Figure 4 Schematic amplified analysis of a target DNA using: (A) An oligonucleotide-enzyme conjugate and a biocatalyzed transformation as amplification route. (B) An oligonucleotide-functionalized particle (liposome or nanoparticle) as an amplifying unit.

Electrical contacting of redox-enzymes with electrode supports was extensively studied to develop amperometric biosensor and other bioelectronic devices [35]. Electrobiocatalytic transformations coupled to DNA recognition events were used to amplify nucleic acid detection process [32, 36]. The hemoprotein cytochrome c lacks direct electrical contact with the bare Au-electrode. Immobilization of the thiolated primer (5′-ACGGATGCTCC-(CH2)3-SH-3′) onto the electrode followed by the formation of the double-stranded assembly with the complementary nucleic acid resulted in the quasi-reversible redox-response of cytochrome c [36], Figure 5. This was attributed to the electrostatic attraction of the hemoprotein by the negatively charged double-stranded DNA that facilitates interfacial electron transfer. Although the DNA-stimulated electrical contacting of cytochrome c with the electrode allows the secondary activation of redoxenzymes, and thus the amplification of sensing events, the differentiation of singlestranded versus double-stranded DNA on the electrical contact effectiveness of cytochrome c needs further investigations.