Highly Uniform Self-Assembly of Gold Nanoparticles by Butanol-Induced Dehydration and Its SERS Applications in SARS-CoV-2 Detection.

We report the development of a reproducible and highly sensitive surface-enhanced Raman scattering (SERS) substrate using a butanol-induced self-assembly of gold nanoparticles (AuNPs) and its application as a rapid diagnostic platform for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The butanol-induced self-assembly process was used to generate a uniform assembly of AuNPs, with multiple hotspots, to achieve high reproducibility. When an aqueous droplet containing AuNPs and target DNAs was dropped onto a butanol droplet, butanol-induced dehydration occurred, enriching the target DNAs around the AuNPs and increasing the loading density of the DNAs on the AuNP surface. The SERS substrate was evaluated by using Raman spectroscopy, which showed strong electromagnetic enhancement of the Raman signals. The substrate was then tested for the detection of SARS-CoV-2 using SERS, and a very low limit of detection (LoD) of 3.1 × 10