AUTOMATED DNA SYNTHESIZER USING TILTED PLATE TECHNOLOGY

这项提议的主题是设计、建造和评估一种新的仪器原型，用于大量寡核苷酸(一批768至12,288种化合物)的自动化、并行固相合成，这将对药物基因分型、基因测序和其他涉及发现过程的寡核苷酸非常有利。该仪器的主要优点是它与目前可用的合成器不同，它是一种通过离心法将固体载体与试剂和洗涤液分离的新技术。在这台仪器中，寡核苷酸将在离心机中的微量板孔中合成。这些平板稍微向离心机中心倾斜，从而在离心机过程中在每个井中形成口袋，在其中收集固体支撑物，同时将液体从井中排出。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、但更便宜的仪器。生产的寡核苷酸阵列将用于实现自组装阵列的Illumina技术。拟议的商业应用：基于半自动或全自动操作模式的倾斜板技术的合成器将对用于遗传和生物医学研究的大型DNA阵列的并行固相合成的简化和加速产生巨大影响。这项合成技术将使Illumina的技术成为可能，预计该技术将占据DNA研究和基因分型市场的重要份额。目前，这一市场的年销售额估计为1亿美元。

The subject of this proposal is the design, construction and evaluation of a prototype of a new instrument for the automated, parallel solid-phase synthesis of large arrays of oligonucleotides (768 to 12,288 compounds in one batch), which will be highly beneficial for the drug genotyping, gene sequencing, and other oligonucleotide involving discovery processes. 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, oligonucleotides 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, thus enabling the manufacture of more robust, flexible, yet less expensive instruments. Produced arrays of oligonucleotides will be utilized for enabling the Illumina technology of self assembled arrays. PROPOSED COMMERCIAL APPLICATIONS: Synthesizers based on the tilted plate technology in semi- or fully automated mode of operation will have an enormous impact on the simplification and acceleration of the parallel solid-phase synthesis of large DNA arrays for genetic and biomedical research. The synthetic technology will enable Illumina's technology, which is expected to capture significant portion of the DNA research and genotyping market. This market is presently estimated at $100 million per annum.