Nanostructuring of patterned microelectrodes to enhance the sensitivity of electrochemical nucleic acids detection.

Disease diagnosis on the basis of biomolecular analysis requires sensitive, cost-effective, and multiplexed assays. Biomarker analysis based on electronic readout has long been cited as a promising approach that would enable the creation of a new family of chip-based devices with appropriate cost and sensitivity for medical testing. The sensitivity of electronic readout, and specifically electrochemical analysis, is in principle sufficient to enable direct detection of small numbers of analyte molecules with simple instrumentation. Over the last several years, very high sensitivities have been demonstrated for nanomaterial-based electrochemical assays in particular, whereby nanowireand nanotube-based electrodes have shown some of the highest sensitivities to date. Whether these assays can be made practical and multiplexed remains to be seen, however, as the materials used have not been readily amenable to arrayed and straightforward fabrication. Herein, we present a new system that enables nanostructured materials to be produced and used as nucleic acids sensors in an arrayed format. By using lithographically defined apertures as a template, we grew microelectrodes on a silicon chip by metal electrodeposition (Figure 1). Drawing upon the numerous studies of nanostructures with diverse morphologies generated as dispersions in solution, we sought to manipulate precisely the surface morphology of these electrodes to control the level of nanostructuring present. We show that the production of nanostructured features on electrode surfaces is essential for the performance of the microelectrodes as ultrasensitive electrochemical detectors. A variety of studies have suggested that nanostructures are highly beneficial for biosensing applications because of the increased surface area, enhanced delivery of amplification agents, or precise biomolecule–electrode connections that are possible; however, the role of nano-