An ionic liquid (IL)-based liposome, consisting of an imidazolyl head and two undecene tails (N, Ń-bis(10-undecenyl)-2-methylimidazolium bromide, [MimV11, V11]Br), was prepared through self-assembly and used as a carrier to create an isotropic surface-enhanced Raman scattering (SERS) platform. The bridging of IL terminals was employed to enable the co-assembly in both hotspot formation and the induced localization of analytes. Specifically, gold nanoparticles (Au NPs) were grown and stabilized on the surface using the anion exchangeability and coordination effect of IL. Besides, the confinement effect of the isotropic surface spatially arranges the Au NPs in an array-like pattern, which not only facilitates the formation of hotspot-rich planes but also provides a uniform electrostatic driving force for molecular loading. This contributes to the improvements in detection sensitivity and reproducibility of the SERS signal. On this basis, the co-assembled platform presented an ideal enhancement factor (3.04 × 107) and a low detection limit (10-12 M) for methyl orange (MO). Additionally, the detection performance, adsorption orientation, and their influencing factors were investigated. The results showed that the adsorption of MO on the liposome exhibited two typical orientations, lying-type, and standing-type. It was mainly regulated by the resonance structures of MO and the steric effect of the SERS substrate. The isotropic co-assembly strategy achieves ultrasensitive trace detection and draws a fascinating application prospect for this hotspot-motivated and hot region-located SERS detection mode.
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