Y-Shaped DNA Duplex Structure-Triggered Gold Nanoparticle Dimers for Ultrasensitive Colorimetric Detection of Nucleic Acid with the Dark-Field Microscope

Herein, we present a novel gold nanoparticle (AuNP) enumeration-based colorimetric aptamer biosensor for ultrasensitive detection of nucleic acid. This AuNP enumeration-based colorimetric method takes advantages of the distinctive and strong localized surface plasmon resonance light scattering with the dark-field microscope. In our model system, first, cost-effective DNA1 instead of expensive 2-thioethyl ether acetic acid was capped on the surface of AuNPs to form a dense DNA1 layer. Then, two DNA strands (DNA2 and DNA3) in two different solutions were separately asymmetrically functionalized on the AuNPs capped dense DNA1 layer. The subsequent binding of the target DNA could trigger the formation of perfect complementary DNA with a Y shape and adjust the distance between nanoparticles to form AuNP dimers, accompanied by a color change from green to yellow as observed, and thereby modulated the performance of the sensor, which resulted in the ultrahigh sensitivity. With this design, a 43 aM limit of detection was obtained, which exhibited an increase of at least 5-9 orders of magnitude in sensitivity over other colorimetric sensors fabricated using conventional strategies.