High-throughput DNA analysis by time-of-flight mass spectrometry

Progress in medicine and genomics research has increased the desire for ever faster genetic analysis tools, outstripping the capacity of existing technology. Characteristics that need to be measured include differential gene expression, gene mutational spectra and protein-DNA/RNA interactions, as well as the identification of new disease-related genes. Current DNA sequencing and sizing technology is based largely on gel electrophoresis separation and fluorescent or radioactive detection. Much of our knowledge comes from this technology and it will continue to contribute. The separation speed limitation is due to the fact that migration of a DNA molecule through the dense structural network of a gel, even with capillary-sized containment, is an inherently slow process. An alternative separation and detection technology is based on mass spectrometry, where ions are separated as they travel in a vacuum. Mass spectrometry has been applied successfully to a variety of chemical problems for decades, most notably in the analysis of metabolites and synthetic organic compounds. It is well known that under optimal conditions, a mass spectrum for a given sample can be acquired in only seconds. Moreover, mass spectrometry can be automated.