Mass spectrometry imaging and profiling of individual cells and subcellular 
structures provide unique analytical capabilities for biological and biomedical 
research, including determination of the biochemical heterogeneity of cellular 
populations and intracellular localization of pharmaceuticals. Two mass 
spectrometry technologies-secondary ion mass spectrometry (SIMS) and matrix 
assisted laser desorption/ionization mass spectrometry (MALDI MS)-are most often 
used in micro-bioanalytical investigations. Recent advances in ion probe 
technologies have increased the dynamic range and sensitivity of analyte 
detection by SIMS, allowing two- and three-dimensional localization of analytes 
in a variety of cells. SIMS operating in the mass spectrometry imaging (MSI) 
mode can routinely reach spatial resolutions at the submicron level; therefore, 
it is frequently used in studies of the chemical composition of subcellular 
structures. MALDI MS offers a large mass range and high sensitivity of analyte 
detection. It has been successfully applied in a variety of single-cell and 
organelle profiling studies. Innovative instrumentation such as scanning 
microprobe MALDI and mass microscope spectrometers enables new subcellular MSI 
measurements. Other approaches for MS-based chemical imaging and profiling 
include those based on near-field laser ablation and inductively-coupled plasma 
MS analysis, which offer complementary capabilities for subcellular chemical 
imaging and profiling.