Nucleic acid electrochemistry

Electrochemical studies of nucleic acid are closely related to the strong need of sensitive but also cost-effective analytical tools for DNA detection in modern life sciences. Particularly, the application of the electrochemistry of DNA in the sensor field plays an important role in bioelectrochemical research. Because of the bases DNA has an inherent electrochemistry. Often guanine oxidation has been used since this base shows the lowest redox potential. Electroactivity can however, also be introduced by molecules which specifically bind to DNA. Intercalators are particularly suited, but also a covalent coupling of a redox molecule is feasible. Based on the inherent or added electroactive character of DNA specific binding to nucleic acids can be analyzed. Here, direct or mediated electron transfer are often exploited. The binding reaction can be a hybridization reaction with another (complementary) nucleic acid strand, but also the binding of small molecules to the DNA (intercalation, groove binding) or the interaction with proteins. A particular group of nucleic acids can provide a 3D structure and thus, allows a specific binding of molecules. This has resulted in increasing application of these aptamers in biosensing. The figure illustrates some different principles of electrochemical DNA analysis based on the detection of a current signal:

1. Use of a redox-active mediator to electrochemically detect DNA.
2. Direct detection of DNA by electro-oxidation of guanine, the bases with the lowest potential for oxidation.
3. Detection of duplex DNA formation using an intercalator
4. Detection of DNA molecules via a redox molecule

1 direct reaction of the redox molecule with the electrode by movements of the nucleic acid strand or
2 using DNA as a `molecule wire´ allowing electron transport through the arranged base staple in a double strand

5. Electrochemical detection of hybridised DNA exploiting an enzyme label
6. DNA detection using diffusing redox molecules penetrating the DNA layer

In addition to the illustrated schemes, there are several alternative strategies to study DNA on electrode surfaces - for example by impedance measurements or by changing the gate voltage in field effect structures due to the accumulation of negative charge. Other developments are focusing on the combination of new technologies in molecular biology (e.g. CRISP-CAS system) with electrochemical detection or the use of nanomaterials to improve signal generation.

References

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R. Aman, A. Mahas, M. Mahfouz, Nucleic Acid Detection Using CRISPR/Cas Biosensing Technologies, ACS Synthetic Biology 9(6) (2020) 1226-1233