In this paper, we present the development of a highly sensitive, specific and reproducible nanobiosensor to detect one specific liver cancer biomarker, the manganese super oxide dismutase (MnSOD). The high sensitivity and reproducibility was reached by using SERS on gold nanostructures (nanocylinders and coupled nanorods) produced by electron-beam lithography (EBL). The specificity of the detection was provided by the use of a specific aptamer with high affinity to the targeted protein as a recognition element. With such a sensor, we have been able to observe the SERS signal of the MnSOD at concentrations down to the nM level and to show with negative control that this detection is specific due to the use of the aptamer. This latter issue has allowed us to detect the MnSOD in different body fluids (serum and saliva) at concentrations in the nM range. We have then demonstrated the effectiveness of our SERS nanobiosensor using aptamer as a bioreceptor for the detection of disease biomarker at low concentration and in complex fluids.

A billion-fold increase in the Raman signal over conventional tip-enhanced Raman spectroscopy/microscopy (TERS) is reported. It is achieved by introducing a stimulating beam confocal with the pump beam into a conventional TERS setup. A stimulated TERS spectrum, closely corresponding to its spontaneous TERS counterpart, is obtained by plotting the signal intensity of the strongest Raman peak of an azobenzene thiol self-assembled monolayer versus the stimulating laser frequency. The stimulated TERS image of azobenzene thiol molecules grafted onto Au ⟨111⟩ clearly shows the surface distribution of the molecules, whereas, when compared to the simultaneously recorded surface topography, it presents an image contrast of different nature. The experimentally obtained stimulated gain is estimated at 1.0 × 10(9), which is in reasonable agreement with the theoretically predicted value. In addition to the signal increase, the signal-to-noise ratio was 3 orders of magnitude higher than in conventional spontaneous TERS. The proposed stimulated TERS technique offers the possibility for a substantially faster imaging of the surface with respect to normal TERS.