We report an improved electrochemistry-based sequence-specific detection technique by modifying the electrode surface using polyelectrolytes or utilizing the electrode whose surface exhibits the lowest background signal. The objective of the present work is to develop DNA-detection platforms that offer high sensitivity and selectivity in transducing the hybridization event and are compatible with the microfabrication process. Gold nanoparticle labels, coupled with signal amplification by the silver-enhancement technique, would be a suitable choice of detection scheme. However, common electrodes used in microfabrication, such as gold, are susceptible to silver depositions, making the extraction of the analytical signal (silver on a gold nanoparticle) from the background signal (silver on a gold substrate) impossible. In this study, the background silver deposition on the gold electrode is significantly reduced by modifying its surface with polyelectrolyte multilayer films of poly(allylamine hydrochloride) and poly(styrenesulfonate). Moreover, indium tin oxide (ITO), a conductive material that is compatible with microfabrication, is found to exhibit low silver-enhancing properties. With the low background signal achieved by electrode-surface modification and selection, sensitive (high signal-to-noise ratio) electrochemical detection of the hybridization event using the silver-enhanced gold nanoparticle approach is demonstrated. The gold and ITO-detection platforms described here are readily applicable to miniaturized bioanalytical microdevices for integrated and point-of-care viral and bacterial infections diagnostics.