AUTOMATED SYNTHESIZER USING TILTED PLATE CENTRIFUGATION

本提案的主题是设计、构建、评估和生产一种用于自动化、平行固相或氟相合成768种化合物的新仪器，以解决药物发现过程中对新化合物的持续需求。该仪器的主要优点，使其与目前可用的合成器不同，是一种通过离心从试剂和洗涤溶液中分离固体载体的新技术。在该仪器中，化合物将在离心机的微量滴度板孔中合成。板向离心中心略微倾斜，因此在离心过程中在每孔中形成口袋，在口袋中收集固体支撑（或多相系统中的下液相），同时将液体从孔中排出。与目前使用的技术相比，这一过程在机械上更简单、更有效，从而能够制造出更坚固、更灵活、更便宜的仪器。倾斜离心技术还可以应用于固相萃取、液-液萃取和生物检测中的洗板。离心仪器家族的商业化努力将包括制造一系列试验产品，这些产品将在多个试验点进行测试。建议的商业应用：Spyder Instruments倾斜板生物处理器将加快许多对生物技术和药物研究和开发至关重要的限速任务。目前这种仪器的市场估计每年总额为5 000万美元；包括自动化分析，提取仪器和合成组合文库和复合阵列。主要竞争对手是Argonaut， Advanced ChemTech, Bohdan Automation, Tecan, Rapp Polymere。Spyder Instruments预计在SBIR二期成功结束后的两年内占据该市场10%的份额。

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.