We report a technique for quantitative three-dimensional (3D) mapping of refractive index in live cells and tissues using a phase-shifting laser interferometric microscope with variable illumination angle. We demonstrate tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure. Our results will permit quantitative characterization of specimen-induced aberrations in high-resolution microscopy and have multiple applications in tissue light scattering.

Ultrasensitive Raman measurements in single living cells are possible through exploiting the effect of surface-enhanced Raman scattering (SERS). Colloidal gold particles (60 nm in size) that are deposited inside cells as “SERS-active nanostructures” result in strongly enhanced Raman signals of the native chemical constituents of the cells. Particularly strong field enhancement can be observed when gold colloidal particles form colloidal clusters. The strongly enhanced Raman signals allow Raman measurements of a single cell in the 400–1800 cm−1 range with 1-μm lateral resolution in relatively short collection times (1 second for one mapping point) using 3–5 mW near-infrared excitation. SERS mapping over a cell monolayer with 1-μm lateral resolution shows different Raman spectra at almost all places, reflecting the very inhomogeneous chemical constitution of the cells. Colloidal gold supported Raman spectroscopy in living cells provides a tool for sensitive and structurally selective detection of native chemicals inside a cell, such as DNA and phenylalanine, and for monitoring their intracellular distributions. This might open up exciting opportunities for cell biology and biomedical studies.