A new methodology for sub-femtomolar detection of organic molecules through the combination of surface-enhanced Raman...

A specific device that combines (1) surface-enhanced Raman spectroscopy (SERS) and (2) superhydrophobic surfaces is developed to detect traces of analytes diluted at sub-femtomolar concentration in water solutions. The first step of the analysis consists in the evaporation of a drop of the solution on the device, designed to concentrate all the analytes on a central functionalized small area (80 µm diameter). This analytical zone is covered with Ag nanoparticles dedicated to enhance Raman signals. In a second step, this zone is scanned pixel by pixel to accumulate around 2200 Raman spectra. The third step is an algorithmic analysis of the pile of spectra to identify Raman peaks that are specific to the targeted molecules. We detail an original analysis method that allows (1) to select spectra that are significantly different from those obtained when a pure solvent is evaporated (control experiment), (2) to classify the spectra by a criterion of similarity and, finally, (3) to select the SERS spectra of the analytes. This method uses hierarchical correlation clustering techniques, the originality being to classify the different spectra on the basis of their peak positions, with all peaks being normalized at the same intensity and bandwidth. The method leads to a convincing identification of spectra of the targeted molecules (i.e. rhodamine B), down to atto-molar concentrations.