Small-molecule diagnostics based on functional DNA nanotechnology: A dipstick test for mercury

Detecting small molecular targets such as metal ions is just as important as detecting large molecules such as DNA, RNA and proteins, but the field of metal ion sensors has not yet been well developed. A good example of a metal ion target is mercury, which is highly toxic, widely distributed in the environment and affects human health. To develop a diagnostic platform for metal ions, we demonstrate that functional DNA-linked gold nanoparticles (AuNPs) can quickly and simply detect and quantify Hg²⁺ ions in aqueous solution, with high sensitivity and selectivity over competing metal ions. A linker DNA molecule containing thymine residues and sequences complementary to the DNA on the AuNPs was designed to aggregate DNA-functionalized AuNPs. When Hg ²⁺ ions were introduced into this system, they induced the linker DNA to fold by forming thymine-Hg²⁺-thymine bonds. The linker DNA's folding caused the AuNPs to rapidly disassemble, which caused a discernable color change in the solution from purple to red. The limit of detection for Hg²⁺ in the present method is 5.4 nM, which is below the 10 nM maximum contaminant level defined by the US Environmental Protection Agency (EPA) for drinking water. Our results show that this Hg²⁺ detection method has excellent selectivity over other divalent metal ions (e.g. Pb ²⁺, Cu²⁺, Mn²⁺, Co²⁺, Zn ²⁺, Cd²⁺, Mg²⁺, Ca²⁺, and Ba ²⁺). This system has been converted into a dipstick test using lateral-flow devices, making it even more practical for point-of-care diagnostics.