Raman microspectroscopy: a noninvasive tool for studies of individual living cells in vitro

There is an increasing need for noninvasive methods that are able to monitor individual live cells in vitro, including in vitro testing of chemicals and pharmaceuticals, monitoring the growth of engineered tissues and the development of cell-based biosensors. Raman spectroscopy is a pure optical technique based on inelastic scattering of laser photons by molecular vibrations of biopolymers, which provide a chemical fingerprint of cells or organelles without fixation, lysis or the use of labels and other contrast-enhancing chemicals. Changes in cells during the cell cycle, cell death, differentiation or during the interaction with various chemicals or materials involve biochemical changes that can be measured with high spatial (∼300 nm) and temporal (seconds to minutes) resolution. The latest technological developments, especially high-sensitivity charged coupled detectors and high-power near-infrared lasers, have spurred the growth of Raman microspectroscopy towards being a well established analytical tool. This review covers the recent applications of this technique, including studies of individual cells, both pro- and eukaryotes, and emphasizes the potential impact on modern scientific endeavors, such as tissue engineering and drug discovery.