Exploiting the interactions of PNA–DNA films with Ni2+ ions: Detection of nucleobase mismatches and electrochemical genotyping of the single-nucleotide mismatch in apoE 4 related to Alzheimer's disease

The presence of Ni2+ enables us to distinguish the presence of single-nucleotide mismatches in PNA (peptide nucleic acids)–DNA films on gold electrodes by electrochemical impedance spectroscopy (EIS). With the help of a modified Randles’ equivalent circuit, differences in the charge transfer resistance (ΔRCT) before and after the addition of Ni2+ are a diagnostic measure for the presence of single-nucleotide mismatch. The approach works under real-life conditions with concentrations of the DNA target strand down to 10 fM, and a PNA capture probe is used to genotype the single-nucleotide mismatch in apoE 4 related to Alzheimer's disease (AD).