Automated Synthesizer Utilizing Tilted Plate Centrifuge

Lebl, Michal

Abstract

application): The subject of this proposal is the design, construction, and evaluation of a prototype for a new instrument for the semi- and fully automated, parallel solid-phase synthesis of 768 compounds, which will be highly beneficial to drug discovery and other biomedical research. The advantages of this instrument compared to currently available synthesizers are a significantly higher synthesis throughput, as well as a novel technology for the separation of the solid support from reagent and wash solutions, which is one of the key processes in the automation of solid-phase synthesis, by centrifugation. In this instrument, compounds will be synthesized in the wells of microtiter plates in a centrifuge. The plates are slightly tilted towards the center of centrifugation, thus forming pockets in each well during centrifugation, in which the solid support is collected, while the liquid is expelled from the wells. This process is mechanically simpler and more efficient compared to currently used technologies (e.g., vacuum filtration), thus enabling the manufacture of more robust, flexible, yet less expensive instruments.

Proposed Commercial Applications

Spyder Instruments' synthesizers based on the tilted plate technology in semi- or fully automated mode of operation, once commercially available, will have an enormous impact on the simplification and acceleration of the parallel solid-phase synthesis of large compound arrays for drug discovery and biomedical research. Tilted plate centrifugation based fluorous-phase synthesizer will be the first instrument for this emerging technology for parallel synthesis. Simple instruments for solid phase extraction will find application in analytical laboratories, and instruments dedicated to plate washing will be applied in biological laboratories.