Oriented Assembly of Gold Nanoparticles with Freezing-Driven Surface DNA Manipulation and Its Application in SERS-Based MicroRNA Assay

Exceptional amplification of electronic, magnetic, and optical signals can be achieved by assembling inorganic nanoparticles with well-defined structures in certain orientations. DNA-programmed assembly of gold nanoparticles (AuNPs) has been employed to construct highly ordered nanostructures for surface-enhanced Raman scattering (SERS)-based biosensing. However, the performance of SERS signal amplification is seriously compromised due to limitations in controlling the number and orientation of the conjugated DNA strand on AuNPs surface and the cross-linked aggregations. Herein, a high-throughput approach is developed based on freezing-driven DNA binding, which is capable of precisely manipulating the DNA conjugation number on the surface of AuNPs. It avoids complex post-treatments and no additional reagents, e.g., salts, acids, or surfactants, are necessary. Most importantly, the DNA-AuNP conjugates are analogous to atoms and serve as building blocks for precise construction of molecule-like assemblies. The structures such as dimers, trimers, and core-satellite assemblies are obtained in a short period of time with excellent stability by simply varying the DNA conjugation density on the surface of AuNPs. As a result, robust SERS signals in controllable assemblies are successfully achieved, which facilitate highly sensitive detection of microRNAs with a detection limit of 0.12 x 10(-12) M, thereby demonstrating their potential in bioassays.