Limit-Defying μ-Total Analysis System: Achieving Part-Per-Quadrillion Sensitivity on a Hierarchical Optofluidic SERS Sensor

[Image: see text] Optofluidic sensors have accelerated the growth of smart sensor platforms with improved sensitivity, reliability, and innovation. In this article, we report the integration of a surface-enhanced Raman scattering (SERS) material consisting of silver nanoparticle-decorated diatomaceous earth (AgNPs–DE) with a flow-through microfluidic device, building up a hierarchical structured micro-total analysis system (μ-TAS) capable of achieving part-per-quadrillion (ppq)-level sensitivity. By the synergic integration of millimeter-scale microfluidic devices and porous laboratory filter paper with a micrometer-sized crosslinked cellulosic network that carries SERS-active AgNPs–DE, which possesses submicron to nanometer regimes of photonic crystals and plasmonic nanostructures, we achieved enhanced mass-transfer efficiency and unprecedented detection sensitivity. In our experiment, fentanyl as the testing analyte at different concentrations was measured using a portable Raman spectrometer. The limit of detection (LOD) was estimated to be 10 ppq from a small detection volume of 10 mL with an ultrafast time of sensing (TOS) of 3 min. To attain comparable signals, the traditional soaking method took more than 90 min to detect 10 part-per-trillion fentanyl from a 10 mL sample. Compared with existing SERS sensing results of fentanyl, the limit-defying μ-TAS reduced the LOD-TOS product by almost 4 orders of magnitude, which represents a new stage of ultrafast sensing of extremely low concentration analytes.