Insight into Ultrasensitive and High-stability Flocculation-enhanced Raman Spectroscopy for the Noninvasive Probing of Cupping Effect Substances

The aggregation of nanoparticles is the key factor to form hot spots for the flocculation-enhanced Raman spectroscopy (FLERS) method. However, the structure of flocculation is still not clear. It is therefore necessary to explore and analyze the aggregation process of nanoparticles more carefully, so as to realize a better application of FLERS. Here, we report the application of liquid cell transmission electron microscopy (TEM) combined with an high-speed camera to analyze the particle behaviors. The results showed that flocculation can exist stably and the gap between the nanoparticles in the flocculation always remained at 7-9 nm, which ensured the high stability and sensitivity of the FLERS method. We successfully applied FLERS to the noninvasive probing of cupping effect substances. The results indicated the scientific principle behind the traditional Chinese medicine method to some extent, which thus provides a new and effective method for the dynamic monitoring of biological systems.