To put disease-related biomarkers to work in the clinic, new high-performance technologies are needed to enable rapid and sensitive analysis of clinical specimens. Electrochemical methods providing low cost and direct biomarker readout have attracted a great deal of attention for this application. We exploit controlled nanostructuring of electrode surfaces to enhance biomolecular capture rates and efficiencies to solve this long-standing problem, and showed that the nanoscale morphologies of electrode surfaces control their sensitivities. An electrocatalytic reporter system that leverages a pair of redox reagents is used to readout the presence of specific nucleic acids and other analytes bound to electrode surfaces. Recently, we have developed assays that are able to detect nucleic acids, proteins and small molecules, with universally high sensitivity levels. This presentation will highlight how electrodeposited metals can be used to create high performance sensors that can be applied to the analysis of circulating tumor DNA (Das et al, JACS (2016)) and RNA (Das et al, Nature Chemistry (2015) for the realization of liquid biopsy as an alternative to invasive methods.