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

这个小企业技术转让（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，在数小时内从头制造大量用户指定的寡核苷酸。 低聚物将在平行的玻璃载玻片上使用光引导的亚磷酰胺化学与计算机控制的成像合成，然后选择性地使用一种新的光敏释放过程洗脱。 无掩模曝光将使得快速合成任何数量（高达700，000）的10-40个碱基对寡聚体的不同序列成为可能，在产生的数量和种类之间具有用户定义的权衡。 从原理验证仪器扩展到大规模并行低聚物合成器（MPOS）工具需要更大的产品吞吐量（低聚物的皮摩尔），这将通过光学研究的组合来促进，以增加曝光面积和强度，以及评估各种工程化表面以增加寡聚物之间的密度。本项目的商业应用是在寡核苷酸领域。合成. 成功的基因组测序计划已经导致迫切需要大量不同的DNA寡核苷酸组用作各种类型的基因测试中的亲和试剂。 目前这一代的DNA合成器被设计成仅生产大量的几种寡核苷酸。 该项目提出开发一种能够在与高通量遗传测定兼容的规模上生产数千种寡核苷酸的系统。 预计几乎每个进行分子生物学或遗传学研究的实验室都将从该项目中受益匪浅，因为寡核苷酸引物的使用是PCR、DNA测序和定点诱变等基本和常规实验室方案的基础。 将直接受益于这一项目的商业部门的具体群体包括生产基因筛选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.