Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (∼150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically relevant ssDNA sequences (70–140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration.
Our approach suggest that spherical nucleic acids can disturb the secondary structure of long DNA sequences, making feasible the detection of relevant mutations in biological targets. As future directions, we foresee the use of the present assay in the detection of long sequences from dsDNA to study its validity in the detection of other mutations, and to decrease the discrimination time by varying the particle shape.