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Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for direct detection of
chemical and biological analytes because of high sensitivity, selectivity, and rapid response. Here we propose and
develop a novel optofluidic SERS structure, i.e., nanoparticle-functionalized flow-through multihole capillary. This
unique platform provides many advantages. First, its 3-dimensional (3-D) structure, similar to nanoporous aluminum
membranes, nanoporous polymer monoliths, and photonic crystal fibers (PCFs), provides large surface area for the
deposition of noble nanoparticles or nanoclusters to achieve high SERS intensity. Second, it has well-defined flow-through
channels. It provides robust and controllable nanoparticle immobilization like PCFs, but much higher
nanoparticle density thus large SERS-active sites due to large surface within the detection volume, and also enables fast
and convenient analyte delivery for real-time, online detection. Third, the well-defined multihole capillary can also
confine and transmit light along the longitudinal direction, accumulating large SERS signal like PCFs. Fourth, it is easy
to integrate with other sensing platforms, such as label-free biosensors, to provide comprehensive information on
molecular interaction. Moreover, the multihole capillary can be mass-produced easily and cost effectively using the fiber
drawing method. In this report, using a capillary consisting of thousands of micrometer-sized holes adsorbed with gold
nanoparticles, we investigated the proposed optofluidic SERS system using the transverse and longitudinal detection
methods, where the SERS excitation and collection were perpendicular to and along the capillary, respectively. A
detection limit better than 100 fM for rhodamine 6G was achieved with an enhancement factor exceeding 108.
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