Natural <3 nm Interbedded Gaps to Trap Target Molecules and Provide an Enhanced Raman Spectroscopy Method

Abstract To improve the sensitivity of surface‐enhanced Raman spectroscopy (SERS) by constructing smaller hot spots and making the target molecules more accessible, a liquid–liquid interface assembly method is used to construct a three‐layer Ag nanoparticle film structure, wherein the nanoparticles between the adjacent upper and lower layers form natural smaller gaps of 1–3 nm. The target solution is pumped into these gaps using the principle of natural transpiration (the nanopump effect). The resulting hot spot density and efficiency are significantly higher than that of the normal dry‐state method. In addition, the detection limit reaches 1 amol, which is a reduction of 2–3 orders of magnitude compared to the dry‐state method. It is also demonstrated that this dynamic detection process is suitable for detecting the substance changes occurring during sperm–oocyte binding. This method therefore provides a new means for target molecules to actively enter naturally interbedded smaller gaps and provides essentially unlimited possibilities for SERS detection.