M.SssI-catalyzed DNA methylation alters the protein-binding affinity of the device. A device containing a single M.SssI binding site was taken through the illustrated steps (left) and the corresponding relative conductances (top right) were measured in (1) buffer containing 10 nM BSA before addition of M.SssI, (2) buffer and M.SssI without SAM, (3) buffer and M.SssI with SAM (represented by the blue hexagon), and (4) buffer after M.SssI has been rinsed away. Note that current attenuation is only observed for step (3). After methylation, the device was taken through the same sequence of steps (5)–(8) with no attenuation observed. The sequence was H2N-5′-GACAGTCGACATGTC -3′-NH2, with the single 5′-CG-3′ binding site located in the middle. The buffer conditions were 50 mM NaCl, 10 mM Tris-HCl, 10 mM MgCl2, 1 mM Dithiothreitol, pH 7.9.