Abstract: Methods and systems for synthesizing an oligonucleotide in a reaction chamber comprising a solid support. A nucleotide monomer is selected for addition to an oligonucleotide. An inlet stream comprising the selected monomer is fed to the reaction chamber (column) of the reaction chamber and conditions are provided in the reaction chamber for oligonucleotide synthesis. An outlet stream from the reaction chamber can be split and directed to the waste drain and/or to an analysis station where the eluent is analyzed by mass spectrometry (MS) to confirm the identity of the monomer fed through the inlet to the reaction chamber. Based on results from analyzing by MS, it is determined whether the outlet stream comprises the selected nucleotide monomer or a derivative thereof.

Abstract: Methods and systems for synthesizing an oligonucleotide in a reaction chamber comprising a solid support. A nucleotide monomer is selected for addition to an oligonucleotide. An inlet stream comprising the selected monomer is fed to the reaction chamber (column) of the reaction chamber and conditions are provided in the reaction chamber for oligonucleotide synthesis. An outlet stream from the reaction chamber can be split and directed to the waste drain and/or to an analysis station where the eluent is analyzed by mass spectrometry (MS) to confirm the identity of the monomer fed through the inlet to the reaction chamber. Based on results from analyzing by MS, it is determined whether the outlet stream comprises the selected nucleotide monomer or a derivative thereof.