SBIR-STTR Award

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 APPLICATION: 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.

The subject of this proposal is the design, construction, evaluation, and production of a new instrument for the automated, parallel solid-phase or fluorous-phase synthesis of 768 compounds, which addresses an ongoing need for new compounds for the drug discovery process. The principal advantage of this instrument, which sets it apart from currently available synthesizers, is a novel technology for the separation of the solid support from reagent and wash solutions 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 (or lower liquid phase in multiphase systems) is collected, while the liquid is expelled from the wells. This process is mechanically simpler and more efficient compared to currently used technologies, thus enabling the manufacture of more robust, flexible, yet less expensive instruments. The technology of tilted centrifugation can also be applied for solid phase extraction, liquid-liquid extraction, and plate washing in bioassays. The commercialization efforts of the family of centrifugation based instruments will include the manufacture of a pilot series, which will be tested at multiple beta-sites. PROPOSED COMMERCIAL APPLICATIONS: The Spyder Instruments tilted plate bioprocessor will expedite many rate- limiting tasks vital to biotechnology, and to pharmaceutical research and development. The current market for such instrumentation is estimated to total $50,000,000 per annum; including automated assays, extraction instrumentation and synthesis of combinatorial libraries and compound arrays. Leading competitors are Argonaut, Advanced ChemTech, Bohdan Automation, Tecan, Rapp Polymere. Spyder Instruments expects to capture 10% of this market within 2 years following successful conclusion of SBIR Phase II period.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
Biomedical Automation, Biomedical Equipment Development, Centrifugation, Chemical Synthesis Combinatorial Chemistry, Drug Discovery /Isolation, Isoquinoline, Robotics, Solid State