Patterned DNA Metallization by Sequence-Specific Localization of a Reducing Agent Kinneret Keren, † Rotem S. Berman, † and Erez Braun* ,†,‡ Department of Physics, Solid State Institute, Technion- Israel Institute of Technology, Haifa 32000, Israel Received December 4, 2003 ABSTRACT Localization of a reducing agent, glutaraldehyde, on DNA molecules directs their metallization into highly conductive wires. DNA can be marked for metallization by aldehyde derivatization while retaining its biological functionality. Patterning the aldehyde derivatization of the DNA molecules in a sequence-specific manner allows to embed the precise metallization pattern into the DNA scaffold without compromising its recognition capabilities or biological functionality. We demonstrate scaffold DNA patterning by hybridization of aldehyde-derivatized and underivatized DNA molecules and by sequence-specific protection against aldehyde derivatization. This approach opens new possibilities in wiring of complex molecular-scale electronic circuits. DNA with its remarkable molecular recognition properties and self-assembly capabilities has been proposed as a scaffold for organizing and interwiring electronic components into nanoelectronic circuits. 1,2 However, the intrinsic conductivity of bare DNA is too low to allow its utilization as a molecular wire. 3-5 DNA metallization has been proposed as a possible route to overcome this difficulty and convert the insulating DNA molecules into highly conductive wires. 1 Several different DNA metallization schemes have been reported 6 utilizing various metals, including silver, 1 palladium, 7 and platinum. 8 In general, they consist of two steps. Metallic clusters are first formed on the DNA, and then used as nucleation sites for selective metal deposition until a continu- ous wire is formed. The formation of metallic nucleation centers relies on binding of metal ions or complexes to the DNA and their subsequent reduction to form metallic clusters, or on binding of small metallic particles to the DNA. These metallization schemes suffer from two major draw- backs. First, the metallization process is uniform over the entire DNA scaffold, while functional electronic circuits require controlled wiring. More importantly, metallization destroys the recognition properties of the DNA, thus prevent- ing any subsequent biological processes. We have recently developed a method that solves the first problem by patterning the DNA metallization using a molecular lithog- raphy method, protecting specific sequences of the DNA molecules from the metallization process. 9,10 Here we present a new method that also solves the second problem; the metallization pattern is embedded into the DNA scaffold molecules by sequence-specific derivatization with glutaral- dehyde, which acts a localized reducing agent on the DNA. 9,10 Glutaraldehyde binding marks the DNA for metal- lization prior to the actual metallization process, leaving the marked DNA available for subsequent biological manipula- tions. Silver ions are then specifically reduced by the DNA- bound aldehyde groups in the aldehyde-derivatized regions, resulting in the formation of a silver cluster chain along the DNA. An electroless gold deposition process, 11 catalyzed by the silver clusters, is used to generate continuous DNA- templated gold wires. Thus, the metallization patterning information is embedded into the scaffold DNA by aldehyde- derivatization without compromising the recognition proper- ties of the DNA. This method opens new possibilities for DNA-templated electronics since it allows the construction of elaborate scaffolds using biological processes, imprinting the metallization pattern into the scaffold DNA at any stage along the way while performing the actual metallization process only as a final step. Patterning of aldehyde deriva- tization of DNA was achieved both by hybridization of aldehyde-derivatized and underivatized DNA molecules and by sequence-specific protection against aldehyde derivati- zation using homologous recombination processes by the RecA protein. DNA molecules are first aldehyde-derivatized by reacting them with glutaraldehyde (see Supporting Information). The derivatization is stable in aqueous solutions and leaves the DNA intact. Aldehyde-derivatized DNA is stretched by * Corresponding author. E-mail: erez@physics.technion.ac.il. ² Department of Physics. ‡ Solid State Institute. NANO LETTERS 2004 Vol. 4, No. 2 323-326 10.1021/nl035124z CCC: $27.50 © 2004 American Chemical Society Published on Web 01/03/2004