STTR Phase I: Optics Design Feasibility for a Massively Parallel Oligonucleotide Synthesizer

这个小型企业技术转移(STTR)第一阶段项目是开发仪器和工艺，使用专有的桌面生产系统，在几个小时内制造大量用户指定的原始寡核苷酸。利用计算机控制成像的光引导亚磷酰胺化学在玻片上平行合成低聚物，然后使用一种新的光敏释放过程选择性洗脱。无掩膜暴露将使快速合成任何数量(高达700,000)不同序列的10-40碱基对低聚物成为可能，并在生产的数量和种类之间进行用户定义的权衡。从原理验证仪器扩展到大规模并行齐聚物合成器(MPOS)工具需要更大的产品产量(低聚物的皮摩尔)，这将通过结合光学研究研究来增加曝光面积和强度，以及评估各种工程表面以增加低聚物之间的密度来促进。该项目的商业应用是在寡核苷酸合成领域。成功的基因组测序计划导致了对大量不同DNA寡核苷酸的迫切需求，以便在各种类型的基因测试中用作亲和试剂。当前一代的DNA合成器被设计成只生产大量只有几个寡核苷酸。该项目建议开发一种能够在与高通量基因分析相兼容的规模上生产数千个寡核苷酸的系统。预计几乎每个从事分子生物学或遗传学研究的实验室都将从这个项目中受益匪浅，因为寡核苷酸引物的使用是聚合酶链式反应、DNA测序和定点突变等基本和常规实验室程序的基础。商业部门中将直接受益于该项目的具体群体包括为基因筛查生产产品的生物技术公司和进行基因分析的临床实验室。

This Small Business Technology Transfer (STTR) Phase I project is to develop the instrumentation and processes to fabricate ex-novo large numbers of user-specified oligonucleotides in hours, using a proprietary tabletop production system. Oligomers will be synthesized in parallel on a glass slide using light-directed phosphoramidite chemistry with computer-controlled imaging, and then selectively eluted using a novel photosensitive release process. Maskless exposure will make possible the rapid synthesis of any number (up to 700,000) of different sequences of 10-40 base pairs oligomers, with a user-defined tradeoff between the quantity and variety produced. Scaling up from a proof-of-principle instrument to a Massively Parallel Oligomer Synthesizer (MPOS) tool requires larger product throughput (picomoles of oligomers) which will be facilitated through the combination of an optical research study to increase the exposure area and intensity, and the evaluation of various engineered surfaces to increase the density among the oligomers.The commercial application of this project is in the area of oligonucleotide synthesis. Successful genome sequencing programs have led to an urgent need for massive sets of different DNA oligonucleotides to be used as affinity reagents in various types of genetic tests. The current generation of DNA synthesizers are designed to produce large quantities of only a few oligonucleotides. This project proposes to develop a system capable of producing thousands of oligonucleotides on a scale compatible with high throughput genetic assays. It is expected that practically every laboratory performing molecular biology or genetic research will benefit tremendously from this project, since the use of oligonucleotide primers is basic to such fundamental and routine laboratory protocols as PCR, DNA sequencing, and site-directed mutagenesis. Specific groups in the commercial sector that will directly benefit from this project include biotechnology companies that manufacture products for genetic screening and clinical laboratories performing genetic analysis.