SERS Spectra of Oligonucleotides as Fingerprints to Detect Label-Free RNA in Microfluidic Devices

Probing specific RNA sequences is an issue of major significance for which fluorescence dominates most of the investigation strategies and relies heavily on the use of specific labels. In this paper, we report the detection by SERS (Surface-Enhanced Raman Scattering) of unlabeled model purified oligonucleotides RNA poly-adenosine (5�??-AAAAAAAAAA-3�??) and poly-cytosine (5�??-CCCCCCCCCC-3�??) combining silver nanoparticles as enhancing surfaces with microfluidic platforms to control species movement and the aggregation state of the nanoparticles, which is critical for the sensitivity. Two types of microfluidic platforms have been evaluated and compared: one based on laminar streams and the other involving flowing droplets acting as chemical reactors. Both platforms provide homogeneous and controlled mixing conditions of nanoparticles with oligonucleotides: laminar streams induce mixing driven by diffusion whereas droplets permit fast and efficient mixing through internal fluid recirculation, and prevent channel clogging by nanoparticles. We demonstrate that in both cases, the bases can be de-tected selectively. In the droplet microfluidic system, the Raman maximum enhancement is localized in the center of the droplet and observed after a certain period of mixing time that appears specific for each base, after droplet formation. It appears to be a highly promising approach for probing unlabeled nucleotides using SERS.

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