The detection of a single-nucleotide mismatch in a 20 base pair duplex DNA, using EIS, is presented. Mismatched DNA monolayers on Au electrodes were studied as normal duplex DNA (B-DNA) and after conversion to Zn metalated duplex DNA (M-DNA). Modeling of the impedance data to an equivalent circuit provides parameters that are useful in discriminating each monolayer configuration. The conversion to M-DNA caused a decrease in the resistance to charge transfer (R CT)- Contrary to expectations, R CT for B-DNA was also found to decrease for duplexes containing a mismatch. Dehybridization rehybridization studies to form DNA duplex with incomplete hybridization efficiencies showed that mismatch can still be detected for M-DNA but not for B-DNA. The R CT for a perfect duplex was 76(12) Ohm·cm 2, whereas a mismatch in the middle of the sequence yielded a R CT value of 30(15) Ohm·cm 2. The detection limit was measured and the impedance methodology reliably detected single DNA base pair mismatches at concentrations as low as 100 pM.
