Automated high throughput mass spectral analysis of oligonucleotides

The DNA Technology Group currently produces an average of 110 synthetic oligomers per day, all requiring quality assurance analysis. The addition of delayed extraction (DE) technology to matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry enables the rapid mass analysis of multiple oligonucleotide samples. We have incorporated a matrix diluting and liquid spotting automated work station (AWS) for precise and repeatable sample placement, and a DE MALDI mass spectrometer (MS) to provide high throughput analysis of synthetic oligonucleotides. Prior to the development of these systems, the only methods of analysis with sufficient throughput were trityl cation analysis and polyacrylamide gel electrophoresis (PAGE). Unfortunately, PAGE can only give a qualitative analysis of the product and is unable to unambiguously verify the identity of the oligomers. The DE MALDI MS reliably determines the mass of each sample to within 0.35 percent of the expected mass. This mass accuracy allows us to confirm the identity and purity of the oligonucleotides we produce with an unprecedented degree of confidence. Using this automation suite, sample preparation, spotting and analysis of 96 samples and a standard can be completed in less than 90 minutes.