Mirrorlike Plasmonic Capsules for Online Microfluidic Raman Analysis of Drug in Human Saliva and Urine

Plasmonic capsules are emerging for novel applications in biochemical sensing, tunable optics, targeted delivery, etc. Here, we develop an online mirrorlike plasmonic capsule microfluidic (PCM) system through citrate-capped Au nanoparticle (GNP) arrays on three-dimensional (3D) oil/water (O/W) two- liquid interface without any inducers or promoters. The PCM-based surfaceenhanced Raman scattering (PCM-SERS) system realizes multisample, multiplex, and high-throughput analysis of targeted molecules in complex media by a portable Raman device. Excellent O-in-W features of the GNP capsules ensure less surface contamination of the inner channel and avoid cross-contamination between different capsules. Sequential detection of five analytes in different capsules is easily achieved in about 1 min, and both dual-analyte and triple-analyte detection in a single capsule demonstrate the excellent sensitivity even with analyte concentrations differing by 2 orders of magnitude. The uniform distribution of GNPs at the two-liquid interface leads to excellent reproducibility of SERS signals. In addition, the O phase of the capsule filling produces fingerprint vibrations in SERS signals and is used as the inherent internal standard (IIS) to improve the quantitation of SERS detection. The O phase also as a good extraction agent realizes efficient separation and enrichment of an illicit drug, methamphetamine (MA), in human saliva and urine. By virtue of principal component analysis (PCA), the PCM-SERS platform easily realizes autoclassification of trace MA, with concentrations down to ppm levels. This study promises great potentials of plasmonic capsules for in situ monitoring molecular events in confined spaces, especially in multiliquid systems.