We report the development of a surface plasmon resonance sensor based on the silver ion (Ag+)-induced conformational change of a cytosine-rich, single-stranded DNA for the detection of Ag+ and cysteine (Cys) in aqueous solutions. In the free state, single-stranded oligonucleotides fold into double-helical structures through the addition of Ag+ to cytosine–cytosine (C–C) mismatches. However, in the presence of Cys, which competitively binds to Ag+, the formation of the C–Ag+–C assembly is inhibited, resulting in free-state, single-stranded oligonucleotides. To enhance sensitivity, the DNA intercalator, daunorubicin, was employed to achieve signal enhancement. The detection limit for Ag+ was 10 nM with a measurement range of 50–2,000 nM, and the detection limit for Cys was 50 nM with a measurement range of 50–2,000 nM. This simple assay was also used to individually determine the spiked Ag+ concentration in water samples and Cys concentrations in biological fluid samples.
