Automated high-throughput mass spectrometric analysis of synthetic oligonucleotides

The use of automated sample preparation and data collection coupled with delayed ion extraction matrix-assisted laser desorption ionization with time-of-flight detection mass spectrometry (DE MALDI-TOF MS) enables the rapid mass analysis of oligonucleotide samples. We have incorporated a matrix-diluting and liquid-spotting automated work station and a DE MALDI mass spectrometer to provide high-throughput analysis of synthetic oligonucleotides. Automated sample preparation greatly speeds processing while the spotting function allows for precise sample placement on a 100-well sample plate. The DE MALDI MS typically determines the mass of each sample to within 0.13 +/- 0.10% of the theoretically expected mass. This mass accuracy allows confirmation of identity and detection of low-level impurities present in synthetic oligonucleotide samples with an unprecedented degree of confidence. Using this automation suite, sample preparation, spotting, and analysis of 100 samples ranging from 12 to 70 bases in length can be routinely completed in less than 90 min.