We describe the development of small molecule-sensitive plasmonics-active fiber-optic nanoprobes suitable for
intracellular bioanalysis in single living human cells using surface-enhanced Raman scattering (SERS) detection. The
practical utility of SERS-based fiber-optic nanoprobes is illustrated by measurements of intracellular pH in HMEC-
15/hTERT immortalized "normal" human mammary epithelial cells and PC-3 human prostate cancer cells. The results
indicate that fiber-optic nanoprobe insertion and interrogation provide a sensitive and selective means to monitor
biologically-relevant small molecules at the single cell level.
A critical aspect of the use of nanoprobes for intracellular studies in chemical and biological sensing involves a fundamental understanding of their uptake and trajectory in cells. In this study, we describe experiments using surface-enhanced Raman scattering (SERS) spectroscopy and mapping to track cellular uptake of plasmonics-active labeled nanoparticles. Three different Raman-active labels with positive, negative, and neutral charges were conjugated to silver colloidal nanoparticles with the aim of spatially and temporally profiling intracellular delivery and tracking of nanoprobes during uptake in single mammalian cells. 1-D Raman spectra and 2-D Raman mapping are used to identify and locate the probes via their SERS signal intensities. Because Raman spectroscopy is very specific for identification of chemical and molecular signatures, the development of functionalized plasmonics-active nanoprobes capable of exploring intracellular spaces and processes has the ability to provide specific information on the effects of biological and chemical pollutants in the intracellular environment. The results indicate that this technique will allow study of when, where, and how these substances affect cells and living organisms.