Ex situ and in situ surface-enhanced Raman spectroscopy for macromolecular profiles of cell nucleus

Cytobiological methods for cell nucleus-related studies start with the extraction processes of intranuclear components with many cell lysis buffers, following with the structural characterizations and quantitative analysis of the extracted components. In this study, we tried to evaluate the availability and reliability of these extraction-based analytical methods from their spectral features. We implemented an in situ surface-enhanced Raman scattering spectroscopy (SERS) strategy with the help of the nucleus-targeting nanoprobes to investigate the molecular information of nucleus, in comparison with these ex situ methods. This study provides valuable references for choosing an appropriate detection method according to different detection purposes, and also points out the risks of many developing cell-related analytical methods that combine the traditional cytobiological techniques from exogenous interferences during sample preprocesses. Graphical abstract.