Quantitative Evaluation of Surface-Enhanced Raman Scattering Nanoparticles for Intracellular pH Sensing at a Single Particle Level

Abstract

Intracellular pH is one of the key factors for understanding various biological processes in biological cells. Plasmonic gold and silver nanoparticles (NPs) have been extensively studied for surface-enhanced Raman scattering (SERS) applications for pH sensing as a local pH probe in a living cell. However, the SERS performance of NPs depends on material, size, and shape, which can be controlled by chemical synthesis. Here, we synthesized 18 types of gold and silver NPs with different morphologies such as sphere, rod, flower, star, core/shell, hollow, octahedra, core/satellites, and chainlike aggregates, and quantitatively compared their SERS performance for pH sensing. The SERS intensity from the most commonly utilized SERS probe molecule (para-mercaptobenzoic acid, p-MBA) for pH sensing was measured at the single nanoparticle level under the same measurement parameters such as low laser power (0.5 mW/μm2), short integration time (100 ms) at wavelengths of 405, 488, 532, 584, 676, and 785 nm. In our measurement, the Ag chain, Ag core/satellites, Ag@Au core/satellites, and Au core/satellites nanoassemblies showed efficient pH sensing at the single particle level. By using p-MBA-conjugated Au@Ag core/satellites, we performed time-lapse pH measurements during apoptosis of HeLa cells. These experimental results confirmed that the pH measurement using p-MBA-conjugated Au@Ag core/satellites can be applied for long-term measurements of intracellular pH during cellular events