Statistical and Fourier Analysis for In-line Concentration Sensitivity in Single Molecule Dynamic-SERS

The Raman intensity fluctuations are the initial source of a lack of accuracy or reproducibility of SERS based nanosensors to reliably estimate the molecular concentration in microfluidics. Here, we show that the statistical analysis of the weighting of Raman scattering of the probed molecules compared to the photoluminescence of gold nanoparticles is particularly effective as a concentration indicator in a single molecule regime. We present a novel approach in the Fourier domain that is not limited by a multipoint precalibration or even the knowledge of the enhancement factor of the transducer. The analysis of pink noise in the frequency domain reveals a subdiffusion motion of individual adsorbed molecules in the hot-spot. The cutoff frequency between the white and pink noise is used to determine the in-line molecular concentration over a wide range between 10–11 and 10–6 M.