Rapid delivery of silver nanoparticles into living cells by electroporation for surface-enhanced Raman spectroscopy

In current intracellular surface-enhanced Raman spectroscopy (SERS) measurements, gold or silver nanoparticles are delivered into living cells by "passive uptake". This procedure is time-consuming, could take up to several to twenties hours of incubation with nanoparticles in the culture medium. It is a less optimal method for certain applications such as high-throughput disease screening. Here, we present a method based on electroporation for fast delivery of silver nanoparticles into living cells for intracellular SERS spectroscopy. This new method for nanoparticle delivery averts the shortcoming of "passive uptake" and allows for quick acquisition of robust SERS spectra from living C666, A431, and CA46 cancer cell lines in our study. Our study also shows that the silver nanoparticles are localized only in the cell cytoplasm for electroporation delivery, while for "passive uptake", the nanoparticles have gone beyond the cytoplasm and into the nucleus. However, the whole-cell detection SERS spectra using electroporation delivery are more reproducible than for "passive uptake", thus are favored for practical applications. As a result, the process of SERS detection is accelerated significantly and the data reproducibility is improved as well, demonstrating great potential for biomedical applications, such as for high-throughput cancer cell screening.