Electrical Detection of Dna Binding Proteins

The base pair stack of double helical DNA has proven to be an effective medium for charge transport. The π-stacked DNA base pairs can mediate charge transport (CT) chemistry over distances as long as 20 nm, and the reaction is exquisitely sensitive to DNA sequence-dependent conformation and dynamics. This sensitivity to perturbations in DNA structure and base pair stacking makes DNA-mediated charge transport chemistry an ideal methodology for the electrical detection of base mismatches, lesions, and protein binding. Efforts toward expanding the scope of electrochemistry at DNAmodified surfaces for biosensing applications are presented here. The first conclusive study of the single-molecule conductivity of DNA is demonstrated. A pristine single DNA duplex in its native conformation can be utilized to covalently bridge an oxidatively etched, single-walled carbon nanotube gap. The effective resistance is on the order of ~ 1 MΩ, which is similar to the c-axis resistance of kish graphite. Furthermore, the inclusion of either the CA or GT mismatches within the DNA duplex is seen to increase the resistance of DNA by over two orders of magnitude. This study underscores the fact that conductivity is an intrinsic property of each individual DNA molecule and not, in fact, an ensemble property of the DNA monolayer. The characterization of DNA monolayers at high oriented pyrolytic graphite is described. Graphite electrodes are modified with duplex DNA containing a pendant pyrene; the yield of electrochemical reduction/oxidation to DNA-bound probes on graphite provides an indicator of base stacking within the DNA. The inclusion of even a single thermodynamically stable yet poorly stacked GT mismatch dramatically attenuates