Engineering DNA-electrode connectivities: manipulation of linker length and structure Original Research Article

The development of electrical or electrochemical DNA-based biosensors requires the attachment of oligonucleotides to electrode surfaces through linkages with appropriate structural and electronic properties. Using a straightforward and versatile synthetic method, we prepared DNA molecules with a series of thiol-terminated linkers containing either ethane, hexane, or xylene spacers connected either to a terminal deoxyribose C5′ or thymine C5. The modified oligonucleotides self-assemble on gold electrodes and form densely-packed monolayers. The kinetics and extent of monolayer formation are sensitive to the rigidity of the tether, with the xylene-based linker slowing adsorption to the gold surface relative to the more flexible hexane-based linker. The monolayer formation is also less efficient for double-stranded versus single-stranded DNA. The redox-active intercalator methylene blue (MB) was used to study charge transport through the series of different DNA films. The heterogeneous electron-transfer kinetics are modulated by the structure of the DNA-electrode connection, with a linker attached directly to the 5-CH3 of thymine facilitating the most efficient charge transport through the film. These studies constitute the first systematic analysis of the effect of linker structure on DNA-electrode coupling, and provide important information for the development of new electrical DNA biosensors.