Matrix‐Assisted Laser Desorption/Ionization Time‐of‐Flight Mass Spectrometry of Oligonucleotides

MALDI-MS is one of the most useful techniques available for determining biomolecule mass. It offers high mass accuracy, good sensitivity, simplicity, and speed. Because singly charged ions of oligonucleotides are typically observed, MALDI-MS spectra are easy to interpret. This unit presents protocols for sample preparation and purification, matrix preparation, and matrix/analyte sample preparation. It provides an introduction to the instrumentation and its calibration, and a discussion of some of the useful applications of MALDI-MS analysis in the study of oligonucleotides. This technique is typically used for 120-mer or smaller oligonucleotides.