Highly Sensitive and Reliable microRNA Detection with a Recyclable Microfluidic Device and an Easily Assembled SERS Substrate.

Surface-enhanced Raman spectroscopy (SERS) detection in microfluidics is an interesting topic because of its high sensitivity, miniaturization, and ability to perform online detection. However, the difficulties in generating SERS-based microfluidic devices with uniform signal reproducibility and high sensitivity have hindered their widespread application. In addition, the recyclability of the SERS-based microfluidic devices can contribute to their broad commercialization, but the possible contamination in the detection area and cumbersome cleaning procedures remain a challenge. In this study, we describe a repeatable SERS-based microfluidic device comprising a disposable SERS substrate and a reusable microfluidic channel. The microfluidic channel was prepared via mechanical processing, and the SERS substrate was fabricated by nanoimprint lithography and electrodeposition. The SERS substrate and microfluidic channel can be attached easily because they were assembled using screws. The SERS substrate achieved an excellent SERS enhancement factor greater than 10 over a large sample area, signal uniformity, and substrate-to-substrate reproducibility. This guaranteed reliable and sensitive signals in every experiment. Furthermore, the disposable SERS substrate contributed exact detection of target molecules. Finally, their practical application was demonstrated with the repeated use of the microfluidic device by detecting a specific micro-RNA, (miR-34a) at a concentration as low as 5 fM.