Fully Automated Parallel Oligonucleotide Synthesizer

Abstract

Design and construction of automated synthesizers using the tilted plate centrifugation technology is described. Wash solutions and reagents common to all synthesized species are delivered automatically through a 96-channel distributor connected to a gear pump through two four-port selector valves. Building blocks and other specific reagents are delivered automatically through banks of solenoid valves, positioned over the individual wells of the microtiterplate. These instruments have the following capabilities: Parallel solid-phase oligonucleotide synthesis in the wells of polypropylene microtiter plates, which are slightly tilted down towards the center of rotation, thus generating a pocket in each well, in which the solid support is collected during centrifugation, while the liquid is expelled from the wells. Eight microtiterplates are processed simultaneously, providing thus a synthesizer with a capacity of 768 parallel syntheses. The instruments are capable of unattended continuous operation, providing thus a capacity of over two millions 20-mer oligonucleotides in a year.