LAUSR

Electrochemical biosensors have shown great potential for simple, fast, and cost-effective point-of-care diagnostic tools. However, direct analysis of complex biological fluids such as plasma has been limited by the loss of sensitivity caused by biofouling. By increasing surface area, the nanostructured electrode can improve detection sensitivity. However, like a double-edged sword, a large surface area increases the non-specific adsorption of contaminating proteins. The use of nanoporous structures may prevent fouling proteins. However, there is no straightforward approach for creating nanostructured and nanoporous surfaces compatible with microfabricated thin-film electrodes. Herein, we demonstrate the preferential etching of chloride and surfactant-assisted anisotropic gold reduction to create homogeneous, nanostructured, and nanoporous gold electrodes, yielding 190 ± 20 times larger surface area within a minute without using templates. We named this process Surfactant-based Electrochemical Etch-Deposit Interplay for Nanostructure/Nanopore Growth (SEEDING). SEEDING on electrodes enhanced the sensitivity and anti-biofouling capabilities of amperometric biosensors, enabling direct analysis of tumor-derived extracellular vesicles (tEVs) in complex biofluids with a limit of detection of 300 tEVs/μL from undiluted plasma and good discrimination between patients with prostate cancer from healthy ones with an area under the curve (AUC) of 0.91 in urine and 0.90 in plasma samples. This article is protected by copyright. All rights reserved.