LESS is more: Achieving sensitive protein detection by combining electric field effects and surface-enhanced Raman scattering

Abstract

We present a novel and effective sensing method that combines surface-enhanced Raman scattering (SERS) with electric fields for achieving sensitive and label-free detection of proteins in physiologically relevant media. Using as an example the detection and quantification of human serum albumin (HSA) and creatinine in artificial urine, we combine experiments and simulations to demonstrate how properly applied electric field effects facilitate accelerated transport and deterministic capture of proteins and silver nanoparticles onto the SERS-active substrate. Our experimental approach yields a sandwich assay that amplifies protein concentration and creates higher surface density of hotspots on SERS-active substrates. We call our method “LESS” for brevity, an acronym that captures its key attributes: Label-free, Electric field-assisted, Sandwich-based, and Surface-enhanced Raman scattering. LESS was compared with a standard SERS assay and was shown to produce over 10-fold signal enhancement. Moreover, it offers protein detection and identification even in cases where the standard SERS assay produces no results. Reproducible SERS signals and detection thresholds well below the physiological levels of these proteins in urine were achieved. When combined with chemometric analysis, LESS allows us to extract diagnostic information by classifying SERS spectra acquired from solutions of the individual proteins or their mixtures.