A single-nucleotide polymorphism (SNP) detection method was developed by combining single-base primer extension and salt-induced aggregation of gold nanoparticles densely functionalized with double-stranded DNA (dsDNA-AuNP). The dsDNA-AuNPs undergo rapid aggregation in a medium of high ionic strength, whereas particles having a single-base protrusion at the outermost surface disperse stably, allowing detection of a single-base difference in length by color changes. When SNP typing primers are used as analytes to hybridize to the single-stranded DNA on the AuNP surface, the resulting dsDNA-AuNP works as a visual indicator of single-base extension. A set of four extension reaction mixtures is prepared using each of ddNTPs and subsequently subjected to the aggregation assay. Three mixtures involving ddNTP that is not complementary to the SNP site in the target produce the aggregates that exhibit a purple color. In contrast, one mixture with the complementary ddNTP generates the single-base protrusion and appears red. This method could potentially be used in clinical diagnostics for personalized medicine.

Self-assembled structures of metallic nanoparticles with dynamically changeable interparticle distance hold promise for the regulation of collective physical properties. This paper describes gold nanoparticle dimers and trimers that exhibit spontaneous and reversible changes in interparticle distance. To exploit this property, a gold nanoparticle is modified with precisely one long DNA strand and approximately five short DNA strands. The long DNA serves to align the nanoparticles on a template DNA via hybridization, while the short DNAs function to induce the interparticle distance changes. The obtained dimer and trimer are characterized with gel electrophoresis, dynamic light scattering measurements, and transmission electron microscopy (TEM). When the complementary short DNA is added to form the fully matched duplexes on the particle surface in the presence of MgCl2 , spontaneous reduction of the interparticle distance is observed with TEM and cryo-electron microscopy. By contrast, when the terminal-mismatched DNA is added, no structural change occurs under the same conditions. Therefore, the single base pairing/unpairing at the outermost surface of the nanoparticle impacts the interparticle distance. This unique feature could be applied to the regulation of structures and properties of various DNA-functionalized nanoparticle assemblies.

The interparticle distance in gold nanoparticle trimers is modulated by T. Takarada and co‐workers on page 3153. Each particle has one long DNA (green) and several short DNAs (orange). The long DNA serves to align the particles on a template DNA (purple). When the complementary DNA (blue) is hybridized to the short DNA, the interparticle distance is spontaneously decreased in the presence of salt (right front). However, no shrinkage occurs with the terminal‐mismatched DNA (yellow) under the same conditions (left front).

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