An approach toward SNP detection by modulating the fluorescence of DNA-templated silver nanoclusters

A rapid, homogeneous, and in-situ labelable format designed to detect single nucleotide polymorphism (SNP) is presented. Fluorescent silver nanoclusters produced following hydride-mediated reduction of Ag+ bound to a partial double-stranded oligodeoxynucleotide were employed as probes for SNPs. The sensing mechanism is based on the fluorescence enhancement of silver nanoclusters through an irreversible cluster transfer upon hybridization. The key element of our design is modulating the “turn on” mechanism by introducing a competitor that can be displaced in response to a target DNA. In a controlled model system, the fluorescence intensity of silver nanoclusters is approximately 3-fold enhanced upon hybridization with a perfectly matched target DNA, and single-base mismatch detection is achieved within 5 min, regardless of the position of mismatches. Human aldehyde dehydrogenase 2 (ALDH2), which is responsible for the oxidation of aldehydes to carboxylic acids, is then utilized as a target for SNP. Upon addition of a perfectly matched sequence, dramatically enhanced fluorescence intensity is observed (ca. 48-fold), and prompt SNP genotyping is accomplished.

► This work demonstrates the detection of SNPs using DNA-templated silver nanoclusters (DNA–AgNCs). ► A key principle is to modulate the fluorescence enhancement of DNA–AgNCs by introducing a “competitor”. ► Competitor was designed to respond differently to perfectly matched or mismatched target DNAs. ► By utilizing DNA–AgNCs, one-mismatch discrimination for SNP was achieved within minutes.