Unveiling Electrostatic\nInteraction Modulated Sensitive\nand Selective SERS Detection for Negatively Charged Molecules

Strengthening the interaction between\nthe target and\nSERS substrate\nis crucial for sensitive SERS detection; we thereby explored the molecular\nstructure-dependent SERS sensitivity for negatively charged targets\non the positively charged SERS substrate. Both experimental and theoretical\nstudies confirm that the SERS sensitivity is determined by the electrostatic\ninteraction between the target and linker. This interaction is not\nonly manipulated by the protonation capacity of the linker and its\nsurface adsorption configuration and geometry but also significantly\ndetermined by the target’s structure, encompassing electronegativity\nand the number of interaction sites. The optimized interaction leads\nto a marked improvement in detection sensitivity of up to 1–3\norders of magnitude. The interaction mechanism revealed in this work\nnot only provides theoretical guidance and technical support for electrostatically\ndriven SERS detection but also offers a conceptual framework that\ncan be extended to various SERS detections based on diverse surface\nforces.