SEEDING to enable sensitive electrochemical detection of biomarkers in undiluted biological samples

The interface between an electrode and a liquid plays a critical role in the overall performance of electrochemical biosensors. Surface morphology and roughness affect key parameters, such as the active area, diffusion profiles, and apparent electron transfer kinetics, whereas porosity may hinder the diffusion of fouling proteins. However, there is no simple and rapid method compatible with photolithographic electrodes to generate both nanostructured and porous surfaces. Herein, we demonstrate the interplay between the preferential etching of chloride and surfactant-assisted anisotropic gold reduction to create homogeneous, nanostructured, and nanoporous substrates on photolithographic gold electrodes within a minute and without using templates. We coined this process, SEEDING, that is, Surfactant-based Electrochemical Etch-Deposit Interplay for Nanostructure/Nanopore Growth. SEEDING on electrodes enhanced the sensitivity and anti-biofouling capabilities, enabling direct analysis of small molecules, proteins, and cancer-derived extracellular vesicles in complex biological fluids such as undiluted plasma and urine samples.