP) molecules under the concentration of 1 ppm, implying a good reproducibility. Moreover, dual-analyte detection at organic and aqueous phases was also realized and confirmed a good capability for analytes detection by liquid interfacial SERS platform, which promises nonengineering detection of analytes dissolved in often-inaccessible environments.

A portable kit was demonstrated for rapid and reliable surface-enhanced Raman scattering (SERS) detection of drugs in human urine. This kit contains two sealed reagent tubes, a packet of standardized SERS substrates, and a mini Raman device. A 3 min pretreatment for separating amphetamines from human urine was developed with an extraction rate of >80% examined by ultraperformance liquid chromatography (UPLC). Simultaneously, highly reproducible two-dimensional (2D) gold nanorod (GNR) arrays were assembled by the use of methoxymercaptopoly(ethylene glycol) (mPEG-SH) capping. Thirty batches of GNR arrays produced the 1001 cm(-1) intensity of methamphetamine (MA) molecules with a relative standard deviation (RSD) of 7.9%, and a 21 × 21 μm(2) area mapping on a 2D GNR array produced a statistical RSD of <10%, implying an excellent reproducibility and uniformity. The detection limit of amphetamines in human urine was at least 0.1 ppm. Moreover, the portable kit was successfully used for detecting MA, 3,4-methylenedioxymethamphetamine (MDMA), and methcathinone (MC) in 30 volunteers' urine samples with various clinical natures, and the dual-analyte detection of MA and MDMA implied a good capability of multiplex analysis. UPLC examination and the SERS recovery test clearly indicated that our pretreatment procedure was sufficient to lower the high background signals caused by complex components in urine and demonstrated the practicability and the resistance to false positives, which is a vital problem for law enforcement applications. The excellent performance of our portable kit promises a great prospective toward a rapid, reliable, and on-spot analyzer, especially for public safety and healthcare.